Acute glomerulonephritis clinical guidelines. Clinical guidelines for the diagnosis, treatment and prognosis of membranoproliferative glomerulonephritis

Size: px

Start impression from page:

transcript

1 1 Clinical guidelines on the diagnosis, treatment and prognosis of membranoproliferative glomerulonephritis Developer: Research Institute of Nephrology of the First St. Petersburg State Medical University. acad. I.P. Pavlova (2013) Authors: 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, pathologist, immunomorphologist

2 2 Methodology for assessing the strength of recommendations and the level of their predictive power used in the preparation of these clinical guidelines * According to the strength of recommendations, they are divided into three categories in descending order: level 1 (experts recommend); level 2 (experts suggest); "undifferentiated level" (Table 1). The predictive power of recommendations is subdivided into 4 levels (Table 2). Table 1. Evaluation of the strength of recommendations Level Level 1 "Experts recommend" Level 2 "Experts believe" "Undifferentiated level" Not Graded - NG Evaluation of recommendations by patients The vast majority of patients in a similar situation would prefer to follow the recommended path and only a small part of them would reject this path Most of the patients in a similar situation would be in favor of following the recommended path, but a significant proportion would reject this path On the part of the doctor The vast majority of his patients the doctor will recommend to follow this path For different patients should select different options for recommendations that are suitable for them. Each patient needs assistance in choosing and making a decision that is consistent with the values ​​and preferences of the patient Further direction of use The recommendation can be accepted as a standard for action by medical personnel in most clinical situations as a clinical standard This level is used when the recommendation is based on the judgment of the expert investigator or when the topic under discussion does not allow for an adequate application of the system of evidence used in clinical practice.

3 3 Table 2 Predictor levels of recommendations Level Characteristic Meaning/description of the level of predictiveness A High Experts are absolutely sure that if this recommendation is followed, the observed effect will almost completely coincide with the expected one. B Moderate The experts expect that if this recommendation is followed, the observed effect is likely to be close to the expected one, but the possibility that it will be materially different from it cannot be ruled out. C Low The predicted effect may differ significantly from the actual one. Y Very low Prediction of the effect is extremely unreliable and will very often differ from reality. Note: * Compiled in accordance with KDIGO clinical guidelines. Section 1. Definition of membranoproliferative glomerulonephritis. Terminology. Recommendation 1.1. Membranoproliferative glomerulonephritis (MBPN) is a generic term (“morphological syndrome”) that unites a group of glomerulopathies that have a similar morphological picture on biopsy light microscopy, but differ in etiology, pathogenesis, immunohistochemical and ultrastructural (electron microscopy) changes in the renal parenchyma (NG). Comment At present, significant progress has been made in understanding the etiology and especially the pathogenesis of MBPH, 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 Europe, the prevalence of MBPGN varies from 4.6% to 11.3%, and in the USA it does not exceed 1.2%, amounting to approximately 16 people per 1 million population. On the contrary, in the countries of Eastern Europe, Africa and Asia, according to some data, the prevalence of MBPGN 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 emerging recent years a clear downward trend in the prevalence of MBGN in most regions

4 4 of the world, however, MBPGN remains the 3rd and 4th cause of terminal kidney failure(ESRD) among all other forms of primary glomerulonephritis. Synonyms for the term membranoproliferative glomerulonephritis are mesangiocapillary glomerulonephritis, and in the domestic literature, membranoproliferative glomerulonephritis. The term membranoproliferative glomerulonephritis should be considered preferred. Section 2. Clinical presentation of MBPHN Recommendation 2.1. The clinical presentation of MBPHN (renal syndromes) is identical in idiopathic (with unknown etiology) and secondary variants of the disease (1B). Recommendation 2.2. Based on the nature of the clinical picture, it is impossible to predict the morphological type of MBPHN (1B). Recommendation 2.3. Clinical differential diagnosis of MBPHN should initially be based on the complete and reliable exclusion of all possible secondary causes (Tables 3, 4) (NG). 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, the clinical phenomenon of synpharyngitis macrohematuria is revealed, which forces a differential diagnosis with IgA nephropathy. Among the clinical symptoms prevail: arterial hypertension, which is noted in the debut in more than 30% of patients, but eventually develops in almost all patients, sometimes acquiring a malignant course; macro- and microhematuria (almost 100%); high proteinuria (nephrotic); progressive decrease in glomerular filtration rate (GFR). Leading clinical syndrome in the debut of the disease in 20-30% of cases it is presented by acute or rapidly progressive nephrotic syndrome (ANS, BPNS). 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 performed 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

5 5 there is recurrent gross hematuria (often synpharyngitis). However, in 20-30% of patients it is possible to register (usually by chance) 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 multifaceted disorders of tubular functions (decreased renal concentrating ability, 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), immunoglobulin-positive type I MBGN is diagnosed, which affects people of any age and gender. An immunoglobulin-positive variant of type III MBPGN is detected less frequently (5-10%). Currently, there is a consensus among nephrologists regarding idiopathic, immunoglobulin-positive MBPHN type I (rarely type III), the diagnosis of which can be established only after the exclusion of secondary causes (Table 3). In the clinical picture of C 3 -negative glomerulopathy, as a rule, clinical and laboratory symptoms of the underlying disease prevail in the debut (Table 4) in combination with acute kidney injury, most often in the form of BPNS. Only after the expiration of the acute period, high proteinuria, microhematuria or nephrotic syndrome are formed. Clinical diagnostics Dense deposit disease (DDD) is alleviated if, in addition to renal syndromes, associated conditions are detected in the form of acquired partial lipodystrophy and / or macular degeneration of the retina (see below). Section 3. Morphological and immunomorphological differential diagnosis of MBPHN 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). Recommendation 3.2. To conduct a light-optical study of nephrobiopsy specimens, it is necessary to carry out the following stains on paraffin sections: hematoxylin and eosin, Masson's trichromic stain, PAS reaction, Congo-rot, staining for elastic fibers and fibrin (AFOG) (1A).

6 6 Recommendation 3.3. For immunomorphological study, it is necessary to use the following antibodies to detect diagnostically significant epitopes: IgA, M, G, lambda light chains, kappa and fibrinogen, complement fractions C3, C1g, C 2 and C 4 (2B). Recommendation 3.4. Based on the data of ultrastructural analysis (electron microscopy), one should distinguish: type I membrane proliferative glomerulonephritis, dense deposit disease, and type III membrane proliferative glomerulonephritis (1A). Recommendation 3.5. Morphological differential diagnosis of MBPGN is carried out on the basis of immunomorphology and electron microscopy data (1A). Recommendation 3.6. The result of morphological differential diagnosis should be the establishment of the following pathogenetic variants of MBGN: immunoglobulin-positive, C3-positive MBGN I or III types, immunoglobulin-negative, C3-positive MBGN types I or III 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 fluorescent 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 MBGN) (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 2+ glomeruli in both fluorescent and light-optical (in transmitted light) microscopy (C3-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 (C3-negative variant of MBPGN) (2B). Recommendation 3.9. In the absence of the possibility of ultrastructural analysis (electron microscopy), a morphological diagnosis should be formulated on the basis of data from light microscopy and immunomorphology (2B). Recommendation Based on light microscopy and immunomorphology, three variants of MBGN (2B) should be distinguished: immunoglobulin-positive and C3-positive MBGN; C3 glomerulopathy; immunoglobulin- and C3-negative MBPGN. Recommendation The term C3 glomerulopathy refers to immunoglobulin-negative and C3-positive MBGN, including 2 forms of MBGN that can be further refined on ultrastructural analysis as: immunoglobulin-negative, type I or III C3-positive MBGN, or dense deposit disease (1A). Comment. Main morphological features under light microscopy, they are represented by proliferation of cells and the main substance of the mesangium and thickening of the walls of capillaries (basement membranes), which often undergo pseudo-cleavage with the formation of double-loop basement membranes

