Glomerulonephritis clinical guidelines. Clinical guidelines for general practitioners glomerulonephritis: diagnosis, treatment, prevention

FOR GENERAL PRACTITIONERS

Glomerulonephritis: DIAGNOSIS, TREATMENT, PREVENTION

1. Definition, ICD, epidemiology, risk factors and groups, screening.

2. Classification.

3. Principles and algorithm of clinical laboratory and instrumental diagnostics diseases in adults, children, the elderly, pregnant women and other groups of patients on an outpatient basis. Differential diagnosis (list of nosological forms).

4. Criteria for early diagnosis.

5. Complications of the disease.

6. General principles of therapy on an outpatient basis.

7. Treatment depending on the severity, characteristics of the course of the disease and the nature of the comorbidity.

8. Treatment in certain categories of patients: adults, children, the elderly, pregnant women.

9. Management of patients after treatment in a hospital.

10. Indications for consultation of specialists.

11. Indications for hospitalization of the patient.

12. Prevention. Patient education.

13. Forecast.

14. The procedure for providing medical and diagnostic care in an outpatient setting: flowchart, organization of the route of patients, monitoring, interaction with social security authorities.

15. List of references.
List of abbreviations:

AG - arterial hypertension

AT - antibodies

RPGN - rapidly progressive glomerulonephritis

GN - glomerulonephritis

AGN - acute glomerulonephritis

AKI - acute kidney injury

NSAIDs - non-steroidal anti-inflammatory drugs

MCTD - systemic connective tissue diseases

GFR - glomerular filtration rate

CKD - chronic illness kidney

CGN - chronic glomerulonephritis

Glomerulonephritis (GN)

1. Definition.

Glomerulonephritis, more precisely, glomerulonephritis, is a group concept that includes diseases of the glomeruli of the kidneys with an immune mechanism of damage, characterized by: in acute glomerulonephritis (AGN), a nephritic syndrome that first developed after streptococcal or other infection with an outcome in recovery; with subacute / rapidly progressive GN (RPGN) - nephrotic or nephrotic-nephritic syndrome with rapidly progressive deterioration of renal functions; in chronic GN (CHN) - a slowly progressive course with the gradual development of chronic kidney failure.

2. Codes according to ICD-10:

N00 Acute nephritic syndrome. N03 Chronic nephritic syndrome.

When conducting a biopsy, morphological classifying criteria for CGN are used:

N03.0 Minor glomerular disorders;

N03.1 Focal and segmental glomerular lesions;

N03.2 Diffuse membranous glomerulonephritis; .

N03.3 Diffuse mesangial proliferative glomerulonephritis;

N03.4 Diffuse endocapillary proliferative glomerulonephritis;

N03.5 Diffuse mesangiocapillary glomerulonephritis;

N03.6 Dense sediment disease;

N03.7 Diffuse crescentic glomerulonephritis;

N03.8 Other changes;

N03.9 Unspecified change.
3. Epidemiology.

Incidence of AGN in adults, 1-2 diseases per 1000 cases of CGN. AGN occurs more often in children aged 3–7 years (in 5–10% of children with epidemic pharyngitis and in 25% with skin infections) and less frequently in adults aged 20–40 years. Men get sick 2-3 times more often than women. Sporadic or epidemic cases of nephritis are possible. There are no racial or ethnic characteristics. Higher morbidity in socioeconomic groups with poor hygiene practices. Incidence of CGN― 13–50 cases per 10,000 population. CGN is observed more often in men. CGN can develop at any age, but is most common in children 3–7 years of age and adults 20–40 years of age. Mortality in GN is possible from complications of hypertension, nephrotic syndrome: stroke: acute renal failure, hypovolemic shock, venous thrombosis ov. Mortality in CGN at III-V stages of chronic kidney disease (CKD) is due to cardiovascular diseases.

Risk factors: streptococcal pharyngitis, streptoderma, infective endocarditis, sepsis, pneumococcal pneumonia, typhoid fever, meningococcal infection, viral hepatitis B, Infectious mononucleosis, parotitis, chicken pox, infections caused by Coxsackie viruses, etc.). At-risk groups: people who do not follow the rules of hygiene, with a low social status, suffering from streptococcal infections. Screening for GN not carried out .

4. Classification.

Clinical classification of GN

(E.M. Tareev, 1958; 1972; I.E. Tareeva, 1988).

With the flow: 1. Acute GN. 2. Subacute (rapidly progressive). GN.

3. Chronic GN.

By etiology : a) post-streptococcal, b) post-infectious.

By epidemiology : a) epidemic; b) sporadic.

According to clinical forms. latent form(changes only in the urine; there are no peripheral edema, blood pressure is not elevated) - up to 50% of cases of chronic GN. Hematuric form- Berger's disease, IgA nephritis (recurrent hematuria, edema and hypertension in 30-50% of patients) - 20-30% of cases of chronic GN. Hypertonic form(changes in urine, AH) - 20-30% of cases. Nephrotic form(nephrotic syndrome - massive proteinuria, hypoalbuminuria, edema, hyperlipidemia; no hypertension) - 10% of cases of chronic GN. FROM mixed form(nephrotic syndrome in combination with hypertension and / or hematuria and / or azotemia) - 5% of cases of chronic GN.

By phase.Aggravation(active phase, relapse) - the appearance of nephritic or nephrotic syndrome. Remission(inactive phase) - improvement or normalization of extrarenal manifestations (edema, hypertension), kidney function and changes in the urine.

By pathogenesis.Primary GN (idiopathic). Secondary GN associated with a general or systemic disease is established when a causative disease is detected (systemic lupus erythematosus, rheumatoid arthritis, Schonlein-Genoch disease, bacterial endocarditis, and others).

BPGN

Distinguish between idiopathic RPGN and RPGN syndrome, which develops during an exacerbation of CGN - “like RPGN”. Differential diagnosis between these variants is possible based on biopsy findings.

Morphological classification of GN

1. Diffuse proliferative GN. 2. GN with "crescents" (subacute, rapidly progressive). 3. Mesangioproliferative GN. 4. Membranous GN. 5. Membrane-proliferative, or mesangiocapillary GN. 6. GN with minimal changes or lipoid nephrosis. 7. Focal segmental glomerulosclerosis. 8. Fibroplastic GN.

Diffuse proliferative GN corresponds to acute glomerulonephritis, GN with crescents corresponds to rapidly progressive GN, other morphological forms correspond to chronic GN. In the absence of diseases that could cause the development of GN, the diagnosis of primary GN is established.
4. Principles and algorithm for outpatient diagnostics.
For the diagnosis of GN, a kidney biopsy is absolutely necessary - it allows you to determine the morphological type (variant) of GN, the only exception is steroid-sensitive NS in children, when the diagnosis is established clinically, a biopsy in such patients remains in reserve in case of atypical NS (KDIGO GN, 2012).

At the outpatient stage, GN should be suspected and the patient should be referred to the nephrology department for a biopsy and a definitive diagnosis of GN. However, in the absence or limited availability of a biopsy, the diagnosis of GN is established clinically.

Diagnosis of GN at the outpatient stage

Complaints headache, dark urine, swelling or pastiness of the legs, face or eyelids. There may be complaints of nausea, vomiting, headache.

OGN should be suspected in the first developed nephritic syndrome C - the appearance 1-3 weeks after streptococcal or other infection of a triad of symptoms: hematuria with proteinuria, hypertension and edema. With a late visit to the doctor (a week from the onset and later), it is possible to detect changes only in the urine without edema and AH C. Isolated hematuria in post-infectious nephritis is resolved within 6 months.

At CGN comes to light one of the clinical and laboratory syndromes (urinary, hematuric, hypertonic, nephrotic, mixed). With an exacerbation edema of the eyelids appears or increases lower extremities, decreased diuresis, dark urine, increased blood pressure, headache; with latent CGN, there may be no clinical manifestations of the disease. In remission clinical manifestations and complaints may be absent. For IgA nephritis, as for OGN, hematuria is characteristic, but persistent microhematuria is more typical of IgA nephropathy. For IgA nephritis incubation period often short - less than 5 days.

With CGN, unlike AGN, left ventricular hypertrophy is detected; angioretinopathy II–III degree; signs of CKD. For BPGN characterized by an acute onset with nephritic, nephrotic or mixed syndromes, a progressive course with the appearance of signs of renal failure during the first months of the disease. Clinical manifestations diseases are steadily increasing; azotemia, oligoanuria, anemia, nocturia, resistant arterial hypertension, heart failure join. Progression to terminal renal failure is possible within 6-12 months, with the effectiveness of treatment, an improvement in the prognosis is possible.

