chronic renal failure b is the gradual decline in renal function due to the death of nephrons due to chronic kidney disease. At the initial stages, it is asymptomatic, later on, disorders of the general condition and urination, edema, and pruritus join. The gradual deterioration of kidney function leads to disruption of the body's vital functions, the occurrence of complications from various organs and systems. Diagnosis includes clinical and biochemical tests, Reberg and Zimnitsky tests, ultrasound of the kidneys, ultrasound of the renal vessels. Treatment of chronic renal failure is based on the treatment of the underlying disease, elimination of symptoms and repeated courses of extracorporeal hemocorrection.

General information

(CRF) is an irreversible violation of the filtration and excretory functions of the kidneys, up to their complete cessation, due to the death of renal tissue. CRF has a progressive course, in the early stages it manifests itself as a general malaise. With an increase in chronic renal failure - pronounced symptoms of intoxication of the body: weakness, loss of appetite, nausea, vomiting, swelling, skin - dry, pale yellow. Sharply, sometimes to zero, diuresis decreases. In the later stages, heart failure develops, pulmonary edema, bleeding tendency, encephalopathy, uremic coma. Shown hemodialysis and kidney transplant.

Causes of CRF

Chronic renal failure can be the outcome of chronic glomerulonephritis, nephritis in systemic diseases, chronic pyelonephritis, diabetic glomerulosclerosis, renal amyloidosis, polycystic kidney disease, nephroangiosclerosis and other diseases that affect both kidneys or a single kidney.

Pathogenesis

The pathogenesis is based on the progressive death of nephrons. Initially, renal processes become less efficient, then kidney function is impaired. The morphological picture is determined by the underlying disease. Histological examination indicates the death of the parenchyma, which is replaced by connective tissue. The development of CRF is preceded by a period of suffering from chronic kidney disease lasting from 2 to 10 years or more. The course of kidney disease before the onset of CRF can be divided into a number of stages. The definition of these stages is of practical interest, since it affects the choice of treatment tactics.

Classification

The following stages of chronic renal failure are distinguished:

1. Latent. Occurs without significant symptoms. Usually detected only by the results of in-depth clinical studies. Glomerular filtration is reduced to 50-60 ml/min, there is periodic proteinuria.
2. Compensated. The patient is worried about increased fatigue, a feeling of dry mouth. An increase in the volume of urine with a decrease in its relative density. Decreased glomerular filtration to 49-30 ml/min. Increased creatinine and urea levels.
3. Intermittent. The severity of clinical symptoms increases. There are complications due to the increasing CRF. The patient's condition changes in waves. Decreased glomerular filtration rate to 29-15 ml/min, acidosis, persistent increase in creatinine levels.
4. Terminal. It is characterized by a gradual decrease in diuresis, an increase in edema, gross violations of acid-base and water-salt metabolism. There are phenomena of heart failure, congestion in the liver and lungs, liver dystrophy, polyserositis.

CKD symptoms

In the period preceding the development of chronic renal failure, renal processes persist. The level of glomerular filtration and tubular reabsorption is not impaired. Subsequently, glomerular filtration gradually decreases, the kidneys lose their ability to concentrate urine, and renal processes begin to suffer. At this stage, homeostasis is not yet disturbed. In the future, the number of functioning nephrons continues to decrease, and with a decrease in glomerular filtration to 50-60 ml / min, the patient has the first signs of CRF.

Patients with a latent stage of CKD usually do not complain. In some cases, they note mild weakness and decreased performance. Patients with chronic renal failure in the compensated stage are concerned about a decrease in efficiency, increased fatigue, and a periodic feeling of dry mouth. With the intermittent stage of chronic renal failure, the symptoms become more pronounced. Weakness increases, patients complain of constant thirst and dry mouth. Appetite is reduced. The skin is pale, dry.

Patients with end-stage renal failure lose weight, their skin becomes gray-yellow, flabby. Characterized by itching, reduced muscle tone, tremor of the hands and fingers, small muscle twitches. Thirst and dry mouth intensify. Patients are lethargic, drowsy, unable to concentrate.

With an increase in intoxication, a characteristic smell of ammonia from the mouth, nausea and vomiting appear. Periods of apathy are replaced by excitement, the patient is inhibited, inadequate. Characterized by dystrophy, hypothermia, hoarseness, lack of appetite, aphthous stomatitis. The abdomen is swollen, frequent vomiting, diarrhea. Stool dark, offensive. Patients complain of excruciating skin itching and frequent muscle twitches. Anemia increases, hemorrhagic syndrome and renal osteodystrophy develop. Typical manifestations of chronic renal failure in the terminal stage are myocarditis, pericarditis, encephalopathy, pulmonary edema, ascites, gastrointestinal bleeding, uremic coma.

Complications

CRF is characterized by increasing disorders of all organs and systems. Blood changes include anemia due to both inhibition of hematopoiesis and a reduction in the life of red blood cells. Coagulation disorders are noted: prolongation of bleeding time, thrombocytopenia, a decrease in the amount of prothrombin. On the part of the heart and lungs, arterial hypertension is observed (in more than half of the patients), congestive heart failure, pericarditis, myocarditis. In the later stages, uremic pneumonitis develops.

Neurological changes in the early stages include distraction and sleep disturbance, in the later stages - lethargy, confusion, in some cases delirium and hallucinations. On the part of the peripheral nervous system, peripheral polyneuropathy is detected. On the part of the gastrointestinal tract in the early stages, a deterioration in appetite, dry mouth is detected. Later there is an eructation, nausea, vomiting, stomatitis. As a result of irritation of the mucosa during the release of metabolic products, enterocolitis and atrophic gastritis develop. Superficial ulcers of the stomach and intestines are formed, often becoming sources of bleeding.

On the part of the musculoskeletal system, CRF is characterized by various forms of osteodystrophy (osteoporosis, osteosclerosis, osteomalacia, fibrous osteitis). Clinical manifestations of renal osteodystrophy are spontaneous fractures, skeletal deformities, compression of the vertebrae, arthritis, pain in the bones and muscles. On the part of the immune system, lymphocytopenia develops in chronic renal failure. Reduced immunity causes a high incidence of purulent-septic complications.

Diagnostics

If the development of chronic renal failure is suspected, the patient needs to consult a nephrologist and conduct laboratory tests: a biochemical analysis of blood and urine, a Reberg test. The basis for the diagnosis is a decrease in the level of glomerular filtration, an increase in the level of creatinine and urea.

During the Zimnitsky test, isohyposthenuria is detected. Ultrasound of the kidneys indicates a decrease in the thickness of the parenchyma and a decrease in the size of the kidneys. A decrease in intraorganic and main renal blood flow is detected on ultrasound of the kidney vessels. Radiocontrast urography should be used with caution due to the nephrotoxicity of many contrast agents. The list of other diagnostic procedures is determined by the nature of the pathology that caused the development of CRF.

Treatment of chronic renal failure

Specialists in the field of modern urology and nephrology have extensive capabilities in the treatment of CRF. Timely treatment aimed at achieving a stable remission can often significantly slow down the development of pathology and delay the appearance of severe clinical symptoms. When conducting therapy for a patient with an early stage of chronic renal failure, special attention is paid to measures to prevent the progression of the underlying disease.

Treatment of the underlying disease continues even in violation of renal processes, but during this period the importance of symptomatic therapy increases. If necessary, prescribe antibacterial and antihypertensive drugs. Shown sanatorium treatment. It is required to control the level of glomerular filtration, the concentration function of the kidneys, renal blood flow, the level of urea and creatinine. In case of violations of homeostasis, the acid-base composition, azotemia and water-salt balance of the blood are corrected. Symptomatic treatment consists in the treatment of anemic, hemorrhagic and hypertensive syndromes, maintaining normal cardiac activity.

Patients with chronic renal failure are prescribed a high-calorie (about 3,000 calories) low-protein diet that includes essential amino acids. It is necessary to reduce the amount of salt (up to 2-3 g / day), and with the development of severe hypertension, transfer the patient to a salt-free diet. The protein content in the diet depends on the degree of impaired renal function, with glomerular filtration below 50 ml / min, the amount of protein decreases to 30-40 g / day, with a decrease below 20 ml / min - up to 20-24 g / day.

With the development of renal osteodystrophy, vitamin D and calcium gluconate are prescribed. One should be aware of the danger of calcification of the internal organs caused by large doses of vitamin D in hyperphosphatemia. To eliminate hyperphosphatemia, sorbitol + aluminum hydroxide is prescribed. During therapy, the level of phosphorus and calcium in the blood is monitored. Correction of the acid-base composition is carried out with a 5% solution of sodium bicarbonate intravenously. In oliguria, to increase the volume of urine excreted, furosemide is prescribed at a dosage that provides polyuria. To normalize blood pressure, standard antihypertensive drugs are used in combination with furosemide.

With anemia, iron preparations, androgens and folic acid are prescribed, with a decrease in hematocrit to 25%, fractional transfusions of erythrocyte mass are performed. The dosage of chemotherapeutic drugs and antibiotics is determined depending on the method of excretion. Doses of sulfonamides, cephaloridine, methicillin, ampicillin and penicillin are reduced by 2-3 times. When taking polymyxin, neomycin, monomycin and streptomycin, even in small doses, complications may develop (neuritis of the auditory nerve, etc.). Patients with CRF are contraindicated in derivatives of nitrofurans.

The use of glycosides in the treatment of heart failure should be done with caution. The dosage is reduced, especially with the development of hypokalemia. Patients with an intermittent stage of chronic renal failure during an exacerbation are prescribed hemodialysis. After the patient's condition improves, they are again transferred to conservative treatment. Effective appointment of repeated courses.

With the onset of the terminal stage and the absence of the effect of symptomatic therapy, the patient is prescribed regular hemodialysis (2-3 times a week). Transfer to hemodialysis is recommended when creatinine clearance falls below 10 ml/min and its plasma level rises to 0.1 g/l. When choosing the tactics of therapy, it should be taken into account that the development of complications in chronic renal failure reduces the effect of hemodialysis and excludes the possibility of kidney transplantation.

Forecast and prevention

The prognosis for chronic renal failure is always serious. Sustainable rehabilitation and a significant prolongation of life is possible with timely hemodialysis or kidney transplantation. The decision on the possibility of carrying out these types of treatment is made by transplantologists and doctors of hemodialysis centers. Prevention involves the timely detection and treatment of diseases that can cause chronic renal failure.

Slowly developing symptoms: anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, apathy, chronic fatigue, itching, decreased clarity of thought, muscle convulsions and convulsions, fluid retention, nutritional deficiencies, gastrointestinal ulcers and bleeding, peripheral neuropathies, epileptic seizures. Diagnosis is based on laboratory tests of renal function, sometimes supplemented by renal biopsy. Treatment is directed at the underlying disease, but also includes normalization of fluid and electrolyte balance, restoration of erythropoietin levels in anemia, often dialysis and transplantation.

Causes of Chronic Kidney Disease

Chronic kidney disease can be caused by any cause of significant impairment of kidney function. The most common cause of chronic kidney disease in the US is diabetic nephropathy. Metabolic syndrome, characterized by hypertension and type 2 diabetes mellitus, is a common cause of kidney damage with an ever-increasing prevalence.

Cause	Examples
Glomerulopathies (primary)	focal glomerulosclerosis Idiopathic sickle glomerulonephritis IgA nephropathy Membranoproliferative glomerulonephritis Membranous nephropathy
Glomerulonephritis associated with systemic disease	Amyloidosis Diabetes Hemolytic uremic syndrome Post-infectious glomerulonephritis Wegener's granulomatosis
Hereditary nephropathies	Hereditary nephritis (Alport syndrome) Medullary cystic kidney disease Patellar nail syndrome Polycystic kidney disease
Arterial hypertension	Malignant glomerulosclerosis Nephroangiosclerosis
Obstructive uropathy	benign prostatic hyperplasia Posterior ureteral valves Retroperitoneal fibrosis Obstruction of the ureter (congenital, stones, cancer)
Vesiculourethral reflux	Macrovascular pathology of the kidneys (vasculopathy of the renal arteries and veins) Renal artery stenosis caused by atherosclerosis or fibromuscular dysplasia

Pathophysiology of Chronic Kidney Disease

Initially, the loss of function of the kidney tissue has little to no pathological manifestations, because the remaining tissue is working hard (functional adaptation of the kidneys); the loss of 75% of kidney tissue causes a decrease in GFR by only 50% compared to the norm.

Decreased renal function correlates with the ability of the kidneys to maintain water and electrolyte homeostasis. Changes increase regularly, but can occur in parallel and there is significant individual variability.

Plasma creatinine and urea concentrations (which are highly dependent on glomerular filtration) begin to increase non-linearly as GFR decreases. At first, these changes are minimal. Urea and creatinine levels are not the main symptoms of uremia; they are markers for many other substances (some not yet identified) that lead to symptoms.

Heart failure develops due to sodium and water overload, in particular in patients with reduced cardiac reserve.

Adaptation usually keeps levels of substances controlled primarily by distal nephron secretion (eg, potassium) within normal limits until renal failure progresses. K-sparing diuretics, ACE inhibitors, beta-blockers, β-NSAIDs, cyclosporine, tacrolimus may increase K levels in patients with less severe renal impairment.

There are metabolic disorders of calcium, phosphates, vitamin D, parathyroid hormone and renal osteodystrophy. Decreased renal production of calcitriol leads to hypocalcemia. Decreased renal excretion of phosphate leads to hyperphosphatemia. Secondary hyperparathyroidism is widespread and can develop in renal failure to abnormal levels of calcium or phosphate. Therefore, PTH control is recommended in patients with moderate chronic kidney disease, even before the onset of hyperphosphatemia.

Renal osteodystrophy (impaired bone mineralization due to hyperparathyroidism, calcitriol deficiency, elevated serum phosphate, or low or normal serum calcium levels) usually results in accelerated bone metabolism due to the bone form of hyperparathyroidism (osteitis fibrosis), but can also lead to suppressed bone metabolism due to adynamic bone loss. disease (with increased suppression of parathyroid function) or osteomalacia. Calcitriol deficiency can cause osteopenia or osteomalacia.

Moderate acidosis and anemia are typical. Anemia in chronic kidney disease normochromic-normocytic, hematocrit 20-30% (35-50% in patients with polycystic kidney disease). It is usually caused by a deficiency in the production of erythropoietin due to a decrease in functioning renal mass. Other causes: deficiency of iron, folate and vitamin B 12.

