Treatment regimen for glomerulonephritis - clinical recommendations. Clinical guidelines for the diagnosis, treatment and prognosis of membranoproliferative glomerulonephritis

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

Working group:

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

hemodialysis IPO GBOU VPO First Moscow State Medical University named after. 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, senior researcher Department of Nephrology 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 IPO GBOU VPO First Moscow State Medical University named after. 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:

blood pressure - arterial pressure AZA -azathioprine

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

ANCA-GN - ANCA-associated glomerulo-

AT - antibodies

RPGN - rapidly progressive glomerulonephritis ARBs - angiotensin receptor blockers URT - upper Airways VIG - intravenous immunoglobulin HD - hemodialysis

GPA - granulomatosis with polyangiitis (Wegener's)

GK - glucocorticoids

GN - glomerulonephritis

RRT - renal replacement therapy

ACEi - angiotensin-converting inhibitors

enzyme

IHD - ischemic disease hearts

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

eGFR - estimated rate glomerular filtration

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

From the patient's side From the doctor's side Further direction of use

Level 1 “Expert 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 doctor will recommend that the vast majority of his patients follow this path The recommendation can be accepted as the standard of action medical personnel in the majority clinical situations

Level 2 “Experts believe” Most patients in a similar situation would be in favor of following the recommended path, but a significant proportion would reject this path. different patients should be selected various options recommendations that are suitable for them. Each patient needs assistance in choosing and making decisions that are consistent with that patient's values and preferences Guidelines will likely require discussion among all stakeholders before they are accepted as a clinical standard

“No gradation” (NG) This level is applied in cases where the basis of the recommendation fits common sense expert researcher or when the topic under discussion does not allow for adequate application of the system of evidence used in clinical practice

table 2

Quality control evidence base(compiled in accordance with clinical guidelines KEYO)

Quality of evidence Meaning

A - high Experts are confident 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 The 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 acute nephritic syndrome with rapidly progressing renal failure (doubling of creatinine within 3 months), morphologically by the presence of extracapillary cellular or fibrocellular crescents in more than 50% of glomeruli.

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

Epidemiology

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

Etiology

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

3. Pathogenesis (Table 4)

Table 4

Crescents are a consequence of severe damage to the glomeruli with rupture of the capillary walls and penetration of plasma proteins and inflammatory cells into the space of the Shumlyansky-Bowman capsule. The main cause of this severe damage is exposure to ANCA, anti-BMK antibodies and immune complexes. The cellular composition of the crescents is represented mainly by proliferating parietal epithelial cells and macrophages. Evolution of half moons - 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 rupture of the capsule, the subsequent entry of fibroblasts and myofibroblasts from the interstitium, and the synthesis by these cells of matrix proteins - collagen types I and III, fibronectin, which leads to irreversible fibrosis of the crescents. An important role in regulating the processes of attraction and accumulation of macrophages in the crescents belongs to chemokines - monocyte chemoattractant protein-I (MCP-I) and macrophage inflammatory protein-1 (MIP-1). High expression of these chemokines at the sites of crescent formation with high content macrophages are found in RPGN with the most severe course and a poor prognosis. An important factor, leading to fibrosis of the crescents, is fibrin, into which fibrinogen is transformed, entering 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 define each type of RPGN are the type of luminescence of immunoreactants in the renal biopsy and the presence of a damaging factor (antibodies to BMK, immune complexes, ANCA) in the patient’s serum (Table 5).

Table 5

Characteristics of immunopathogenetic types of ECGN

Pathogenetic type ECGN Serum

IF microscopy renal tissue(type of glow) Anti-BMK Complement (decreased level) ANCA

I linear + - -

II granular - + -

IV linear + - +

Type I (“antibody”, “anti-BMK-nephritis”). Caused by the damaging effect of antibodies to BMK. It is characterized by a “linear” glow of antibodies in a renal biopsy and the presence of circulating antibodies to BMK 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 syndrome).

Type II (“immune complex”). Caused by deposits of immune complexes in various departments renal glomeruli (in the mesangium and capillary wall). In a renal biopsy, a mainly “granular” type of luminescence is revealed; anti-BMK antibodies and ANCA are absent in the serum; in many patients, complement levels may be reduced. It is most typical for RPGN associated with infections (post-streptococcal RPGN), cryoglobulinemia, and systemic lupus erythematosus (SLE).

Type III (“low-immune”). Damage is caused by cellular immune reactions, including neutrophils and monocytes activated by antineutrophil cytoplasmic antibodies (ANCA). The fluorescence of immunoglobulins and complement in the biopsy specimen is absent or insignificant (paradise, “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's).

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 BMK and ANCA are detected in the blood serum, and a linear glow of antibodies to BMK is detected in the renal biopsy, as in classic anti-BMK nephritis. In this case, proliferation of mesangial cells is also possible, which is absent in the classic antibody type of ECGN.

Type V (true “idiopathic”). With this extremely rare type immune factors damage cannot be detected either in the circulation (there are no anti-BMK antibodies and ANCA, the complement level is normal) or in a renal biopsy (the fluorescence of immunoglobulins is completely absent). It is assumed that it is based on a cellular mechanism of damage to 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%). Characteristics of the main types of RPGN are presented in Table. 6.