7 7 (the "tram line" phenomenon). The mechanism of formation of the second basement membrane is associated with the interposition (introduction) of mesangiocyte processes into the subendothelial space, where they, in cooperation with endotheliocytes, produce a new basic substance of the second intracapillary membrane located inside. In addition to the proliferation of resident cells, there is infiltration of the glomeruli by neutrophils and macrophages (exudative component of the inflammatory response). It is important to note that the severity of proliferative and exudative changes may vary from case to case. So, in some observations, these changes may be focal in nature (i.e., part of the glomeruli may remain intact). It is believed that in this case we can talk about the debut of the disease. In other observations, noted most often, morphological changes are diffuse. Cases of regression have also been described. diffuse changes in focal, for example, in the elimination of a secondary cause of glomerulopathy. In 10% of all cases of MBPGN, crescents can be recorded in more than 50% of the glomeruli, as a reflection of the severity of the activity of the proliferative-exudative reaction. As a rule, in this case, rapidly progressive nephritic syndrome (RPNS) is clinically noted. Pronounced proliferative changes in the mesangium very often lead to the division of glomerular capillary loops into separate bundles (lobules), giving the glomerulus a lobular structure. Previously, such changes were classified as special form MBPGN lobular. Today, glomerular lobulation is considered one of the variants of the course of the pathological process, reflecting the severity of the proliferative reaction and, possibly, associated with the duration of the course of MBPHN. With further progression, the zones of hypercellularity of the mesangium are replaced by the matrix and sclerosis of the glomerulus develops. At this stage, pathological changes may mimic nodular diabetic glomerulosclerosis. Changes in the vessels reflect the duration and severity of the course arterial hypertension. Morphological changes in the cells of the tubules and interstitium are usually significantly pronounced, as a rule, do not correlate with glomerular lesions, but are associated in the clinic with kidney dysfunction. A more detailed characterization of morphological changes in MBPGN is possible only with ultrastructural analysis, which

8 8 makes it possible to distinguish three types of MBPGN. In type I MBPGN, electron microscopy reveals subendothelial and mesangial deposits. In type II MBPHN, intramembranous electron-dense deposits are noted, which can give the membrane a "sausage bundle" appearance, and mesangial deposits are also present. In type III MBPH, in addition to subendothelial, subepithelial (subpodocytic) deposits (subtype Burkholder a) are recorded, in some cases, outgrowths near subepithelial deposits are formed on the basement membrane (the morphological picture resembles membranous nephropathy), combined with the presence of intramembranous deposits (as in type II MBPN) , The latter give the lamina densa an uneven appearance (subtype Strife a and Anders a). We emphasize that there are no typical morphological features in light microscopy that would allow predicting the diagnosis of one of the three types of MBPHN in electron microscopy. Moreover, in BPD only 25% of cases show typical signs of MBPHN (described above) with light microscopy; 44% are diagnosed with mesangial proliferative glomerulonephritis, 17% with crescentic glomerulonephritis, 11% with acute exudative proliferative glomerulonephritis, and in 3% of cases morphological signs cannot be classified. Many investigators also draw attention to the existence of many transitional types in electron microscopy, meaning that even ultrastructural analysis does not guarantee a definitive diagnosis. That is why the modern classification of MBPGN was based on information about immunopathogenesis, which can be judged from the data of immunomorphology (immunohistochemistry) of sections of kidney biopsy specimens. Based on the analysis of deposits (deposits) in the kidney biopsy of immunoglobulins and complement fractions, immunoglobulin-positive and immunoglobulin-negative MBPH are isolated (Fig. 1). The presence of immunoglobulins and complement C3 fraction indicates an immunocomplex variant of MBPGN, which is characterized by activation of the complement system along the classical pathway. As a result, in addition to globulins and C 3 complement fractions in the renal biopsy, complement fractions C1 q, C 2, C 4, characteristic of the classical pathway of complement activation, are detected. In immunoglobulin-negative MBPGN, detection positive reaction on the C3 fraction of complement in the absence of fractions

9 9 C1 q, C 2, C 4 will indicate complement activation via an alternative pathway. Already on the basis of these data, it is possible to formulate a preliminary diagnosis of C3-positive glomerulopathy or C3-glomerulopathy, which can be further refined using electron microscopy as C3-MBPHN type I or III or dense deposit disease (Fig. 1).

10 10 Given the fact that in BPD the light-optical morphological picture may not include signs characteristic of MBPHN (see above), a diagnosis of C3 glomerulopathy is allowed, but we emphasize once again that there should be no deposits of immunoglobulins, C1g and C4 complement fractions , and the intensity of deposition of the product of the reaction to C 3 - the complement fraction should be at least 2+. The absence of immunoglobulins in the immunomorphological study and a negative reaction to the C 3 -complement fraction (less than 2+) will allow diagnosing C3-negative glomerulopathy. Section 4. Clinical and pathogenetic and laboratory diagnostics MGBGN Recommendation 4.1. The term idiopathic MBGN should be understood as an immunoglobulin- and C3-complement-positive variant of type I or III MBGN of unknown etiology (1A). Recommendation 4.2. Immunoglobulin-negative, C3-positive type I or III MBGN and dense deposit disease are due to hereditary or acquired disorders in the alternative complement pathway system (1A). Recommendation 4.3. Clinical and pathological diagnosis of various variants of MBPHN should include the determination of the total level of serum complement (CH 50), as well as its fractions in blood serum: C3 and C4 (1A). Recommendation 4.4. Normal level C4 fraction of complement indicates an alternative pathway of complement activation (immunoglobulin-negative, C3-positive MBPH), and a decrease in its concentration indicates the classical pathway of complement activation (immunoglobulin-positive, C3-positive MBPH). In both of these cases, the total level of serum complement (CH 50) and its C3 fraction (1A) is reduced. Recommendation 4.5. For a more complete judgment on the pathogenesis of immunoglobulin-negative, C3-positive MBPH I or III types and dense deposit disease, it is necessary to determine the titer of C3-nephritic factor in the blood serum, to investigate the level of regulatory proteins of the alternative pathway of complement activation: factors H, I, B, properdin (1A). Recommendation 4.6. Immunoglobulin- and C3-negative MBPGN should be considered as a reparative phase inflammatory process caused by primary damage to endotheliocytes (Table 4) (2B). Recommendation 4.7. With immunoglobulin and C3-negative MBPGN, the concentration of the total complement level in blood serum (CH 50) and its fractions (C3, C4) does not change (1A). Comment Immunoglobulin and complement positive MBGN types I and III (Fig. 1) are usually secondary and are associated with chronic antigenemia, circulating autoimmune complexes in the blood, or deposition of monoclonal immunoglobulins in the glomerulus. In relatively rare cases, when it is not possible to establish the cause of chronic antigenemia, confirm

