Membranous proliferative glomerulonephritis. Chronic glomerulonephritis with isolated urinary syndrome

Chronic glomerulonephritis is a chronic immune inflammatory disease kidneys with long-term persistent or recurrent urinary syndrome(proteinuria and/or hematuria) and gradual deterioration of renal function. Chronic glomerulonephritis is one of the main causes of chronic renal failure requiring program hemodialysis or kidney transplantation.

CLASSIFICATION

The classification of chronic glomerulonephritis has recently undergone significant transformation. If previously the classification was based on the clinical picture of the disease, now throughout the world chronic glomerulonephritis is classified according to pathomorphological changes detected during histological examination of a kidney biopsy. To make a diagnosis according to pathomorphological criteria, a puncture biopsy of the kidney is necessary, which, however, is not always possible. In this regard, both classifications are still used, although preference is given to the pathomorphological one.

CLINICAL CLASSIFICATION

In our country, the clinical classification of chronic glomerulonephritis E.M. is used. Tareeva (1958, 1972, table 33-1).

Table 33-1. Clinical classification of chronic glomerulonephritis

MORPHOLOGICAL CLASSIFICATION

Based on pathomorphological characteristics, the following forms of chronic glomerulonephritis* are distinguished (based on the classification of V.V. Serov et al., 1978, 1983, as well as later additions).

* It is believed that any of these pathos morphological forms can occur in both acute and chronic version. Acute glomerulonephritis is most often represented by a diffuse proliferative variant, rapidly progressive glomerulonephritis - glomerulonephritis with “crescents”. All other options are more typical for chronic glomerulonephritis, which is why we present the pathomorphological classification in the chapter devoted to chronic glomerulonephritis.

Diffuse proliferative (discussed in Chapter 30 “Acute glomerulonephritis”).

With "crescents" (discussed in Chapter 31, "Rapidly Progressive Glomerulonephritis").

Mesangioproliferative.

Membrane-proliferative (mesangiocapillary).

Membranous with minimal changes.

Fibrillar-immunotactoid.

Fibroplastic.

For more information about each form of glomerulonephritis, see below in the section “Pathomorphology and pathogenesis of individual forms.”

EPIDEMIOLOGY

It is noted in 5-10% of cases of idiopathic nephrotic syndrome in adults. Berger's disease is a hematuric variant with IgA deposits; predominantly develops in young men; one of the most common glomerulopathies.

Occurs equally often in men and women. Membranoproliferative glomerulonephritis accounts for 15% of cases of idiopathic nephrotic syndrome in children and 30% of cases of this syndrome in adults.

Membranous glomerulonephritis is usually noted at the age of 30-50 years, twice as often in men. It is found in 30-40% of cases of nephrotic syndrome in adults and in 5% of cases of nephrotic syndrome in children.

The peak frequency occurs at the age of 6-8 years. This morphological form causes nephrotic syndrome in children in 80% of cases.

Focal segmental glomerulosclerosis is the cause of 10-15% of cases of nephrotic syndrome in children and 15-25% of cases in adults.

Less than 1% of all cases of glomerulonephritis in adults.

ETIOLOGY

The etiology of chronic glomerulonephritis is presented in table. 33-2.

Table 33-2. Etiology of chronic glomerulonephritis

PATHOGENESIS

The development and maintenance of immune inflammation involves the same mechanisms as in acute glomerulonephritis. After the initiating damaging factors are triggered, the cells of the inflammatory infiltrate and the glomerular cells release various mediators. Complement is activated, the cytokines TNF-α, IL-1 and IL-6, γ-IF), growth factors (platelet and transforming growth factors-β), somatomedins, chemokines are produced, proteolytic enzymes and oxygen radicals are released, the coagulation cascade is activated, pro-inflammatory prostaglandins.

Proliferation and activation of mesangial cells play key role in the processes of accumulation and changes in the structure of the extracellular matrix, which end in sclerosis of the glomerulus.

However, non-immune factors are also important for the further progression of glomerulonephritis.

Changes in hemodynamics (intraglomerular hypertension and hyperfiltration) occupy a leading place among the non-immune mechanisms of progression of chronic glomerulonephritis. An increase in intraglomerular pressure is promoted by systemic hypertension, adaptive hypertrophy and hyperfunction of surviving nephrons, a concomitant decrease in arteriolar tone (more afferent than efferent) with the creation of a transcapillary pressure gradient. Against the background of high intraglomerular pressure, the permeability of the glomerular filter increases, which is accompanied by the deposition of various blood plasma macromolecules in the nephron tissues. Under the influence of intraglomerular hypertension, the renin-angiotensin-aldosterone system is activated. It has been established that angiotensin II promotes the synthesis of transforming growth factor-β, and the latter, in turn, stimulates the production of extracellular matrix. On the other hand, angiotensin II directly or through the production of transforming growth factor-β stimulates the expression of plasminogen activator inhibitor, which leads to a decrease in local renal production of plasmin, which suppresses the formation of extracellular matrix components. This is one of the important mechanisms for the development of glomerulosclerosis and tubulointerstitial fibrosis.