Symptoms and signs of chronic kidney disease

With a moderate decrease in renal reserve, the course is usually asymptomatic. Even in patients with mild or moderate renal insufficiency, there may be no symptoms of elevated BUN and creatinine levels. Nocturia is often observed, especially due to an inability to concentrate urine. Apathy, fatigue, lack of appetite, and decreased clarity of thought are often the earliest manifestations of uremia.

In more severe renal insufficiency, neuromuscular symptoms may appear, including severe muscle twitches, peripheral sensory and motor neuropathies, muscle cramps, hyperreflexia, and epileptic seizures. Anorexia, nausea, vomiting, weight loss, stomatitis, and bad taste in the mouth are very common. Skin tone may turn yellow-brown. Sometimes urea crystals are shed on the surface of the skin with sweat, forming a uremic frost. Particular discomfort can be caused by itching. Nutritional deficiencies leading to generalized tissue loss are the hallmark of chronic uremia.

In severe chronic kidney disease, pericarditis, peptic ulcer and bleeding in the gastrointestinal tract are often observed. Arterial hypertension is present in more than 80% of patients with chronic kidney disease, usually associated with hypervolemia. Heart failure caused by hypertension or sodium and water retention can lead to secondary edema.

Diagnosis of Chronic Kidney Disease

• Determination of the levels of electrolytes, BUN, creatinine phosphate, calcium in the blood, urinalysis (including microscopy of the urinary sediment).
• Sometimes a kidney biopsy.

As a rule, the presence of chronic kidney disease is first suspected with an increase in serum creatinine. The first step is to determine whether the kidney failure is acute, chronic, or acute to chronic (eg, an acute disease that impairs kidney function in a patient with chronic kidney disease). The cause of the kidney failure has also been determined. Sometimes determining the duration of kidney failure helps determine the cause; sometimes it is easier to determine the cause than the duration, and finding the cause helps determine the duration.

Examination: urinalysis with microscopy of urinary sediment, assessment of electrolyte levels, urea nitrogen, creatinine, phosphate, calcium and CBC.

Classification of chronic kidney disease

• Stage 1: Normal GFR in association with persistent albuminuria or known structural or hereditary pathology of the kidney.
• Stage 2: GFR 60-89 ml/min/1.73 m 2 .
• Stage 3: GFR 30-59 ml/min/1.73 m 2 .
• Stage 4: GFR 15-29 ml/min/1.73 m 2 .
• Stage 5: GFR<15 мл/мин/1,73 м 2 .

Treatment of chronic kidney disease

• Treatment of the causative disease.
• If possible, restriction in the diet of protein, phosphates and K.
• Vitamin D supplements.
• Treatment of anemia and heart failure.
• Adjust doses of all drugs as needed.
• Hemodialysis with a significant decrease in GFR, symptoms of uremia, sometimes - hyperkalemia or heart failure.

Water and electrolyte metabolism. Fluid intake is limited only when the sodium concentration is less than 135 mmol / l.

Limiting sodium intake to 2 g/day has a beneficial effect.

Potassium intake is associated with the consumption of meat, vegetables and fruits and often does not need to be adjusted. However, foods (especially salt substitutes) rich in potassium should be avoided.

Limiting phosphate intake to 1 g/day is often sufficient to maintain phosphate levels within the target range in stages 3 and 4 of chronic kidney disease. However, in later stages phosphate-binding drugs such as calcium salts (acetate or citrate) and calcium-free (sevelamer). As a binder, no more than 1500 mg calcium per day can be given (total 2000 mg Ca: binder+food).

Moderate acidosis (pH 7.3-7.35) does not require treatment. However, most patients with chronic metabolic acidosis and pH less than 7.3 have plasma HCO 2 levels of less than 15 mmol/l and have symptoms of anorexia, apathy, dyspnea, and increased protein catabolism and renal osteodystrophy. Assign NaHCO 2 1-2 g 2 r / day with a gradual increase until the concentration of HCO 3 reaches a value of 20 mEq / l or until sodium overload prevents further therapy.

Anemia and coagulation disorders. The goal of treating anemia is to keep the hemoglobin level between 11 and 12 g/dL. Anemia responds slowly to administration of recombinant human erythropoietin.

Heart failure. Symptomatic heart failure is treated with sodium restriction and diuretics.

Hemodialysis. Patients with uremic symptoms (eg, anorexia, nausea, weight loss, pericarditis, pleurisy) or fluid overload for no other reason should be started on dialysis even if the GFR is above these values. Other indications for hemodialysis in chronic kidney disease include hyperkalemia leading to ECG changes or persisting despite dietary restrictions, heart failure poorly controlled by medication, and difficult to control metabolic acidosis.

Department of Health and Social Assistance to the Population of the Administration of Irkutsk

Irkutsk State Institute for Postgraduate Medical Education

Third revision

UDC: 616.61-008.6 BBK 54.1

The recommendations are devoted to the diagnosis and treatment of chronic kidney disease, which not only can lead to the development of end-stage renal disease, but is also a significant risk factor for cardiovascular disease. The recommendations are intended for practitioners.

UDC: 616.61-008.6 BBK 54.1

© Department of Health and Social Assistance to the Population of the Administration of Irkutsk, 2011

Members of the expert group

Andrievskaya Tatyana Grigorievna,

Candidate of Medical Sciences, Associate Professor of the Department of Faculty Therapy, ISMU

Bardymova Tatyana Prokopyevna,

Doctor of Medical Sciences, Professor, Head. Department of Endocrinology, ISIUVa, Chief Endocrinologist of the Department of Health and Social Assistance to the Population of the Administration of Irkutsk

Belov Vyacheslav Vladimirovich

Doctor of Medical Sciences, Professor, Head. Department of Internal Diseases and VPT ChSMA, Chelyabinsk

Belyalov Farid Ismagilevich,

Doctor of Medical Sciences, Professor of the Department of Geriatrics and Gerontology of ISIUV, Chief Therapist of the Department of Health and Social Assistance to the Population of the Administration of Irkutsk, Chairman of the Expert Group

Vinkova Natalya Nikolaevna,

head city ​​department of dialysis, chief nephrologist of the Department of Health and Social Assistance to the Population of the Administration of Irkutsk, head. dialysis department of MSCh IAPO

Kuznetsova Nadezhda Mironovna,

deputy chief physician for medical work of the medical unit "Airport Irkutsk"

Kuklin Sergey Germanovich,

Doctor of Medical Sciences, Professor of the Department of Therapy and Cardiology, ISIUV

Kutuzova Raisa Ivanovna,

head therapeutic department of the City Hospital No. 3

Pogodaeva Svetlana Valerievna,

Head of the Department of Organization and Planning of Medical Activities of the Department of Health and Social Assistance to the Population of the Administration of Irkutsk

Shcherbakova Alexandra Vitalievna,

Candidate of Medical Sciences, Assistant of the Department of Faculty Therapy, ISMU

Organization of nephrological care in Irkutsk....................................................... ....
Epidemiology................................................. ................................................. ...........
Definition and criteria .................................................................. ................................................
Etiology	.......................................................................................................................
Pathogenesis................................................. ................................................. ...................
Classification................................................. ................................................. ...........
Formulation of the diagnosis .................................................. ...............................................
Markers of kidney damage .............................................................. ......................................
Assessment of kidney function .............................................................. ................................................
Glomerular filtration rate .................................................................. ......................
Plasma creatinine ............................................................... ...............................................
Cystatin C .................................................. ................................................. ..........
Treatment................................................. ................................................. ......................
Slowing the progression of PN .............................................................. .........................
Syndromic treatment .................................................................. .........................................
Extracorporeal treatment .............................................................. ...............................
Tactics .............................................................................. ................................................. .........
Application................................................. ................................................. ...............
Literature................................................. ................................................. ................
Abbreviations
	– arterial hypertension
	- arterial pressure
	- angiotensin II receptor blockers
	- angiotensin-converting enzyme inhibitors
	- glomerular filtration rate
	- kidney failure
	– chronic kidney disease

Introduction

Worldwide, there is an increase in the number of patients with chronic renal pathology due to an increase in the incidence of diabetes mellitus, arterial hypertension and the aging of the population. The number of patients requiring renal replacement therapy is steadily increasing.

In connection with the development of numerous criteria for assessing kidney function, it became necessary to unify approaches to the diagnosis, as well as the treatment and prevention of chronic renal failure. Currently, the concept of chronic kidney disease (CKD), proposed by American nephrologists, has received general recognition (K/DOQI, 2002).

Numerous scientific studies are carried out annually, recommendations of international expert groups are issued. At the same time, there are no Russian recommendations on chronic kidney disease, which are sorely needed by practitioners. The specific conditions of municipal healthcare, a large number of voluminous recommendations that often contradict each other, and the lack of timely translations of the most important documents make it expedient to create local recommendations that will help Irkutsk doctors actively implement the concept of chronic kidney disease in everyday practice.

This document reflects the coordinated position of the leading experts of the city of Irkutsk, based on evidence-based medicine and international recommendations. During the preparation process, the text was open for discussion and the proposals received were taken into account in the final version of the recommendations.

To improve the recommendations, comments and suggestions are important, which can be sent to the expert group by email: [email protected] It is planned to update the recommendations annually, and significant additions to the electronic version will be made more frequently.

Chairman of the expert group, chief therapist of the Department of Health and Social Assistance to the Population of the Administration of Irkutsk, Professor Farid Ismagilyevich Belyalov

Organization of nephrological care in Irkutsk

Patients with kidney diseases are identified and treated in municipal polyclinics and hospitals by doctors of therapeutic specialties (general practitioners, cardiologists, endocrinologists).

Specialized nephrology care for adults is provided in the dialysis department of the Medical Unit of the IAPO, city hospital No. 8, as well as in the nephrology department and the chronic hemodialysis department of the Regional Clinical Hospital.

Nephrologists at the Medical Unit of the IAPO maintain a register of city patients with CKD and provide consultations to Irkutsk citizens daily from 10 am to 12 pm, except weekends

(tel. 329704).

Epidemiology

According to large population registries (NHANTS III, Okinawa Stady), the prevalence of CKD is at least 10%, reaching more than 20% in certain categories of people (the elderly, type 2 diabetes).

Estimated data show that there should be about 97,000 patients with CKD in Irkutsk, including 33,000 with stage 1, 31,000 with stages 2 and 3, and 1,200 with stages 4 and 5 (NHANES, 1999–2004). According to the chief nephrologist of Irkutsk, in 2010, patients with CKD stages 1–2, 3, 4 and 5 stages, respectively, were registered 360, 635, 307 and 151 people (Vinkova N.N., 2010).

					Table 1
	The number of patients in the city department of hemodialysis
		Patients	Patients
		with acute PN		patients	hemodialysis

Estimating the true number of patients with CKD is difficult because usually the underlying disease, such as diabetes mellitus or chronic glomerulonephritis, is coded for statistical purposes. In 2010, according to the statistical reporting form No. 12 under headings N17–19, 756 patients with PN were registered.

In the city dialysis department of the Medical Unit of the IAPO, which has 12 dialysis places, 96 patients received substitution therapy in 2010, including 7 with acute PI and 89 with end-stage chronic PI (Table 1). The latter included chronic glomerulonephritis (37%), diabetic nephropathy (22%), hypertensive nephroangiosclerosis (12%), tubulointerstitial kidney disease (11%), polycystic disease (9%).

Definition and criteria

Chronic kidney disease is defined as kidney damage or decreased kidney function for three months or more, regardless of diagnosis. Modern criteria for CKD are shown in Table 2.

table 2

CKD criteria (K/DOQI, 2006)

1. Kidney damage 3 months, defined as structural or functional disorders of the kidneys with or without a decrease in GFR, which is manifested by one of the signs:

 changes in urine or visual tests,  morphological abnormalities.

2. GFR<60 мл/мин/1,73 м² for ≥3 months with or without evidence of kidney damage.

Etiology

Allocate risk factors for the development of CKD, which are divided into predisposing, initiating kidney damage and influencing the rate of progression (table 3).

Table 3

Major risk factors for CKD (K/DOQI, 2002, 2006)

predisposing	Elderly age.
	Family history.
Initiators
	Arterial hypertension.
	Immune diseases.
	Systemic infections.
	Urinary tract infections.
	Urinary stones.
	Obstruction of the lower urinary tract.
	Toxic drugs.
Progression	Arterial hypertension.
	Hyperglycemia.
	Dyslipidemia.
	Severe proteinuria.

Diseases leading to CKD

 Diseases of the glomeruli (chronic glomerulonephritis), tubules and interstitium (chronic tubointerstitial nephritis, including pyelonephritis).

 Diffuse connective tissue diseases (systemic lupus erythematosus, systemic scleroderma, polyarteritis nodosa, Wegener's granulomatosis, hemorrhagic vasculitis).

 Metabolic diseases (diabetes mellitus, amyloidosis, gout, hyperoxalaturia).

 Congenital kidney diseases (polycystic, renal hypoplasia, Fanconi syndrome).

 Primary vascular lesions: hypertension, renal artery stenosis.

 Obstructive nephropathy: urolithiasis, tumors of the genitourinary system.

 Drug damage to the kidneys (non-narcotic analgesics, non-steroidal anti-inflammatory and other drugs).

 Toxic nephropathy (lead, cadmium, silicon, alcohol).

Pathogenesis

Most chronic kidney diseases have a single mechanism of progression. As a result of the death of part of the nephrons caused by the underlying disease (glomerulonephritis, diabetes mellitus, vascular glomerulosclerosis, etc.), compensatory structural and functional changes develop in the remaining unaffected nephrons. These changes are represented by intraglomerular hypertension, hyperfiltration, hypertrophy of nephrons as a result of activation of the intrarenal (tissue) renin-angiotensin system.

In the early stages of the formation of renal failure, there is a decrease in the functional reserve of the kidney, in particular, a decrease in the ability to increase GFR in response to protein load. At this stage, the course of renal dysfunction is asymptomatic. Further loss of functioning nephrons (up to 30% of the norm) leads to more pronounced impairment of kidney function - an increase in the concentration of nitrogenous metabolites (urea, creatinine), electrolyte imbalance, anemia, etc.

Classification

In patients with diseases that cause kidney damage or signs of kidney damage, GFR and the corresponding stage of CKD are assessed (Table 4).

GFR at the level of 90 ml/min/1.73 m2 was taken as the lower limit of normal. Conditions with GFR in the range of 60 to 89 ml/min/1.73 m2 in the absence of evidence of kidney damage are classified as "decrease in GFR", which is appropriate to reflect in the diagnosis. A slight decrease in GFR in older people without initiating risk factors for CKD is regarded as the age norm.