History and physical examination

History there may be indications of a previous streptococcal (pharyngitis) or other infection 1-3 weeks before the exacerbation. Cause of GN may be hemorrhagic vasculitis, chronic viral hepatitis B and C, Crohn's disease, Sjögren's syndrome, ankylosing spondylitis, carcinomas, non-Hodgkin's lymphoma, leukemia, SLE, syphilis, filariasis, malaria, schistosomiasis, drugs (gold and mercury preparations, penicillamine, cyclosporine, NSAIDs , rifampicin); cryoglobulinemia, interferon-alpha, Fabry disease, lymphoproliferative pathology; sickle cell anemia, renal transplant rejection, surgical excision of part of the renal parenchyma, vesicoureteral reflux, heroin use, nephron dysgenesis, HIV infection. At the same time, GN can also be idiopathic. With a history of CGN CGN symptoms/syndromes (edema, hematuria, hypertension) may be detected.

Physical examination allows you to detect the clinical symptoms of nephritic syndrome: urine of the color "coffee", "tea" or "meat slops"; swelling on the face, eyelids, legs; increased blood pressure, symptoms of left ventricular heart failure. CGN is often detected incidentally by changes in urinalysis. In some patients, CGN is first detected in the later stages of CKD. Body temperature is usually normal, Pasternatsky's symptom is negative. With secondary GN, symptoms of the disease that caused CGN may be detected. When CGN, first detected at the stage of CRF, symptoms of uremic syndrome are detected: dry, pale skin with a yellowish tinge, scratching, orthopnea, left ventricular hypertrophy.

Laboratory and instrumental research. Helps confirm the diagnosis of GN

With fire and exacerbation CGN in the UAC moderate increase in ESR, which can be significant in secondary GN. Anemia is detected in hydremia, autoimmune disease, or CKD stage III-V.

Biochemical research blood: with poststreptococcal AGN, the titer of antistreptococcal antibodies (antistreptolysin-O, antistreptokinase, antihyaluronidase) is increased, with CGN it rarely increases. Hypocomplementemia of the C3 component, to a lesser extent of C4 and total cryoglobulin, is sometimes detected in primary, constantly in lupus and cryoglobulinemic nephritis. An increase in IgA titer in Berger's disease, Ig G - in secondary GN with CTD. Increased concentrations C-reactive protein, sialic acids, fibrinogen; reduced - total protein, albumin, especially - with nephrotic syndrome. In the proteinogram, hyper-α1- and α2-globulinemia; with nephrotic syndrome - hypo-γ-globulinemia; with secondary GN caused by systemic diseases of the connective tissue - hyper-γ-globulinemia. Decrease in GFR, increase in plasma concentration of creatinine and / or urea - with AKI or CKD.

In secondary GN, changes in the blood specific to the primary disease are detected: in lupus nephritis, antinuclear antibodies, a moderate increase in the titer of antibodies to DNA, LE cells, antiphospholipid antibodies. With CGN associated with viral hepatitis C, B - positive HBV, HCV, cryoglobulinemia; with membrane-proliferative and cryoglobulinemic GN, the level of mixed cryoglobulins is increased. In Goodpasture's syndrome, antibodies to the basement glomerular membrane are detected.

In the urine during exacerbation: an increase in osmotic density, a decrease in daily volume; in the sediment, altered erythrocytes from single to covering the entire field of view; leukocytes - in a smaller amount, but can prevail over erythrocytes in lupus nephritis, nephrotic syndrome, while they are represented mainly by lymphocytes; cylinders; proteinuria from minimal to 1–3 g/day; proteinuria more than 3 g/day develops with nephrotic syndrome. Sowing from the tonsils, blood sometimes allows you to clarify the etiology of AGN. FROM

Special studies. Kidney biopsy is the gold standard for diagnosing CGN. Indications for nephrobiopsy: clarification of the morphological form of GN, activity, differential diagnosis. Ultrasound of the kidneys is performed, to exclude focal kidney diseases, urinary tract obstruction: in GN, the kidneys are symmetrical, the contours are smooth, the dimensions are not changed or reduced (in CKD), echogenicity is increased. ECG: signs of left ventricular hypertrophy in CGN with AH.

Early diagnosis. It is possible with dynamic monitoring of patients after an acute infectious and disease within 2-3 weeks. The appearance of nephritic syndrome (AH, edema, hematuria) indicates the development of GN or its exacerbation.

5. Differential diagnosis.

Pyelonephritis: episodes of urinary tract infection in history, fever, back pain, dysuria are characteristic; in the urine - leukocyturia, bacteriuria, hypostenuria, ultrasound of the kidneys - deformation and expansion of the pyelocaliceal system, asymmetry and deformation of the contours of the kidneys are possible; excretory urography - deformation of the pelvicalyceal system and asymmetry of kidney function, radioisotope renography - urodynamic disturbances are possible.

Nephropathy of pregnancy: characteristic triad - edema, proteinuria, arterial hypertension; no history of chronic GN, development in the second or third trimester of pregnancy.

Tubulo-interstitial nephritis: fever, hypostenuria, leukocyturia, back pain, increased ESR.

Alcoholic kidney disease: history, hematuria, hypostenuria, back pain.

Amyloidosis: history of chronic purulent diseases, rheumatoid arthritis, helminthiases; systemic lesions, proteinuria, often the absence of erythrocyturia.

diabetic nephropathy: diabetes mellitus, a gradual increase in proteinuria, often the absence of hematuria.

Kidney damage in diffuse connective tissue diseases: signs of a systemic disease - fever, carditis, arthritis, pulmonitis, hepato-lienal syndrome, etc .; high ESR, hyper-gammaglobulinemia, positive serological tests. Lupus nephritis: female predominates; signs of a systemic disease are revealed: arthralgia, arthritis, fever, erythema of the face like a "butterfly", carditis, hepatolienal syndrome, lung damage, Raynaud's syndrome, alopecia, psychosis; typical laboratory changes: leukopenia, thrombocytopenia, anemia, lupus cells (LE-cells), lupus anticoagulant, high ESR; development of nephritis several years after the onset of SLE; specific morphological changes: fibrinoid necrosis of capillary loops, karyorrhexis and karyopyknosis, hematoxylin bodies, hyaline thrombi, "wire loops". Nodular periarteritis: the male sex predominates; signs of a systemic disease are detected: fever, myalgia, arthralgia, weight loss, severe hypertension, skin manifestations, asymmetric polyneuritis, abdominal syndrome, myocarditis, coronaritis with angina pectoris and myocardial infarction, bronchial asthma; typical laboratory changes: leukocytosis, sometimes eosinophilia, high ESR; specific changes in the biopsy of the musculoskeletal flap; renal biopsy is not indicated. Wegener's granulomatosis: signs of a systemic disease: damage to the eyes, upper respiratory tract, lungs with infiltrates and destruction; typical laboratory changes: leukopenia, anemia, high ESR, antineutrophil antibodies; specific changes in the biopsy of the mucous membrane of the nasopharynx, lung, kidney. Goodpasture's syndrome: signs of a systemic disease: fever, hemoptysis or pulmonary bleeding, infiltrates in the lungs, weight loss; kidney damage occurs after hemoptysis, renal failure rapidly progresses with oliguria and anuria; anemia, increased ESR, with serological study- the presence of antibodies to the basement membrane of the renal glomeruli. Hemorrhagic vasculitis: signs of systemicity (hemorrhagic purpura on the skin and mucous membranes, arthritis, abdominal syndrome), increased ESR.

Urolithiasis disease: detection of calculus, history of renal colic, detection of signs of obstruction and hematuria without proteinuria.

Tumor of the kidneys and urinary tract: focal formation in the urinary tract, asymmetry of kidney function, biopsy data.

Primary antiphospholipid syndrome Keywords: livedo, miscarriages, antibodies to phospholipids.