A direct correlation has been noted between the progression of chronic glomerulonephritis and the presence of tubulointerstitial changes. In their development, great importance is attached to proteinuria, primarily with the release of albumin and transferrin. Proteins subjected to excessive filtration cause activation and release of vasoactive and inflammatory factors by tubular epithelial cells, among which chemokines, MCP-1, are of great importance ( M onocyte C hemoattractant P rotein-1 - monocyte chemotactic protein-1), RANTES ( R egulated upon A ctivation N ormal T-cell E expressed and S ecreted - a factor that regulates the activation of normal T-cell expression and secretion) and endothelin. These factors cause an inflammatory interstitial reaction, pronounced accumulation of fibroblasts and increased production of extracellular matrix, leading to an increase in tubulointerstitial fibrosis. Establishing the role of proteinuria in the development of tubulointerstitial fibrosis, which forms the pathomorphological basis renal failure, played an important role in the development of nephroprotective strategies (see below).

Hyperlipidemia accompanying nephrotic syndrome contributes to the development of glomerulosclerosis. Lipid peroxidation products have a toxic effect on nephron cells, cause mesangial proliferation, and stimulate collagen synthesis.

Intercurrent recurrent urinary tract infections may play a decisive role in the deterioration of renal function.

Recently, much attention has been paid to the role of obesity in the pathogenesis of chronic renal failure. Obesity is considered not only as an unfavorable “non-immune” factor in the progression of renal disease, but also as an independent etiological factor kidney damage. On early stages Obesity develops a state of relative oligonephronia (deficiency of nephron mass in relation to increased body weight), which leads to an increased filtration load of the glomeruli (hyperfiltration). Hyperfiltration is initiated and maintained by metabolites and hormones of the adipose tissue itself, primarily leptin, through the activation of intrarenal hormones (aniotensin II, endothelin) and the expression of transforming growth factor-β receptors on nephrocyte membranes with the development of glomerulo- and tubulointerstitial fibrosis.

PATHOMORPHOLOGY AND PATHOGENESIS OF SEPARATE FORMS

Pathological examination of a renal biopsy is of great importance for diagnosis, treatment and prognosis.

MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS

Mesangioproliferative glomerulonephritis is characterized by expansion of the mesangium due to the proliferation of mesangial cells and infiltration of monocytes. For the activation and proliferation of mesangial cells, platelet-derived growth factor and transforming growth factor-β are most important.

IgA nephropathy is a form of mesangioproliferative glomerulonephritis with deposition of immune complexes containing IgA in the mesangium. In the development of IgA nephropathy, dysregulation of the synthesis or structure of IgA is important - the glycosylated isotype IgA 1 is found in glomerular deposits. It is believed that abnormal glycosylation of IgA helps immune complexes containing IgA avoid elimination by cells of the reticuloendothelial system and promotes their deposition in the glomeruli of the kidneys.

MEMBRANO-PROLIFERATIVE (MESANGIOCAPILLARY) GLOMERULONEPHRITIS

The main signs are proliferation of mesangial cells and expansion of the volume of the mesangial matrix with a diffuse increase in vascular loops, creating a picture of lobulation of the glomerulus, as well as thickening of the basement membrane. Proliferation of mesangial cells is caused by the influence of growth factors: epidermal growth factor, platelet-derived growth factor; thrombospondin. The combination of damage to the glomerular membrane and mesangial proliferation causes the development of signs of nephrotic and nephritic syndromes. Ultrastructural examination distinguishes two main types of mesangiocapillary nephritis: type 1 (with a subendothelial location of immune complexes) and type 2 ("dense deposit disease") with the detection of dense deposits within the glomerular basement membrane. Approximately 30% of cases of mesangiocapillary nephritis type 1 are associated with infection with the hepatitis C virus.

MEMBRANOSAL GLOMERULONEPHRITIS

Membranous glomerulonephritis is characterized by diffuse thickening of the glomerular basement membrane with the formation of subepithelial projections surrounding immune complex deposits. Immune deposits deposited under epithelial cells (podocytes) significantly impair their functions, which is manifested by massive proteinuria. Gradually, the basement membrane grows, bifurcates and “absorbs” immune deposits, forming so-called “spines”. Sclerotic processes develop, involving the collecting ducts and interstitium. The most likely reason for the development of this variant of glomerulonephritis is considered to be “molecular mimicry” and loss of tolerance to autoantigens. Circulating complement-fixing Abs combine with Ag on podocyte processes to form in situ immune complexes. Activation of complement leads to the formation of a membrane attack complex (C5b-C9) with damage to podocytes.