When GFR does not reach 60 ml/min/1.73 m2 for 3 or more months, regardless of whether there are other signs of nephropathy, CKD of the appropriate stage should be diagnosed.

				Table 4
		Classification of Chronic Kidney Disease (K/DOQI, 2006)
		Characteristic
			ml/min/1.73 m²
		kidney damage		Treatment of the underlying disease
				slowdown in the rate of GFR,
		with normal or
				reducing the risk of cardiovascular
				diseases.
		kidney damage		Estimation of the rate of progression
		with mild GFR
		Moderate GFR		Identification and treatment of complications
		Expressed GFR		Preparation for substitution
		renal		Renal replacement therapy
		failure

Formulation of the diagnosis

The concept of CKD expands the concept of "chronic renal failure" by assessing the initial stages of kidney disease, which allows you to start preventive measures earlier, slow down the progression of renal failure and reduce the increasing frequency of terminal renal failure.

Since the current International Classification of Diseases (ICD) was recommended for use in 1994, there is no CKD heading in the official Russian translation of the classification. However, in October 2007, the World Health Organization significantly revised N18 (Table 5).

AT In order to preserve the generally accepted structure of the diagnosis, it is recommended that the diagnosis of CKD be listed after the underlying disease. The coding of the disease is set in accordance with the ICD for the underlying disease, and if it is impossible to identify the latter - headings N18.1–9.

AT in the case of dialysis or a transplanted kidney, it is recommended to make appropriate marks in the diagnosis, for example, “stage 5D” or “stage 3T”, respectively.

Examples of some common clinical diagnoses based on Russian guidelines and agreed upon by leading experts and practitioners are shown in Table 6.

Table 5

	Updated coding for N18 in the ICD (WHO, 2007)
	Description
	chronic kidney disease
	Inclusions: chronic uremia, diffuse sclerosing glo-
	merulonephritis.
	Excludes: chronic renal failure with hypertension
	Use an additional code, if necessary, to identify
	evidence of an underlying disease or hypertension.
	Chronic kidney disease, stage 1
	Kidney damage with normal or elevated GFR
	(>90 ml/min/1.73 m2).
	Chronic kidney disease, stage 2
	Kidney damage with mild decrease in GFR
	(60–89 ml/min/1.73 m2)
	Chronic kidney disease, stage 3
	Kidney damage with moderate decrease in GFR
	(30-59 ml / min / 1.73 m2).
	Chronic kidney disease, stage 4
	Kidney disease with marked decrease in GFR
	(15-29 ml / min / 1.73 m2).
	Chronic kidney disease, stage 5
	kidney failure (<15 мл/мин/1,73 м2 или диализ).
	Inclusions: chronic uremia, end stage disease
	Chronic kidney disease, unspecified
	Inclusions: renal failure, unspecified, uremia, unspecified
	clarified.
	Excludes: renal failure with hypertension (I12.0).

Recall that in the absence of signs of kidney damage and GFR 60-89 ml / min / 1.73 m2, the stage of CKD is not established, and “decrease in GFR” is noted in the diagnosis. In the elderly (>65 years), GFR values ​​in the range of 60–89 ml/min/1.73 m2 are regarded as a variant of the norm. Patients on dialysis are diagnosed with Stage 5 CKD.

Examples of clinical diagnosis formulations	Table 6
Chronic glomerulonephritis, urinary syndrome, CKD stage 2.
Chronic glomerulonephritis, membranous proliferative,
nephrotic syndrome, exacerbation, CKD stage 3.
Type 2 diabetes mellitus, severe course, decompensation.
Complication: CKD stage 4.
Hypertension stage III, risk 4.
Complications: CHF I FC, stage 1. Decrease in GFR (64 ml/min/1.73
m2, 25.04.08).
Hypertension stage II, risk 3.
Complication: CKD stage 2.
Systemic lupus erythematosus, subacute course, activity II
degrees, polyarthritis, right-sided exudative pleurisy,
membranoproliferative glomerulonephritis, CKD stage 4.
Chronic tubulointerstitial nephritis caused by parace-
tamol, CKD stage 2.
Chronic kidney disease, unspecified, stage 4.

Markers of kidney damage

Chronic kidney injury is defined as structural abnormalities of the kidney that can lead to reduced kidney function. Experts have proposed laboratory and visual markers of kidney damage used to diagnose CKD (K/DOQI, 2002).

Laboratory markers include proteinuria, hematuria, leukocyturia, cylindruria.

Proteinuria is an early and sensitive marker of kidney damage in many nephropathies. In this case, the main protein of urine, as a rule, is albumin with a small molecular weight (table 7).

Albuminuria. Normally, in adults, urinary albumin excretion is<30 мг/сут. Микроальбуминурия (30–300 мг/сут) является ранним маркером повреждения почек. В связи с вариативностью альбуминурии необходимо получить не менее двух положительных тестов из трех (UKRA, 2011).

The ratio of the concentration of protein (albumin) to the concentration of creatine

nina in the same portion of urine eliminates the influence of changes in urine concentration, which equally affect the concentration of protein in the urine

and creatinine. It was found that the ratio of protein concentration to creatinine concentration in the first morning portion of urine most closely correlates with the level of nocturnal proteinuria, while its values ​​in the middle of the first half of the day more reflect daily proteinuria. In diabetic patients, the albumin/creatinine ratio can be used to detect and monitor diabetic nephropathy (SIGN, 2008). In non-diabetic patients, the protein/creatinine ratio can be used to diagnose

and assessment of the risk of disease progression. Estimation of the protein/creatinine ratio is unreliable in patients with very large or small muscle mass.

					Table 7
	Assessment of proteinuria and albuminuria (K/DOQI, 2002)
	Urinalysis			Microalbu–	Albuminuria/
					proteinuria
	24 hour excretion				>300 mg/day
	Free
					>30 mg/dl
	portion - strip
	Protein/creatinine
	in random portion
	24 hour excretion		<30 мг/сут	30–300 mg/day	>300 mg/day
	random portion -
Albumen
				17–250 mg/g
	Albumin/creatinine in
	arbitrary portion			25–355 mg/g

When detecting microhematuria, it is required to exclude urinary tract infection, and in patients after 40 years, kidney cancer. If microhematuria is accompanied by proteinuria and a decrease in GFR, then the probability of glomerular or vascular damage to the kidneys is high.

Visual markers of kidney damage are determined with the instrument

tal research:

 ultrasound examination - changes in the size of the kidneys, increased echogenicity, volumetric formations, stones, nephrocalcinosis, cysts;

 computed tomography - obstruction, tumors, cysts, stones of the bladder and ureters, stenosis a. renalis;

 isotope scintigraphy - asymmetry of function, size of the kidneys.

Kidney damage can also be manifested by clinical and laboratory syndromes:

 nephrotic syndrome - proteinuria> 3.5 g / day, hypoalbuminemia, hyperlipidemia, edema;

 nephritic syndrome - hematuria, erythrocyte casts, proteinuria >1.5 g/day, edema, hypertension;

 tubulointerstitial syndrome - decrease in urine density, electrolyte disturbances, proteinuria<1,5 г/сут.

Assessment of kidney function

In general therapeutic practice, kidney function is usually assessed using the following methods:

 Glomerular filtration rate. o Calculation formulas.

o Creatinine clearance.

 Plasma creatinine.

 Cystatin C.

Glomerular filtration rate

For a quick assessment and monitoring of kidney function, it is recommended to estimate the value of GFR, which quite informatively reflects the state of the kidneys. There is a close relationship between the level of GFR and the presence of certain manifestations or complications of CKD. However, a decrease in GFR to 20-30 ml/min/1.73 m2 usually does not show clinical symptoms.

If reduced GFR is detected, the test should be repeated after 2 weeks and then after >90 days to assess the stability of the indicator changes.

It should be noted that the use of GFR as the main measure of CKD severity, and not the serum creatinine more familiar to many practitioners, is preferable, because. the relationship between creatinine concentration and GFR is not linear. Therefore, in the early stages of chronic kidney disease, with very similar values ​​of serum creatinine levels, GFR values ​​can differ by almost two times. In this regard, GFR should be considered as a much more sensitive indicator of the functional state of the kidneys.

In chronic nephropathy, a decrease in GFR reflects a decrease in the number of active nephrons, that is, it is an indicator of the preservation of the mass of the functioning renal parenchyma. In wide practice, simple calculation methods for estimating GFR are used (Table 8).

In general, estimated GFR is less reliable in stages 1–2 of CKD, when hyperfiltration and hypertrophy of active nephrons are possible, which maintains a normal level of total GFR. Among the methods for calculating GFR, the MDRD formula is recommended, but at present, the estimate of the estimated GFR using the CKD-EPI formula (Levey A.S. et al, 2009) is considered the most accurate.

Estimated creatinine clearance according to the Cockcroft-Gault formula is still considered the standard in dose adjustment of drugs.

It is better to calculate GFR in the laboratory rather than using GFR calculators as with each set of reagents for assessing plasma creatinine, a correction factor for the indicator is given.

Table 8

Calculation formulas for estimating creatinine clearance and GFR

	Formula for calculating GFR
	a × (plasma creatinine (µmol/l)/b)c × (0.993) age
(ml/min/1.73 m2)				c, dependent on plasma creatinine
				≤62 µmol/l	>62 µmol/l
	32788 * [plasma creatinine (µmol/l)] - 1.154 * age - 0.203 *
(ml/min/1.73 m2)	0.742 (for women)
	1.228 * * body weight (kg) * 0.85 (for women)
Gault (ml/min)	plasma creatinine (µmol/l)

Area 0.007184 × height (cm) 0.725 × weight (kg) 0.425

body (m 2 ) is used to standardize GFR in the Cockroft-Gault formula: (GFR/body area)*1.73

Note: 1 mg/dL plasma creatinine = 88.4 µmol/L.

For 12 hours before assessing plasma creatinine, the patient should not eat meat, and drugs that affect the concentration of creatinine, such as trimethoprim, which is secreted by the tubules and can compete with creatinine, should be discontinued.

Estimates of GFR based on creatinine clearance (preferably inulin, which is not secreted by the tubules) are preferable to the above calculation formulas in the initial stages of PI, with rapid changes in kidney function, cachexia or obesity, muscle disease, paraplegia, a diet with limited or excess creatine, taking nephrotoxic drugs, dialysis.

Plasma creatinine

There is no generally accepted estimate of the norm of plasma creatinine. Approximate relationships between plasma creatinine and GFR are presented in the Appendix. The level of creatinine significantly depends on gender (15% lower in women), race, body weight, chronic diseases, diet (vegetarians or heavy meat consumption) and this reduces the diagnostic value of the method.

Cystatin C

Cystatin C is a cysteine ​​protease inhibitor produced by all nucleated cells and enters the bloodstream at a constant rate. Low molecular weight allows it to be freely filtered into the glomerulus

In patients without impaired renal function, the level of cystatin C is 0.50–0.95 mg/l (conversion factor to nmol/l = 75).

Slowing the progression of PN

The main goal of treating patients with CKD is to slow down the rate of progression of renal failure and delay the start of renal replacement therapy. Achieving this goal, along with the treatment of the underlying disease, requires a whole range of measures:

 Hypertension control with BP achievement<130/80 мм рт. ст.

 Use of angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs).

 Glycemic control in diabetic patients by achieving HbA1c<7%.

 To give up smoking.

ACE inhibitors are widely used, which reduce intraglomerular hypertension and hyperfiltration by expanding the efferent arterioles of the glomeruli. Long-term treatment with ACE inhibitors can preserve the filtration function of the kidneys and slow down the rate of decline in GFR, regardless of the presence of hypertension. The drugs were effective even in severe CKD with creatinine levels of 440–530 µmol/L. In case of intolerance to ACE inhibitors, an ARB is recommended. The combination of an ACE inhibitor and an ARB appears to reduce proteinuria more than either alone, but more often causes hypotension and is less effective in slowing the progression of kidney disease (Kunz R. et al, 2008; ONTARGET).

In non-diabetic CKD, drugs that block the renin-angiotensin system are effective in proteinuria >0.5 g/day (KDOQI, 2004; UKRA, 2007).

Table 9 Monitoring intervals for BP, GFR, and plasma potassium during treatment

ACE inhibitor or ARB (K/DOQI, 2006)

		BP systolic, mm Hg Art.
	Index	GFR, ml/min/1.73 m²
		Previous GFR, %
		Plasma potassium, mmol/l
		After initiation/dose escalation
	Interval
		After reaching the target BP and
		dose stabilization

ACE inhibitors and ARBs slow the progression of diabetic CKD with microalbuminuria even in the absence of hypertension (RENAAL, IDNT, CSG trial of Captopril). Titrate ACE inhibitors and ARBs to moderate to high doses to reduce albuminuria (ROAD, IRMA 2). The dose regimen of drugs is indicated in the appendix.

After the start of treatment with ACE inhibitors, an increase in plasma creatinine is noted, which correlates with a slowdown in the progression of CKD. ACE inhibitor treatment can be continued if GFR decreases<30% от исходного в течение 4 мес после начала лечения и гиперкалиемии ≤5,5 ммоль/л (K/DOQI, 2006). Интервалы мониторинга АД, СКФ и калия плазмы при лечении ИАПФ/БРА представлены в таблице 9.

A low protein diet (0.6–0.8 g/kg) is prescribed for stages 4–5 of CKD and helps to reduce the filtration load on the kidneys. At the same time, protein intake of 0.6 g/kg does not reduce mortality and the time to start dialysis, compared with a dose of 0.8 g/kg (Bruno C., et al, 2009).

Patients with CKD, including stage 5, most often die from cardiovascular diseases. Moreover, CKD is a major risk factor for cardiovascular events. Therefore, already in the early stages of CKD, it is necessary to actively treat dyslipidemia, hypertension, obesity, hyperglycemia, stop smoking and increase physical activity.

With dyslipidemia with elevated levels of low-density lipoprotein cholesterol, the appointment of statins is indicated. Perhaps statins slow the progression of CKD. The goal of treatment is to achieve plasma low-density lipoprotein cholesterol levels.<2,5 ммоль/л, а при диабете или атеросклеротической сердечно–сосудистой патологии <2,0 ммоль/л (ESC, 2007).

Verapamil, sulodexide and statins do not have sufficiently reliable evidence to effectively slow the rate of GFR decline.