11 11 the presence of plasma cell dyscrasia or an autoimmune process, diagnosis of the idiopathic form of MBPHN type I or III is allowed. The cause of chronic antigenemia, as a rule, is torpid viral, bacterial, protozoal and other infections (Table 3). The pathogenesis of immunoglobulin-positive MBPHN types I and III has common features. Immune complexes formed in the blood circulation or in situ due to chronic antigenemia (infection), or circulating immune complexes in autoimmune processes (SLE, Sjögren's syndrome, mixed cryoglobulinemia, etc.), or immune complexes formed during paraproteinemias (monoclonal gammopathy, lymphoproliferative diseases) are deposited in glomeruli mesangially (with large sizes), subendothelially (with medium sizes) or subepithelially (with small sizes). Table 3. Secondary causes of immunoglobulin- and C3-positive MBPH A. Infections viral hepatitis B, C human immunodeficiency virus bacterial infective endocarditis abscessing septicemia infected ventriculoatrial and ventriculoperitoneal shunts protozoal malaria schistosomiasis other mycoplasmal mycobacterial B. Autoimmune diseases mixed systemic volleyman's syndrome cryoglobulinemia transplant nephropathy C. Hematological malignancies lymphoma lymphocytic leukemia MGUS* myeloma Waldenstrom macroglobulinemia D. Other diseases cirrhosis of the liver carcinomas (lungs, kidneys, stomach, intestines) sarcoidosis Immune complexes activate complement through the classical pathway, which involves complement fractions C1q, C2, C4 c formation of the C3-convertase of the classical pathway (C4bC2a), which cleaves the C3-fraction into C3a and C3b subfractions, followed by the formation of the C5-convertase of the classical pathway of complement activation (C4bC2aC3b) . C5-convertase, acting on the C5-complement fraction, leads to the formation of C5a and C5b subfractions, the latter

12 12 ultimately leads to the formation of a membrane attack complex (MAC) (C5b-9). Complement subfractions C3a and C5a, acting chemotactically, cause an influx of immune complexes of macrophages and neutrophils from the circulating blood to the location, which, due to pro-inflammatory cytokines and proteolytic enzymes, cause the formation of an exudative-inflammatory reaction in the glomerulus. Resident cells of the glomerulus (endotheliocytes, mesangiocytes), in response to damage by pro-inflammatory cytokines and the cytopathic action of MAC (C5b-9), respond with proliferation, synthesis of the basic substance (basement membranes, mesangial matrix) and production of growth factors (transforming growth factor β1, platelet factor growth). Ultimately, morphological signs are formed in the form of doubling of the basement membranes, proliferation of mesangiocytes and mesangial matrix with glomerular lobulation, and the formation of sclerosis zones (glomeruli and tubulointerstitium). Note that secondary MBPGN in HCV infection (hepatitis C virus - hepatitis C virus) can have a dual pathogenesis. In some cases, it may be associated with the formation of immune complexes to the antigens of the hepatitis C virus, which were originally deposited in the glomerulus (i.e., formed in situ), in other cases, we are talking about circulating immune complexes of mixed cryoglobulins (type II cryoglobulinemia). Mixed cryoglobulins (type II) in HCV infection are immune complexes precipitating in the cold, consisting of IgMκ-rheumatoid factor, polyclonal IgG and hepatitis C virus RNA. The lymph nodes) under the influence of the hepatitis C virus, which synthesize monoclonal IgMκ (rheumatoid factor). The presence of mixed cryoglobulinemia associated with HCV infection is considered by some authors as a subclinical form of lymphoma. Transplantation glomerulopathy occupies a special place among immunoglobulin-positive variants of MBGN. For a long time, pathomorphological changes in the transplanted kidney were considered from the point of view of the mechanisms of chronic transplant rejection (chronic transplant nephropathy). Currently, scientific data have been accumulated that make it possible to distinguish transplant glomerulopathy into an independent clinical and morphological nosological unit with immune pathogenesis. Transplantation glomerulopathy is

13 13 is the initial damage to endotheliocytes by autoantibodies to HLA-II class antigens that are present on the outer cell membrane of endothelial cells. In the acute phase, the so-called glomerulitis develops, characterized by damage to glomerular capillaries migrating from the circulating blood, mononuclear cells and neutrophils. An acute, exudative reaction in the glomerulus (glomerulitis) is replaced by a reparative phase, in which proliferation and expansion of the mesangial matrix occurs, duplication of basement membranes develops, and the morphological picture under light microscopy becomes similar to immunoglobulin-positive MBPHN. Immunofluorescence reveals deposition along the capillary loops of the glomerulus of the C4d complement fraction, a product of complement activation along the classical pathway, however, even the absence of C4d deposits will not contradict the diagnosis of transplantation glomerulopathy. The etiology of immunoglobulin-negative, C3-positive glomerulonephritis, termed C3 glomerulopathy, is attributed to dysregulation of the alternative pathway of complement activation and impaired terminal MAC formation (C5b-9). Violation of the normal physiology of the alternative pathway of complement activation may be due either to a mutation in the genes of various factors of the complement system, or to be acquired. In the latter case, autoantibodies to regulatory factors of complement activation are formed in the body along an alternative pathway. The chemical structure of deposits in C3 glomerulopathy has not been fully established, but it has been found that they consist of glycosaminoglycans with inclusions of the C3b complement fraction, its degradation products (ic3b, C3dg, C3c), as well as MAC components (C5b-9). In contrast to the classical pathway of complement activation, when cascade-type reactions are triggered by immune complexes, the alternative pathway is normally characterized by a constant, persistent activity of a low degree, consisting in the formation of small amounts of the C3b fraction, due to spontaneous hydrolysis of the thioether bond of the C3 protein. The complement C3b fraction generated in small amounts then binds to the membranes of various cells, including the membranes of pathogenic microorganisms, which is the physiological meaning of this reaction. In order to prevent the transition of this spontaneous activity into an uncontrolled reaction (cascade), the body has a whole system of regulatory factors (proteins) that act on various levels

14 14 cascade reaction, especially during the formation of C3 and C5 convertases. Factor "H" (CFH) promotes the breakdown of spontaneously formed C3-convertase of the alternative pathway (C3bBb), and together with factor "I" (CFI) (for which CFH is a cofactor) lead to the inactivation of the C3b subfraction. A group of proteins (from 1 to 5) similar to factor H (CFHR 1-5 complement factor H related proteins) is also involved in the regulation of the complement activation system along an alternative pathway in the circulating blood (“fluid phase” regulators). Their function has not been completely studied. It is believed that CFHR1 inhibits the action of MAC, and the mechanism of action of CFHR5 is similar to the regulatory activity of factor "H". The reason for the formation of C3-positive MBPHN, including BPD, may be mutations in the H factor gene. A monogenic CFHR5 mutation inherited in an autosomal dominant manner is the cause of endemic Cypriot nephropathy, which is C3-positive MBGN type I or III. It should be noted that factors "H" and CFHR5, acting in blood plasma, also have a tropism for extracellular membranes, where they retain their inactivating activity against the membrane-bound complement subfraction C3b. Several circumstances important for understanding the pathogenesis of C3-positive glomerulopathy follow from this fact. It is known that the pathogenesis of atypical hemolytic uremic syndrome (agus) can also be associated with genetic mutations of the regulatory factor "H". However, in this disease, dysregulation of the alternative pathway of complement activation occurs mainly on the surface of endotheliocyte cell membranes, without affecting the complement activation system in the circulating blood. Therefore, although in rare cases the initial formation of C3-positive glomerulopathy in a-gus is possible, the most typical scenario of the pathological process in it is the initial damage to endotheliocytes with the formation of microthromboses of the glomerular capillaries and only after some time, when reparative (proliferative) processes are activated, as response of resident cells of the glomerulus to endothelial damage, the morphological picture of MBPGN begins to form (C3-negative and without deposits of electron-dense deposits). CFHR5 has an affinity for glycosaminoglycans, and therefore, when the gene of this factor (Cypriot nephropathy) is mutated, the primary activation of the alternative complement pathway on the glomerular basement membrane occurs. As a result, C3-positive MBPHN is formed with subendothelial and/or