Hypersensitivity vasculitis: the presence of two of the following criteria - palpable purpura, abdominal pain, gastrointestinal bleeding, hematuria, age not older than 20 years.

hereditary nephritis (Alport syndrome); thin membrane disease: history, urinalysis in family members - massive hematuria is characteristic of IgA nephritis and hereditary nephritis and is rare in thin membrane disease. Hereditary nephritis is associated with familial renal failure, deafness, and chromosomal dominant inheritance. A family history of hematuria is also found in thin membrane disease, in isolated cases - in IgA nephritis. A patient with episodes of gross hematuria and a negative family history is most likely to have IgA nephritis. With persistent microhematuria in a patient and hematuria in family members without renal insufficiency, thin membrane disease is most likely. A patient with a family history of renal failure and deafness has hereditary nephritis. Skin biopsy is a method for establishing x-linked hereditary nephritis. The final diagnosis can only be established after nephrobiopsy. Given the low likelihood of progression to end-stage renal failure with isolated hematuria, a study of urine, kidney function, and proteinuria is sufficient to establish the diagnosis.
6. Complications of the disease.

Hypertensive crisis, eclampsia, acute left ventricular failure or acute renal failure (with high GN activity), hypovolemic nephrotic crisis, intercurrent infections, rarely - stroke, vascular complications (thrombosis, heart attacks, cerebral edema).
7. General principles of therapy on an outpatient basis.

At the outpatient stage, it is important to suspect active GN and refer the patient for inpatient treatment in the therapeutic or nephrology department. In the presence or threat of complications, hospitalization is carried out according to urgent indications, in other cases - in a planned manner. Prior to admission to the hospital, the patient is given recommendations on diet, regimen, consultations of narrow specialists are held. At acute infection antimicrobial therapy is given.
Management of patients after hospital treatment.

Fluid balance is monitored, adherence to the regimen and diet, blood pressure measurement; taking drugs prescribed by a doctor. Phytotherapy is not used, a short-term intake of a decoction of wild rose, chokeberry is possible. Exclusion of hypothermia, stress, physical overload. Compliance with the regimen and diet, smoking cessation, self-control of blood pressure.

Compliance with the diet, restriction of salt C in edema and volume-dependent hypertension. Protein restriction somewhat slows the progression of A nephropathies. Exclude spicy seasonings, meat, fish and vegetable broths, gravies, strong coffee and tea, canned food. Prohibition on the use of alcohol, tobacco C.

In women of reproductive age with GN, pregnancy should be planned during the period of GN remission, taking into account kidney function and AH levels, as well as predicting the course of pregnancy and GN. Exacerbations of GN during pregnancy usually do not occur due to physiological characteristics- high levels of glucocorticoids. Pregnancy is usually carried well with IgA nephropathy. Women with a GFR below 70 mL/min, uncontrolled hypertension, or severe vascular and tubulointerstitial changes in a renal biopsy are at risk of decreased renal function.
8. Indications for specialist consultation

Consultations of specialists help in establishing the diagnosis of C. If you suspect focal infection the patient can be consulted if necessary otorhinolaryngologist, gynecologist, dermatologist. To identify angiopathy and assess its prescription (for the differential diagnosis of AGN and CGN), a consultation is indicated optometrist Consultation infectiologist carried out in cases of suspected viral hepatitis or HIV infection. If there are signs of a systemic disease (may debut with AGN C), consultation rheumatologist will clarify the diagnosis and to decide on the treatment of the disease. With high clinical and laboratory activity of inflammation, febrile fever, heart murmurs, a consultation is indicated. cardiologist.

9. Indications for hospitalization.

Active or newly diagnosed GN (AGN, CGN, RPGN) or suspected GN are indications for hospitalization urinary symptom or differential diagnosis), to perform a biopsy to clarify the morphological diagnosis and assess the activity of GN), peer review, and immunosuppressive therapy and the initiation of active therapy.

10. Prevention.

impact studies primary prevention relapses of GN, long-term prognosis, renal survival is insufficient. Primary prevention not carried out. Nonetheless, antibiotic treatment patients with pharyngitis and contacts (1), initiated within the first 36 hours results in negative cultures and may (but not necessarily) prevent nephritis D level of evidence: 1)

secondary prevention. Treatment with prednisolone, sometimes in combination with cyclophosphamide, reduces the likelihood of recurrence of nephrotic syndrome in IGA nephritis. Steroids for IGA nephropathy by mouth for a long time (up to 4 months) improve the number of remissions of nephritic syndrome. Combination therapy with prednisolone and cyclophosphamide GMI reduces the incidence of disease recurrence compared with prednisolone monotherapy.

In some forms of glomerulonephritis, in particular, in idiopathic membranous glomerulonephritis, the preventive role of alkylating drugs (chlorambucil or cyclophosphamide), in contrast to glucocorticoids, in reducing proteinuria and reducing the risk of relapses in the next 24–36 months after treatment has been proven. Prednisolone used long-term (for 3 months or more) at the first episode of nephrotic syndrome in children prevents the risk of relapse for 12–24 months, and 8-week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporine and levamisole reduce the risk of relapse in children with steroid-sensitive nephrotic syndrome compared with glucocorticoid monotherapy.

Patient education. Control of fluid balance, adherence to the regimen and diet, measurement of blood pressure; taking drugs prescribed by a doctor. Phytotherapy is not used, a short-term intake of a decoction of wild rose, chokeberry is possible. Exclusion of hypothermia, stress, physical overload. Compliance with the regimen and diet, smoking cessation, self-control of blood pressure. The patient should be informed about the need to control the level of GFR and blood creatinine, about the exclusion of potentially nephrotoxic drugs, radiopaque drugs.
11. Treatment in a hospital

(depending on the severity, characteristics of the course of the disease and the nature of the comorbidity).

Purpose of treatment. At OGN: achievement of recovery, elimination of complications. At CGN: induction of remission, slowing down the rate of progression, prevention and elimination of complications. At BPGN- Decreased disease activity and rate of progression to end-stage renal failure.

Not drug treatment. With active GN, semi-bed or bed regimen for until the disappearance of edema and normalization of blood pressure (1–3 weeks), then the expansion of the regimen follows. Prolonged bed rest does not improve the prognosis of GN. Diet: with edema - restriction of table salt (up to 4-6 g / day), fluid with massive edema and nephrotic syndrome (the volume of fluid received is calculated taking into account diuresis for the previous day + 300 ml), protein up to 0.5-1 g / kg / day. In remission of GN, salt and protein restriction is less stringent. Protein restriction somewhat slows down the progression of nephropathies, although the degree of effect somewhat weakens as chronic GN progresses. Exclude spicy seasonings, meat, fish and vegetable broths, gravies, strong coffee and tea, canned food. Prohibition on the use of alcohol, tobacco. Physiotherapy treatment for GN is not indicated.

With drug-induced MGN, drug withdrawal sometimes leads to spontaneous remission: after the abolition of penicillamine and gold - within a period of 1-12 months to 2-3 years, after the abolition of NSAIDs - up to 1-36 weeks. In patients with concomitant diabetes replacing porcine insulin with human insulin.

Glomerulonephritis is a disease that occurs due to an allergic or infectious nature.

Disease history

Diagnosis of the disease

At the first visit, the patient is examined for the first signs glomerulonephritis.

The visible signs of glomerulonephritis include high blood pressure and confirmation by the patient of the fact that he has recently had infection or inflammation in the region of the kidneys, or may have undergone severe hypothermia.

Since complaints and visible ones may be similar to signs of pyelonephritis, the specialist will prescribe a series of tests for a more accurate picture of the disease.

The doctor during the appointment tries to understand whether the complaints indicate on the inflammatory process in the kidneys Or is it a symptom of another disease?

Diagnostic studies to identify acute glomerulonephritis always require a thorough study of the general analysis of blood and urine patient. To do this, the patient must pass the following types of tests:

1. Clinical analysis of urine.
2. Analysis of urine according to the method.
3. Urinalysis according to the Kakovsky-Addis method.

Based on the results of the analysis, the doctor will determine glomerulonephritis according to the following indicators:

• oliguria, that is, a decrease in the amount of urine excreted from the body;
• proteinuria, which means the amount of protein in urine;
• hematuria, that is, the presence of blood particles in the urine.

First of all, for the presence of glomerulonephritis indicates proteinuria, which is a consequence of improper filtration by the kidneys. Hematuria also indicates damage to the glomerular apparatus, as a result of which blood particles enter the urine.

Sometimes you need to take renal tissue biopsy and tests that reveal an immunological predisposition to this disease.

In order to accurately determine whether the inflammation is glomerulonephritis, the doctor will give a referral for an ultrasound scan that can find the main signs of this disease.