GLOMERULONEPHRITIS WITH MINIMAL CHANGES

Glomerulonephritis with minimal changes - with light microscopy and immunofluorescence studies, no pathological changes are detected, however, with electron microscopy, fusion (smoothing) of the small podocyte legs along the entire length of the glomerular capillaries is found, which causes the loss of the negative charge of the glomerular basement membrane and, usually, the “large” proteinuria. No immune deposits are detected. Damage to the glomeruli is associated with circulating permeability factors - lymphokines, due to an impaired T-cell response. In some patients, transformation into focal segmental glomerulosclerosis is observed.

FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Individual glomeruli are involved in the process (focal changes), and sclerosis of individual segments occurs in them (segmental changes); the remaining glomeruli are intact. In the pathogenesis of focal segmental glomerulosclerosis, importance is attached to humoral factors permeability, as well as molecular mechanisms. In familial forms of focal segmental glomerulosclerosis, mutations in the genes of several podocyte proteins (podocin, α-actin, nephrin) have been identified, with impaired expression and function of which are associated with a defect in the barrier properties of glomerular capillaries and the development of proteinuria in these and some sporadic forms of focal segmental glomerulosclerosis. Sclerosis is accelerated by hyperfiltration and increased intraglomerular pressure, which contribute to excessive accumulation of extracellular matrix. Transforming growth factor-β, angiotensin II, reactive oxygen radicals, endothelins, and cyclin-dependent kinase inhibitors p21 and p27 are considered modulators of this process. A frequent sign, in most cases preceding focal segmental glomerulosclerosis, is single “tender” synechiae of the capillaries with the glomerular capsule. Subsequently, hyaline material appears in individual glomerular capillaries in the form of single or multiple spherical deposits, usually associated with the glomerular capsule. Foci of collapse and atrophy of the tubules in combination with stromal sclerosis are pathognomonic. The difficulty of morphological diagnosis of focal segmental glomerulosclerosis as an independent form is that the development various types glomerulonephritis may result in similar changes. It is important to assess the dynamics of morphological changes. Immune deposits are usually not detected; in some cases, segmental IgM fluorescence is noted.

There is a so-called collapsing nephropathy, characterized by significant damage to podocytes and pronounced collapse of glomerular capillary loops in the affected segments. The collapsing form of focal segmental glomerulosclerosis is the most common type of kidney damage in HIV-infected people (marker - detection of the HIV genome in podocytes and tubular cells using PCR) and heroin users.

FIBRILLARY IMMUNOTACTOID GLOMERULONEPHRITIS

On light microscopy, changes range from mesangial expansion and basement membrane thickening to proliferative glomerulonephritis and extracapillary crescents. Typical changes are detected by electron microscopy - extracellular amyloid-like fibrillar inclusions in the mesangium or capillary wall; They are distinguished from amyloid by their larger diameter; in addition, they are not stained with Congo red.

Fibroplastic glomerulonephritis is characterized by a significant severity of fibrotic processes: adhesions (synechias) of the vascular lobules with the capsule are formed, the capillary loops of the glomerulus are sclerosed. Sclerosis of the glomerular capillaries is caused by the progressive accumulation in the mesangium and beyond the extracellular matrix synthesized by mesangial cells under the influence of transforming growth factor-β. When the integrity of the capillary walls is violated, plasma components penetrate into the extracapillary space, and the resulting fibrin provokes the development of sclerotic changes. In general, fibroplastic changes are the final link in the “damage-inflammation-fibrosis” chain.

CLINICAL PICTURE

The clinical picture of chronic glomerulonephritis varies significantly depending on the clinical and morphological variant.

CLINICAL PICTURE DEPENDING ON CLINICAL VARIANT

CHRONIC GLOMERULONEPHRITIS WITH ISOLATED URINARY SYNDROME (LATENT FORM)

This form accounts for up to 50% of all cases of chronic glomerulonephritis. The disease proceeds unnoticed by the patient (edema and hypertension are absent). The examination reveals proteinuria (no more than 1-2 g/day), microhematuria, leukocyturia, cylindruria (hyaline and erythrocyte casts). The relative density of urine is not changed. A primary latent and secondary latent course is possible (with partial remission of another clinical form of chronic glomerulonephritis). In turn, latent chronic glomerulonephritis can transform into nephrotic or hypertensive forms. The development of chronic renal failure against the background of a latent form occurs slowly (over 10-15 or more years).

HEMATURIC FORM

Changes in urine - microhematuria and usually mild proteinuria (less than 1.5 g/day). There are no extrarenal symptoms (edema, hypertension). CRF develops slowly.