15 15 subepithelial electron-dense deposits (type I or III). The inhibitory effect of factors "H" and CFHR5 against C3b on the surface of the glomerular basement membrane forms a physiological "protection" of the kidneys from immunocomplex glomerulonephritis and explains those rare cases of immunoglobulin-positive MBGN (i.e., immunocomplex), in which gene mutations are detected factor "H". The literature also describes mutations in the genes of the main proteins of the complement system. So, with a heterozygous mutation of the C3 protein, both the mutant C3 protein and the native allele synthesized by the gene that are not involved in the mutation are present in the blood plasma. As a result of spontaneous hydrolysis of the mutant C3 protein, C3 convertase is formed, which is resistant to the action of factor "H", which cleaves the C3 protein synthesized by the normal gene, as a result of which degradation products of the complement C3 fraction are formed in excess, which triggers a cascade reaction of complement activation along alternative path. A similar mechanism may underlie the response glomerular reaction in the form of BPD formation. Genetic polymorphism of the complement system factors, leading to a change in the structure of proteins and to a violation of their function, may also play an important role in the pathogenesis of C3-positive glomerulopathy. It should be emphasized that the complement system has a multi-stage regulation system, and therefore not every genetic mutation or gene polymorphism is realized clinically. In most cases, the combined action of environmental factors is necessary for the formation of a genetically programmed phenotype. Among such provoking factors, first of all, infections should be attributed, and possibly other causes (lifestyle, nutrition, chronic intoxication, concomitant diseases, etc.). Well-known to the clinician, cases of synpharyngitis macrohematuria in MBPGN, well known to the clinician, can serve as confirmation of the foregoing. The reason for the acquired disorders in the system of regulation of the alternative pathway of complement activation is the formation in the body of autoantibodies to regulatory proteins (factors H, B, etc.) or to the main complement fractions. The best known and most studied is C3-nephritic factor (C3NeF), which is an autoantibody (IgG) to C3-convertase (C3bBb) of an alternative pathway of complement activation. Attachment of an autoantibody to C3 convertase makes it more resistant to action.

16 16 regulatory proteins (CFH, factor I, CFHR 1-5), which prolongs the time of its circulation in the blood. The result of the unregulated activity of C3-convertase is complement activation with a gradual depletion of the C3-fraction pool and a decrease in its concentration in blood plasma. C3NeF is found in 86% of patients with BPD and in 49% of patients with C3-positive glomerulonephritis, however, not in all patients this is combined with a decrease in the complement C3 fraction, which indicates the existence of other regulatory mechanisms in the body that counteract C3NeF. The presence of dysregulation of the alternative complement pathway in BPD has been associated with two conditions often associated with this disease. The first is represented by acquired partial lipodystrophy, clinically characterized by a gradual (over many years), symmetrical loss of subcutaneous fat in the "cephalocaudal" direction, starting from the face, neck, hands, chest. At the final stage, subcutaneous fat may be involved lower extremities. It is believed that C3NeF causes complement activation on the cell surface of adipocytes, which leads to their death through apoptosis. The second condition is characterized by the formation of whitish-yellow "drusen" (plaques) in the pigment membrane of the retina. The visual picture of the fundus and the clinical course are similar to age-related macular degeneration of the retina. It is believed that the leading pathogenetic mechanism this process is a violation of the local regulatory activity of the factor "H". Electron microscopy of the autopsy material (retina) reveals electron-dense deposits along the basement membranes of the retinal capillaries. Due to choroidal neovascularization that develops over time, there is a gradual loss of vision. The reason for the fact that in one case of C3-positive glomerulopathy a morphological picture of type I or III MBPH is formed, and in another case BPD is detected, remains unclear. Apparently, the heterogeneity of genetic mutations, the initial localization of the process, and the degree of activation of the complement system are important. Activation of the alternative complement pathway, as mentioned above, can also be involved in cases of the primary immune complex mechanism of damage, especially when the main pathological process is accompanied by genetic polymorphism of regulatory protein genes (CFH, CFI). With monoclonal gammopathy, with

17 17 which usually form immunoglobulin-positive MBGN (which is characterized by the classical pathway of complement activation), a different path of pathogenesis has recently been discovered. It turned out that monoclonal immunoglobulin can act as an antibody to factor H and other regulatory proteins, leading to dysregulation of the alternative complement pathway and to the formation of C3-positive glomerulopathy. The etiology of immunoglobulin- and C3-negative MBGN is the primary lesion of endotheliocytes (thrombotic microangiopathy, malignant hypertension syndrome, etc.), followed by a reparative phase in the form of proliferative changes in the glomerulus, identified by light as MBGN. Electron microscopy in these cases does not reveal electron-dense deposits, and therefore it is not possible to establish the type of MBPGN (Fig. 1, Table 4). Table 4 Causes of immunoglobulin and C3-negative MBPH thrombotic thrombocytopenic purpura atypical HUS associated with disturbances in the complement regulation system antiphospholipid syndrome drug-induced thrombotic microangiopathy nephropathy after bone marrow transplantation radiation nephritis malignant hypertension syndrome α-1-antitrypsin deficiency sickle cell anemia Morphopathogenesis of C3-negative glomerulopathy in most of the diseases listed in Table. 4, is reduced to damage to endotheliocytes in the acute phase, which is manifested by their swelling, mesangiolysis develops, fibrin thrombi are formed in the capillaries of the glomeruli. The acute phase of damage is replaced by a reparative phase, characterized by a response of resident cells of the glomerulus. There is an increase in the mesangial matrix and proliferation of mesangial cells, double-circuit basement membranes of capillaries appear, i.e. a morphological picture of MBPGN is formed.