Such signs include increase in kidney volume with smooth contours, thickening of tissue structures and, of course, a change in the diffuse nature in the tubules, glomerular apparatus and connective tissue.

Kidney biopsy in case of disease

The kidney tissue biopsy method is used to study in detail a small fragment taken from the kidney tissue. During the study, a morphological analysis will be carried out to identify the factor that served as the beginning inflammatory process and other indicators.

This is a method of intravital examination of an organ for the presence of a pathological process.

This type of study allows you to study the immune complex for exact definition shapes and sizes, and severity and form of the disease in the body.

In cases where the definition of glomerulonephritis has become difficult or the doctor cannot differentiate this disease from another, this method becomes indispensable in terms of its informativeness.

There are several methods for conducting such a study. These include:

1. Open.

This type of sampling is carried out during surgery when there is a need to remove resectable tumors or when there is only one kidney. This procedure is carried out under general anesthesia. In most cases, taking a small piece of tissue ends without complications.

2. Biopsy in tandem with ureteroscopy.

This method is done for people suffering from urolithiasis as well as pregnant women and children. Sometimes it is carried out for those patients who have an artificial kidney.

3. Transjugular.

This type of research is carried out through catheterization of the renal vein. The doctor prescribes this type of sampling in the case when the patient has obvious obesity or poor blood clotting occurs.

4. Transcutaneous.

This method is carried out under the control of x-rays, as well as ultrasound or magnetic resonance imaging.

Is it possible to cure glomerulonephritis permanently?

Glomerulonephritis can progress in two forms: acute and chronic. The acute form is curable, with timely diagnosis and the right methods treatment.


If the time for drug treatment was missed, and the disease smoothly flowed into a chronic form, then you cannot completely get rid of this disease, but you can maintain your body in a state where the disease cannot develop further and affect more and more kidney elements.

In this case, the doctor will prescribe a specific diet and tell on the observance of a special regime, which is able to save the patient from the manifestation of a new relapse of the disease.

If a complete cure cannot be achieved, the doctor recommends that you follow all the established rules and preventive actions to make symptoms less noticeable. Sometimes, with good luck therapeutic treatment achieve temporary disappearance of symptoms.

It is necessary to maintain the body as long as possible before the appearance of a new relapse.

Treatment

When acute stage glomerulonephritis the patient should be hospitalized.

At the same time, he will be prescribed bed rest without fail. This is important in order for the kidneys to be at a certain temperature, that is, the regime for maintaining a special temperature must be balanced. This method, with timely hospitalization, is capable of optimize kidney function.

The average duration of hospitalization is two weeks to one month, that is, until the symptoms are completely eliminated and the patient's condition improves.

If the doctor considers that there is an additional need to extend the inpatient regimen, then the length of the patient's stay in the ward may be extended.

Medical

If, according to the results of the studies, it was proved that the disease is caused by infectious way then the patient is prescribed antibiotics to take.

In most cases, a few weeks before the onset of the acute phase of the disease, the patient suffered an infectious sore throat or other disease. Almost always, the causative agent of the disease is β-hemolytic streptococcus.

In order to get rid of the causative agent of the disease, the patient is prescribed the following drugs:

• Ampicillin;
• Penicillin;
• Oxacillin;
• Ampioks with intramuscular injection;
• Sometimes doctors prescribe Interferon for rapidly progressive glomerulonephritis.

A frequent occurrence in such a disease is the damaging effect against the glomerular apparatus by its own antibodies in the body. That's why use of immunosuppressants It is an integral part complex treatment against glomerulonephritis. These drugs are able to establish a depressing reaction of the immune response.

With the rapid development of the disease, large doses of droppers are prescribed for the patient for several days. After several days of administration of such a drug, the dose is gradually reduced to the usual level. For such purposes, it is often prescribed cytostatics such as prednisolone.

Treatment with Prednisolone in the early stages is prescribed by a doctor in the allotted dosage, which is also prescribed by a specialist. The course of admission is continued for one and a half or two months. In the future, with the onset of relief, the dose is reduced up to twenty milligrams in one day, and if the symptoms begin to disappear, then the drug can be canceled.

In addition to this drug medical specialists it is often advised to take Cyclophosphamide or Chlorambucil at the dosage prescribed by your doctor. Experienced medical professionals prescribe anticoagulants such as Curantil or Heparin in addition to immunosuppressants.

The combination of these funds should be justified by the form of the disease and the degree of its neglect.

After the main symptoms have receded and a period of remission has begun in the body, then maintenance and treatment of glomerulonephritis is allowed. traditional medicine.

exercise therapy

Physiotherapy exercises in the treatment and prevention of glomerulonephritis should be prescribed by the attending specialist, taking into account all the analyzes and indicators of a person.

In this matter, the doctor also focuses to activity mode patient, which can be bed, general or ward. Usually, a set of exercises is prescribed for a stable condition during the acute course of the disease or for chronic glomerulonephritis during remission.

Similar species exercise carried out for the purpose of:

1. Improving blood flow to the kidneys and other organs.
2. Reduce blood pressure and improve metabolism in the body.
3. Increase the strength of the body to fight the disease.
4. Increasing efficiency.
5. Elimination of congestion formed in the human body.
6. Creating a general positive attitude to fight the disease.

Before proceeding with the exercise, it is recommended to measure the level of blood pressure and only after that proceed with the set of exercises.

The classic complex of exercise therapy for the elimination of glomerulonephritis includes exercises performed in the supine position or on a chair. The attention of the practitioner should be fully concentrated on the time of inhalation and exhalation.

All kinds of movements must be performed at a slow pace with smooth amplitude. Types of loads alternate for different muscle groups in order not to overload any of them in excessive volume.

The duration of such lessons should not be more than half an hour, otherwise it can be a negative effect for the patient and cause various complications.

ethnoscience

When visiting the attending physician, they may be prescribed various herbal infusions and decoctions that favorably affect the functioning of the renal system.

• 100 grams of walnut;
• 100 grams of figs;
• a few spoons of honey;
• three lemons.

All ingredients are crushed and mixed. The mixture is taken within three times a day one tablespoon, usually before meals. These components must be consumed until the tests show improved results.

There are special decoctions designed to eliminate puffiness and bring blood pressure back to normal. These decoctions include the following recipe:

• Flaxseed in the amount of four tablespoons is mixed with three tablespoons of dry birch leaves.
• To this mixture, you must add three tablespoons of the root of the field harrow.
• The resulting mixture is recommended to pour 0.5 liters of boiling water and insist for two hours.

Infusion is consumed three times a day for a third of a glass. The effect will be visible in one week.

For the preparation of medicinal infusions, all herbs with antimicrobial and anti-inflammatory effects will be suitable. These herbs include:

• rose hip;
• calendula;
• St. John's wort;
• sea ​​buckthorn;
• sage;
• yarrow;
• birch leaves, as well as its buds;
• burdock root.

Herbs can be brewed separately or combined with each other, of course, according to certain recipes.

In addition to decoctions and infusions, experts in the field of traditional medicine recommend drinking as much as possible. natural juices mainly from cucumber and carrots, as well as eat a lot of fruits and vegetables that can fill a weakened body with vitamins.

In addition, the doctor will prescribe a special diet, called, which will strengthen the body while fighting the disease. The main rule of the diet is to exclude salty, smoked and fried foods from the diet. Eating protein foods should be somewhat limited.

Alcohol during the treatment period is prohibited, as is coffee.

Disease prevention

In order to avoid further development of the disease and its transition to a chronic form, it is necessary to adhere to dietary nutrition and fully give up alcoholic beverages.

If a person works in a chemical plant or is engaged in other activities where he may be threatened by the action of heavy metals, he needs to protect his body from harmful effects or change his profession.

If glomerulonephritis has passed into the stage, then it is necessary to make every effort to avoid recurrence illness. It is necessary to be vaccinated according to the schedule set by the specialist, as well as to keep calm in psychological and physical terms.

Regular examination in the office of a specialist will protect the body from a new manifestation of the disease. The main rule is to prevent the penetration of bacteria into the human body. It is necessary to refuse to work in a damp room or activities associated with lifting weights.

The patient must follow a therapeutic diet and fill the body with vitamins. Preferably at least once a year spa treatment.