HYPERTENSIVE FORM

The course is long, it takes 20-30 years before the development of chronic renal failure. The clinical picture is dominated by symptoms of increased blood pressure (headaches; visual disturbances - a veil, flashing “spots” before the eyes; characteristic changes in the fundus; pain in the precordial region; signs of left ventricular hypertrophy). At first, hypertension is intermittent in nature and is well tolerated by patients. Urinary syndrome is minimally expressed - slight proteinuria, sometimes microhematuria, cylindruria. Unlike hypertension, these changes in urine in chronic glomerulonephritis are observed from the very beginning of the disease. AH gradually becomes stable and resistant to drug therapy, and in the terminal period it often becomes malignant. Against the background of a significant increase in blood pressure, acute left ventricular failure may develop.

NEPHROTICA FORM

This form is characterized by the development of nephrotic syndrome - daily proteinuria above 3.5 g/day (more precisely, more than 3.5 g/1.75 m2 in 24 hours), hypoalbuminemia, hyperlipidemia followed by lipiduria, hypercoagulation, edema. The key symptom is massive (“large”) proteinuria associated with damage to the renal filter, i.e. basement membrane and podocytes. The remaining manifestations of nephrotic syndrome are derived from proteinuria and can be expressed to varying degrees.

So, the higher the level of proteinuria, the lower the albumin content in the blood. The consequence of hypoalbuminemia is a decrease in plasma oncotic pressure, which leads to the appearance of edema. A decrease in intravascular fluid volume leads to activation of the renin-angiotensin-aldosterone system, as well as an increase in tone sympathetic division vegetative nervous system. Antidiuretic hormone is released and the synthesis of atrial natriuretic factor is inhibited. The combination of neurohumoral mechanisms leads to the retention of salts and water in the body.

Excretion of transferrin in urine explains the microcytic hypochromic anemia associated with nephrotic syndrome.

Loss of cholecalciferol-binding protein in urine leads to vitamin D deficiency and, as a consequence, to hypocalcemia and secondary hyperparathyroidism.

Urinary excretion of thyroxine-binding protein is accompanied by a decrease in the concentration of thyroxine in the blood.

Hypoalbuminemia significantly changes the pharmacokinetics of drugs transported in the blood in a protein-bound state, which significantly increases the risk of side and toxic effects of drugs in conditions of nephrotic syndrome.

Hyperlipidemia may result from urinary loss of a protein that regulates lipid homeostasis; in addition, with a decrease in plasma oncotic pressure, the synthesis of lipid substances by the liver increases. In most patients, the concentration of triglycerides, total cholesterol, LDL, and in severe nephrotic syndrome - VLDL increases. Changes in lipid metabolism can contribute to atherosclerotic changes in blood vessels (the development of myocardial infarction has been noted in patients with long-term nephrotic syndrome) and non-immune progression of glomerulopathy.

The tendency to hypercoagulation is associated with the excretion of antithrombin III in the urine, changes in the concentrations of proteins C and S, and hyperfibrinogenemia due to increased synthesis fibrinogen by the liver in combination with a weakening of fibrinolysis processes. In addition, in conditions of nephrotic syndrome, platelet hyperaggregation is observed.

The tendency to hypercoagulation in nephrotic syndrome determines an increased risk of renal vein thrombosis and pulmonary embolism. The likelihood of renal vein thrombosis is highest in conditions of nephrotic syndrome with membranous and membrano-proliferative glomerulonephritis, as well as with amyloidosis. Thrombosis of the renal veins (as a complication of nephrotic syndrome) can be acute (abdominal pain, gross hematuria, left-sided hydrocele of the testicular membranes develops, and GFR decreases) or chronic (the course is asymptomatic, often presenting difficulties for diagnosis).

In addition to a large amount of protein, red blood cells, leukocytes (mainly lymphocytes) and casts can be found in the urine in small quantities. An increase in ESR and anemia are also characteristic.

MIXED FORM

This form involves a combination of nephrotic syndrome and hypertension. It is usually noted in secondary chronic glomerulonephritis (for example, in SLE, systemic vasculitis). It has an unfavorable prognosis: chronic renal failure develops over 2-3 years.

TERMINAL GLOMERULONEPHRITIS

This form is considered as the final stage of any glomerulonephritis (the identification of this form is not recognized by all authors). The clinical picture corresponds to chronic renal failure and eliminates the differences between the forms of chronic glomerulonephritis that led to its development. Recently, the term " chronic illness kidney" (CKD - C chronic K idney D isease) for all forms of kidney damage, indicating the stage of chronic renal failure, which is justified by solving general tactical problems: renal replacement therapy and kidney transplantation.

CLINICAL PICTURE DEPENDING ON MORPHOLOGICAL FORM

MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS

Mesangioproliferative glomerulonephritis manifests itself as isolated urinary syndrome, acute nephritic or nephrotic syndromes.