18 18 In rare cases of a genetic anomaly of α-1-antitrypsin deficiency, a mutant Z protein is synthesized in the liver, which, when it enters the glomeruli with circulating blood, is polymyrized and deposited subendothelially. Z-protein deposits are the cause of the response of the resident cells of the glomerulus, which at the final stage leads to the formation of a morphological picture of MBPHN by light microscopy. The diagnosis can be clarified by immunofluorescence using specific antisera to the Z-protein. Section 5 Treatment of idiopathic MBGN Guideline 5.1. When deciding on the nature of the pathogenetic therapy of idiopathic MBPHN, it is necessary to take into account the leading clinical syndrome and data from a morphological study of kidney biopsy specimens (NG). Recommendation 5.2. Immunosuppressive therapy for idiopathic MBPH is indicated only in cases with nephrotic syndrome, with a slowly progressive but steady decline in kidney function despite ongoing nephroprotective therapy, or with rapidly progressive nephritic syndrome (2D). Recommendation 5.3. The most optimal immunosuppressive therapy regimen for idiopathic MBPHN in nephrotic syndrome or with a slowly progressive decline in kidney function is the use of cyclophosphamide (2-2.5 mg / kg / day) or mycophenolate mofetil (1.5-2 g / day) in combination with prednisolone ( 40 mg / day) according to the alternating scheme. The duration of therapy should be at least 6 months (2D). Recommendation 5.4. In idiopathic MBPHN with rapidly progressive nephritic syndrome, plasmapheresis is indicated (3 liters of plasma per session 3 times a week), pulse therapy with methylprednisolone (0.5-1.0 g / day for 3 days) and then maintenance immunosuppressive therapy according to the scheme (see. rec 5.3) (2D). Commentary There is currently no consensus regarding the management of immunoglobulin-positive idiopathic MBGN. When deciding on the nature of the pathogenetic therapy of idiopathic MBPHN, it is necessary to take into account the clinical variant of the course of the disease (the leading clinical syndrome) and the data of a morphological study of kidney biopsy specimens. If isolated urinary syndrome (UIS) or recurrent macrohematuria syndrome dominates in the clinical picture, then they are limited to renoprotective therapy (ACE inhibitors, AT 1 antagonists, statins, diet) and strive for complete normalization of blood pressure (not higher than 130/80 mm Hg. Art.). If the patient has subnephrotic proteinuria (less than 3.5 g / day) and a decrease in kidney function to the level of CKD 3 4 tbsp. , and in the morphological study

19 19 severe tubulo-interstitial sclerosis is detected, then aspirin (975 mg / day) and dipyridamole (325 mg / day) can be additionally prescribed (there is no evidence base for the effectiveness of such therapy). In cases of nephrotic syndrome and progressive deterioration of kidney function, use a combination of cyclophosphamide (2-2.5 mg / kg per day) or mycophenolate mofetil (1.5-2 g / day) in combination with low doses of prednisolone (40 mg / day) preferably on an alternating schedule for 6 months (KDIGO recommendations). In BPNS with crescents in more than 50% of the glomeruli, plasmapheresis, pulse therapy with methylprednisolone followed by oral cyclophosphamide in combination with prednisolone is recommended (see scheme above). We emphasize that for all clinical options the course of MBPGN, measures for renoprotection are always carried out. Section 6. Treatment of secondary MBPHN Recommendation 6.1. In secondary forms of MBPGN, the main direction in treatment is the therapy of the underlying disease (Tables 3, 4) (1A). Recommendation 6.2. The use of immunosuppression in secondary forms of MBGN is allowed only in cases with rapidly progressive nephritic syndrome (2B). Comment. With immunoglobulin-positive MBPH, first of all, it is necessary to establish or exclude a secondary cause of the disease (Tables 3, 4). In secondary forms of MBPGN, the main condition is the treatment of the underlying disease. This is especially true for infections. With HCV associated MBPGN with CKD 1 and 2 tbsp. regardless of the pathogenesis (non-cryoglobulinemic or cryoglobulinemic variants), the first line of therapy is the use of pegylated interferon alfa and ribavirin in the usual doses, taking into account the virus genotype. With CKD 3, 4 and 5 tbsp. (regardless of dialysis therapy) recommended: pegylated interferon alfa 2a: 135 mcg subcutaneously once a week or interferon alfa 2b: 1 mcg/kg subcutaneously once a week. Recent KDIGO guidelines recommend that ribavirin be used with caution in GFR< 50 мл/мин/1,73 м 2 (табл. 5). При криоглобулинемическом варианте МБПГН, который резистентен к применению антивирусных препаратов или протекает с выраженными признаками криоглобулинемического васкулита (кожа, легкие, гломерулонефрит с полулуниями) препаратом выбора является ритуксимаб (анти-cd-20 моноклональное антитело), применение которого приводит к истощению пула В-

20 20 lymphocytes producing cryoglobulins (375 mg/m 2 once a week for 4 weeks). Table 5. Treatment of hepatitis C infection according to CKD staging (KDIGO) CKD staging Interferon a Ribavirin b 1 and 2 PEGylated IFNα-2a: 180 µg s/c weekly PEGylated IFN-α-2b: 1.5 µg/kg s/c weekly mg/day divided into two doses 3 and 4 PEGylated IFNα-2a: 135 mcg s/c weekly PEGylated IFN-α-2b: 1 mcg/kg s/c weekly -2b: 1 µg/kg s/c weekly * rskf estimated glomerular filtration rate, IFN - interferon; s / c subcutaneously. a Patients with genotypes 1 and 4 should receive IFN therapy for 48 weeks if an early viral/virological response is achieved within 12 weeks (>2 log reduction in viral titer). Genotypes 2 and 3 should receive therapy for 24 weeks b Patients with genotypes 2 and 3 should receive 800 mg/day in stages 1 and 2 of CKD. Infected patients with genotypes 1 and 4 should receive mg/day in stages 1 and 2 of CKD *Since the publication of the KDIGO guidelines on hepatitis C in patients with CKD, the package leaflet has changed and co-administration of ribavirin is now permitted in patients with CKD 3 -5 stages if the side effects are minimal and can be corrected. With clearance (creatinine)<50 мл/мин рекомендуется осторожность, что может потребовать существенного снижения дозы. Информация о модификации дозы изложена в инструкции по применению препарата. Менее эффективной альтернативой в этих случаях является плазмаферез (3 л плазмы 3 раза в неделю, 2-3 недели) в сочетании с пульс-терапией метилпреднизолоном (0,5 1 г/сут 3 дня), преднизолоном (1-1,5 мг/кг в день) и циклофосфамидом (2 мг/кг в день) в течение 2 4 мес. Дозы препаратов следует соотносить со значениями СКФ. При некриоглобулинемическом HCVассоциированном МБПГН от иммуносупрессии следует воздержаться, за исключением случаев с БПНС и наличием полулуний в клубочках. При бактериальных инфекциях (например, при инфекционном эндокардите) иммуносупрессия не рекомендуется (рекомендации KDIGO). При остальных заболеваниях, перечисленных в табл. 3 и являющихся причиной вторичного МБПГН, проводят лечение основной болезни. При иммуноглобулин-негативных вариантах МБПГН лечение назначается также с учетом данных о патогенезе заболевания. При С3-позитивной гломерулопатии, обусловленной мутациями генов регуляторных факторов системы комплемента (H, I) показаны инфузии свежезамороженной донорской плазмы крови (донатор

21 21 native factors). If the cause of C3-positive glomerulopathy is autoantibodies to C3-convertase (C3NeF), regulatory factors H, I, etc., then it is advisable to start treatment with plasmapheresis (in the plasma exchange mode and using a replacement solution in the form of donor plasma and albumin). Further, as a rule, glucocorticoids or rituximab are indicated (block the production of autoantibodies). Recently, there have been works on high efficiency in genetic variants of C3-positive glomerulopathy of eculizumab, which is a monoclonal antibody to the C5 fraction of complement (blocks the formation of MAC). As is known, eculizumab was originally proposed for the treatment of paroxysmal nocturnal hemoglobinuria and atypical HUS. In other pathogenetic variants of C3-negative glomerulopathy, the tactics of therapy depend and are determined by the underlying disease. Section 7. Forecast of MBPGN Recommendation 7.1. When determining the prognosis of MBPHN, clinical, laboratory and morphological factors must be taken into account (Table 6) (2C). Comment It is difficult to accurately determine the prognosis for the development of MBPHN, since in recent years ideas about the pathogenesis of the disease have changed, which makes it impossible to use "historical control". The 10-year renal survival for immunoglobulin-positive MBPH appears to be 50-60% and depends on many factors (Table 6), the main one being the formation of crescents in more than 50% of the glomeruli. With C3 glomerulopathy, the 10-year renal survival is 30-50% (lower with genetic variants). The frequency of recurrent glomerulonephritis in the graft with immunoglobulin-positive MBPH ranges from 18-50% (HLA haplotype B8DR3 is a prognostically unfavorable predictor). Graft survival can be improved by adding cyclophosphamide to immunosuppressive therapy. In BPD, the frequency of recurrent glomerulonephritis ranges from 67 to 100%. If the cause of BPD is a factor H gene mutation, plasmapheresis and fresh frozen plasma infusions are indicated before and after kidney transplantation.