Based on 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 RPGN

Type of RPGN Characteristics Clinical Frequency options, %

I Mediated by antibodies to BMK: linear IgG deposits on immunohistological examination of kidney tissue Goodpasture's syndrome Isolated kidney damage associated with antibodies to BMK 5

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

III ANCA-associated: Low-immune with the absence of immune deposits in the immunological study of GPA MPA EGPA 50

IV Combination of types I and III - -

V ANCA-negative renal vasculitis: with absence of 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 kidney tissue should be carried out with the mandatory use of fluorescence microscopy.

Comment: ANCA-SV is the most common reason BPGN. Renal involvement in these diseases is a factor of poor prognosis 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 BPGN (Table 7)

Table 7

Clinical syndrome BPGN includes two components:

1. acute nephritic syndrome (syndrome acute nephritis);

2. rapidly progressive renal failure, which, in terms of the rate of loss of kidney function, takes intermediate position between acute renal failure and chronic renal failure, 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 the serum creatinine level for every 3 months of illness. However, often fatal loss of function occurs in just a few (1-2) weeks, meeting the criteria for AKI

6. Principles of diagnosing RPGN

RPGN is diagnosed based on assessing the rate of deterioration of renal function and identifying the leading nephrological syndrome (acute nephritic and/or nephrotic).

6.1. Laboratory diagnostics BPGN (Table 8)

Table 8

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

General urine analysis: proteinuria (from minimal to massive), erythrocyturia, usually severe, the presence of erythrocyte casts, leukocyturia

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

Decrease in GFR (determined by creatinine clearance - Rehberg test and/or calculation methods SKR-EP1, MRY; 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 using enzyme immunoassay with determination of specificity for PR-3 and MPO

Anti-BMK antibodies

6.2. Histological studies kidney biopsy

Comment: All patients with RPGN undergo a kidney biopsy. It is necessary to carry it out primarily for the purpose of assessing the prognosis and choosing optimal method treatment: timely applied aggressive regimen immunosuppressive therapy sometimes allows you to restore the filtration function of the kidneys even in a situation where the degree of deterioration has reached terminal renal failure(ESRD). In this regard, in case of RPGN, a kidney biopsy must also be performed in cases of severe renal failure requiring hemodialysis (HD).

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

6.3. Differential diagnosis

When identifying RPGN syndrome, it is necessary to exclude conditions that superficially 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 sizes and different nature (thrombosis and embolism large vessels kidneys, scleroderma nephropathy, thrombotic microangiopathies of various origins). In most cases, these conditions can be excluded clinically (see Table 9).

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

7. Treatment of RPGN

7.1. General principles treatment of RPGN (extracapillary GN)

RPGN is more common as a manifestation systemic disease(SLE, systemic vasculitis, essential mixed cryoglobulinemia, etc.), less often - as idiopathic disease, however, the principles of treatment are general.

It is necessary - if possible - to urgently test serum for the presence of anti-BMK antibodies and ANCA; A kidney biopsy is necessary for timely diagnosis (detection of ECG and the type of antibody glow - linear, granular, “low-immune”), assessment of prognosis and choice of treatment tactics.

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

Comments: Delaying treatment for several days may impair the effectiveness of treatment, since treatment is almost always unsuccessful once anuria develops. This the only form GN, in which the risk of development side effects immunosuppressive therapy is not comparable 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

Conditions reproducing RPGN Distinctive features

Antiphospholipin syndrome (APS nephropathy) The presence of serum antibodies to cardiolipin classes 1gM and!dv and/or antibodies to B2-glycoprotein 1, lupus anticoagulant. Increased plasma concentration of d-dimer, fibrin degradation products. Absence or minor changes in urine analysis (usually “trace” proteinuria, scanty urinary sediment) with a pronounced decrease in GFR. Clinical manifestations of arterial diseases (acute coronary syndrome/acute myocardial infarction, acute disorder cerebral circulation) and venous (deep vein thrombosis of the legs, thromboembolism pulmonary arteries, thrombosis of renal veins) vessels, livedo reticularis

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

Scleroderma nephropathy Skin and organ signs systemic scleroderma. Pronounced and intractable rise in blood pressure. No changes in urine tests

Acute tubular necrosis Relation to intake medicinal product(especially NSAIDs, non-narcotic analgesics, antibiotics). Gross hematuria (possible passage of blood clots). Fast development oliguria

Acute tubulointerstitial nephritis Typically has a clear cause (drug use, sarcoidosis). Decreased relative density of urine in the absence of severe proteinuria

Cholesterol embolism of intrarenal arteries and arterioles* Association 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. Livedo mesh with trophic ulcers(usually on the skin lower limbs). Systemic signs cholesterol embolism (sudden one-sided blindness, acute pancreatitis, gangrene of the intestine)

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

Recommendation 1. 1. Treatment of RPGN should begin even before receiving 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 impossible to perform a kidney biopsy in patients whose severity of condition prevents this procedure. Immediately after verification of the diagnosis of RPGN, alkylating agents [cyclophosphamide (CP) in ultra-high doses] should be added to glucocorticoids, especially in patients with vasculitis (local renal or systemic) and circulating ANCA and lupus nephritis. It is advisable to combine intensive plasmapheresis (IP) with immunosuppressants in the following cases:

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

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

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

Table 10

Initial therapy RPGN (ECGN) depending on the pathogenetic type

Type Serology Therapy/need for HD

I Anti-BMK disease (a-BMK +) (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-BMK -), (ANCA -) GC (orally or “pulses”) ± cytostatics (CP) - orally (2 mg/kg/day) or intravenously (15 mg/kg, but not > 1 G)

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

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

V “Idiopathic” (a-BMK -) (ANCA -) As with III type As with type III

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

diagnosis, having 100% crescents according to adequate nephrobiopsy and without pulmonary hemorrhages) immunosuppression with cyclophosphamide, corticosteroids and plasmapheresis should be started. (1B)

A comment:

When the blood creatinine level is less than 600 µmol/l, prednisolone is prescribed orally 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 discontinued after 10 weeks of treatment. Therapy with immunosuppressive drugs is combined with intensive plasmapheresis, which is performed 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 treatment regimen allows for improvement of renal function in almost 80% of patients, and a decrease in azotemia begins within a few days after the start of plasmapheresis.