Patients with CKD are at increased risk of an acute decrease in GFR when taking non-steroidal anti-inflammatory drugs [including selective], aminoglycosides, cyclosporine, vancomycin, intravenous administration of radiopaque agents.

Syndromic treatment

Arterial hypertension

Correction of blood pressure slows down the onset of terminal renal failure and reduces the risk of cardiovascular disease. Salt restriction is important (<6 г/сут или натрия <2,4 г/сут) в диете.

The goal of antihypertensive therapy is to maintain systolic blood pressure at 120–139 mm Hg. Art., diastolic blood pressure<90 мм рт. ст. (UKRA, 2011). В случае протеинурии >1 g / day there is reason to consider the target systolic blood pressure at the level of 120-129 mm Hg. Art., diastolic blood pressure<80 мм рт. ст.

Hypotension should be avoided as decrease in systolic blood pressure<110 мм рт. ст. может увеличить прогрессирование ХБП (AIPRD; K/DOQI, 2004; UKRA, 2007).

At the stage of PN, as a rule, monotherapy does not lead to stabilization of the level of blood pressure, therefore, combination therapy with antihypertensive drugs belonging to different groups is recommended. Along with ACE inhibitors and ARBs, beta-blockers, diuretics, alpha-blockers, calcium antagonists can be prescribed. It is necessary to take into account the dose adjustment of drugs excreted by the kidneys.

hyperglycemia

Diabetic nephropathy develops in 20–40% of diabetic patients on average 5–7 years after the onset of proteinuria. Diabetic nephropathy is the leading cause of ESRD (40–50% of all cases) in which dialysis or kidney transplantation is performed. In this regard, albuminuria and GFR are monitored annually in patients with type 1 diabetes 5 years after the onset of the disease, and with type 2 diabetes - immediately after diagnosis.

Good glycemic control reduces the risk and slows down the development of diabetic nephropathy (DCCT, UKPDS). However, the effectiveness of intensive glycemic control in nephropathy with severe proteinuria has not been proven.

In the early stages of diabetic nephropathy, continued treatment with oral hypoglycemic drugs is possible, and in the later stages, insulin therapy is preferable. The goal of diabetes treatment is to achieve glycated hemoglobin (HbA1c) levels<7%. Особенности коррекции доз сахароснижающих препаратов представлены в таблице 10,

			Table 10
	Doses of antidiabetic drugs in CKD
		(K/DOQI, 2007, with additions)
		Preparations	Doses for stages 3-4 of CKD
		Glibenclamide	not shown
	Preparations	Glipizide	Does not change
		Gliquidone	Does not change
	sulfonylurea
		Gliclazide	Does not change
		Glimeperide	Start at 1 mg/day
	Thiazolidinediones	Rosiglitazone	Does not change
	biguanides		Contraindicated in creatinine
		Metformin	plasma >124 µmol/l (w),
			>133 µmol/l (m)
		Repaglinide	Does not change
		Nateglinide	Start with 60 mg before meals
	Inhibitors	Acarbose
	alpha-glucosidase		plasma >176 µmol/l
			Dose reduced by 25%

With edema, regular weight control is necessary in the morning after the toilet. A sodium-restricted diet is recommended<2,4 г/сут (соли соответственно <6 г/сут). Заменители соли содержат большое количество калия и не рекомендуются при ХБП.

To eliminate fluid retention, thiazide diuretics are used once at stages 1–3 of CKD, loop diuretics 1–2 times a day at stages 4–5. With severe edema, a combination of thiazide and loop diuretics is possible. In patients with GFR<30 мл/мин/1,73 м2 калийсберегающие диуретики могут быть опасны вследствие гиперкалиемии.

In nephrotic syndrome, despite the massive loss of protein, the content of animal protein in food should not exceed 0.8 g / kg. With a decrease in the concentration of albumin in the blood<2,5 г/л рекомендуют инфузии бессолевого альбумина 1 г/кг*сут.

Anemia is often observed in patients with PN, is associated with increased mortality, worsens the course of concomitant diseases (ischemic heart disease, heart failure) and reduces the quality of life.

Partially the cause of anemia can be iron deficiency associated with shortening of the life of red blood cells, malabsorption, blood loss. At the pre-dialysis stage, ferritin levels<25 мг/л у мужчин и <12 мг/л у женщин свидетельствует о вкладе дефицита железа в развитии анемии. Для лечения применяют препараты железа из расчета 200 мг элементарного железа в сутки в течение 6 месяцев.

Severe anemia is associated with reduced synthesis of renal erythropoietin, a hormone that provides erythropoiesis. When prescribing erythropoietin, you need to carefully weigh the risk (hypertension, hyperkalemia, thrombosis) and benefit (improved quality of life, refusal of blood transfusions). With uncontrolled hypertension and severe coronary heart disease, treatment with erythropoietin is contraindicated.

Against the background of treatment with erythropoietin, iron deficiency in the blood serum increases, therefore, for more effective treatment, it is advisable to combine erythropoietin therapy with iron-containing drugs.

The goal of treating anemia is to achieve a hemoglobin level of 110–120 g/L (K/DOQI, 2007).

Metabolic disorders

The development of PN is characterized by hyperkalemia due to a decrease in renal excretion of potassium. Therefore, it is recommended to exclude foods rich in potassium (bananas, dried apricots, citrus fruits, raisins, potatoes). In cases where hyperkalemia threatens with complete cardiac arrest (> 6.5 mmol / l), 10 ml of 10% calcium gluconate solution or 10 units of insulin in 60 ml of 40% glucose or sodium bicarbonate 8.4% is administered intravenously over 5 minutes 40 ml. The most effective treatment for life-threatening hyperkalemia is hemodialysis.

With hyperphosphatemia, foods rich in phosphorus are limited (fish, cheese, buckwheat), drugs that bind phosphorus in the intestine (carbo-

nat calcium). For the treatment of hypocalcemia and the prevention of hyperparathyroidism, calcium carbonate 0.5–1 g orally 3 times a day with meals is prescribed, and in case of ineffectiveness, active vitamin D metabolites (calcitriol) are prescribed.

In the case of hyperparathyroidism (hypercalcemia, increased alkaline phosphatase, vascular calcification), active vitamin D metabolites are prescribed, and if necessary, hyperplastic parathyroid glands are removed.

It should be noted that at present, studies do not show an obvious benefit in the treatment of disorders of phosphorus-calcium metabolism and bone

structure (K/DOQI, 2009).

Enterosorbents are able to a small extent to bind toxic products in the intestine and remove them from the body. Enterodez, polyphepan can be used as enterosorbents. When using enterosorbents, it must be remembered that they are prescribed on an empty stomach and 1.5–2 hours after taking the main drugs.

It is important to monitor the regularity of the action of the intestines, if necessary - to prescribe laxatives (lactulose) or to produce cleansing enemas.

With GFR<15 мл/мин/1,73 м2 требуется ограничение белка до 0,6 г/кг массы тела. Только в случае сочетания ХБП и нефротического синдрома допустимо потребление белка в объеме 0,8 г/кг массы тела.

When following a low-protein diet, malnourished patients may experience problems associated with the catabolism of their own proteins. In such cases, ketone analogues of amino acids (ketosteril) are recommended, which are enzymatically converted in the body into the corresponding L- amino acids, while splitting urea.

Extracorporeal treatment

AT Currently, there are three methods of replacement therapy for patients with end-stage renal failure: hemodialysis, peritoneal dialysis, and kidney transplantation.

Extracorporeal treatment is indicated for stage 5 CKD, characterized by

current GFR<15 мл/мин/1,73 м2 (KDOQI, 2006; ERA, 2002). По–видимому, не-

it is advisable to start dialysis before GFR reaches 6-10 ml/min

(ERA, 2002; CANUSA, 1996; IDEAL, 2010).

AT cases of hyperkalemia, resistant edema, hyperphosphatemia, hyper- or hypovolemia, metabolic acidosis, anemia, neurological disorders (encephalopathy, neuropathy), weight loss, pericarditis, pleurisy,

gastrointestinal symptoms, persistent hypertension, replacement therapy can be started at GFR >15 ml/min/1.73 m2. It is undesirable to delay treatment until the state of GFR<6 мл/мин/1,73 м2 .

Hemodialysis is the most common type of replacement therapy. This hardware method of blood purification is carried out 3 times a week and requires constant attachment of the patient to the dialysis center. AT

Currently, home dialysis methods are being developed using portable devices and mobile medical teams.

Preparation for hemodialysis begins in patients with progressive CKD already at stage 4 and is carried out by a specialist. Before starting hemodialysis, it is necessary to correct anemia, disorders of calcium and phosphorus metabolism, and immunization against viral hepatitis B.

Peritoneal dialysis does not require inpatient treatment and vascular access, provides more stable indicators of systemic and renal hemodynamics, but is often complicated by peritonitis. The procedure is carried out daily several times a day.

Kidney transplantation is the most effective method of replacement therapy, it allows to achieve a complete cure for the period of the functioning of the transplant and provides a better survival compared to dialysis. At the same time, kidney transplantation requires surgical intervention, treatment with cytostatics, is often complicated by infections and is quite expensive.

Tactics of conducting

Therapists, nephrologists, substitution therapy specialists are involved in the treatment of patients with CKD. A general practitioner in a polyclinic or hospital screens for CKD in patients who have (UKRA, 2011):

 Diabetes.

 arterial hypertension.

 Heart failure.

 Atherosclerosis of the coronary, cerebral or peripheral vessels.

 Obvious anemia.

 Family history of stage 5 CKD or hereditary kidney disease.

 Structural kidney disease, kidney stones, prostate hypertrophy.

 Multisystemic disease involving the kidneys.

 Long-term use of nephrotoxic drugs, such as non-steroidal anti-inflammatory drugs.

			Table 11
	Diagnostic measures for CKD
	(K/DOQI, 2006, UKRA, 2011, as amended)
	BP, GFR, lipidogram,		Annually.
	microalbuminuria/proteinuria.
	Potassium, sodium, calcium, phosphorus, urinary		After 6 months
	acid, plasma glucose, Hb.
	Parathyroid hormone, bicarbonate.		4 tbsp. - after 3 months,
			5 st. - after 6 weeks.
Note. * - decrease in GFR<2 мл/мин/1,73 м2 за 6 мес.

Catad_tema Chronic kidney disease - articles

Chronic kidney disease as a general medical problem: modern principles of nephroprophylaxis and nephroprotective therapy

Chronic kidney disease (CKD) is a general medical problem that has profound socio-economic consequences associated with its widespread prevalence in the population (10-15% of the population), disability and mortality due to the development of end-stage renal disease (ESRD) and cardiovascular complications ( CVC), the risk of which in patients with impaired renal function increases tenfold.

The danger of CKD, as well as other "silent killers" - diabetes mellitus (DM), hypertension, oncological diseases - is that patients do not experience changes in their state of health for a long time, which leads to late detection of CKD, when the possibilities of nephroprotective therapy have been exhausted. The peculiarity of the problem of CKD is the predominance of secondary nephropathies, and therefore patients are observed by therapists and specialists - "non-nephrologists" for a long time, and cases of CKD as a secondary disease are practically not taken into account by official statistics.

In 2002, in order to create a methodological base for a system of effective care for patients with kidney disease and prevention of ESRD, experts from the KDOQI (Kidney Disease Outcomes Quality Initiative) group of the US National Kidney Foundation formulated the concept of CKD, which replaced the concept of "chronic renal failure", not which has clear and universal criteria and focuses only on the late stages of kidney disease, which makes it unsuitable for primary and secondary prevention programs. The concept is accepted all over the world, including in Russia (there are National recommendations for CKD, created by experts from the Scientific Society of Nephrologists of Russia).

CKD is understood the presence of markers of kidney damage(characterizing disease activity) and/or decrease in glomerular filtration rate (GFR) below 60 ml / min / 1.73 m 2(characterizing the stage and rate of progression of the disease), persisting for 3 months or more(Table 1).

Table 1. Diagnostic criteria for CKD

Note. The diagnosis of CKD is made when one or more markers of kidney damage and/or decreased kidney function are detected that are persistent, i.e., persist during repeated studies for 3 months.

CKD is not a new disease, but supra-nosological concept, those. a tool that allows for kidney diseases of various etiologies to determine the stage of progression - from intact function to ESRD, timely prescribe nephroprotective and renal replacement therapy, assess the risk of cardiovascular events and implement effective cardioprotection.

The concept of CKD does not contradict the priority of the nosological approach in modern medicine. On the contrary, it is designed to ensure timely referral of patients with signs of kidney damage to a nephrologist, who conducts differential diagnostics and establishes a nosological diagnosis, assesses the risk of progression, and determines etiotropic and pathogenetic therapy. At the same time, the value of the concept of CKD is that it allows, even in the case when the nosological diagnosis is not yet fully established, to plan and carry out secondary prevention measures that affect the universal mechanisms of CKD progression, aimed at preserving kidney function and reducing the risk of CVD. .

Population epidemiological studies conducted in the last decade give an idea of ​​the magnitude of the CKD problem. CKD prevalence high and not inferior to the prevalence of such socially significant diseases as diabetes, hypertension, heart failure. In the US, it is 14%, while kidney disease ranks 4th in the structure of causes of death. According to studies conducted on different continents in countries with different ethnic composition and economic development (Table 2), signs of CKD are observed in 12-18% of the population, and CKD of the most unfavorable stages 3-5 - in 5.9-8.1 % of residents (in Japan - up to 18.7%).

Table 2. The prevalence of CKD in the world, according to national epidemiological studies

Country	Study	CKD prevalence, %
		stages 1-5	stages 3-5
USA	NHANES, 2005-2010	14,0	6,7
USA	KEEP, 2000-2011*	23,8	15,7
Netherlands	PREVEND, 2005	17,6	-
Spain	EPIRCE, 2005	12,7	-
Portugal	E. De Almeida et al., 2012	-	6,1
China	Beijing study, 2008	14	6,5
Japan	E. Imam et al., 2007	-	18,7
India	SEEK-India, 2013	17,2	5,9
Australia	Aus Diab, 2008	13,4	7,7
Congo	Kinshasa study, 2009	12,4	8,0

"Study includes American adults at increased risk of developing CKD

Thus, at least every tenth inhabitant of the Earth has signs of CKD. This means that in our country CKD suffers at least 14 million people. Although population-based studies on CKD have not been conducted in Russia, however, studies performed in certain categories of the population confirm the assumption of a high prevalence of CKD. Thus, according to a survey of elderly patients observed in the city polyclinic No. 107 in Moscow in 2008, in persons over 60 years of age, signs of CKD were noted in 1/2 of cases, and in older age groups - in 66.3%. Among patients of working age who were examined in the therapy departments of the Kolomna Central District Hospital, the incidence of CKD, which was diagnosed by the criterion of a decrease in GFR, was 16%, and in people suffering from cardiovascular diseases, it reached 26%. According to another Russian study, more than 1/3 of patients with chronic heart failure (CHF) have signs of CKD.