IgA nephropathy (Berger's disease) is the most common clinical variant (50-60% of all cases), observed mainly in people under 25 years of age with a predominance in men. Characteristic episodes of gross hematuria with pain in lumbar region associated with nasopharyngeal or gastrointestinal infections. Unlike acute post-infectious glomerulonephritis, the time of onset of renal symptoms coincides with the impact of provoking factors. Proteinuria is insignificant, so there is no edema or it is mild. Blood pressure is within normal limits. In approximately 30% of cases (usually in people over 25 years of age, regardless of gender), persistent microhematuria with concomitant proteinuria is noted to varying degrees expressiveness. In 10% of patients, acute nephritic or nephrotic syndromes may develop.

In most cases, the course is benign, but in 20-40% of patients progression to the final stage of chronic renal failure is noted in a period of 5 to 25 years.

MEMBRANO-PROLIFERATIVE (MESANGIOCAPILLARY) GLOMERULONEPHRITIS

Membrane-proliferative glomerulonephritis (mesangiocapillary) often begins with acute nephritic syndrome (like acute glomerulonephritis); approximately 50% of patients develop nephrotic syndrome. Isolated urinary syndrome with hematuria is possible. Severe hypertension, hypocomplementemia and anemia are characteristic; cryoglobulinemia is possible, especially in patients chronic hepatitis C. The course is steadily progressive, and a rapidly progressive variant is also observed.

MEMBRANOSAL GLOMERULONEPHRITIS

In 80% of cases it manifests itself as nephrotic syndrome and is more often than with other variants complicated by the development venous thrombosis, including renal vein thrombosis.

GLOMERULONEPHRITIS WITH MINIMAL CHANGES

In the foreground of the clinical picture is nephrotic syndrome. Hypertension and renal failure occur rarely, and the process tends to resolve spontaneously. Proteinuria is massive, mainly due to albumin, but IgG and α 2 -macroglobulin are detected in small quantities. Gradually, the selectivity of proteinuria disappears, and it becomes non-selective. Microhematuria is noted in 20-30% of cases.

FOCAL SEGMENTAL GLOMERULOSCLEROSIS

In almost 70% of cases, persistent nephrotic syndrome is observed. Erythrocytes and leukocytes are found in the urinary sediment. AG is an important component clinical picture. The development of chronic renal failure is natural; in 20% of patients, renal failure is noted at the onset of the disease. The collapsing form of focal segmental glomerulosclerosis associated with HIV infection has a severe progressive course.

FIBRILLARY IMMUNOTACTOID GLOMERULONEPHRITIS

It manifests itself as severe proteinuria, in 50% of cases - nephrotic syndrome. Most patients experience hematuria, hypertension and impaired renal function. In some cases, monoclonal gammopathy is found. The course is progressive.

FIBROPLASTIC GLOMERULONEPHRITIS

In 43% of cases, nephrotic syndrome persists. Chronic renal failure is characteristic, associated with the loss of functional properties of sclerotically altered nephrons.

All of the named clinical variants and morphological forms of chronic glomerulonephritis differ in the duration of the course, the rate of formation of renal failure, and the tendency to relapse of the process. The importance of identifying an exacerbation, which sometimes manifests as a picture of rapidly progressing glomerulonephritis, should be taken into account, which requires an urgent solution to the issue of more active treatment(See Chapter 31, Rapidly Progressive Glomerulonephritis).

COMPLICATIONS

Complications of chronic glomerulonephritis are renal failure, left ventricular failure due to hypertension, stroke, intercurrent infections (including urinary tract infections), thrombosis, nephrotic crisis. The latter is characterized by fever, abdominal pain, migrating erysipelas-like erythema, and the development of hypovolemic shock. The pathogenesis of nephrotic crisis continues to be studied, important impart activation of the kallikrein-kinin system, DIC. Special mention should be made of possible complications of active immunosuppressive therapy - cytopenia (agranulocytosis, etc.), infections (including “steroid tuberculosis”), osteoporosis, hemorrhagic cystitis, hyperglycemic conditions.

DIAGNOSTICS

Diagnosis of chronic glomerulonephritis is based on determining the leading syndrome - isolated urinary, acute nephritic, nephrotic syndromes, hypertension syndrome. Additional feature consider symptoms of chronic renal failure.

SYNDROME DIAGNOSIS

NEPHROTICA SYNDROME

Nephrotic syndrome most often noted in glomerulonephritis with minimal changes, membranous glomerulonephritis (both primary and secondary), focal segmental glomerulosclerosis, diabetic glomerulosclerosis, renal amyloidosis.

ACUTE NEPHRITICA SYNDROME

Acute nephritic syndrome is a combination of hematuria, proteinuria, hypertension and, often, decreased renal function. Possible with rapidly progressing glomerulonephritis, mesangiocapillary glomerulonephritis, mesangioproliferative glomerulonephritis, exacerbation of lupus nephritis.