22 22 Tab. 6. Predictors of poor prognosis for renal survival in immunoglobulin-positive MBPH Clinical male gender nephrotic syndrome arterial hypertension gross hematuria no spontaneous or drug-induced clinical remission during the course of the disease Laboratory low level of Hb creatinine increase and/or decrease in GFR at the onset of the disease Morphological diffuse doubling of basal membranes compared with focal segmental crescents in more than 20% of the glomeruli pronounced mesangial proliferation (lobular variant) mesangial deposits and sclerosis pronounced tubulo-interstitial changes References 1. Dobronravov V.A., Dunaeva N.V. Kidney damage and chronic viral hepatitis C// Nephrology; v.12, 4, with Laura Sh., Fremu-Bachi V. Atypical hemolytic-uremic syndrome// Nephrology; v. 16, 2, with Ferry S. Mixed cryoglobulinemia// Nephrology; v.14, 1, with Appel G.B. Membranoproliferative glomerulonephritis - mechanisms and treatment// Contrib Nephrol. 2013; 181: D Agati V.D., Bomback A.S. C3 glomerulopathy: what's in a name? // Kidney Int. 2012; 82: Bomback A.S., Appel G.B. Pathogenesis of the C3 glomerulopathies and reclassification of MPGN// Nat. Rev. Nephrol. 2012; 8: Bomback A.S., Smith R.J., Barile G.R. et al. Eculisumab for dense deposit disease and C3 glomerulonephritis// Clin. J. Am. soc. Nephrol. 2012; 7:

23 23 8. KDIGO Clinical practice guideline for glomerulonephritis// Kidney Int. Suppl. 2012; 2(2): Fervensa F.C., Sethi S., Glassock R.J. Idiopathic membrane proliferative glomerulonephritis: does it exist? // Nephrol Dial Transpant. 2012; 27(12): Fregonese L., Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical conseguence// Orphanet J. Rare Diseases. 2008; 3: Hou J., Markowitz G.S., Bomback A.S. et al. Toward a working definition of C3 glomerulopathy by immunofluorescence // Kidney Int 2013; Sept 25 12. Morales J.M., Kamar N., Rostaing L. Hepatitis C and renal disease: epidemiology, diagnosis, pathogenesis and therapy// Contrib Nephrol. Bazel Karger 2012; 176: Pickering M.C., Cook H.H. Complement and glomerular disease: new insights// Curr Opin. Nephrol Hypertens. 2011; 20: Pickering M.C., D Agati V.D., Nester C.M. et al. C3 glomerulopathy: consensus report// Kidney Int 2013, Oct 30 15. Sethi S., Fervenza F.C. Memranoproliferative glomerulonephritis a new look at an old entity// N. Engl. J. Med. 2012; 366: Servias A., Noel L-H., Roumenina L.T. et al. Acguired and complement genetic abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies// Kidney Int 2012; 82: Smith R.J.H., Harris C.Z., Pickering M.C. Dense Deposit Disease// Mol. Immunol. 2011; 48: Sun Q., Huang X., Jiang S. et al. Picking transplant glomerulopathy out of the CAN: evidence from a clinicopathological evaluation// BMC Nephrology 2012; 13:128

St. Petersburg April 18, 2017 E.V. Zakharova Chapter 2: Basic principles of treatment of glomerular diseases Kidney biopsy A kidney biopsy is absolutely essential for establishing a diagnosis.

Endothelial dysfunction in glomerulonephritis Chapter 2 DAMAGE TO THE STRUCTURE OF THE KIDNEY IN MESANGIAL GLOMERULONEFRITIS Mesangioproliferative GN (MPGN) is the most common morphological form of chronic

Treatment for HCV-associated cryoglobulinemic vasculitis - rituximab or antivirals? Ignatova T.M., Kozlovskaya L.V., Milovanova S.Yu., Chernova O.A. I.M. Sechenov First Moscow State Medical University Clinic

PLASMAPHERESIS IN THE TREATMENT OF INTERSTITIAL LUNG DISEASES V.A. Voinov, M.M. Ilkovich, K.S. acad. I.P. Pavlova

Goodpasture's syndrome, laboratory diagnostic algorithms. Anniversary XX Forum "National days of laboratory medicine in Russia - 2016" Moscow, September 14-16, 2016 Moruga R. A., MD Kazakov S.P. Syndrome

Annotation to the work program of the discipline (module) "PRIMARY KIDNEY DISEASES" 1. Purpose and objectives of studying the discipline (module). The purpose of mastering the module: Mastering the methods of diagnosis and principles of treatment of primary

Autoimmune hepatitis is a progressive hepatocellular inflammation of unknown etiology, characterized by the presence of periportal hepatitis, hypergammaglobulinemia of liver-associated serum autoantibodies

IN Leonchik CRYOGLOBULINEMIA AS AN EXTRAHEPATIC MANIFESTATION OF CHRONIC VIRAL HEPATITIS C Supervisor Cand. honey. Sciences, Assoc. S. P. Lukashik Department of Infectious Diseases, Belarusian State

Experience of anti-β-cell therapy of membranous nephropathy Biryukova L.S., Stolyarevich E.S., Artyukhina L.Yu., Frolova N.F., Tomilina N.A. Department of Nephrology, FDPO MGMSU named after A.I. A.I. Evdokimova St. Petersburg, 2016 Membranous

Laboratory diagnosis of rheumatological and systemic diseases With the approach of spring, rheumatological diseases become aggravated in many people. Approximately 12.5 patients visit doctors about this every year.

MOSCOW CITY HEALTH DEPARTMENT Clinical Algorithm for Diagnosis and Treatment of CKD Materials for Training Primary Care Physicians 20160919_CKD Clinical Algorithm v2.indd 1 16.11.16 12:47 Proposed

GLOMERULONEPHRITIS Definition. Genetically determined immune-mediated kidney diseases with a primary lesion of the glomerular apparatus and subsequent involvement of all structures in the pathological process

KIDNEY DISEASES (PART 1). PRIMARY GLOMERULOPATHY (ACUTE POST-INFECTIOUS GLOMERULONEPHRITIS, RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS, MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS, MEZANGIOPROLIFERATIVE GLOMERULONEFRITIS,

RUSSCO Working Group Project on Maintenance Therapy: Individualization of maintenance therapy (correction of anemia, neutropenia and administration of osteomodifying agents) PRACTICAL RECOMMENDATIONS FOR TREATMENT

Page 1 of 4 Exam questions in the specialty R009 "Nephrology, including children's" 1. The structure of the renal tissue is normal. Structural and functional unit of the kidney. Development and malformations

A.V. Smirnov, V.A. Dobronravov, A.Sh. Rumyantsev, I.G. Kayukov ACUTE KIDNEY INJURY Medical Information Agency Moscow 2015 UDC 616.61-036.11 BBC 56.9 C50 C50 Smirnov A.V. Acute kidney injury

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS I APPROVE First Deputy Minister D.L. Pinevich 22.03.2013 Registration 233-1212 ALGORITHM FOR DETECTION AND MANAGEMENT OF PATIENTS WITH CHRONIC KIDNEY DISEASE

Presentation of Wegener's granulomatosis >>> Presentation of Wegener's granulomatosis Presentation of Wegener's granulomatosis Unilateral appearance of shadows of small nodules can often be misinterpreted as lung cancer.