When the blood creatinine level is more than 600 μmol/L, aggressive therapy is ineffective, and improvement of renal 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 prescribe cyclophosphamide (CP) (1B) intravenously at a dose of 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 GCS in the form of intravenous “pulses” of methylprednisolone at a dose of 500-750 mg for 3 consecutive

days, and then prednisolone orally 1.0-0.5 mg/kg/day for 4 weeks gradual decline before<10 мг/сут к 4-6 мес (1А).

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.

Visible signs of glomerulonephritis include high blood pressure and confirmation by the patient of the fact that he has recently suffered an infectious disease or inflammation in the kidney area, and may be subject to severe hypothermia.

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

During the appointment, the doctor tries to understand whether the complaints indicate on the inflammatory process in the kidneys or is it a manifestation of another disease.

Diagnostic tests to detect acute glomerulonephritis always require thorough examination of general blood and urine tests patient. To do this, the patient must undergo the following types of tests:

Clinical urine analysis.
Urine analysis using the method.
Urinalysis using 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 volume of urine excreted from the body;
proteinuria, which means the protein content 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 it takes taking kidney 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, which 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, changes in diffuse character in the tubules, glomerular apparatus and connective tissue.

Kidney biopsy to identify the 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 initiated the 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 research allows you to study the immune complex to accurately determine the shape and size, as well as severity and form of the disease in organism.

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 research. These include:

Open.

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

Biopsy in tandem with urethroscopy.

This method is used for people suffering from urolithiasis, as well as pregnant women and children. Sometimes it is performed on those patients who have an artificial kidney.

Transjugular.

This type of research is carried out through catheterization of the renal vein. The doctor prescribes this type of material collection when the patient is clearly obese or has poor blood clotting.

Transdermal.

This method is carried out under control using X-rays, as well as ultrasound or magnetic resonance imaging.

Is it possible to cure glomerulonephritis forever?

Glomerulonephritis can occur in two forms: acute and chronic. The acute form is curable with timely diagnosis and correct treatment methods.

If time for drug treatment was missed, and the disease smoothly turned 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 you on compliance with a special regime, which can protect the patient from developing a new relapse of the disease.

If a complete cure cannot be achieved, the doctor recommends following all established rules and preventive measures so that the symptoms become less noticeable. Sometimes, with successful therapeutic treatment, it is possible to achieve temporary disappearance of symptoms.

It is necessary to support the body for as long as possible before a new relapse occurs.

Treatment

When the acute stage of glomerulonephritis appears, the patient should be hospitalized.

At the same time, he will be required to be placed on bed rest. This is important in order for the kidneys to be at a certain temperature, that is, the regime for maintaining a particular temperature must be balanced. This method, with timely hospitalization, can optimize kidney function.

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

If the doctor considers that there is an additional need to extend the hospital stay, then the patient's stay in the ward may be increased.

Medication

If, based on the results of studies conducted, it has been proven that the disease is caused by infectiously, then the patient is prescribed antibiotics to take.

In most cases, several 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;
Ampiox with intramuscular administration;
Sometimes doctors prescribe Interferon for rapidly progressing glomerulonephritis.

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

If the disease develops rapidly, the patient is prescribed large doses of IV drips for several days. After several days of administration of this 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 first stages is prescribed by a doctor in the prescribed dosage, which is also prescribed by a specialist. The course of treatment is continued for one and a half or two months. In the future, when relief occurs, the dose is reduced up to twenty milligrams per day, and if the symptoms begin to disappear, then the drug can be discontinued.

In addition to this drug, medical experts often advise taking Cyclophosphamide or Chlorambucil in the dosage prescribed by the doctor. Experienced medical specialists, in addition to immunosuppressants, prescribe anticoagulants such as Curantil or Heparin.

The combination of these remedies must be justified by the form of the disease and the degree of its neglect.

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

Exercise therapy

Physical therapy for the treatment and prevention of glomerulonephritis should be prescribed by the treating specialist, taking into account all the tests and indicators of the person.

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

These types of physical exercises are carried out for the purpose of:

Improves blood flow to the kidneys and other organs.
Reducing blood pressure and improving metabolism in the body.
Increasing the body's strength to fight the disease.
Increased performance.
Elimination of stagnation formed in the human body.
Creating a general positive attitude to fight the disease.

Before starting the exercises, it is recommended to measure your blood pressure level and only then begin the set of exercises.

The classic exercise therapy complex for eliminating glomerulonephritis includes exercises performed in a lying position or on a chair. The practitioner's attention should be completely concentrated on the time of inhalation and exhalation.

All types 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 excessively.