ARTERIAL HYPERTENSION

Hypertension in combination with proteinuria and minimal changes urinary sediment occurs, in addition to chronic glomerulonephritis, with diabetic nephropathy, kidney damage as part of hypertension. In the latter case, hypertension significantly precedes the appearance of renal symptoms; Hypertensive crises occur more often than with glomerulonerite.

URINARY SYNDROME

Urinary syndrome usually consists of symptoms of hematuria, proteinuria, leukocyturia with lymphocyturia, cylindruria and their combinations (Table 33-3).

Table 33-3. Causes of isolated hematuria

. Hematuria. Based on the above reasons, isolated hematuria is an indication for excretory urography, cystoscopy and selective angiography. In most nephrological diseases, hematuria is combined with proteinuria.

. Proteinuria may be associated with inflammatory (glomerulonephritis) or non-inflammatory (diabetic nephropathy, amyloidosis) glomerular or tubulointerstitial lesions of various etiologies(See Chapter 36 "Tubulointerstitial nephropathies"). In the latter case, proteinuria is never massive. Filling proteinuria is distinguished - a special variant, often “large” proteinuria, associated with multiple myeloma with the presence of paraprotein in the blood (hyperproteinemia). There is also benign proteinuria (occurs during a febrile reaction, hypothermia, emotional stress, accompanies heart failure and obstructive syndrome). sleep apnea). The term "benign" reflects a favorable prognosis for renal function. Orthostatic proteinuria occurs only in vertical position; it is usually observed in adolescents, it can be constant or periodic, and has a favorable prognosis.

. Leukocyturia with glomerulonephritis, it often has the character of lymphocyturia (more than 20% of leukocytes in urinary sediment are lymphocytes).

KIDNEY BIOPSY

A puncture biopsy of the kidney is performed to determine the morphological form of chronic glomerulonephritis, which is necessary for an adequate choice of treatment tactics. This procedure contraindicated in the following cases.

Having a single functioning kidney.

Hypocoagulation.

Increased venous pressure in big circle blood circulation - in case of right ventricular failure.

Suspicion of renal vein thrombosis.

Hydro- and pyonephrosis.

Polycystic kidney disease.

Renal artery aneurysm.

Impaired consciousness.

Suspicion of a malignant neoplasm.

DIFFERENTIAL DIAGNOSTICS

Chronic glomerulonephritis must be differentiated from chronic pyelonephritis, acute glomerulonephritis, nephropathy in pregnant women, chronic tubulointerstitial nephritis of various etiologies, alcoholic kidney damage, amyloidosis and diabetic nephropathy, as well as kidney damage in systemic diseases connective tissue(primarily SLE) and systemic vasculitis, myeloma, thrombosis of the renal and inferior vena cava (see “Complications” above).

Chronic pyelonephritis is characterized by asymmetry of the lesion, changes in the collecting system, exacerbations with fever and chills, bacteriuria, neutrophiluria (with glomerulonephritis, there are lymphocytes in the urine sediment, there is no microbial flora).

In acute glomerulonephritis, a connection with previous streptococcal infection, however, unlike IgA nephropathy, exposure is 10-14 days. Characterized by an acute onset and spontaneous recovery. Children and young people are usually affected.

Chronic tubulointerstitial nephritis is manifested by disorders of tubular functions: proteinuria (not reaching values ​​characteristic of nephrotic syndrome), polyuria, decreased relative density and impaired acidification of urine, hyperproteinemia, etc.

If amyloidosis is suspected, detection of underlying pathology (chronic inflammation, primarily rheumatoid arthritis; multiple myeloma; familial Mediterranean fever) is of great importance. The persistence of normal or enlarged kidney size and nephrotic syndrome in chronic renal failure increases the likelihood of amyloidosis (as well as diabetic nephropathy). Tissue biopsy (detection of amyloid in the tissue of the kidney, gum, rectum, adipose tissue) is of decisive importance.

If the patient has diabetes mellitus or its complications (for example, diabetic retinopathy), scant changes in urinary sediment, normal or slightly enlarged kidney sizes, the diagnosis of diabetic nephropathy is likely even without a puncture biopsy of the kidneys.

Nephropathy in pregnant women: symptoms of kidney damage appear in the second half of the gestational period, accompanied by high hypertension and other signs of pre- and eclampsia. A special form of severe preeclampsia is HELLP syndrome ( H emolysis, E levated L iver enzymes, L ow P latelet), in which, along with hypertension and kidney damage, hemolysis, liver damage and thrombocytopenia develop.

Features of alcoholic nephropathy include persistent painless microhematuria in combination with minimal or moderate proteinuria, a persistent increase in the concentration of IgA in the blood and hyperuricemia.