A urologist will tell you more about the causes of the development of the disease in a video clip:

Developer: Research Institute of Nephrology of the First St. Petersburg State medical university them. acad. I.P. Pavlova (2013)

Smirnov A.V. - Doctor of Medical Sciences, Professor, Nephrologist Dobronravov V.A. – Doctor of Medical Sciences, Professor, Nephrologist Sipovsky V.G. – senior researcher, pathologist Trofimenko I.I. – Candidate of Medical Sciences, Associate Professor, Nephrologist

Pirozhkov I.A. – junior researcher, pathologist, specialist in immunomorphology Kayukov I.G. – Doctor of Medical Sciences, Professor, Nephrologist, Clinical Physiologist Lebedev K.I. – junior researcher, pathologist, immunomorphologist

Note: * compiled in accordance with clinical guidelines

Section 1. Definition of membranoproliferative glomerulonephritis.

term (“morphological syndrome”), which unites a group of glomerulopathies that have a similar

morphological picture with light microscopy of biopsy specimens, but differing in etiology,

pathogenesis, immunohistochemical and ultrastructural (electron microscopy) changes

renal parenchyma (NG).

Comment Considerable advances have been made in understanding the etiology and

especially the pathogenesis of MBPHN, which allows us to consider this morphological form as a very heterogeneous group of diseases.

Previous ideas about the clinical division of MBPGN into idiopathic (with unknown etiology) and secondary forms have been preserved, the latter being predominant. In this regard, past data on the prevalence of MBGN in the population should be taken with caution.

According to large morphological registries in Western European countries, the prevalence of MBPGN varies from 4.6% to 11.3%, and in the USA it does not exceed

1.2%, accounting for approximately 1-6 people per 1 million population. On the contrary, in the countries of Eastern Europe, Africa and Asia, the prevalence of MBPGN, according to some data, reaches 30%, which is associated with a higher prevalence of infections, primarily viral hepatitis B and C. Active infection prevention measures seem to explain the apparent downward trend in the prevalence of MBGN over the past 15–20 years in most regions.

However, MBPH remains the 3rd and 4th cause of end-stage renal disease (ESRD) among all other forms of primary glomerulonephritis.

Synonyms of the term membranoproliferative glomerulonephritis are mesangiocapillary glomerulonephritis, and in the domestic literature - membranoproliferative glomerulonephritis. The preferred term is membranoproliferative glomerulonephritis.

Section 2. Clinical presentation of MBGN

Comment:

Despite the pathogenetic and morphological heterogeneity of MBPGN, the clinical presentation on the part of the kidneys is identical. Half of the patients have a history of indications of a recent (up to one week) infection of the upper respiratory tract. In some cases, a clinical phenomenon is revealed - synpharyngitis macrohematuria, which makes it necessary to carry out differential diagnosis with IgA nephropathy. Among clinical symptoms prevail: arterial hypertension, which in the debut is noted more than

than in 30% of patients, but develops over time in almost all patients,

sometimes acquiring a malignant course; macro- and microhematuria

(almost 100%); high proteinuria (nephrotic); progressive decrease in glomerular filtration rate (GFR). The leading clinical syndrome at the onset of the disease in 20–30% of cases is represented by acute or rapidly progressive nephrotic syndrome (ANS, BPNS). In the first case, there is a need for differential diagnosis with acute poststreptococcal glomerulonephritis, especially since in 20-40% of cases of MBPGN there is a high titer of ASL-O, in the second case, differential diagnosis is carried out with anti-GBM-nephritis, ANCA-

associated vasculitis and thrombotic microangiopathies. In 40 - 70% of patients, nephrotic syndrome develops from the very beginning (if it is not present, then in most patients it appears later, in 10 - 20% of cases

there is recurrent gross hematuria (often synpharyngitis).

However, in 20 - 30% of patients it is possible to register (usually by accident)

only changes in the general analysis of urine in the form of a combination of proteinuria with microhematuria and cylindruria (isolated urinary syndrome). In all patients with ANS, BPNS, and in 50% of cases with other variants of clinical presentation, there is a decrease in GFR (progressive in BPNS) and

multiform disturbances of tubular functions are revealed (decrease in the concentration ability of the kidneys, aminoaciduria, glucosuria,

hyperkalemia, etc.). Based on the clinical picture of kidney damage, it is impossible to predict the type of MBPGN or speak definitely about its cause. More often (up to

80% of all cases) are diagnosed with immunoglobulin-positive MBGN type I,

that affects people of all ages and genders. An immunoglobulin-positive variant of type III MBPGN is detected less frequently (5-10%). There is currently a consensus among nephrologists regarding idiopathic,

immunoglobulin-positive MBPHN type I (rarely type III), the diagnosis of which can be established only after exclusion secondary causes(Table 3). AT

clinical picture of C3-negative glomerulopathy, as a rule, clinical and laboratory symptoms of the underlying disease prevail in the debut (Table 4) in

combined with acute kidney injury, most often in the form of BPNS. Only after the acute period, high proteinuria joins,

microhematuria or nephrotic syndrome is formed. Clinical diagnostics Dense deposit disease (DDD) is alleviated if, in addition to renal syndromes, associated conditions are identified in the form of acquired partial lipodystrophy and / or macular degeneration of the retina (see below).

differential diagnosis of MBPGN

Recommendation 3.1. To diagnose MBPH according to world standards, it is necessary to combine several methods of morphological examination of intravital biopsy specimens of renal tissue, namely: light microscopy, immunomorphology, ultrastructural analysis (transmission electron microscopy) (NG).

Masson's trichromic stain, PAS reaction, Congo-mouth, staining for elastic fibers and fibrin (AFOG) (1A).

Recommendation 3.3. For immunomorphological studies, the following antibodies should be used to detect diagnostically significant epitopes: IgA, M, G, lambda light chains, kappa and fibrinogen, complement fractions C3, C1g, C2 and C4 (2B).

should be distinguished: type I membranoproliferative glomerulonephritis, dense deposit disease, and type III membranoproliferative glomerulonephritis (1A).

positive MBGN I or III, immunoglobulin-negative, C3-positive MBGN I or III

types and dense deposit disease, immunoglobulin- and C3-negative MBGN (1A).

Recommendation 3.7. When conducting an immunomorphological study, it is necessary to consider the intensity of deposition of the product of the reaction to immunoglobulins A, M, G in the structures of glomeruli ≥2+ both with fluorescence and light-optical (in transmitted light) microscopy (immunoglobulin-positive variant of MBPGN) as diagnostically significant. The remaining variants of the intensity of deposition of the product of the reaction to immunoglobulins (less than 2+) should be considered negative (immunoglobulin-negative variant of MBPGN) (2B).

Recommendation 3.8. When conducting an immunomorphological study, it is necessary to consider the intensity of deposition of the product of the reaction to the C3 fraction of complement in the structures of glomeruli ≥2+ as diagnostically significant both with fluorescent and light-optical (in

transmitted light) microscopy (C3-positive variant of MBPGN). The remaining variants of the intensity of deposition of the product of the reaction to immunoglobulins (less than 2+) should be considered negative (C3-negative variant of MBPGN) (2B).

(electron microscopy), a morphological diagnosis should be formulated on the basis of light microscopy and immunomorphology data (2B).

immunoglobulin and C3-positive MBPGN;

C3 glomerulopathy;

immunoglobulin and C3-negative MBPGN.

positive MBGN, including 2 forms of MBGN, which, upon further ultrastructural analysis, can be refined as: immunoglobulin-negative, C3-positive MBGN I or III

type or dense deposit disease (1A).

Clinical guidelines for glomerulonephritis are certain provisions that are designed to help the doctor and the patient follow rational tactics in the treatment of a particular pathology. They are developed on the basis of scientific achievements not only in our country, but also foreign practices. The recommendations are reviewed and updated annually.

Based on the results of the implementation of clinical recommendations, the attending physician controls the tactics of patient management. Previously, they were advisory in nature, but since 2017 they have been introduced for mandatory implementation by the attending physician. At the same time, the characteristics of each patient are taken into account. The doctor must be very thoughtful in the treatment of each patient, following certain standards.

Glomerulonephritis refers to a group of kidney diseases when the renal parenchyma suffers directly due to various reasons. These are inflammatory changes in the renal medulla with proliferation of connective tissue.

Options for the course of glomerulonephritis

According to the variants of development, acute and chronic are distinguished. Glomerulonephritis in general practice occur quite frequently. Primary glomerulonephritis is predominantly recorded in children under 15 years of age and adults under 30 years of age. The chronic form is typical for the older age group.