Duration of such classes should not be more than half an hour, otherwise it may have a negative impact on the patient and cause various complications.

ethnoscience

When visiting your doctor, they may be prescribed various infusions and decoctions of herbs, which have a beneficial effect on the functioning of the renal system.

100 grams of walnuts;
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 tests show improved results.

There are special decoctions designed to eliminate swelling and bring blood pressure back to normal. The following recipe applies to such decoctions:

Flaxseed in the amount of four tablespoons is mixed with three tablespoons of dry birch leaves.
To this mixture you need to add three tablespoons of field steelroot.
It is recommended to pour the resulting mixture with 0.5 liters of boiling water and leave for two hours.

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

All herbs that have an antimicrobial and anti-inflammatory effect will be suitable for preparing medicinal infusions. 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, and also 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 salted, smoked and fried foods from the diet. Eating protein foods should be somewhat limited.

Drinking alcohol during treatment 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 completely give up alcoholic drinks.

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

If glomerulonephritis has advanced to the stage, then every effort must be made to avoid recurrence of exacerbation diseases. It is necessary to be vaccinated according to the schedule established by a specialist, and also to remain calm psychologically and physically.

Regular examination in the office of a specialist will protect the body from new manifestations of the disease. The main rule is to prevent bacteria from entering the human body. It is necessary to avoid working in damp areas or activities involving heavy lifting.

The patient must follow a therapeutic diet and fill the body with vitamins. It is advisable to carry out at least once a year sanatorium treatment.

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

Medical science does not stand still, constantly expanding with new methods for diagnosing various diseases and methods of treating them. Based on the latest scientific and practical developments in each country, including ours, recommendations for practicing doctors regarding many diseases are updated annually. Based on the diagnostically and therapeutically complex renal disease glomerulonephritis, let us consider the clinical recommendations that were published in 2016.

Introduction

These recommendations, which summarize diagnostic and therapeutic approaches to some forms of glomerulonephritis, are collected on the basis of progressive world practice. They were compiled taking into account domestic and international standards for the treatment of this type of nephropathy, based on clinical observations and scientific research.

These recommendations are not considered as a certain standard for the provision of medical care, taking into account the different diagnostic capabilities of clinics, the availability of certain medications and the individual characteristics of each patient. Responsibility regarding the appropriateness of the recommendations below rests with the attending physician on an individual basis.

Features of the disease

Acute glomerulonephritis, which occurs after a streptococcal infection, manifests itself morphologically as diffuse inflammation of the renal medulla with a predominance of proliferation of intervascular tissue of the renal parenchyma. Mostly this form of the disease occurs in childhood between 4 and 15 years (about 70% of registered cases). The pathology is also typical for adults under 30 years of age, but with a lower incidence for a certain number of the population in this age group.

Causes and mechanism of pathological changes

The main cause of inflammatory processes in the renal medulla is considered to be an autoimmune attack by immune complexes based on immunoglobulins (antibodies) produced in response to streptococcal infection localized in the upper respiratory tract (pharyngitis, tonsillitis). Once in the renal intervascular tissue, immune complexes damage connective tissue cells, simultaneously provoking the production of bioactive substances that stimulate proliferative processes. As a result, some cells become necrotic, others grow. In this case, there is a violation of capillary circulation, dysfunction of the glomeruli and proximal tubules of the renal medulla.

Morphology

Histological examination of tissue from the medullary layer of the kidneys taken for biopsy reveals proliferative inflammation with deposition of immune complexes, accumulation of neutrophilic leukocytes in intercapillary cells and in the endothelium of glomerular vessels. They are deposited as merging granules that form conglomerates. Damaged cells are filled with fibrin and other connective tissue substances. The cell membranes of glomerular and endothelial cells are thinned.

Clinical manifestations

The severity of symptoms is very variable - from microhematuria to the full-blown form of nephrotic syndrome. Symptoms appear after a certain period after a streptococcal infection (2-4 weeks). Among the manifestations of a detailed clinical picture, the following symptoms are noted, including laboratory ones:

Decreased amount of urine excreted associated with impaired glomerular filtration, retention of fluid and sodium ions in the body.
Swelling localized on the face and in the ankle area of the lower extremities, which also becomes a consequence of insufficient removal of fluid from the body by the kidneys. The renal parenchyma often swells, which is determined by instrumental diagnostic methods.
Increased blood pressure numbers observed in approximately half of the patients, which is associated with an increase in blood volume, an increase in peripheral vascular resistance, and an increase in cardiac (left ventricle) output. Various degrees of hypertension are observed, from slight increases in blood pressure to high numbers, at which complications are possible in the form of hypertensive encephalopathy and congestive heart failure. These conditions require urgent medical intervention.
Hematuria of varying degrees severity accompanies almost all cases of the disease. Approximately 40% of patients have macrohematuria, in other cases microhematuria determined by laboratory tests. Approximately 70% of red blood cells are determined to have a violation of their shape, which is typical when they are filtered through the glomerular epithelium. Cylinders of red blood cells, characteristic of the pathology in question, are also detected.
Leukocyturia is present in approximately 50% of patients. The sediment is dominated by neutrophilic leukocytes and a small number of lymphocytes.
Proteinuria with this type of glomerulonephritis is rarely detected, mainly in adult patients. The content of protein in urine, characteristic in quantity for nephrotic syndrome in children, is practically not found.
Impaired renal function(increased serum creatinine titer) is detected in a quarter of patients. Cases of rapid development of severe renal failure with the need for hemodialysis are extremely rarely recorded.