Kidney damage in SLE (lupus nephritis) and systemic vasculitis is accompanied by signs of systemic disease (articular and skin syndromes; detection of LE cells, hypergammaglobulinemia, autoantibodies, for example, ANCA, etc.).

TREATMENT

Treatment of chronic glomerulonephritis includes:

Elimination of the etiological factor (including during exacerbation);

Elimination of CEC and other factors of immune inflammation from the blood;

Carrying out immunosuppressive therapy;

Reducing high blood pressure and other effects that reduce intraglomerular hypertension;

Correction of hyperlipidemia and hypercoagulation;

Reducing swelling;

Removal of nitrogen metabolism products (hemodialysis and hemosorption).

In case of advanced chronic renal failure, chronic hemodialysis and kidney transplantation are indicated.

One of the promising areas in nephrology recent years- development of nephroprotective therapy aimed at inhibiting the progression of kidney diseases by influencing the general non-immune links of their pathogenesis. Among the approaches to nephroprotection, great importance is attached to leveling the nephrotoxic effects of proteinuria, which ultimately leads to remodeling of tubulointerstitial tissue - tubulointerstitial fibrosis (see below).

GENERAL EVENTS

It is necessary to avoid hypothermia and physical overexertion. Unfavorable ones are contraindicated temperature conditions(work in conditions of increased and low temperature environment). Particular care must be taken in the event of acute respiratory diseases or exacerbation chronic lesions infections (tonsillitis, sinusitis, etc.). In these situations, bed rest is indicated and antibiotic therapy is administered.

A low-protein diet is recommended (it has a positive effect on intraglomerular hypertension). The exception is cases of nephrotic syndrome with hypoalbuminemia below 30 g/l, when protein restriction is ineffective. A strict low-protein diet (0.3 g/kg per day) in patients with chronic renal failure is possible while taking medications simultaneously essential amino acids and their keto analogues (for example, "Ketosteril" 10-12 tablets per day). In case of nephrotic syndrome, a hypocholesterol diet and food containing polyunsaturated fatty acids are rational. fatty acid (sea ​​fish, sunflower oil).

IMMUNOSUPRESSIVE THERAPY

This type of therapy involves the prescription of two groups of drugs - GCs and cytostatics (both individually and in combination). The feasibility of their use depends significantly on the morphological form of glomerulonephritis.

GCs are indicated in the presence of nephrotic syndrome or severe proteinuria with a high probability of developing nephrotic syndrome. High (poorly correctable) hypertension and chronic renal failure are considered contraindications to the use of GCs in chronic glomerulonephritis. The most effective drugs in this group are for mesangioproliferative glomerulonephritis and glomerulonephritis with minimal changes. With membranous glomerulonephritis, the effect is doubtful. For membrano-proliferative glomerulonephritis and focal segmental glomerulosclerosis, GCs are less effective. Two routes of administration of HA are used.

◊ Orally: the average dose in terms of prednisolone is 1 mg/kg/day (usually prescribed for a period of 2 months) followed by a gradual reduction (5 mg/week to a dose of 30 mg/day, then 2.5-1. 25 mg/week until complete withdrawal).

◊ Pulse therapy involves intravenous drip administration of methylprednisolone at a dose of 1000 mg once a day for 3 days in a row. Usually prescribed for severe nephrotic syndrome and rapid progression of the disease.

Cytostatics (cyclophosphamide 2-3 mg/kg/day, chlorambucil 0.1-0.2 mg/kg/day, cyclosporine 2.5-3.5 mg/kg/day) are indicated for active forms glomerulonephritis with high risk progression of renal failure, as well as in the presence of contraindications for the use of GCs, the absence of a therapeutic effect or the development of pronounced side effects during their use (in the latter case, combined use is preferred, allowing a reduction in the dose of GCs). Drugs in this group are prescribed orally; cyclophosphamide also in the form of pulse therapy 15 mg/kg (or 0.6-0.75 g/m2 body surface) intravenously monthly.

The combined use of GC and cytostatics is considered more effective than GC monotherapy. The Ponticelli regimen involves alternating 6 months of cycles of therapy with prednisolone (lasting 1 month) and chlorambucil (lasting 1 month). At the beginning of a monthly course of treatment with prednisolone, a three-day pulse therapy with methylprednisolone is carried out, then prednisolone is prescribed at 0.4 mg/kg/day orally for the remaining 27 days. A monthly course of treatment with chlorambucil involves oral administration drug 0.2 mg/kg/day.

Selective immunosuppressants: drugs from the calcineurin group - cyclosporine, nucleotide synthesis inhibitor - mycophenolate mofetil, inhibitor of intracellular signal transmission from growth factor receptors - sirolimus. The greatest experience has been accumulated with cyclosporine (see below - “Treatment of individual morphological forms”). Indications for cyclosporine therapy include frequent relapses of GC-sensitive nephrotic syndrome (with minimal change glomerulonephritis) and GC-resistant nephrotic syndrome (with focal segmental glomerulosclerosis and membranous glomerulonephritis). Due to a possible nephrotoxic effect, the use of cyclosporine is limited in cases of severe sclerotic changes with impaired renal function and severe hypertension.