Glomerulonephritis may develop during pregnancy with a frequency of up to 0.2%. Glomeruli are predominantly affected. The tubules and interstitial tissue also suffer. Glomerulonephritis during pregnancy is a very serious condition. requiring immediate treatment. The disease threatens the life of the child and mother. Downstream, this may be a latent state. There are clinical guidelines for the management of pregnant women with glomerulonephritis.

Causes of the disease

The main causative agent in which glomerulonephritis occurs is group A hemolytic streptococcus. Glomerulonephritis can develop after erysipelas, scarlet fever, tonsillitis, pyoderma. Viruses and bacteria can be pathogens. The main reason for the development of the disease is the launch of immunological mechanisms that have a tropism for the kidney parenchyma. This causes chronic kidney disease.

Provoking agents - hypothermia, viral infections.

Symptoms of glomerulonephritis during pregnancy

Symptoms of the disease during pregnancy may be hidden. With the development of glomerulonephritis in pregnant women in the initial stage, there can only be changes in the urine. This is the appearance of red blood cells, protein. The difficulty of diagnosis in pregnant women lies in the fact that changes can occur during pregnancy. Renal disorders are caused by the load on the body, compression of the kidneys.

Impaired kidney function leads to edema, increased blood pressure up to eclampsia. Family doctors can be mistaken for preeclampsia.

Clinical manifestations

Chronic glomerulonephritis, clinic. In this case, there may be minimal manifestations in the form of microhematuria - traces of blood in the urine.

In the nephrotic form, the clinic of the disease manifests itself:

• A decrease in the amount of urine excreted, swelling in the legs and face, an increase in blood pressure numbers.
• Protein, macro- and microhematuria, cylindruria, leukocyturia are found in the urine.
• In the blood, the levels of urea and creatinine increase.

Diagnostic methods

To confirm the diagnosis of glomerulonephritis, it is necessary to conduct a thorough examination of the patient. Diagnosis of the disease is not as easy as it seems. To confirm the diagnosis, a morphological study of the renal parenchyma is performed. For this, a kidney biopsy and a biopsy study are performed. Biopsy required:

• Prolonged urinary syndrome
• Severe manifestations of nephrotic syndrome
• Rapid progression of symptoms leading to renal failure
• A study of blood and urine, in particular an increase in the titer of ASLO and CRP.
• Differential Diagnosis with nephropathy, membranoproliferative glomerulonephritis and secondary glomerulonephritis against the background of systemic diseases.

Treatment

Treatment of glomerulonephritis is a rather lengthy and complex process. The treatment is complex. Great importance is given to nutrition with the exception of acute, salt restriction, extractive substances. A plant-based diet is used.

Etiotropic therapy. This is the sanitation of the focus of streptococcal infection. For this, antibiotic therapy is used, taking into account the sensitivity of the flora. These are macrolides and penicillin antibiotics last generation.

pathogenic treatment. When the immune response is pronounced and the proliferation of connective tissue is prevented, hormones and anticancer drugs-cytostatics. These are the drugs of choice, which are prescribed only when the process is severe. In mild forms, the use is unacceptable due to serious side effects.

Symptomatic therapy. In severe hypertension, antihypertensive drugs are prescribed. The development of edematous syndrome requires the use of diuretics. In chronic renal failure, diuretics are used to relieve edematous syndrome and respiratory failure.

By forms:

• Diffuse nephritic syndrome - antiplatelet agents, antihypertensive drugs, diuretics;
• Diffuse nephrotic syndrome - requires complex treatment with the use of hormones and cytostatics.

The criterion for the effectiveness of treatment is the absence of edema, lowering blood pressure, normalization of urine and blood.

Possible Complications

Possible complications of glomerulonephritis are:

• Development of chronic renal failure;
• Respiratory and cardiovascular insufficiency;
• A poor prognostic sign is persistent arterial hypertension;
• Elderly age;
• The rapid progression of symptoms - an increase in edema, severe proteinuria, hematuria.

© E.M. Shilov, N.L. Kozlovskaya, and Yu.V. Korotchaeva, 2015 UDC616.611-036.11-08

Developer: Scientific Society of Nephrologists of Russia, Association of Nephrologists of Russia

Working group:

Shilov E.M. Vice-President of NORR, Chief Nephrologist of the Russian Federation, Head. Department of Nephrology and

hemodialysis IPO GBOU VPO First Moscow State Medical University. THEM. Sechenov of the Ministry of Health of the Russian Federation, Dr. med. Sciences, Professor Kozlovskaya N.L. Professor of the Department of Nephrology and Hemodialysis, IPO, Leading Researcher Department of Nephrology, National Research Center

First Moscow State Medical University named after I.M. Sechenov, Dr. med. Sciences, Professor Korotchaeva Yu.V. senior researcher Department of Nephrology, Research Center, Associate Professor of the Department of Nephrology and Hemodialysis, Institute of Postgraduate Education, SBEI HPE First Moscow State Medical University. I.M., Ph.D. honey. Sciences

CLINICAL GUIDELINES FOR DIAGNOSIS AND TREATMENT OF RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (EXTRACAPILLARY GLOMERULONEPHRITIS WITH CRESCENT FORMATION)

Developer: Scientific Society of Nephrologists of Russia, Association of Nephrologists of Russia

Shilov E.M. Vice President of SSNR, chief nephrologist of the Russian Federation, head of Department

of Nephrology and hemodialysis FPPTP of the First Moscow state medical university. I. M. Sechenov, MD, PhD, DSci, professor Kozlovskaya N.L. professor of Department of Nephrology and hemodialysis FPPTP, leading researcher of the Department of Nephrology of Scientific Research Center of the First Moscow state medical university. I. M. Sechenov, MD, PhD, DSci, professor Korotchaeva Ju.V. senior researcher of the Department of Nephrology of Scientific Research Center of the First Moscow state medical university. I. M. Sechenov, MD, PhD

Abbreviations:

BP - blood pressure AZA -azathioprine

ANCA - antibodies to the cytoplasm of neutrophils ANCA-CB - ANCA-associated systemic vasculitis

ANCA-GN - ANCA-associated glomerulo-

AT - antibodies

RPGN - rapidly progressive glomerulonephritis ARB - angiotensin receptor blockers URT - upper respiratory tract IVIG - intravenous immunoglobulin HD - hemodialysis

GPA - granulomatosis with polyangiitis (Wegener's)

GC - glucocorticoids

GN - glomerulonephritis

RRT - renal replacement therapy

and ACE inhibitors - angiotensin-converting inhibitors

enzyme

IHD - ischemic heart disease

LS - medicines MMF - mycophenolate mofetil MPA - microscopic polyangiitis MPO - myeloperoxidase MPA - mycophenolic acid NS - nephrotic syndrome PR-3 - proteinase-3 PF - plasmapheresis

eGFR - estimated glomerular filtration rate

SLE - systemic lupus erythematosus Ultrasound - ultrasound examination UP - periarteritis nodosa CKD - ​​chronic kidney disease CKD - ​​chronic renal failure CNS - central nervous system CF - cyclophosphamide ECG - electrocardiogram EGPA - eosinophilic granulomatosis with polyangiitis (synonymous - Churg-Strauss syndrome)

Patient side Physician side Further direction of use

Level 1 "Experts recommend" The vast majority of patients in a similar situation would prefer to follow the recommended path, and only a small proportion of them would reject this path The physician will recommend that the vast majority of his patients follow this path The recommendation can be accepted as a standard of medical action personnel in most clinical situations

Level 2 "Experts believe" Most patients in this situation would favor following the recommended path, but a significant proportion would reject this path. For different patients, different recommendations should be selected to suit them. Each patient needs assistance in choosing and making a decision that is consistent with the patient's values ​​and preferences

No Grade (NG) This level is used when the recommendation is based on the judgment of an expert investigator or when the topic under discussion does not allow adequate application of the system of evidence used in clinical practice.

table 2

Assessment of the quality of the evidence base (compiled in accordance with the clinical guidelines of the KESO)

Quality of the evidence base Meaning

A - high Experts are sure that the expected effect is close to the calculated one

B - average Experts believe that the expected effect is close to the calculated effect, but may differ significantly

C - low Expected effect may differ significantly from the calculated effect

O - very low The expected effect is very uncertain and may be very far from the calculated one.

2. Definition, epidemiology, etiology (Table 3)

Table 3

Definition

Rapidly progressive glomerulonephritis (RPGN) is an urgent nephrological situation requiring urgent diagnostic and therapeutic measures. RPGN is clinically characterized by an acute nephritic syndrome with rapidly progressive renal failure (doubling of creatinine within 3 months), morphologically - by the presence of extracapillary cellular or fibrocellular crescents in more than 50% of the glomeruli.