Data about nosological composition of CKD require clarification, since population-based studies, as a rule, do not imply a detailed nephrological examination, and currently created CKD registries do not include patients in its early stages. In addition, there are differences between countries in the prevalence of kidney diseases of a different nature (high incidence of urolithiasis in the Middle East, IgA nephropathy in Japan, infectious kidney diseases in developing countries, etc.). However, there is no doubt that, as already mentioned, the leading place in the structure of CKD and the causes of ESRD development is not occupied by primary kidney diseases, such as glomerulonephritis, polycystic kidney disease, but by secondary nephropathy in diabetes and hypertension.

CKD strikes deep damage to public health and has serious social and economic consequences. The most obvious consequence of CKD is the enormous cost of life-saving kidney replacement therapy (dialysis and kidney transplantation), which places a heavy burden on the health care system.

In the US, in 2011, renal replacement therapy costs reached 7.2% of the total Medicare health care budget, while these patients accounted for 1.4% of the total number of people covered by this system. At the same time, an average of $87,945 was spent on the treatment of one patient with ESRD receiving hemodialysis treatment within the Medicare system. USA, peritoneal dialysis - 71 630 dollars. USA, for a patient with a transplanted kidney - 32,922 dollars. USA. In Russia, at least 1-1.5 million rubles are spent on the treatment of one dialysis patient during the year, which is more than 100 times higher than the per capita standard of the Program of State Guarantees of Free Medical Care for Citizens.

Patients receiving renal replacement therapy are just the tip of the CKD iceberg, attracting the most attention from health care providers, health care providers, and the medical community. Meanwhile, even a moderate decline in kidney function leads to a significant reduction in life expectancy, deterioration in other health indicators and increased costs of treatment. In the United States, 28.9% of the Medicare budget was spent on treating CKD patients not receiving renal replacement therapy in 2011, who accounted for 12.7% of the total number of people covered by the Medicare system. The need for hospitalizations in patients with CKD is 38% higher than in people without CKD, mortality is 43%.

The main cause of high mortality in patients with CKD is MTR, infectious complications are in second place.

As has been shown in numerous studies, including those performed in Russia, signs of remodeling of the heart and blood vessels are observed in more than 1/2 of patients with a moderate decrease in function, i.e. long before dialysis. According to an American study, among elderly patients with CKD, the incidence of congestive heart failure was 42.9% vs 18.5% in patients without CKD, the incidence of myocardial infarction (MI) was 15.1 and 6.4%, respectively, acute cerebrovascular accident and transient ischemic attacks - 26.7 and 20.3%.

The kidneys eliminate factors that damage the endothelium, therefore, if their work is disturbed, the adverse effect on the cardiovascular system of traditional, “Framingham” risk factors (FRs) increases: arterial hypertension (AH), insulin resistance, hyperlipidemia. At the same time, in GFR2, the role of specific “renal” risk factors for CSR begins to manifest itself and increases with its further decrease: disorders of phosphorus-calcium metabolism, protein-energy deficiency syndrome (PEN), anemia, chronic inflammation, hyperuricemia. New predictors of CVS are emerging: serum levels of phosphorus, calcium, hemoglobin, albumin, parathyroid hormone, fibroblast growth factor 23, Klotho protein, requiring special correction methods. As a result, assessment of prognosis in patients with CKD using the traditional Framingham score is inaccurate and significantly underestimates both mortality and cardiac events.

At the same time, GFR, as an integrative indicator of CKD progression, starting from a level below 60 ml/min/1.73 m 2 , is a powerful predictor of CV events and mortality. Each subsequent stage of CKD, starting from 3a, is characterized by an additional increase in cardiovascular risk by 1.5-3 times. Thus, traditional strategies for cardioprotection need to be modified and supplemented for patients with impaired renal function.

The high prevalence of CKD, its unfavorable outcomes and complications give grounds to raise the problem of the expediency of the development and implementation of measures for its prevention at the population level. early detection, nephroprotection and nephroprophylaxis. The issues of rational organization of screening, the effectiveness of nephroprotection agents in different categories of patients, the range of target values ​​of the most important factors of progression and predictors of complications are widely discussed and do not have unambiguous solutions due to the small evidence base to date.

Contradictory and ambiguous opinions are expressed both about the need to screen the entire population for the purpose of early detection of CKD, and about the inappropriateness of monitoring patients with already diagnosed CKD. However, there is no doubt that both individuals at risk of developing CKD and patients with already developed CKD are characterized by a large inhomogeneity in its forecast. For some, even though there are risks, such as having diabetes, there will be no signs of CKD until old age, for others, CKD will not only develop, but will lead to ESRD in a few years.

The idea of ​​population screening can be recognized as rational if the huge costs of its implementation are justified by a significant improvement in public health indicators, which gives a noticeable pharmacoeconomic effect. Large prospective studies are needed to substantiate this view.

Therefore, to date, all national recommendations on the tactics of detecting CKD consider it appropriate to regularly determine laboratory markers of CKD in humans. with FR its development (Table 3).

Table 3 CKD risk factors that are indications for regular examinations to exclude it

Hypertension, other cardiovascular diseases (ischemic heart disease, CHF, damage to peripheral arteries and cerebral vessels)

Obstructive urinary tract diseases (stones, urinary tract abnormalities, prostate disease, neurogenic bladder)

History of nephrectomy or kidney resection

Autoimmune and infectious systemic diseases (systemic lupus erythematosus, vasculitis, rheumatoid arthritis, subacute infective endocarditis, HBV-, HCV-, HIV infection)

Diseases of the nervous system and joints requiring regular intake of analgesics and NSAIDs (at least 1 dose per week or 4 doses per month)

Family history of ESRD or hereditary kidney disease

AKI or nephropathy of pregnancy in history

Incidental detection of hematuria or proteinuria, changes in the kidneys according to ultrasound in the past

Note. Here and in Table. 5: NSAIDs - non-steroidal anti-inflammatory drugs.

Since these factors are also risk factors for accelerated progression of CKD, this approach allows selective identification of the most unfavorable cases of CKD requiring active intervention.

Risk factors include: a number of chronic diseases, primarily cardiovascular, metabolic, autoimmune, obstructive urinary tract diseases and previous kidney surgeries, frequent use of analgesics and other nephrotoxic drugs, family history of CKD, acute renal failure (ARF) or history of gestational nephropathy (see Table 3). Hyperlipidemia, obesity, age over 50 years, smoking, and harmful alcohol consumption are recognized risk factors for CKD but are not considered in most guidelines as independent indications for screening for CKD. However, their consideration is undoubtedly important for individual planning of measures for nephroprophylaxis and nephroprotection.

For CKD diagnostics, based on its definition, it is necessary to investigate the markers of kidney damage and the state of kidney function. The most accessible laboratory method for studying markers of kidney damage is general urine analysis, allowing to detect an increased level of total protein (proteinuria) in a single portion of urine, as well as other signs of damage to the kidneys and urinary tract - hematuria, which may be a manifestation of a tumor of the kidney or urinary tract, leukocyturia, indicating the presence of a urinary infection, impaired concentration ability and tubular reabsorption, characteristic of chronic tubulointerstitial nephritis and tubulopathies. The disadvantages of this method include insufficient accuracy, especially at proteinuria levels below 0.5 g/L. A normal urinalysis result does not rule out CKD.

Albuminuria test makes it possible to detect CKD at the earliest stages, when a general urinalysis may be uninformative. Therefore, screening programs typically use an assessment of albuminuria. Qualitative or semi-quantitative dipstick testing of urine needs to be confirmed by more accurate quantitative methods. In a Polish study of 2471 participants, elevated albuminuria was found in 15.6% of cases; after re-examination by the turbidimetric method, the frequency of increased albuminuria was 11.9%. Of particular value is the test for albuminuria in the diagnosis of CKD in patients with hypertension, diabetes and obesity, in which even a moderate increase in albuminuria has an unfavorable value, and the appearance of significant proteinuria is observed only in the later stages.

The “gold standard” for assessing kidney function remains the determination of GFR by clearance methods, however, for outpatient examinations, it is preferable to use the calculation of GFR using special formulas based on the determination of serum creatinine concentration, since this eliminates organizational difficulties and technical errors associated with the collection of daily urine. The most accurate to date are CKD-EPI equations. The Cockcroft-Gault formula is not accurate enough (may give overestimated results), the MDRD formula is unsuitable for GFR> 60 ml / min / 1.73 m 2, since in such cases it underestimates the result. The use of formulas makes it possible to avoid erroneous assessments of kidney function associated with differences in creatinine kinetics due to age, gender, race and other characteristics of the subjects. It is important to note that a serum creatinine level within the reference range in women and the elderly may be consistent with GFR.<60 мл/мин/1,73 м 2 , т.е. наличию ХБП.

Ultrasound examination (ultrasound) of the kidneys allows to detect structural signs of kidney damage and occupies an important place in the diagnosis of polycystic kidney disease, which is the cause of 10% of cases of ESRD, urolithiasis, kidney tumor, nephrocalcinosis, but is not used for screening for CKD due to the possibility of both hypo- and overdiagnosis, as well as relatively high cost. However, regular ultrasound is advisable for people over 20 years of age who have relatives suffering from polycystic kidney disease or ESRD of unknown origin. Ultrasonography is also necessary for the examination of patients with already diagnosed CKD in GFR.<30 мл/мин или при ее быстром снижении - на 25% от исходного уровня или в абсолютном значении на 15 мл/мин/1,73 м 2 , при наличии гематурии и признаков обструкции мочевых путей .

Although it appears that an increase in albuminuria as an early marker of CKD should always outpace a decrease in GFR, and a test for albuminuria might be sufficient to detect CKD, this is not the case. According to the NHANES 2005-2010 study, in different subgroups (in patients with diabetes, hypertension and other cardiovascular diseases, obesity), cases prevailed when an increase in albuminuria or a decrease in GFR was observed in isolation, and only in a minority of those examined, these signs of CKD were combined. In a study of the prevalence of CKD among residents of Moscow over 60 years of age, CKD was diagnosed in 49.5% of cases, while proteinuria of 0.1 g/l and above was detected only in 17.1% of those examined. Although this study did not use a test for albuminuria, it reflects the significant contribution of an isolated decrease in GFR to the diagnosis of CKD in the elderly. At the same time, another Russian study on the prevalence of CKD among Muscovites of working age revealed albuminuria of more than 30 mg/l in 50% of those examined, and GFR<60 мл/мин/1,73 м 2 наблюдалась только в 2% случаев, т.е. в этой возрастной категории для выявления подавляющего большинства случаев ХБП было достаточно теста на альбуминурию.

Thus, even scientific studies use different approaches to detecting CKD. The albuminuria test has the undeniable advantage of being highly sensitive and does not require blood sampling from a vein, which allows it to be widely used in screening programs. The most correct approach is parallel study of urine and serum creatinine with calculation of GFR, especially when it comes to elderly and senile people.

question of rational screening organization CKD is one of the most important. In many countries there are so-called screening centers CKD, created with the support of the state or charitable foundations, in which everyone can take a free survey and interview for the presence of CKD RF, as well as the necessary laboratory tests. Screening centers may operate on a full-time basis or as part of World Kidney Day and other community events. For this, mobile screening centers are sometimes used, which are installed in crowded places and serve both for screening and for informing the population about the importance of a healthy lifestyle and rational nutrition for the prevention of CKD.

Screening centers are of great value in facilitating the early detection of CKD, public health education and providing valuable information on the prevalence of CKD. For example, in Brazil between 2005 and 2010, a total of 37,771 people were screened during community health events in São Paulo using proteinuria test strips and a CKD risk factor questionnaire. The average age of the surveyed was 44.6±21.7 years, among them 27.7% suffered from hypertension, 6.5% had it for the first time during this survey, 9.5% had diabetes, 0.3% had it. first diagnosed. Significant proteinuria (1+ and above) was detected in 7.3% of the examined, while 85.5% of them did not know about the presence of changes in their urine tests in the past.

However, the role of screening centers is, first of all, to draw attention to the problem of CKD; to solve it, constant systematic work is needed using the existing structures of the preventive medicine system. So, when determining albuminuria in 1623 people (mean age 46 ± 16 years, DM in 4%, AH in 40%) who applied to Health Centers Moscow region for examination and preparation of an individual recovery plan, its elevated level (above 30 mg / l) was detected in 42% of cases, while only 11% of the surveyed indicated in the questionnaire that they had proteinuria in the past, 11% in the past revealed changes in the kidneys according to ultrasound. The survey method revealed a number of factors associated with CKD in the examined patients: in addition to the presence of hypertension (detected in 39.7% of respondents) and diabetes (4.0%), these are obesity (30.0%), smoking (37.4%) , abuse of analgesics (30.1%), sedentary lifestyle, restriction of fluid intake, the presence of CKD in direct relatives. Questioning not only allows you to determine the risk group for CKD that needs clinical and laboratory examination, but also helps to develop for this patient the main directions of therapeutic and preventive measures in order to prevent the development of CKD or its progression, taking into account his history, heredity, lifestyle.

Unfortunately, the current work program of the Health Centers does not yet include a questionnaire for the presence of CKD risk factors and the determination of albuminuria. The mentioned scientific study also showed another “stumbling block” in the way of detecting CKD through health centers: due to organizational difficulties, lack of continuity between preventive and nephrological services, and low motivation of the examinees themselves, only a small part of the persons with high albuminuria were further nephrological examination.

adopted in our country Medical examination program adult population offers great opportunities for early detection of CKD. It includes a general urine test, a biochemical blood test with the determination of creatinine concentration, sufficient to diagnose the most unfavorable cases of CKD and determine indications for a consultation with a nephrologist. In addition, the medical examination program makes it possible to identify the most important risk factors for the development and progression of CKD: hypertension, hyperglycemia, obesity, hypercholesterolemia, lower urinary tract diseases.