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS I APPROVE First Deputy Minister D.L. Pinevich 16.02.2012 Registration 133-1211 METHOD OF TREATMENT OF IMMUNITY RECOVERY INFLAMMATORY SYNDROME

Lupus nephritis Lupus nephritis (LN) is kidney damage in systemic lupus erythematosus (SLE). VN - the most severe visceritis in SLE, often determining the prognosis of the disease, occurs in 50-70% of patients,

Https://doi.org/10.17116/terarkh201789669-77 Team of authors, 2017 Changes in the complement system in membranoproliferative glomerulonephritis V.A. Yurova 1, L.A. BOBROV 1, N.L. KOZLOVSKAYA 1, Yu.V. KOROTCHAYEVA

Analysis of the statistical reporting form 61 “Information on the population of patients with HIV infection” in the Volga Federal District for 2014 Based on the data of the annual statistical form 61 “Information on the population of patients with HIV infection”

Anemic syndrome in hemoblastoses А.V. Kolganov 2006 Anemic syndrome in hemoblastoses. Anemic syndrome in hemoblastoses is a natural phenomenon and a manifestation of the underlying disease.

CLINICAL AND MORPHOLOGICAL FEATURES OF MULTIPLE MYELOMA (STUDY OF MYELOFIBROSIS) IN THE DEBUT AND RECURRENCE OF THE DISEASE State Budgetary Institution of Healthcare "Novosibirsk Regional Clinical Hospital", Research Institute of Regional

1.2.4. Immunophenotypic diagnosis of chronic lymphoproliferative diseases. Chronic lymphoproliferative diseases (CLPD) unite a whole group of biologically different tumors, the possibility

Lupus nephritis. Modern classification and approaches to the treatment of S.N. Mammaev Department hospital therapy 1 State Budgetary Educational Institution of Higher Professional Education "Dagestan State Medical Academy of the Ministry of Health of the Russian Federation" MAKHACHKALA 2014 System

1. The purpose of studying the discipline is: The purpose of studying the discipline "Diseases associated with disorders in the immune system in the practice of an outpatient doctor" is to study general patterns

Individual choice of drug for the treatment of hypertension in patients with kidney disease Davydova Irina Vladimirovna Associate Professor of the Department of Cardiology NMAPE named after P.L.Shupyk Relationship between arterial hypertension and pathology

Payment rates medical care in day hospitals by clinical and statistical groups Appendix 8 to the Additional Tariff Agreement dated November 27, 2018. Appendix 6 to the Tariff Agreement dated 01/09/2018

Appendix 7 to the Supplementary Tariff Agreement dated May 24, 2018 to the Tariff agreement dated 09.01.2018 71 Tariffs for payment for medical care in day hospitals by clinical and statistical groups n

FGBOU VO RNIMU them. N.I. Pirogov Department of Faculty Therapy named after. A.I. Nesterova Department: Doctor of Medical Sciences, Professor Shostak N.A. "A rare case of nonspecific aortoarteritis Takayasu, debuting with glomerulonephritis"

TREATMENT OF CHRONIC VIRAL HEPATITIS B Based on the latest guidelines from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD),

Diagnosis of HHC Denis Godlevsky Baku, December 2014 Types of diagnostics Laboratory Express diagnostics Topics Antibodies / Non-structural proteins Polymerase chain reaction (PCR) Genotyping Fibroscanning

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS I APPROVE First Deputy Minister R.A. Chasnoit April 10, 2009 Registration 195-1208 ALGORITHM FOR THE DIAGNOSIS AND TREATMENT OF CHRONIC VIRAL HEPATITIS

FEATURES OF THE COURSE OF ANEMIC SYNDROME AND EFFECTIVENESS OF TREATMENT OF PATIENTS WITH CHRONIC RENAL INSUFFICIENCY Speaker: student of group 09ll2 Ziboreva Kristina Andreevna Leaders: Doctor of Medical Sciences, Professor

Tariffs for payment for medical care in day hospitals by clinical and statistical groups Appendix 6 1.1 nb 1.2 1.3 1.4 1 Complications of pregnancy, childbirth, postpartum period 0.83 1.0 4,990.1 7,485.1

Https://www.printo.it/pediatric-rheumatology/en/intro NLRP-12 Relapsing Fever 2016 Version 1. WHAT IS NALP-12 Relapsing Fever 1.1 What is it? relapsing fever,

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS I APPROVE First Deputy Minister D.L. Pinevich November 25, 2016 Registration 101-1116 METHOD OF IMMUNOSUPPRESSION INDUCTION USING ALLOGENIC MESENCHIMAL

Https://www.printo.it/pediatric-rheumatology/en/intro What is Blue's Disease/Juvenile Sarcoidosis Version 2016 1. WHAT IS BLOW'S DISEASE/JUVENILE SARCOIDOSIS 1.1 What is it? Blau's syndrome is genetic

Pathogenesis of changes in the immune status in CKD or à la guerre comme à la guerre Shurygina Anna-Polina December 2016 Main combat units Adapted by A.K. Abbas Cellular and Molecular Immunology

Tariffs for payment for medical care in day hospitals by clinical and statistical groups Appendix 8 to the Additional Tariff Agreement of 07/20/2018. Appendix 6 to the Tariff Agreement dated 09.0018

Northwestern State Medical University. I.I. Mechnikov, First St. Petersburg State Medical University. I.P. Pavlova Systemic lupus erythematosus with antiphospholipid

Appendix 6 to the Tariff Agreement dated 09.01.2018 116 Tariffs for payment for medical care in day hospitals by clinical and statistical groups Coefficients Coefficient Cost of a case of treatment, rub.

Management of Thrombotic Microangiopathic Hemolytic Anemias with Therapeutic Plasma Exchange When It Works and When It Does Not

MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION State budgetary educational institution of higher vocational education“Saratov State Medical University named after V.I.