Important! Due to the wide variety of clinical manifestations, including in children, the disease requires careful diagnosis, where modern laboratory and instrumental techniques come first in terms of information content.

When making a diagnosis, an important role is played by anamnestic data on an acute infection of the upper respiratory organs suffered several weeks ago with confirmation of hemolytic streptococcus as the causative agent. Next, the necessary laboratory tests of urine are carried out to detect changes characteristic of the disease. Blood is also examined, and an increase in the titer of antibodies to streptococcus is of diagnostic significance.

In cases with rapid development of clinical manifestations, a puncture biopsy of renal medulla tissue is allowed for cytological studies to confirm the diagnosis. If the clinical picture is not aggravated and corresponds to the main manifestations of acute glomerulonephritis of streptococcal origin, a biopsy is not indicated as an additional diagnostic method. Tissue collection for research is mandatory in the following situations:

severe long-lasting (more than 2 months) urinary syndrome;
severe manifestations of nephrotic syndrome;
rapid progress of renal failure (a sharp decrease in glomerular filtration along with an increase in creatinine titer in the blood serum).

With a confirmed history of streptococcal infection shortly before the onset of acute glomerulonephritis, typical clinical and laboratory symptoms, the correctness of the diagnosis is beyond doubt. But with long-term hypertension, hematuria, absence of positive treatment dynamics or undocumented streptococcal infection, it is necessary to differentiate the pathology from other forms of damage to the renal medulla, such as:

IgA nephropathy;
membranoproliferative glomerulonephritis;
secondary glomerulonephritis against the background of systemic autoimmune connective tissue diseases (hamorrhagic vasculitis, SLE).

Treatment

Therapy for this form of glomerulonephritis includes etiotropic effects (sanitation of the focus of streptococcal infection), pathogenetic (inhibition of immune reactions and proliferation of renal cells) and symptomatic treatment.

To influence streptococcal microflora, antibiotics are prescribed to which these microorganisms are most sensitive. These are the latest generations of macrolides and penicillin drugs.

To relieve autoimmune inflammation and prevent the proliferation of renal tissue, hormonal drugs (glucocorticosteroids) and cytostatics (antitumor pharmacological agents) are used. In the presence of an inactive inflammatory process with minimal symptoms and no signs of renal failure, such drugs are used with caution or are not used at all.

To relieve symptoms, antihypertensive drugs (ACE inhibitors) and diuretics are prescribed for significant edema. Diuretics are prescribed only according to indications, including the following conditions:

severe form of arterial hypertension (pressure is not relieved by antihypertensive drugs);
respiratory failure (swelling of lung tissue);
severe swelling in the cavities, threatening the vital functions of organs (hydropericardium, ascites, hydrothorax).

The prognosis for this form of glomerulonephritis is favorable. Long-term cases of total renal failure do not exceed 1%. Unfavorable factors that determine long-term negative prognosis are the following conditions:

uncontrolled arterial hypertension;
elderly age of the patient;
rapid development of renal failure;
long-lasting (more than 3 months) proteinuria.

Association of General Practitioners (Family Doctors) of the Russian Federation

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 diagnosis of the disease in adults, children, elderly people, 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 in an outpatient setting.

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

8. Treatment for certain categories of patients: adults, children, elderly people, pregnant women.

9. Management of patients after hospital treatment.

10. Indications for consultation with specialists.

11. Indications for hospitalization of the patient.

12. Prevention. Patient education.

13. Forecast.

14. The procedure for providing therapeutic and diagnostic care in outpatient settings: flow chart, organization of patient routes, 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

CTD – systemic connective tissue diseases

GFR – glomerular filtration rate

CKD – chronic kidney disease

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), the nephritic syndrome that first developed after streptococcal or other infection with the outcome in recovery; with subacute/rapidly progressive GN (RPGN) – nephrotic or nephrotic-nephritic syndrome with rapidly progressive deterioration of renal function; with chronic GN (CGN) – a slowly progressive course with the gradual development of chronic renal failure.

2. Codes according to ICD-10:

N00 Acute nephritic syndrome. N03 Chronic nephritic syndrome.

When performing a biopsy, morphological classification 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 3–7 years old (in 5–10% of children with epidemic pharyngitis and in 25% with skin infections) and less often in adults 20–40 years old. 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 incidence 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 old and adults 20–40 years old. Mortality in GN is possible from complications of hypertension, nephrotic syndrome: stroke: acute renal failure, hypovolemic shock, venous thrombosis ov. Mortality in CGN at stages III-V of chronic kidney disease (CKD) is caused by cardiovascular diseases.

Risk factors: streptococcal pharyngitis, streptoderma, infective endocarditis, sepsis, pneumococcal pneumonia, typhoid fever, meningococcal infection, viral hepatitis B, infectious mononucleosis, mumps, chicken pox, infections caused by Coxsackie viruses, etc.). At-risk groups: persons who do not comply with hygiene rules, with low social status, and suffer from streptococcal infections. GN screening 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.

In epidemiology : a) epidemic; b) sporadic.