Another important direction is the detection of CKD in people undergoing examinations for other diseases, pregnancy, professional examinations, which include the definition of violations that are risk factors for CKD, and often the study of CKD markers. Unfortunately, in many cases, if not in most cases, this information does not receive due attention and does not contribute to timely referral to a nephrologist.

A method to improve the efficiency of CKD detection is monitoring of registers and medical electronic databases. For example, in the UK, automated screening of 10,975 patient records seen by general practitioners identified 492 cases of CKD with GFR.<60 мл/мин/1,73 м 2 (5,7%) . С широким внедрением современных средств информатизации в медицине в нашей стране этот путь выявления ХБП становится доступным. О перспективности данного направления свидетельствуют результаты упомянутого в начале статьи исследования по эпидемиологии ХБП, построенного на ручном анализе 1032 историй болезни в Коломенской ЦРБ, который показал, что среди пациентов трудоспособного возраста, проходящих обследование и лечение в терапевтических отделениях и не имеющих диагноза «заболевание почек», СКФ<60 мл/мин/1,73 м 2 отмечалась в 16% .

Persons at risk development of CKD, in which its markers have not been identified, should receive recommendations for the correction of modified risk factors (see Table 3). In addition to preventive measures common with other chronic non-communicable diseases (correction of hypertension, hyperglycemia, hyperlipidemia, normalization of body weight, smoking cessation), there are specific measures of nephroprophylaxis: extended water regimen, the maximum possible exclusion of nephrotoxic drugs, a reasonable limitation of radiopaque studies, correction of purine metabolism disorders, urinary tract obstruction.

Fluid intake of at least 2 liters per day today accepted as the norm of a healthy lifestyle. Restriction of fluid intake, leading to hypovolemia, can lead to a decrease in renal perfusion and the development of their chronic ischemia, pathological activation of the renin-angiotensin system (RAS) and the arginine-vasopressin system. The adverse impact of reduced fluid intake on renal function has been shown in epidemiological studies. However, according to a survey of employees of one of the enterprises in Moscow, 65.7% of the respondents tried to limit fluid intake, which was combined with a significantly higher frequency of albuminuria compared to people who consumed a lot of fluid: relative risk - RR 1.357 (0.837-2.199). 23.3% of respondents abused analgesics, which was also associated with an increased risk of CKD - ​​RR 1.266 (0.735-2.180). 25.3% were sedentary - RR CKD 1.332 (0.782-2.267), respectively, 27.0% were obese - RR CKD 1.686 (0.970-2.929), 55.7% were smokers - RR CKD 1.351 (0.852-2.141) .

Hyperuricemia traditionally considered a factor in damage to the renal interstitium, causes endothelial dysfunction, systemic and renal hemodynamic disorders. In recent years, there has been a new round of interest in the problem of purine metabolism disorders in the light of recent studies showing its impact on the risk of developing ESRD and CVC and revealing new mechanisms of this influence.

After the development of directions for individual nephroprophylaxis, follow-up monitoring of the implementation of recommendations, monitoring of target indicators, as well as re-examination of CKD markers is necessary if the risk factors for its development persist. These activities should be carried out by primary health care physicians, district physicians, doctors of medical prevention rooms and health centers.

Persons with identified signs of CKD need to be re-examined to confirm them, after which they are sent to initial consultation with a nephrologist in order to make a nosological diagnosis and determine the tactics of nephroprotection. With identified GFR<30 мл/мин/1,73 м 2 пациент направляется не в кабинет консультанта-нефролога, а directly to the regional nephrology center for registration and special preparation for renal replacement therapy, since the margin of time until ESRD is reached (GFR to a level of less than 15 ml / min / 1.73 m 2), as a rule, is already small.

Patients with diagnosed CKD undergo risk stratification the development of ESRD and CVE, which is important both for assessing the prognosis and for developing rational tactics for managing the patient (see figure).

The modern system of stratification of the combined risk of ESRD and CVE in patients with CKD, proposed by the KDIGO (Kidney Disease Improving Global Outcomes) expert group, is based, as well as the detection of CKD, on its two most important characteristics - the level of GFR and the category of albuminuria/proteinuria (Table 4) .

The 2012 KDIGO CKD Management Guidelines, a milestone in the development of the concept of CKD, were preceded by a meta-analysis of 45 cohorts that included representatives of the general population, CKD risk groups, people with diagnosed CKD - ​​a total of 1,555,332 people. It has been established with a high degree of evidence that in GFR<60 мл/мин/1,73 м 2 отмечается резкое повышение смертности и риска неблагоприятных почечных исходов, что существует прямая связь между выраженностью альбуминурии и риском ССО и ТПН, что пациенты с одной и той же стадией ХБП характеризуются более неблагоприятным прогнозом при более выраженной альбуминурии, причем эти закономерности отмечаются у лиц как моложе, так и старше 65 лет. На основании этого исследования экспертная группа KDIGO подтвердила, что альбуминурия в пределах 30-300 мг/г (т.е. в пределах, когда тест на протеинурию может быть слабоположительным или отрицательным) имеет неблагоприятное значение и служит достоверным критерием ХБП. Более того, повышение общей и сердечно-сосудистой смертности было отмечено даже при альбуминурии 10-29 мг/г по сравнению с категорией альбуминурии менее 10 мг/г.

A series of meta-analyses published over the past 3 years have shown that an adverse effect on the risk of developing ESRD and CVD GFR<60 мл/мин/1,73 м 2 и повышения альбуминурии проявляется вне зависимости от возраста, пола, АГ и СД .

The principle of stratification of the combined risk of ESRD and CVE based on the definition of categories of GFR and albuminuria, proposed by KDIGO experts, is the basis for a coherent system that determines not only an individual prognosis, but also the frequency of examinations, as well as the degree of participation of a nephrologist in the management of a patient.

However, KDIGO approaches are not shared by everyone and are criticized by both individual authoritative specialists and expert groups. At the same time, they indicate a large variability in the values ​​of albuminuria, the absence of large studies to verify the validity, reproducibility of this test, the pharmacoeconomic and psychological consequences of overdiagnosis and unreasonable prescriptions. Thus, the expert group of The American College of Physicians (ACP), which does not include any nephrologist, denying the advisability of population screening for albuminuria (which is consistent, as already mentioned, with all the main recommendations for CKD), at the same time does not recommend monitoring not only albuminuria, but also proteinuria in patients with stage 1-3 CKD receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin-type 1 receptor blockers (ARBs), which are recommended for all patients with CKD and hypertension. This position, based on the fact that the majority of patients with CKD already have indications for the appointment of ACE inhibitors or ARBs to lower blood pressure (BP) and the presence of CKD does not fundamentally change anything, seems to be very controversial. The main purpose of prescribing drugs that suppress the RAS in CKD is nephroprotection, i.e. preservation of kidney function. Prospective controlled studies conducted back in the 90s of the last century showed that the nephroprotective effect of these drugs correlates with the degree of reduction in proteinuria. Albuminuria/proteinuria is the most important marker of the severity of kidney damage, a symptom of great value for the differential diagnosis of kidney diseases, a factor in the progression of CKD and the development of its complications, and the main target indicator of nephroprotective therapy.

In our country, there is a contradiction between the position of the nephrological community, national recommendations for the management of patients with CKD, which recognize the importance of assessing albuminuria, and real clinical practice. The test for albuminuria remains inaccessible and is rarely used even in patients with diabetes and hypertension, contrary to national and international recommendations. The quality of proteinuria testing, especially in smaller primary care laboratories, is often poor, leading to false negative results.

Due to the unreliability of laboratory diagnostics and the frequent underestimation of proteinuria in our country, we consider it appropriate, as mentioned above, examination by a nephrologist of each patient with newly diagnosed CKD with the repetition of analyzes obtained in the primary care, in a specialized laboratory. In our opinion, in Russia, the constant supervision of a nephrologist is needed all patients with CKD from high and very high risk groups, not only patients with albuminuria above 300 mg/g and/or GFR<30 мл/мин, как предлагается KDIGO. Наша позиция соответствует данным метаанализа с оценкой фармакоэкономического эффекта раннего (при СКФ<60 мл/мин/1,73 м 2) направления к нефрологу , показывающего целесообразность такой тактики. Авторы констатировали резкое ухудшение прогноза начиная уже со стадии 3а ХБП и установили, что в случае раннего направления к нефрологу отмечаются наиболее высокие значения индекса QALY (Quality-adjusted life years - добавленные годы жизни с поправкой на качество) и создаются предпосылки для наиболее эффективного использования ресурсов системы здравоохранения.

Secondary prevention of CKD is aimed at minimizing the risk of developing ESRD and CVE (nephrocardioprotective strategy) and includes a complex of non-drug and pharmacological effects on modified risk factors identified during the examination (Table 5).

Table 5 Risk factors for CKD progression and CVD development, ways of their modification

FR	Possibility and means of modifying the FR	Target
Persistence of factors that caused CKD	Correct nosological diagnosis Adequate etiotropic and pathogenetic therapy in accordance with clinical guidelines and protocols Monitoring of markers of disease activity, prevention of exacerbations and their timely relief	Elimination of the etiological factor of secondary nephropathies Achieve sustained remission of primary kidney disease No exacerbations
Persistent proteinuria 0.5 g/day or more	Etiotropic and pathogenetic therapy Antiproteinuric (nephroprotective) therapy with ACE inhibitors and ARBs Controlled restriction of protein intake (0.6-0.8 g / kg of body weight; with nephrotic syndrome - 1.0 g / kg)	Complete disappearance of proteinuria or its persistent decrease to the level<0,5 г/сут In patients with kidney disease with massive proteinuria or nephrotic syndrome, a persistent decrease in proteinuria to the level<1,0 г/сут или уменьшение в 2 раза от исходного уровня
Decrease in GFR	The earliest possible detection of CKD and the appointment of etiotropic, pathogenetic, as well as nephroprotective treatment: drugs that block the RAS, a low-protein diet, ketoanalogues of amino acids Elimination of nephrotoxic factors, including iatrogenic	Stabilization of GFR above 45 ml/min/1.73 m2
AG	low protein diet with salt restriction<5 г/сут) Correction of overweight and obesity Drugs that lower blood pressure	HELL<140/90 мм рт. ст. при протеинурии <0,5 г/сут HELL<130/80 мм рт. ст. при протеинурии 0,5 г/сут и выше Avoid episodes of hypotension!
Excess consumption of food rich in protein	Low-protein diet, keto analogues of amino acids, while protein intake is recommended: with CKD stages 3a-3b - 0.6-0.8 g / kg / day with CKD stage 4 - up to 0.3 g / kg / day	Stabilization of GFR and serum creatinine Decreased urea and uric acid levels Reduced proteinuria Improved response to antihypertensive therapy Correction of hyperkalemia Nutritional status monitoring to rule out PEU (see below)
hyperglycemia	A diet that restricts readily available carbohydrates Effective hypoglycemic therapy	Glucose<6,4 ммоль/л Glycated hemoglobin<7%
Obesity	Diet, high physical activity, exercise therapy with high aerobic loads	BMI 20-24.9 kg / m 2 Waist circumference<94 см для мужчин и <80 см для женщин
Hyperlipidemia	Diet with restriction of animal fats and caloric content of the diet, consumption of at least 400 g of vegetables and fruits per day, sufficient physical activity Statins and other lipid-lowering drugs	Cholesterol<5,0 ммоль/л, triglycerides<1,7 ммоль/л
Hyperuricemia	Low-protein diet with additional restriction of purine bases, keto analogues of amino acids. If the diet is not effective enough, the appointment of allopurinol (with caution in GFR<60 мл/мин/1,73 м 2 !)	Uric acid in blood serum for men<415 мкмоль/л, для женщин <385 мкмоль/л
PEN associated with anorexia	Ensuring sufficient calorie content of the diet at the rate of 30-35 kcal / kg Inclusion in the diet of special nutritional mixtures, the appointment of ketoanalogues of essential amino acids with an increase in their usual dose	BMI not lower than 20 kg / m 2 Increase in muscle mass (circumference of the biceps), thickness of the fat fold Serum albumin >35 g/l
Violations of phosphorus-calcium metabolism, secondary hyperparathyroidism	Low-protein or low-protein diet with additional restriction of phosphorus intake (<800 мг/сут), кетоаналоги аминокислот Phosphate binders Vitamin D preparations Vitamin D receptor agonists Calcimimetics Parathyroidectomy	Phosphorus<1,4 ммоль/л Calcium 2.2-2.5 mmol/l Approaches to assessing the level of PTH depending on the stage of CKD, signs of impaired bone metabolism and calcification of blood vessels and heart, see National guidelines on mineral and bone disorders in chronic kidney disease
Anemia and chronic inflammation	Careful sanitation of all foci of chronic infection Identification and correction of iron deficiency Drugs that stimulate erythropoiesis	Hemoglobin 100-115 g/l Normalization of ESR, C-reactive protein
metabolic acidosis	Low-protein diet, keto analogues of amino acids Adding sodium bicarbonate to food	Blood bicarbonate >22 mmol/l
Obstructive diseases of the urinary tract	Observation of the urologist Timely diagnosis of disorders and complete restoration of urinary tract patency	No signs of obstruction according to the survey and instrumental studies
Development of acute kidney injury in CKD	Rational limitation of X-ray contrast studies, the use of nephrotoxic drugs	Stabilization of kidney function
Harmful consumption of analgesics and NSAIDs, as well as body shaping and muscle building supplements	Examination by a neurologist, vegetologist, elimination of the causes of pain, development of complex non-drug treatment and prevention of pain syndrome, including exercise therapy and daily routine correction Informing patients about the dangers of self-medication	If possible, limit the use of analgesics and NSAIDs (no more than 2 doses per month)
Smoking	Visit to the prevention room to develop and implement an individual smoking cessation plan Anti-Smoking School	Complete cessation of smoking
Deficiency in fluid intake	Selection of an individual water regime taking into account the characteristics of CKD	Extended fluid regime (more than 2 L/day), except for patients with nephrotic syndrome, oliguria and dialysis treatment
Harmful consumption of alcohol	Visit to the prevention room to develop and implement an individual plan for quitting alcohol If necessary, the participation of a psychologist	Drinking alcoholic beverages no more than 20 g of pure ethanol per day for men and 10 g of ethanol for women, if there are no indications for the complete exclusion of alcohol
Hypodynamia	Visit to the exercise therapy room, selection of an individual set of exercises (aerobic and power loads) Classes in health groups	Physical activity: regular aerobic exercise - at least 2.5-5 hours per week, evenly distributed throughout the week for several workouts
Age >50 years, belonging to ethnic minorities, low social and educational level	-	-
Initially low number of nephrons (low birth weight, aplasia, hypoplasia of the kidney History of nephrectomy or kidney resection	-	-

Note. Exercise therapy - exercise therapy, BMI - body mass index, PTH - parathyroid hormone, ESR - erythrocyte sedimentation rate.