Synonyms of the term: subacute GN, malignant GN; the generally accepted morphological term for RPGN is extracapillary glomerulonephritis with crescents.

Epidemiology

The frequency of RPGN is 2-10% of all forms of glomerulonephritis registered in specialized nephrological hospitals.

Etiology

RPGN can be idiopathic or develop as part of systemic diseases (ANCA-associated vasculitis, Goodpasture's syndrome, SLE).

3. Pathogenesis (Table 4)

Table 4

Crescents are the result of severe damage to the glomeruli with rupture of the capillary walls and the penetration of plasma proteins and inflammatory cells into the space of the Shumlyansky-Bowman capsule. The main reason for this severe damage is exposure to ANCA, anti-GMB antibodies and immune complexes. Cellular composition semilunar is represented mainly by proliferating parietal epithelial cells and macrophages. The evolution of the crescents - reverse development or fibrosis - depends on the degree of accumulation of macrophages in the space of the Shumlyansky-Bowman capsule and its structural integrity. The predominance of macrophages in the cellular crescents is accompanied by a rupture of the capsule, the subsequent entry of fibroblasts and myofibroblasts from the interstitium, the synthesis of matrix proteins by these cells - collagen types I and III, fibronectin, which leads to irreversible fibrosis of the crescents. Chemokines, monocyte chemoattractant protein-I (MCP-I) and macrophage inflammatory protein-1 (MIP-1), play an important role in the regulation of macrophage recruitment and accumulation in crescents. High expression of these chemokines in crescent formation sites with a high macrophage content is found in RPGN with the most severe course and poor prognosis. An important factor leading to fibrosis of the crescents is fibrin, into which fibrinogen is transformed into the capsule cavity due to necrosis of the capillary loops of the glomerulus.

4. Classification

Depending on the predominant mechanism of damage, clinical picture and laboratory parameters, five immunopathogenetic types of RPGN have now been identified (Glassock, 1997). The main immunopathological criteria that determine each type of RPGN are the type of luminescence of immunoreactants in the renal biopsy and the presence of a damaging factor (antibodies to GMB, immune complexes, ANCA) in the patient's serum (Table 5).

Table 5

Characterization of immunopathogenetic types of ECGN

Pathogenetic type of ECGN Serum

IF-microscopy of kidney tissue (luminescence type) Anti-BMC Complement (decrease in level) ANCA

I linear + - -

II granular - + -

IV linear + - +

Type I ("antibody", "anti-GBM-nephritis"). Due to the damaging effect of antibodies to BMK. It is characterized by a "linear" glow of antibodies in the renal biopsy and the presence of circulating antibodies to BMC in the blood serum. It exists either as an isolated (idiopathic) kidney disease, or as a disease with concomitant damage to the lungs and kidneys (Goodpasture's syndrome).

Type II ("immunocomplex"). Caused by deposits of immune complexes in various parts of the renal glomeruli (in the mesangium and capillary wall). In the renal biopsy, the “granular” type of luminescence is mainly detected, in the serum of anti-GMB antibodies and ANCA are absent, in many patients the complement level may be reduced. Most characteristic of RPGN associated with infections (poststreptococcal RPGN), cryoglobulinemia, systemic lupus erythematosus (SLE).

Type III ("poorly immune"). Damage is caused by cellular immune reactions, including neutrophils and monocytes activated by antineutrophil cytoplasmic antibodies (ANCA). The luminescence of immunoglobulins and complement in the biopsy is absent or insignificant (rai-tshipne, "low-immune" GN), ANCA directed against proteinase-3 or myeloperoxidase are detected in the serum. This type of ECGN is a manifestation of ANCA-associated vasculitis (MPA, GPA, Wegener).

Type IV is a combination of two pathogenetic types - antibody (type I) and ANCA-associated, or low immune (type III). At the same time, both antibodies to GMB and ANCA are detected in the blood serum, and a linear glow of antibodies to GMB is detected in the renal biopsy, as in classical anti-GMB nephritis. At the same time, proliferation of mesangial cells is also possible, which is absent in the classical antibody type of ECGN.

Type V (true "idiopathic"). In this extremely rare type, immune damage factors cannot be detected either in the circulation (no anti-GBM antibodies and ANCA, the complement level is normal) or in the renal biopsy (there is no fluorescence of immunoglobulins). It is assumed that it is based on the cellular mechanism of damage to the renal tissue.

Among all types of RPGN, more than half (55%) are ANCA-associated RPGN (type III), the other two types of RPGN (I and II) are distributed approximately equally (20 and 25%). The characteristics of the main types of BPGN are presented in Table. 6.

By the presence of certain serological markers (and their combinations), one can assume the type of luminescence in the renal biopsy and, accordingly, the mechanism of damage - the pathogenetic type of RPGN, which is important to consider when choosing a treatment program.

Table 6

Classification of types of BPGN

BPGN type Characteristic Clinical Options Frequency, %

I Anti-GBM mediated: linear IgG deposits on immunohistological examination of kidney tissue Goodpasture's syndrome Isolated kidney disease associated with anti-GBM antibodies 5

II Immune complex: granular deposits of immunoglobulin in the glomeruli of the kidney Post-infectious Post-streptococcal With visceral abscesses Lupus nephritis Hemorrhagic vasculitis 1dA nephropathy Mixed cryoglobulinemia Membranoproliferative GN 30-40

III ANCA-associated: Poorly immune with no immune deposits on immunological examination GPA MPA EGPA 50

IV Combination of I and III types - -

V ANCA-negative renal vasculitis: with no immune deposits Idiopathic 5-10

Recommendation 1. In all cases of RPGN, a kidney biopsy should be performed as soon as possible. Morphological examination of the kidney tissue should be carried out with the obligatory use of fluorescent microscopy.

Commentary: ANCA-SV is the most common cause BPGN. Renal involvement in these diseases is a poor prognostic factor for both renal and overall survival. In this regard, kidney biopsy is extremely important not only from a diagnostic, but also from a prognostic point of view.

5. Clinical manifestations of RPGN (Table 7)

Table 7

Clinical Syndrome BPGN includes two components:

1. acute nephritic syndrome (acute nephritis syndrome);

2. rapidly progressive renal failure, which, in terms of the rate of loss of kidney function, occupies an intermediate position between acute renal failure and CRF, i.e. implies the development of uremia within a year from the moment of the first signs of the disease.

This rate of progression corresponds to a doubling of serum creatinine for every 3 months of illness. However, often fatal loss of function occurs in just a few (1-2) weeks, which meets the criteria for ARF.

6. Principles of diagnosis of RPGN

RPGN is diagnosed based on an assessment of the rate of deterioration of kidney function and the identification of the leading nephrological syndrome (acute nephritic and / or nephrotic).

6.1. Laboratory diagnostics RPGN (Table 8)

Table 8

General analysis blood: normochromic anemia, possible neutrophilic leukocytosis or leukopenia, thrombocytosis or thrombocytopenia, increased ESR

General urine analysis: proteinuria (from minimal to massive), erythrocyturia, as a rule, pronounced, the presence of erythrocyte casts, leukocyturia

Biochemical analysis blood: increased concentration of creatinine, uric acid, potassium, hypoprotein- and hypoalbuminemia, dyslipidemia in cases of nephrotic syndrome

Decrease in GFR (determined by creatinine clearance - Rehberg's test and / or calculation methods CKR-EP1, MRIai; the use of the Cockcroft-Gault formula is undesirable due to the "overestimation" of GFR by 20-30 ml

Immunological studies: definition

Immunoglobulins A, M and B

Complement

ANCA in blood serum by indirect immunofluorescence or by enzyme immunoassay with determination of specificity to PR-3 and MPO

Anti-BMC antibodies

6.2. Histological studies kidney biopsy

Comment: All patients with RPGN should undergo a kidney biopsy. It is necessary, first of all, to assess the prognosis and choose the optimal method of treatment: a timely aggressive immunosuppressive therapy regimen sometimes makes it possible to restore the filtration function of the kidneys even in a situation where the degree of its deterioration has reached terminal renal failure (ESRD). In this regard, in RPGN, a kidney biopsy should also be performed in severe renal failure requiring hemodialysis (HD).