According to clinical forms. Latent form(changes only in urine; no peripheral edema, blood pressure not increased) - 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. Hypertensive form(changes in urine, hypertension) - 20–30% of cases. Nephrotic form(nephrotic syndrome - massive proteinuria, hypoalbuminuria, edema, hyperlipidemia; no hypertension) - 10% of cases of chronic GN. WITH mixed form(nephrotic syndrome in combination with hypertension and/or hematuria and/or azotemia) - 5% of cases of chronic GN.

By phases.Exacerbation(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 urine.

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

BPGN

There are idiopathic RPGN and RPGN syndrome, which develops during exacerbation of CGN - “RPGN type”. Differential diagnosis between these options is possible based on biopsy data.

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” - rapidly progressing GN, other morphological forms - chronic GN. In the absence of diseases that could be the cause of the development of GN, a diagnosis of primary GN is made.
4. Principles and algorithm for diagnostics in outpatient settings.
To diagnose 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 the case of atypical NS (GN KDIGO, 2012).

At the outpatient stage, it is necessary to suspect GN and refer the patient to the nephrology department for a biopsy and establish a final diagnosis of GN. However, in the absence or limited availability of biopsy, the diagnosis of GN is established clinically.

Diagnosis of GN on an outpatient basis

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

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

At CGN is revealed one of the clinical and laboratory syndromes (urinary, hematuric, hypertensive, nephrotic, mixed). During exacerbation swelling of the eyelids/lower extremities appears or increases, decreased diuresis, darkening of 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. With IgA nephritis, the incubation period is often short - less than 5 days.

With CGN, unlike AGN, left ventricular hypertrophy is detected; angioretinopathy grade II–III; 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 of the disease are steadily increasing; azotemia, oligoanuria, anemia, nocturia, resistant arterial hypertension, and heart failure are added. Progression to end-stage renal failure is possible within 6-12 months; if treatment is effective, the prognosis may improve.

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 GBV 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, kidney 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 clinical symptoms of nephritic syndrome: urine the color of “coffee”, “tea” or “meat slop”; swelling on the face, eyelids, legs; increased blood pressure, symptoms of left ventricular heart failure. CGN is often detected incidentally by changes in urine analysis. In some patients, CGN is first detected in the later stages of CKD. Body temperature is usually normal, Pasternatsky's sign is negative. With secondary GN, symptoms of the disease that caused CGN may appear. In CGN, first identified at the stage of chronic renal failure, symptoms of uremic syndrome are detected: dry pale skin with a yellowish tint, scratching, orthopnea, left ventricular hypertrophy.

Laboratory and instrumental research. Allows you to confirm the diagnosis of GN C

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

Biochemical blood test: in post-streptococcal AGN, the titer of antistreptococcal antibodies (antistreptolysin-O, antistreptokinase, antihyaluronidase) is increased; in 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. Increased IgA titer in Berger's disease, Ig G - in secondary GN in CTD. Increased concentrations of C-reactive protein, sialic acids, fibrinogen; decreased - total protein, albumin, especially in nephrotic syndrome. The proteinogram shows hyper-α1- and α2-globulinemia; with nephrotic syndrome - hypo-γ-globulinemia; for secondary GN caused by systemic connective tissue diseases - hyper-γ-globulinemia. A decrease in GFR, an increase in the concentration of creatinine and/or urea in the blood plasma - 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; in membrane-proliferative and cryoglobulinemic GN, the level of mixed cryoglobulins is increased. In Goodpasture syndrome, antibodies to the glomerular basement membrane are detected.

In urine during exacerbation: increased osmotic density, decreased daily volume; in the sediment there are altered red blood cells from single ones to covering the entire field of view; leukocytes - in smaller numbers, but can predominate over red blood cells in lupus nephritis, nephrotic syndrome, and are represented predominantly by lymphocytes; cylinders; proteinuria from minimal to 1–3 g/day; proteinuria more than 3 g/day develops with nephrotic syndrome. Cultures from the tonsils and blood sometimes make it possible to clarify the etiology of AGN. WITH

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

Early diagnosis. Possible with dynamic monitoring of patients after an acute infectious disease for 2-3 weeks. The appearance of nephritic syndrome (hypertension, edema, hematuria) indicates the development of GN or its exacerbation.

5. Differential diagnosis.

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

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

Tubulointerstitial nephritis: fever, hyposthenuria, leukocyturia, lower back pain, increased ESR.

Alcoholic kidney damage: medical history, hematuria, hyposthenuria, lower back pain.

Amyloidosis: history of chronic purulent diseases, rheumatoid arthritis, helminthiasis; systemicity of the lesion, proteinuria, often the absence of erythrocyturia.

Diabetic nephropathy: diabetes mellitus, gradual increase in proteinuria, often absence of hematuria.

Kidney damage in diffuse connective tissue diseases: signs of a systemic disease - fever, carditis, arthritis, pneumonia, hepato-lienal syndrome, etc.; high ESR, hyper-gammaglobulinemia, positive serological tests. Lupus nephritis: female gender predominates; signs of a systemic disease are detected: arthralgia, arthritis, fever, facial erythema of the “butterfly” type, 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”. Periarteritis nodosa: male gender predominates; signs of a systemic disease are detected: fever, myalgia, arthralgia, weight loss, severe hypertension, skin manifestations, asymmetric polyneuritis, abdominal syndrome, myocarditis, coronaryitis with angina pectoris and myocardial infarction, bronchial asthma; typical laboratory changes: leukocytosis, sometimes eosinophilia, high ESR; specific changes in the biopsy of the musculocutaneous flap; Kidney 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 sample of the mucous membrane of the nasopharynx, lung, kidney. Goodpasture's syndrome: signs of systemic disease: fever, hemoptysis or pulmonary hemorrhage, pulmonary infiltrates, weight loss; kidney damage occurs after hemoptysis, renal failure progresses rapidly with oliguria and anuria; anemia, increased ESR, with serological testing - 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 a stone, history of renal colic, identification of signs of obstruction and hematuria without proteinuria.