The tactics of nephroprotective treatment has also been significantly revised in recent years. First of all, there was a rejection of an aggressive approach to lowering blood pressure and suppressing the RAS.

The idea of ​​expediency lowering blood pressure to a level below the high normal was based on the results of epidemiological studies. Thus, the MRFIT study (332,544 men, mean follow-up 16 years) showed that in individuals with high normal BP, the risk of ESRD is 1.9 times higher than in individuals with optimal BP (below 120/80 mmHg) .

The MDRD intervention study, which examined the effect of a combination of a low-protein diet and strict BP control on the rate of decline in kidney function, found that more strict BP control compared with standard therapy (BP<140/90 мм рт. ст.) снижал риск ТПН у больных с выраженной протеинурией , что нашло отражение в многочисленных рекомендациях по контролю АД . Однако положение о необходимости более строгого (ниже 130/80 мм рт. ст.) контроля АД при ХБП до настоящего времени остается недоказанным. Оценка отдаленных исходов вне рамок основного исследования MDRD, а также других исследований по контролю АД при ХБП не показала достоверных различий по риску неблагоприятного почечного исхода у больных с более строгим контролем АД . По данным метаанализа, включавшего 37 348 больных, более интенсивный контроль АД оказывал дополнительное вазопротективное действие, однако не уменьшал смертность пациентов с ХБП . Современные американские рекомендации по контролю АД и ведению пациентов с ХБП стадий 1-3 , в отличие от более ранних, не предусматривают более строгого контроля АД при ХБП.

The remaining uncertainty regarding the target level of blood pressure in CKD, one of the most important issues in the nephroprotective strategy, is primarily due to a small evidence base. Evidence of the benefit and safety of tight BP control requires a study with a very large number of patients and long-term follow-up, which is more difficult to design than a drug-specific study. The most commonly used agents for lowering blood pressure in CKD are ACE inhibitors and ARBs, which, in addition to antihypertensive, have antiproteinuric and nephroprotective effects, in addition, a low-protein diet and other components of nephroprotective treatment are prescribed. Therefore, it is a difficult task to analyze the independent contribution of achieving the target blood pressure. In addition, strict BP control can only be achieved in a fraction of patients with CKD, and in elderly patients, who make up a large proportion of people with CKD, strict BP control can be dangerous due to the risk of CV events.

The most important factor influencing the effectiveness of strict BP control is the level of proteinuria, as shown in the MDRD study. Long-term follow-up of individuals included in the AASK study, while not establishing the benefits of more stringent BP control in the whole group, however, showed them in a subgroup of individuals with severe proteinuria. The significance of baseline proteinuria for the advisability of lowering BP targets in CKD in terms of renal outcomes was also established by a meta-analysis.

Thus, the very formulation of the question whether the target BP in CKD should differ from the target BP adopted for all patients with AH seems to be incorrect in the light of these data. In most patients with CKD, it seems necessary to aim for levels below 140/90 mmHg. Art., in elderly patients, the target BP should be higher (as well as in hypertensive patients without CKD). However, data on the nephroprotective and antiproteinuric effect of more stringent BP control (<130/80 мм рт. ст.) у лиц с выраженной протеинурией, составляющих значительную и прогностически наиболее неблагоприятную часть пациентов с ХБП требуют внимания и дальнейшего изучения.

To date, the most balanced approach, reflected in the 2013 European guidelines on blood pressure control and in the Russian guidelines on cardionephrorprotection, which provides for the reduction of blood pressure to a level below 140/90 mm Hg for all patients with CKD, seems to be the most balanced. Art., but does not exclude an attempt to achieve blood pressure below 130/80 mm Hg. Art. in young and middle-aged patients with severe proteinuria, provided that they are well tolerated.

The question of the lower limit of optimal blood pressure values ​​in CKD, which is extremely important for ensuring the safety of therapy, is not sufficiently reflected in current recommendations. The KDOQI guidelines for blood pressure control in CKD indicate the lower limit of optimal systolic blood pressure values ​​of 110 mm Hg. Art. based on data from a meta-analysis completed shortly before they were written, which showed that systolic BP values ​​both above 130 and below 110 mm Hg are unfavorable in relation to kidney function. Art. . With low blood pressure, due to the centralization of blood flow, ischemia of the kidneys develops, leading to their damage. The role of hypoxia as an independent factor in the progression of CKD is discussed in the literature, however, today, unfortunately, there are no available and reliable methods that allow monitoring changes in intrarenal hemodynamics during antihypertensive therapy.

Of great importance in CKD, especially in the later stages, when the instability of blood pressure increases, are automatic daily monitoring of blood pressure (ABPM), as well as self-control. The data of ABPM and regular self-measurements provide a more adequate idea of ​​the state of hemodynamics than random measurements of blood pressure by a doctor, which is important for adjusting drug doses, taking into account the correspondence of the level of average daytime and average nighttime blood pressure to the range of optimal values. The desire to achieve the target level of blood pressure should not lead to episodes of hypotension, which is fraught not only with a deterioration in coronary and cerebral blood flow, but also with the development of renal ischemia.

RAS blockade, playing an important role in the progression of CKD, using ACE inhibitors and ARBs is still central to the nephroprotective strategy. The decrease in blood pressure is only one of the mechanisms of the beneficial effect of these drugs on the course of CKD: they also have an antiproteinuric effect, eliminate glomerular hypertension and ischemia of the renal tubulointerstitium, and suppress the processes of inflammation and fibrogenesis. According to a number of prospective studies, treatment with ACE inhibitors or ARBs significantly reduces the risk of developing ESRD in diabetic and non-diabetic CKD patients. The interpretation of these data has led to two trends in the renal protective strategy:

1. Prescribe drugs that suppress the RAS to all patients with CKD.
2. Use combinations of drugs that block the RAS at different levels, providing the most complete blockade.

Both approaches do not take into account that the RAS in CKD not only interacts with the mechanisms of hemodynamic and proteinuric damage to the kidneys, but its hyperactivation plays a certain adaptive role, maintaining intraglomerular pressure, especially in conditions of kidney hypoperfusion, for example, in congestive heart failure, atherosclerosis of the renal arteries. Both the nephroprotective potential and the incidence of complications with drugs that suppress the RAS vary widely: the initial level of albuminuria / proteinuria, genetic features, in particular the angiotensin-converting enzyme gene polymorphism, affect the effectiveness, and the tolerability is influenced by age and the degree of decrease in kidney function. Of great importance is the early administration of drugs that suppress the RAS: although they do not lose their ability to exert antiproteinuric and nephroprotective effects in the later stages of the disease, however, the duration of their administration plays a decisive role, as the duration of therapy increases, the positive renal effects of these drugs increase when using the same doses.

Hopes placed on combined blockade of the RAS, are not justified, as shown by a number of studies on various combinations of ACE inhibitors, ARBs and a renin inhibitor. Of particular interest are the results of the VA NEPHRON-D study, which, unlike the well-known ONTARGET study, included patients with diabetic nephropathy with severe albuminuria (at least 300 mg / g, on average 862 (488-1789) mg / g in the group receiving losartan and 842 (495-1698) in the combination of losartan and lisinopril, in which the benefits of combined treatment should have been most pronounced.In the combined treatment group, the incidence of adverse renal outcomes was only slightly lower compared with losartan alone, there were no benefits in in relation to mortality and cardiovascular outcomes.At the same time, the incidence of hyperkalemia and AKI was significantly higher with combination therapy.A systematic review including 21,708 patients also showed no advantage of combination treatment in CKD in terms of the risk of reduced kidney function and CVE.

Another combination, which had certain hopes for more effective nephroprotection, is the addition of an aldosterone antagonist to an ACE inhibitor or ARB, the role of which in the progression of nephrosclerosis and cardiosclerosis is being actively studied. A recent meta-analysis of 27 controlled or quasi-controlled studies investigating the effects of adding aldactone to an ACE inhibitor or an ARB or a combination of the two found that the combination treatment was more effective in reducing proteinuria but was more likely to cause hyperkalemia and had no benefit in terms of maintaining function. kidneys and the risk of CVD.

Finally, the recently completed OSCAR study, which included elderly patients with a GFR of 60 ml/min/1.73 m compared with high-dose ARB monotherapy.

In contrast to the tactics of aggressive RAS blockade in CKD, which has been seriously criticized in recent years, the thesis that it is advisable to prescribe an ACE inhibitor or ARB to all patients with CKD without taking into account their individual characteristics retains its supporters: as mentioned above, the authors of the ACP guidelines for the management of patients with Stages 1-3 CKD suggest using these drugs in all cases of CKD with elevated BP, regardless of the level of proteinuria and without monitoring this critical indicator. It is strange that ACP experts, being staunch supporters of the principles of evidence-based medicine in matters of monitoring, completely ignore them in matters of treatment.

Meanwhile, the initial level of proteinuria, as noted above, is crucial for prescribing drugs that suppress the RAS: an analysis of the modern evidence base, according to KDIGO experts, demonstrates their advantages over other antihypertensive drugs with grade B evidence only for very high albuminuria - more than 300 mg /g corresponding to proteinuria 0.5 g/day and above; for albuminuria 30-300 mg/g, the recommendation for the preferred prescription of drugs that suppress the RAS is based only on expert opinion (Evidence D); when albuminuria is less than 30 mg/g, they are not beneficial.

An attempt to make the tactics of managing patients with CKD more accessible to general practitioners and reduce the number of "unnecessary" laboratory tests should not lead to a simplified understanding of the problem, leveling the individual characteristics of patients, ignoring the mechanisms of the nephroprotective action of drugs. The recommendation for the widest possible use of ACE inhibitors or ARBs in CKD should be supplemented by specific measures to control the risk of adverse effects of therapy - acute renal failure and hyperkalemia, which is typical not only for stages 4-5 CKD, but can be realized much earlier. Blockade of the RAS for the purpose of nephroprotection is an intervention in the fine mechanisms of self-regulation of renal blood flow, which can easily get out of balance, so it cannot be carried out without monitoring indicators that characterize the effectiveness and safety of exposure. It is the validity and safety of therapy that should today be put at the forefront when building tactics for prescribing drugs that suppress the RAS, especially in elderly patients with CKD who are prone to impaired renal perfusion, who are indicated for regular Doppler ultrasonography of renal vessels, more careful monitoring of creatinine and potassium levels. blood serum.

Thus, achieving the maximum antiproteinuric effect through the widespread use of ultra-high doses of drugs that suppress the RAS or their combination is a risky path associated with the risk of serious complications. A more correct approach is the maximum individualization of treatment, the impact on the entire spectrum of factors that increase proteinuria, including the use of a low-protein and low-salt diet.

In addition to blockade of the RAS and an adequate reduction in blood pressure, it is necessary to control a variety of metabolic disorder, found in most patients with CKD, including early stages. On the one hand, CKD plays a role in their development, on the other hand, they contribute to its progression in a vicious circle. As GFR decreases, lipid and purine metabolism disorders worsen, and at stages 3b-4, insulin resistance and phosphorus-calcium metabolism disorders are added. Interest in the listed metabolic disorders, their role in the progression of CKD, the development of CVD, and an intensive search for optimal ways to correct them have noticeably intensified in recent years, when the limitations of ACE inhibitor and ARB therapy became apparent.

About the role hyperuricemia in the development of CKD and its progression discussed above. There is no doubt that a low-purine diet is appropriate for all patients with hyperuricemia. The data of a few studies showing that the appointment of allopurinol in patients with CKD and hyperuricemia helps to reduce blood pressure, the risk of cardiovascular events and, possibly, has a nephroprotective effect, are actively discussed. A serious problem is the increased risk of side effects of allopurinol with a pronounced decrease in GFR, which limits its use. Of great interest is a new drug with antihyperuricemic action - febuxostat; its efficacy and safety in CKD needs to be studied.

At the end of 2013, new KDIGO guidelines for correction of hyperlipidemia with CKD. Their authors, on the one hand, recognize the significant impact of hypercholesterolemia and hypertriglyceridemia on the progression of CKD, the development of cardiovascular events and mortality in patients with CKD who do not receive renal replacement therapy, on the other hand, they note an increased risk of side effects of statin treatment in people with impaired renal function, which proportional to the doses used. Therefore, the expert group proposes to move away from the principle of aggressively lowering low-density cholesterol levels with titration of statin doses to high and ultra-high (the “treat-to-target” principle), which, in their opinion, does not have a rigorous evidence base confirming its effectiveness and safety in patients with CKD.

After a detailed examination, including the determination of a lipid profile in order to exclude hereditary forms of hyperlipidemia, assess cardiovascular risk and determine indications for the use of statins, it is proposed to continue using statins according to the “fire-and-forget” principle, t .e. without monitoring the lipid profile and increasing the doses of drugs. As indications for prescribing statins in patients with CKD who are not receiving replacement therapy, the age of 50 years and older is determined, and in younger people, the presence of myocardial infarction or coronary artery revascularization in anamnesis, acute cerebrovascular accident, diabetes mellitus, as well as 10- yearly risk of death from coronary heart disease or non-fatal MI >10%.

The correctness of the principle of not using targets in the correction of hyperlipidemia in CKD is not recognized by everyone and remains the subject of debate. However, there are no doubts about the negative consequences of both neglecting the prescription of antihyperlipidemic therapy in patients with CKD, who are characterized by a high risk of CVD, and the use of excessively high doses without taking into account the state of the kidneys that affects their tolerability.

Correction of violations of phosphorus-calcium metabolism in CKD, today it has ceased to be a narrow problem dedicated to one of the complications of renal failure, but is one of the most important areas of cardionephroprotection, which is undergoing a period of rapid development. The most important achievements are the discovery of new mediators of bone and mineral disorders of fibroblast growth factor 23 and the Klotho protein, revision of the tactics of managing patients with bone and mineral disorders caused by CKD, reflected in modern international and Russian recommendations, clarification of the main targets, the need for the most complete normalization serum phosphorus levels and calcium monitoring, the rejection of routine and uncontrolled prescription of vitamin D 3 preparations to patients with CKD, the discovery of antiproteinuric and nephroprotective properties of the VDR agonist paricalcitol.