Morphological characteristics different types For RPGN, see recommendations for anti-GBM GN, ANCA-GN, and lupus nephritis.

6.3. Differential Diagnosis

When identifying the RPGN syndrome, it is necessary to exclude conditions that outwardly resemble (imitate) RPGN, but are of a different nature and therefore require a different therapeutic approach. By their nature, these are three groups of diseases:

(1) nephritis - acute post-infectious and acute interstitial, usually with a favorable prognosis, in which immunosuppressants are used only in some cases;

(2) acute tubular necrosis with its own patterns of course and treatment;

(3) a group of vascular diseases of the kidneys, combining damage to vessels of different caliber and different nature (thrombosis and embolism of large renal vessels, scleroderma nephropathy, thrombotic microangiopathy of various origins). In most cases, these conditions can be ruled out clinically (see Table 9).

On the other hand, the presence and characteristics of extrarenal symptoms may indicate a disease in which RPGN often develops (SLE, systemic vasculitis, drug reaction).

7. Treatment of RPGN

7.1. General principles for the treatment of RPGN (extracapillary GN)

RPGN occurs more often as a manifestation of a systemic disease (SLE, systemic vasculitis, essential mixed cryoglobulinemia, etc.), less often as an idiopathic disease, but the principles of treatment are common.

An emergency serum test for anti-GMB antibodies and ANCA is needed, if possible; a kidney biopsy is necessary for timely diagnosis (detection of ECGN and the type of antibody luminescence - linear, granular, "low immune"), assessment of the prognosis and choice of therapy tactics.

Recommendation 1. To prevent irreversible catastrophic loss of renal function, it is necessary to urgently begin and immediately after the establishment of a clinical diagnosis of RPGN (acute nephritic syndrome in combination with rapidly progressive renal failure with normal kidney sizes and the exclusion of other causes of AKI). (1B)

Comments: Delaying treatment by several days may impair the effectiveness of treatment, since treatment is almost always unsuccessful when anuria develops. This is the only form of GN in which the risk of developing side effects immunosuppressive therapy is incomparable with the possibility of an unfavorable prognosis in the natural course of the disease and untimely initiation of treatment.

Table 9

Differential diagnosis of RPGN

States reproducing RPGN Distinctive features

Antiphospholipin syndrome (APS-nephropathy) Presence of serum antibodies to cardiolipin classes 1dM and !dv and / or antibodies to B2-glycoprotein-du1, lupus anticoagulant. Increase in plasma concentration of y-dimer, fibrin degradation products. Absence or slight changes in urinalysis (usually "trace" proteinuria, scanty urinary sediment) with a pronounced decrease in GFR. Clinical manifestations of arterial (acute coronary syndrome/acute myocardial infarction, acute cerebral circulation) and venous (deep vein thrombosis of the legs, thromboembolism pulmonary arteries, renal vein thrombosis) vessels, livedo reticularis

Hemolytic-uremic syndrome Associated with infectious diarrhea (with typical hemolytic-uremic syndrome). Identification of complement activation triggers (viral and bacterial infections, trauma, pregnancy, drugs). Severe anemia with signs of microangiopathic hemolysis (increased LDH levels, decreased haptoglobin, schizocytosis), thrombocytopenia

Scleroderma nephropathy Skin and organ signs of systemic scleroderma. Pronounced and intractable rise in blood pressure. No change in urinalysis

Acute tubular necrosis medicinal product(especially NSAIDs, non-narcotic analgesic, antibiotic). Gross hematuria (possible discharge of blood clots). Rapid development of oliguria

Acute tubulointerstitial nephritis Usually clear cause (medication, sarcoidosis). Decrease in the relative density of urine in the absence of severe proteinuria

Cholesterol embolism of intrarenal arteries and arterioles* Associated with endovascular procedure, thrombolysis, blunt abdominal trauma. Marked rise in blood pressure. Signs of an acute phase response (fever, loss of appetite, body weight, arthralgia, increased ESR, serum concentration of C-reactive protein). Hypereosinophilia, eosinophiluria. Mesh livedo with trophic ulcers(usually on the skin of the lower extremities). Systemic signs of cholesterol embolism (sudden unilateral blindness, acute pancreatitis, intestinal gangrene)

* In rare cases, leads to the development of RPGN, including ANCA-associated.

Recommendation 1. 1. Treatment of RPGN should begin even before the results of diagnostic studies (serological, morphological) with pulse therapy with methylprednisolone at a dose of up to 1000 mg for 1-3 days. (1A)

Comments:

This tactic is fully justified even if it is not possible to perform a kidney biopsy in patients whose condition precludes this procedure. Immediately after the diagnosis of RPGN is verified, alkylating agents [cyclophosphamide (CF) at ultra-high doses] should be added to glucocorticoids, especially in patients with vasculitis (local renal or systemic) and circulating ANCA and lupus nephritis. Intensive plasmapheresis (PF) should be combined with immunosuppressants in the following cases:

a) anti-GBM nephritis, provided that treatment is started before the need for hemodialysis appears;

b) in patients with non-anti-GMB ECGN who have signs of renal failure requiring hemodialysis treatment at the time of diagnosis (SCr more than 500 µmol/l) in the absence of signs of irreversible kidney damage according to renal biopsy (more than 50% of cellular or fibrocellular crescents ).

Initial therapy for RPGN depends on its immunopathogenetic type and the need for dialysis from the time of diagnosis (Table 10).

Table 10

Initial therapy for RPGN (ECGN) depending on the pathogenetic type

Type Serology Therapy / need for HD

I Anti-GBM disease (a-GBM +) (ANCA -) GC (0.5-1 mg/kg orally ± pulse therapy at a dose of up to 1000 mg for 1-3 days) PF (intensive) Conservative management

II IR disease (a-BMC -), (ANCA -) GC (orally or "pulses") ± cytostatics (CF) - orally (2 mg / kg / day) or intravenously (15 mg / kg, but not > 1 G)

III "Low-immune" (a-BMK -) (ANCA +) GC (inside or "pulses") ZF GS (inside or "pulses") ZF. Intensive plasma exchange - daily for 14 days with a replacement volume of 50 ml / kg / day

IV Combined (a-BMK +) (ANCA +) As in type I As in type I

V “Idiopathic” (a-MBM -) (ANCA -) As in type III As in type III

7.2.1. Anti-GBM nephritis (type I according to Glassock, 1997), including Goodpasture's syndrome.

diagnosed with 100% crescents on adequate renal biopsy and no pulmonary hemorrhage), immunosuppression with cyclophosphamide, corticosteroids, and plasmapheresis should be started. (1B)

Comment:

At a blood creatinine level of less than 600 µmol/l, oral prednisolone is prescribed at a dose of 1 mg/kg/day and cyclophosphamide at a dose of 2-3 mg/kg/day. Upon reaching a stable clinical effect the dose of prednisolone is gradually reduced over the next 12 weeks, and cyclophosphamide is completely canceled after 10 weeks of treatment. Therapy with immunosuppressive drugs is combined with intensive plasmapheresis, which is carried out daily. If there is a risk of developing pulmonary hemorrhage, part of the volume of removed plasma is replaced with fresh frozen plasma. A stable effect is achieved after 10-14 sessions of plasmapheresis. This regimen of therapy allows to achieve an improvement in kidney function in almost 80% of patients, and the decrease in azotemia begins within a few days after the start of plasmapheresis.

With a blood creatinine content of more than 600 µmol/l, aggressive therapy is ineffective, and improvement in kidney function is possible only in a small number of patients with a recent history of the disease, rapid progression (within 1-2 weeks) and the presence of potentially reversible changes in the kidney biopsy. In these situations, the main therapy is carried out in combination with hemodialysis sessions.

7.2.2. Immune complex RPGN (type II according to Glassock, 1997).

Recommendation 6: For rapidly progressive lupus GN (type IV), it is recommended to give intravenous cyclophosphamide (CF) (1B) 500 mg every 2 weeks for 3 months (total dose 3 g) or mycophenolic acid (MPA) preparations (mycophenolate mofetil [MMF ] (1B) at a target dose of 3 g/day for 6 months, or mycophenolate sodium at an equivalent dose) in combination with corticosteroids in the form of IV "pulses" of methylprednisolone at a dose of 500-750 mg for 3 consecutive

days, and then oral prednisolone 1.0-0.5 mg / kg / day for 4 weeks with a gradual decrease to<10 мг/сут к 4-6 мес (1А).