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

Primary antiphospholipid syndrome: 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: medical history, urine examination of family members - massive hematuria is characteristic of IgA nephritis and hereditary nephritis and is rare in thin membrane disease. Hereditary nephritis is associated with renal failure in the family, deafness, and chromosomal dominant inheritance. A family history of hematuria is also found in thin membrane disease, and in isolated cases in IgA nephritis. In a patient with episodes of gross hematuria and a negative family history, IgA nephritis is most likely. If there is persistent microhematuria in the patient and hematuria in family members without renal failure, 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 of identifying 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, renal 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 in an outpatient setting.

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

Monitoring of fluid balance, adherence to regimen and diet, and measurement of blood pressure are carried out; taking medications prescribed by a doctor. Herbal medicine is not used; short-term use of a decoction of rose hips and chokeberry is possible. Elimination of hypothermia, stress, physical overload. Compliance with the regime and diet, quitting smoking, self-monitoring of blood pressure.

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

In women of reproductive age with GN, pregnancy must be planned during the period of GN remission, taking into account renal function and blood pressure levels, as well as predicting the course of pregnancy and GN. Exacerbation of GN during pregnancy, as a rule, does not occur due to physiological characteristics - high levels of glucocorticoids. Pregnancies are usually well carried with IgA nephropathy. Women with GFR less than 70 mL/min, uncontrolled hypertension, or severe vascular and tubulointerstitial changes on a renal biopsy are at risk for decreased renal function.
8. Indications for consultation with specialists

Consultations with specialists help in establishing the diagnosis of C. If a focal infection is suspected, the patient can be consulted if necessary otorhinolaryngologist, gynecologist, dermatologist. To identify angiopathy and assess its duration (for differential diagnosis of AGN and CGN), a consultation is indicated ophthalmologist Consultation infectious disease specialist carried out if viral hepatitis or HIV infection is suspected. If there are signs of a systemic disease (may debut with AGN C), consultation a rheumatologist will help clarify the diagnosis and resolve the issue of therapy for primary disease. In case of high clinical and laboratory activity of inflammation, febrile fever, heart murmur, a consultation is indicated cardiologist.

9. Indications for hospitalization.

Active or newly diagnosed GN (AGN, CGN, RPGN) or suspicion of GN is an indication for hospitalization C. Indications for hospitalization are also the need to clarify the diagnosis (with a relatively rapid decline in renal function, an isolated urinary symptom or differential diagnosis), for a biopsy to clarify morphological diagnosis and assessment of GN activity), expert assessment, and immunosuppressive therapy and initiation of active therapy.

10. Prevention.

Research on the impact primary prevention on recurrent GN, long-term prognosis, renal survival is insufficient. Primary prevention is not carried out. However, antibacterial treatment of patients with pharyngitis and contacts (1), started within the first 36 hours allows for negative culture results and can prevent (but not necessarily) the development of nephritis D. Antimicrobial therapy for infections can prevent the development of post-infectious GN, but observations are insufficient ( level of evidence: 1)

Secondary prevention. Treatment with prednisolone, sometimes in combination with cyclophosphamide, reduces the likelihood of relapse of nephrotic syndrome in IGA nephritis. Long-term (up to 4 months) oral steroids for IGA nephropathy improve the number of remissions of nephritic syndrome. Combination therapy with prednisolone and cyclophosphamide GMI reduces the incidence of disease relapses compared to prednisolone monotherapy.

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

Patient education. Monitoring fluid balance, adherence to regimen and diet, measuring blood pressure; taking medications prescribed by a doctor. Herbal medicine is not used; short-term use of a decoction of rose hips and chokeberry is possible. Elimination of hypothermia, stress, physical overload. Compliance with the regime and diet, quitting smoking, self-monitoring of blood pressure. The patient must be informed about the need to monitor the level of GFR and blood creatinine, to exclude potentially nephrotoxic drugs and radiocontrast drugs.
11. Treatment in a hospital

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

Goal of treatment. At OGN: achieving recovery, eliminating complications. At CGN: induction of remission, slowing down the rate of progression, preventing and eliminating complications. At BPGN– reduction in disease activity and rate of progression to end-stage renal failure.

Non-drug treatment. With active GN, the regime is half-bed or bed-rest until the edema disappears and blood pressure normalizes (1-3 weeks), then the regime is expanded. Long-term bed rest does not improve the prognosis of GN. Diet: for edema - limiting table salt (up to 4-6 g/day), fluid for 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. During GN remission, salt and protein restrictions are less strict. Protein restriction somewhat slows down the progression of nephropathies, although the degree of effect weakens somewhat as chronic GN progresses. Avoid spicy seasonings, meat, fish and vegetable broths, gravies, strong coffee and tea, and canned food. Prohibition of alcohol and tobacco consumption. Physiotherapeutic treatment for GN is not indicated.