Concept anemia treatment in CKD has also undergone significant changes over the past 10-15 years, having gone from, as it seemed at first, a narrow problem concerning patients receiving renal replacement therapy, to one of the important components of a cardio-nephroprotective strategy. The latest recommendations for the treatment of anemia in CKD are characterized by a broader view of the causes of its development and the recognition of the need for a comprehensive approach to its correction, including the prevention of absolute and relative iron deficiency, warning about the risk of aggressive use of drugs that stimulate erythropoiesis, and the need for individualization of treatment. Very instructive are the disappointing results of studies on the effectiveness of erythropoiesis-stimulating drugs, which showed that achieving a hemoglobin level corresponding to the average in the general population, designed to better protect organs from hypoxia, did not lead to a decrease in the risk of CVD. These data strongly suggest that achieving a population “normal” may not be justified for patients with CKD, that treatment outcomes in terms of health outcomes such as quality and life expectancy are far from consistent, that the widespread use of aggressive therapies in patients with impaired performance kidney disease is associated with high risks - these findings are important for the development of the entire cardionephroprotective strategy.

Non-drug methods cardionephroprotection do not lose their positions; on the contrary, this direction continues to develop actively. Great importance is attached to dosed physical activity, regular exercise, increased physical activity, which play an important role in reducing endothelial and autonomic dysfunction that are characteristic of CKD, correcting metabolic disorders, reducing cardiovascular risk and mortality, including in patients receiving renal replacement therapy. therapy.

Strict salt restriction (less than 5 g of sodium chloride per day) not only reduces blood pressure, but also proteinuria, a significant increase in the effectiveness of treatment with ACE inhibitors and ARBs. Adequate hydration, correct water regime, which, as mentioned above, play an important role in the primary prevention of CKD, occupy an even more important place among the measures of secondary prevention. Of course, informing patients, their systematic education and formation of adherence to the principles of non-pharmacological secondary prevention of CKD are of fundamental importance. Unfortunately, in our country, consultation with a nutritionist is far from available to all patients, even with stage 5 CKD, and the system of preventive medicine, which has been significantly strengthened in recent years, does little to address the tasks of secondary prevention of CKD, as well as its screening, having great potential for this.

low protein diet deserves special attention. It was originally proposed to reduce nitrogen load and symptoms of uremic toxicity in patients with severely impaired renal function. However, later it was found that its capabilities and indications for use are much wider. According to modern concepts, a low-protein diet (0.6-0.8 g of protein per kg of ideal body weight) is indicated already starting from GFR<60 мл/мин/1,73 м 2 и способствует, устраняя клубочковую гипертензию, снижению протеинурии и гемодинамического повреждения почечных клубочков и таким образом замедляет прогрессирование ХБП. Ограничение потребления белка, также как низкосолевая диета, повышает чувствительность к препаратам, снижающим АД, способствует коррекции гиперурикемии, гиперфосфатемии, гиперкалиемии, метаболического ацидоза, связанных с ХБП.

Unfortunately, in practice, the possibilities of a low-protein diet are not used enough. According to a large US study, the actual daily protein intake of patients with stage 3 and 4 CKD varies widely and averages 1.22 and 1.13 g/kg, respectively. In our experience, there is both underutilization of low-protein diets by physicians and patients, and inadequate, uncontrolled protein restriction, especially if the patient is not seen by a nephrologist. Instead of developing a varied, balanced diet containing the required amount of biologically valuable animal proteins, the patient is prescribed to completely eliminate the consumption of meat, unreasonably limit the calorie content of the diet, physical activity, further exacerbating the depression and anorexia associated with CKD. As a result of a deficiency in the intake of essential amino acids and calories, PEI develops, which is characterized by impaired synthesis of vital proteins, clinically manifested by hypoalbuminemia and secondary immunodeficiency, hypercatabolism of muscle tissue proteins, which begin to be used as a reserve of amino acids, which is accompanied by a decrease in muscle mass and an increase in the level of products in the blood. nitrogen metabolism, high mortality from CVS and infectious complications. Therefore, a low-protein diet requires regular monitoring of nutritional status. The appointment of a complex of ketoanalogues of essential amino acids (Ketosteril 1 tablet per 5 kg of body weight per day, or 0.1 g / kg per day) and a high caloric content of the diet (30-35 kcal / kg per day) in combination with sufficient physical activity allow limiting protein intake, avoiding PEU, while slowing down the progression of CKD.

Thus, the concept of CKD, created 12 years ago, has stood the test of time, received recognition from the medical community, has been significantly supplemented and modified, and in its modern form is a universal harmonious system aimed at reducing the need for renal replacement therapy, reducing disability and mortality, caused by kidney diseases of various etiologies. It is a simple and reliable tool that allows primary care physicians, cardiologists, endocrinologists, urologists, rheumatologists and other specialists who are the first to encounter CKD manifestations and who do not have special training in nephrology, to recognize CKD in a timely manner, effectively solve the problems of its primary and secondary prevention, effectively interacting with nephrologists and rationally using the available resources of the nephrological service.

Unfortunately, the effectiveness of implementing the possibilities of nephrocardioprotection in real practice leaves much to be desired. Thus, according to the analysis of a group of patients with CKD included in the American NHANES 2001-2010 study, despite the increasing frequency of use of antihypertensive and antihyperlipidemic drugs after the adoption of the concept of CKD, the simultaneous achievement of target values ​​of BP ≤130/80 mm Hg. Art. and low-density lipoprotein cholesterol below 100 mg/dl was observed only in 19.5% of cases (in the whole sample), somewhat more often in patients with pre-existing CVC and DM (28.1 and 24.9%, respectively). These unsatisfactorily low figures are due not only to objective reasons associated with the more resistant nature of hypertension and hyperlipidemia in CKD. They show the need to revise the system of target indicators based on a more detailed and multifactorial stratification of the risk of developing ESRD and CVE, as well as the risk of complications of therapy, which allows forming groups of those patients for whom simpler approaches to nephrocardioprotection are acceptable, and those who require the most personalized treatment. using more aggressive or more forgiving strategies.

On the other hand, the achievement of target indicators and the fullest use of the potential of nephrocardioprotective therapy in patients with CKD requires systematic and consistent efforts. According to the experience of the "Remission Clinic" in Bergamo (Italy), where the system of managing patients with CKD is organized, ensuring the most complete achievement of targets, only 3.6% of patients included in this program achieved ESRD compared to 30.4% in the group historical control. Even more interesting is the experience of using the CKD management program in the UK, which is based on 4 principles: patient education and motivation, prescribing nephroprotective drugs, diet selection, optimization of tactics of observation and monitoring of achievement of targets. The data of 223,287 patients with CKD stages 4-5 identified at the level of primary health care by monitoring electronic databases were analyzed. 9 months after inclusion in the program, the percentage of patients with normal cholesterol increased from 64 to 75%, with systolic blood pressure<130 мм рт. ст. - с 37 до 56%. Темпы снижения СКФ до включения в программу составляли 3,69 (1,49-7,46), через год - 0,32 (2,61-3,12) мл/мин/1,73 м 2 .

These data are also of great importance for our country, where programs for improving the health of the population have been actively developing in recent years, but the problem of prevention and early detection of CKD is still not given due attention, and the development of the nephrological service occurs solely through the opening of new hemodialysis departments.

To solve the problem of CKD, a set of measures is needed for different segments of the health care system:

Identification of risk factors for CKD in the population using the available capabilities of the preventive medicine system - health centers, medical examination programs, as well as monitoring electronic databases. Questioning of a conditionally healthy population for the presence of risk factors for CKD.

Broad public awareness about the principles of nephroprophylaxis.

Reflection of the tasks of early detection of CKD in clinical guidelines and standards for the treatment of diseases that are risk factors for CKD.

Developing and increasing the availability of nephrological service structures, primarily a network of nephrologist consulting rooms, establishing mechanisms for their interaction with the primary health care system.

Training of district therapists and doctors of medical prevention rooms, health centers on the principles of CKD screening, nephroprophylaxis and nephroprotection.

Wider implementation of the albuminuria test to detect CKD, at least in patients with diabetes and hypertension. Application of GFR calculation using CKD-EPI formulas in addition to determination of serum creatinine.

Monitoring of GFR, albuminuria or proteinuria (when the level of total protein in the urine is above 0.5 g/l) in patients with identified CKD as part of dispensary observation at a frequency determined by the individual risk of developing ESRD and CVE.

Wide and rational use of non-pharmacological means of nephroprotection - a low-protein diet, an extended water regime, physical exercises. Comprehensive accounting and maximum possible correction of various metabolic disorders associated with the development of CKD.

Providing a personalized approach to the choice of tactics of nephrocardioprotective therapy. The principle of using targets for the effectiveness of treatment should not run counter to the principle of monitoring the safety of therapy. CKD is a population problem and requires solutions and programs similar to those for other chronic noncommunicable diseases. At the same time, as the experience of recent years shows, in CKD, template approaches are especially dangerous and unacceptable, leveling the individual characteristics of patients. The nephrocardioprotective strategy continues to evolve. New groups of drugs are being studied, in particular, endothelin-1 receptor antagonists with antiproteinuric action, drugs that suppress fibrogenesis and inflammation - pirfenidone and bardoxolone, an inhibitor of protein glycation aminoguanidine. Favorable results obtained from experimental and short-term, small-patient studies are not always confirmed in long-term prospective follow-ups. Thus, phase III studies of bardoxolone, prescribed for the purpose of nephroprotection, were interrupted due to the high incidence of side effects and mortality in the bardoxolone group. The current direction is the search and implementation of new biomarkers of renal damage and impaired renal function, more sensitive and specific, more dynamically responding to changes in the course of CKD and the development of complications of therapy. The most important task remains to conduct observational prospective studies, create and analyze registries of patients with pre-dialysis CKD, which will improve the system of ESRD and CVE risk stratification, clarify targets, preferred combinations of nephroprotective drugs, and optimize treatment tactics. Literature
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Chronic kidney disease is not a disease, but a syndrome, that is, a similar condition that can occur with various diseases. In some cases, a diagnosis of chronic kidney disease is allowed, but it should be understood that this is not a nosological disease. Chronic kidney disease can only be recognized in a patient when impaired renal function has been observed for three months or more, or during this time there are signs of nephropathy, even with a normal glomerular filtration rate.

Chronic kidney disease causes

There are many reasons for the development of chronic kidney disease. The most common of them, which in about three out of four cases lead to the development of chronic kidney disease, are:

• High blood pressure (arterial hypertension). Poorly controlled or neglected hypertension is the most common cause of chronic kidney disease. However, chronic kidney disease itself contributes to the development of hypertension. That is, blood pressure and the state of the kidneys are interconnected. Moreover, nine out of ten patients develop arterial hypertension at stages 3-5 of chronic kidney disease.
• Diabetes . Quite often, diabetes mellitus develops the so-called diabetic kidney disease, which ultimately leads to chronic kidney disease.
• Age-related decline in kidney function or aging of the kidneys. Almost all older people over 75 years of age have a first or second degree of chronic kidney disease. As a rule, if there are no concomitant diseases affecting the functioning of the kidneys, then chronic kidney disease does not develop beyond the second stage.

There are also other diseases that increase the risk of progression of chronic kidney disease. These diseases include:

• Renal artery stenosis
• Glomerulonephritis
• blockage of urine outflow
• Polycystic kidney disease
• Chronic kidney infections
• Hemolytic uremic syndrome
• Kidney damage due to poisoning or drugs
• Hyperlipidemia
• Urinary tract obstruction or urinary tract infection
• Acute renal failure
• Autoimmune diseases
• Systemic infections
• Hereditary burden
• Obesity
• Smoking and many, many other reasons.

Chronic kidney disease symptoms

Kidney symptoms vary depending on the stage of chronic kidney disease. So at the first and second stages of the disease, as a rule, the patient does not show any complaints and the syndrome is determined by laboratory tests. In the third stage, symptoms of general malaise begin to develop, which usually occur with any disease, so they cannot be called specific either. The patient may complain of fatigue, chronic fatigue, drowsiness, headaches, and so on. Subsequently, the patient may complain of:

• loss of appetite and weight loss
• decrease in performance
• dryness and irritation of the skin, itching,
• skin pallor,
• muscle spasms,
• leg swelling,
• puffiness under the eyes,
• frequent urge to urinate.

In addition, chronic kidney disease is accompanied by one or several clinical syndromes with all the ensuing symptoms:

• anemia,
• azotemia,
• arterial hypertension,
• acidosis,
• electrolyte disturbances.

Diagnostics

The diagnosis is made on the basis of clinical studies:

• Determination of glomerular filtration rate. This is one of the main studies. It should be borne in mind that the absence of a change in the glomerular filtration rate is not an exception to the presence of chronic kidney disease, since in the first stage it may be normal. That is, if the glomerular filtration rate is normal, but there is kidney damage of any etiology for three or more months, then we are dealing with chronic kidney disease of the first degree. However, a decrease in glomerular filtration rate for three months or more always indicates the presence of chronic kidney disease.
• Ultrasound of the kidneys - is necessary to determine the condition of the kidneys, their function and the presence or absence of kidney damage.
• A urinalysis is needed to determine kidney function.
• Blood test to determine the presence of creatinine and control electrolyte levels.

Other additional tests and research methods may be prescribed to determine the underlying cause, as well as treat the primary disease.

chronic kidney disease treatment

In the treatment of chronic kidney disease, two directions are used:

• the first is the treatment of the disease that caused the development of chronic kidney disease
• and second - nephroprotective treatment, which is universal for all renal pathologies.

Treatment of the underlying disease is specific and depends on the underlying disease itself.
Renoprotective treatment is common for all kidney pathologies and is aimed at slowing the progression of chronic kidney disease. Basically, slowing down the process is achieved by blockade of the renin-angiotensin-aldosterone system. a number of drugs are used for this: angiotensin receptor blockers, direct renin inhibitors, angiotensin-converting enzyme blockers, aldosterone antagonists, and so on.
Also, in nephroprotective treatment, it is important to reduce the level of proteinuria due to the normalization of intraglomerular hypertension and protection of proteins of the proximal epithelium from endocytosis.

In the treatment of chronic kidney disease, it is very important to carry out antihypertensive therapy with concomitant hypertension.

In the case of progressive chronic renal failure at stage 4 of the development of chronic kidney disease, the question of dialysis or kidney transplantation is raised. At the fifth degree of the disease, dialysis or kidney transplantation is mandatory.