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS N.F. Soroka, K.A. Chizh ASSESSMENT OF RISK FACTORS FOR THE COURSE OF LUPUUS NEPHRITE AND A WAY TO SLOW DOWN ITS PROGRESSION Instructions for use Minsk 2011 1

Chronic kidney disease Professor Khamitov R.F. Head of the Department of Internal Medicine 2 KSMU Algorithm for diagnosing CKD 2 Glomerular filtration rate (GFR) Creatinine clearance (CC) is an indicator that allows

Appendix 35 to the Tariff Agreement Tariffs for payment for medical care provided in a day hospital for a completed case of treatment of a disease included in the relevant clinical and statistical

The American Society of Nephrology (ASN) AKI Advisory Group published a meta-analysis of the estimated incidence of AKI in the world. The analysis included 154 studies (n = 3 855 911), it was shown that

Tariffs for payment for medical care in a day hospital in accordance with the level of medical care

For intermediate certification 1 semester 1. Nomenclature and classification rheumatic diseases. 2. The role of infectious factors in development chronic inflammation. 3. Basic therapy for rheumatoid arthritis:

New diagnostic criteria and treatment of autoimmune hepatitis and its variant forms D.T. Abdurakhmanov Department of Internal, Occupational Diseases and Pulmonology First Moscow State Medical University. THEM. Sechenova Incidence of AIH Source:

Acute glomerulonephritis in children Angela Ciuntu, Departamentul Pediatrie USMF Nicolae Testemiț anu

SBEI HPE "YUUGMU" MINISTRY OF HEALTH OF RUSSIA CHRONIC GLOMERULONEPHRITIS AND PREGNANCY Ilyicheva O.Ye. Definition Glomerulonephritis is a group concept that includes diseases of the glomeruli of the kidneys with an immune mechanism of damage,

MINISTRY OF HEALTH OF THE REPUBLIC OF BELARUS N.F. Soroka, A.K. Tushina, K.A. Chizh PREDICTION OF THE PROBABILITY OF DEVELOPMENT OF SECONDARY RENAL AMYLOIDOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS Instructions for use

Rice. 23. T-cell affiliation of the bulk of pathological lymphocytes. CD3/CD19 histograms show events gated as lymphocytes. Pronounced predominance of T-lymphocytes in case of suspicion

O.S. Levin POLYNEUROPATHY Clinical guidelines 3rd edition, revised and supplemented Medical News Agency 2016 UDC 618.833 LBC 56.1 L36 L36 Levin O.S. Polyneuropathies: A clinical guide

Federal State Budgetary Educational Institution of Higher Education "Smolensk State Medical University" of the Ministry of Health Russian Federation(FGBOU VO SSMU

Ministry of Health of the Republic of Mordovia GAOUDPO of the Republic of Mordovia "Mordovia Republican Center for Advanced Training of Healthcare Professionals" Prevention and diagnosis of HIV infection

Annex 0 to the Tariff agreement in the field of compulsory medical insurance of the Volgograd region for 208 List of clinical and statistical groups of diseases in a day hospital with an indication of relative and managerial coefficients

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 are quite common. Primary glomerulonephritis is predominantly recorded in children under 15 years of age and adults under 30 years of age. Chronic form characteristic of 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 of the latest 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.

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 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:

AH - 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 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), 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 (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 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. 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, mumps, 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 opportunity 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 swelling of the eyelids / lower extremities appears or increases, diuresis decreases, urine darkens, blood pressure increases, 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 of the disease 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 discover clinical symptoms 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 diseases connective tissue: 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 be established only 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 GFR below 70 ml/min, uncontrolled hypertension, or severe vascular and tubulointerstitial changes in 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 suspicion of GN are indications for hospitalization C. Indications for hospitalization are also the need to clarify the diagnosis (with relatively rapid decline kidney function, isolated 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.

Non-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.

Medical science does not stand still, constantly updated with new methods in the diagnosis of various diseases, methods of their treatment. On the basis of the latest scientific and practical developments in each country, including ours, recommendations to practitioners for many diseases are updated annually. Consider, on the basis of a diagnostically and therapeutically difficult renal disease of glomerulonephritis, clinical guidelines that were published in 2016.

Introduction

These recommendations, summarizing the 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 kind of standard in the provision of medical care, given the various diagnostic capabilities of clinics, the availability of certain medicines and individual characteristics of each patient. Responsibility for the appropriateness of the recommendations below lies with the attending physician on an individual basis.

Feature of the disease

Acute glomerulonephritis, which occurs after a streptococcal infection, manifests itself morphologically as a diffuse inflammation of the renal medulla with a predominance of proliferation of the intervascular tissue of the renal parenchyma. This form of the disease is predominantly found in childhood in the period from 4 to 15 years (about 70% of registered cases). Also, pathology is typical for adults under 30 years of age, but with a lower frequency of occurrence for a certain number of the population of this age group.

Causes and mechanism of pathological changes

The main cause of inflammatory processes in the renal medulla is an autoimmune attack by immune complexes based on immunoglobulins (antibodies) produced in response to a 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, while 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 the tissue taken for a biopsy of the medullary layer of the kidneys reveals proliferative inflammation with the deposition of immune complexes, the accumulation of neutrophilic leukocytes in the intercapillary cells and in the endothelium of the glomerular vessels. They are deposited in the form of confluent granules forming conglomerates. Damaged cells are filled with fibrin and other connective tissue substances. Cell membranes of glomerular and endothelial cells are thinned.

Clinical manifestations

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

• Decreased amount of urine produced associated with a violation of glomerular filtration, a delay in the body of fluid and sodium ions.
• Edema localized on the face and in the area of ​​the ankles of the lower extremities, which also becomes the result of insufficient excretion of fluid from the body by the kidneys. Often, the renal parenchyma also swells, which is determined by instrumental diagnostic methods.
• Increasing BP numbers observed in about half of patients, which is associated with an increase in blood volume, an increase in the resistance of the peripheral vascular bed, an increase in cardiac (left ventricular) ejection. Various degrees of hypertension are observed from slight increases in blood pressure to high numbers, in which complications are possible in the form of hypertensive-type encephalopathy and congestive-type heart failure. These conditions require urgent medical attention.
• Hematuria of varying degrees severity accompanies almost all cases of the disease. Approximately 40% of patients have gross hematuria, in the remaining cases - microhematuria, determined by the laboratory. Approximately 70% of erythrocytes are determined with 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 found.
• Leukocyturia is present in approximately 50% of patients. The sediment is dominated by neutrophilic leukocytes and a small number of lymphocytes.
• Proteinuria in this type of glomerulonephritis is rarely detected, mainly in adult patients. The content of protein in the urine, which is characteristic in terms of the number of nephrotic syndrome in children, is practically not found.
• Violation of the functional activity of the kidneys(increased serum creatinine titer) is detected in a quarter of patients. Very rarely, cases of rapid development of a severe form of renal failure with the need for hemodialysis are recorded.

Important! Due to the wide variety of clinical manifestations, including in children, the disease requires careful diagnosis, where modern laboratory and instrumental methods are in the first place 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 transferred a few weeks ago with confirmation of hemolytic streptococcus as the causative agent. Further, the necessary laboratory tests of urine are carried out to detect changes characteristic of the disease. Blood is also examined, while an increase in the titer of antibodies to streptococcus has a diagnostic value.

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

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

With a confirmed fact of a streptococcal infection, shortly before the appearance of a clinic of acute glomerulonephritis, typical clinical and laboratory symptoms the correctness of the diagnosis is not in doubt. But with long-lasting hypertension, hematuria, the absence of positive therapeutic dynamics or undocumented streptococcal infection, it is necessary to differentiate the pathology from other forms of damage to the medulla of the kidneys, 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 (sanation of the focus of streptococcal infection), pathogenetic (inhibition immune reactions and proliferation of renal cells) and symptomatic treatment.

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

Hormonal drugs (glucocorticosteroids) and cytostatics (antineoplastic pharmacological agents) are used to relieve autoimmune inflammation and prevent the growth of kidney tissues. 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 completely abandoned.

Antihypertensive drugs are prescribed to relieve symptoms ( ACE inhibitors), diuretics with significant edema. Diuretics are prescribed only according to indications, among which are the following conditions:

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

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

• uncontrolled arterial hypertension;
• advanced age of the patient;
• rapid development of renal insufficiency;
• long-term (more than 3 months) proteinuria.