With drug-induced MGN, drug withdrawal sometimes leads to spontaneous remission: after discontinuation of penicillamine and gold - within 1-12 months to 2-3 years, after discontinuation of NSAIDs - up to 1-36 weeks. In patients with concomitant diabetes mellitus, replacement of pork insulin with human insulin is indicated.

Developer: Research Institute of Nephrology, First St. Petersburg State Medical University. 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, pathomorphologist, specialist in immunomorphology Kayukov I.G. – Doctor of Medical Sciences, Professor, Nephrologist, Clinical Physiologist Lebedev K.I. – Junior Researcher, Pathomorphologist, Immunomorphologist


	From the outside	From the outside	Further
	patients		direction
			use
Level 1 “Experts”	Overwhelming	Overwhelming
	majority	to the majority	May be
	patients,	their patients	accepted as
	patients,	their patients	accepted as
	caught in	the doctor will be	standard
	similar situation,		actions
	would prefer	follow	medical
	follow	exactly this	personnel in
			most
	and only a small one		clinical
	some of them were rejected		situations
	this way
Level 2	Most of	For different
"Experts believe"	patients,	patients	probably,
"Experts believe"	caught in		will require
	caught in		will require
	similar	pick up	discussions with
	situations, spoke out	various	participation of all
	I would like to	options	interested
	follow		parties before acceptance
		suitable	them as
	by, however	exactly to them.	clinical
	Substantial part		standard
	would reject this path	to the patient
		necessary
		help in choosing
		and acceptance
		solutions that

		correspond
		values and
		preferences
		of this patient
"Undifferentiated	This level is applied in cases where the basis
level"
level"	expert or when the topic under discussion does not allow
“Not Graded” - NG	expert or when the topic under discussion does not allow
“Not Graded” - NG	adequate application of the system of evidence used
	adequate application of the system of evidence used
	in clinical practice.

	Characteristic	Meaning/Description

	predictability
		Experts are absolutely confident that when performing

		completely coincides with what was expected.
	Moderate	Experts expect that when performing this

		close to expected, but the possibility cannot be ruled out
		that it will be significantly different from it.
		The predicted effect may vary significantly
		from real.
	Very low	Prediction of effect is extremely unreliable and very often
		will be different from the real one.

Note: * compiled in accordance with clinical recommendations

Section 1. Definition of membranoproliferative glomerulonephritis.

term (“morphological syndrome”), uniting 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 Significant advances have now been made in understanding the etiology and

especially the pathogenesis of MBPGN, 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, with the latter being predominant. In this regard, past data on the prevalence of MBPGN in the population should be taken with caution.

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

1.2%, amounting to 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 measures to prevent infections, apparently, explain the emerging trend in the last 15 years. 20 years of clear downward trend in the prevalence of MBPCN in most regions

world, however, MBPGN remains the 3rd and 4th cause of end-stage renal failure (ESRD) among all other forms of primary glomerulonephritis.

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

Section 2. Clinical presentation of MBPGN

A comment:

Despite the pathogenetic and morphological heterogeneity of MBPGN, the clinical presentation from the kidneys is identical. Half of the patients have a history of a recent (up to one week) upper respiratory tract infection. In some cases, a clinical phenomenon is detected - synpharyngitis macrohematuria, which forces a differential diagnosis with IgAnephropathy. Among the clinical symptoms, the following prevail: arterial hypertension, which is observed 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 acute or rapidly progressive nephrotic syndrome (APNS). In the first case, there is a need for differential diagnosis with acute post-streptococcal 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 does not exist, then in most patients it appears later, in 10–20% of cases

recurrent macrohematuria (usually synpharyngitis) is noted.

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

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

multiple disturbances of tubular functions are detected (decrease in the concentrating ability of the kidneys, aminoaciduria, glycosuria,

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) immunoglobulin-positive MBPGN type I is diagnosed,

which affects people of any age and gender. The immunoglobulin-positive variant of type III MBPGN is detected less frequently (5 – 10%). Currently, there is a consensus among nephrologists regarding idiopathic,

immunoglobulin-positive MBPGN type I (less often type III), the diagnosis of which can be established only after excluding secondary causes (Table 3). IN

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

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

microhematuria or nephrotic syndrome is formed. Clinical diagnosis of dense deposit disease (DDD) is facilitated 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 MBPGN in accordance with international standards, it is necessary to combine several methods of morphological examination of intravital renal tissue biopsies, namely: light microscopy, immunomorphology, ultrastructural analysis (transmission electron microscopy) (NG).

trichromic Masson stain, PAS reaction, Congo mouth, elastic fiber and fibrin stain (AFOG) (1A).

Recommendation 3.3. For immunomorphological research, it is necessary to use the following antibodies to identify diagnostically significant epitopes: IgA, M, G, light chains lambda, kappa and fibrinogen, complement fractions C3, C1g, C2 and C4 (2B).

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

positive MBPGN types I or III, immunoglobulin-negative, C3-positive MBPGN I or III

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

Recommendation 3.7. When conducting an immunomorphological study, it is necessary to consider the intensity of deposition of the reaction product to immunoglobulins A, M, G in the structures of glomeruli ≥2+ as diagnostically significant, both with fluorescent and light-optical (transmitted light) microscopy (immunoglobulin-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 (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 reaction product 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 version 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), the 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 MBPGN, including 2 forms of MBPGN, which with further ultrastructural analysis can be specified as: immunoglobulin-negative, C3-positive MBPGN I or III

type or disease of dense deposits (1A).