ANTICOAGULANTS AND ANTIPLAGGRANTS

Drugs of these groups of drugs are used in the composition combined schemes, with hypertensive form of glomerulonephritis and chronic glomerulonephritis with isolated urinary syndrome and reduced renal function. Dipyridamole is prescribed at a dose of 400-600 mg/day, clopidogrel - at a dose of 0.2-0.3 g/day.

COMBINATION THERAPY

Involves the prescription of a three-component regimen (cytostatics or GCs, antiplatelet agents, heparin sodium) or a four-component regimen (GCs, cytostatics, antiplatelet agents, heparin sodium with a switch to warfarin or phenindione).

ANTIHYPERTENSIVE AND NEPHROPROTECTIVE THERAPY

Ideally, it is necessary to compensate not only systemic arterial, but also intraglomerular hypertension. It is necessary to limit the consumption of table salt to 3-5 g/day and observe bed rest in case of high blood pressure. However, drug therapy has the greatest effect.

ACE inhibitors and angiotensin AT1 receptor blockers, in addition to lowering blood pressure, reduce intraglomerular capillary pressure, hyperfiltration and proteinuria. In addition, drugs of this group reduce the proinflammatory effects of proteinuria, preventing proteinuria-induced activation of the transcription factor NF-κ B in tubular epithelial cells and their release of chemokines into the interstitium, inhibit tubulointerstitial fibrosis through inhibition of the synthesis by macrophages and proliferating fibroblasts of the main profibrogenic cytokine - transforming growth factor - β and by reducing the formation of plasminogen activator inhibitor, which inhibits the processes of proteolytic degradation of the extracellular matrix. Due to these multifaceted effects, ACE inhibitors and angiotensin AT1 receptor blockers are currently considered as the central link of a nephroprotective strategy. Early start Therapy with ACE inhibitors and/or angiotensin AT1 receptor blockers contributes to a greater extent to inhibiting the progression of chronic renal failure, and their use is justified even in situations not accompanied by hypertension.

◊ Of the ACE inhibitors, the most commonly used are enalapril 5-20 mg/day in 1-2 doses, fosinopril 10-20 mg once a day, trandolapril 2-8 mg once a day, and among AT1 angiotensin receptor blockers - losartan 25-100 mg/day in 1-2 doses, valsartan 80-160 mg once a day, irbesartan 150-300 mg once a day. The drug dose is adjusted depending on the blood pressure level, serum creatinine and potassium concentrations. These two groups of drugs can be combined with each other to achieve a more pronounced antihypertensive and antiproteinuric effect.

◊ Contraindications for prescribing ACE inhibitors: severe renal failure (hyperkalemia, serum creatinine concentration more than 500-600 µmol/l), bilateral renal artery stenosis.

◊ In case of hyperkalemia or poor tolerance to ACE inhibitors, they are prescribed in lower doses in combination with non-dihydropyridine slow calcium channel blockers.

Of the slow calcium channel blockers, non-dihydropyridine drugs are preferable (verapamil 120-480 mg/day in 2-3 doses, diltiazem 180-360 mg/day in 2-3 doses). Slow calcium channel blockers of the dihydropyridine series can reduce GFR, so they can be used in combination with other drugs for severe hypertension. Slow calcium channel blockers, in addition to antihypertensive, also have an antiproteinuric effect, although to a lesser extent than ACE inhibitors. The antiproteinuric effect of this group of drugs is associated mainly with a decrease in the severity of systemic hypertension and an antiplatelet effect.

Statins (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) also have nephroprotective properties, and the anti-inflammatory effect of statins is no less important for the implementation of nephroprotection than their antilipidemic effect. Statins inhibit the expression of plasminogen activator inhibitor and enhance the synthesis of tissue plasminogen activator. Prescribe simvastatin 20-40 mg/day, fluvastatin 20-80 mg/day, etc.

Currently, the possibility of using new classes of drugs for nephroprotective purposes, such as vasopeptidase inhibitors, endothelin-1 antagonists, antichemokine drugs (ATs, neutralizing chemokines, chemokine receptor antagonists), inhibitors of protein kinase that activates the transcription factor NF-κ B, etc. Some of them have already undergone successful preclinical testing.

ANTIOXIDANT THERAPY

Antioxidants (eg, tocopherol, trimetazidine) have attracted the attention of many researchers, but convincing data on their effectiveness have not yet been obtained.

TREATMENT OF EDEMA

In case of severe edema syndrome, limit the consumption of table salt and prescribe bed rest. The most commonly used diuretic is furosemide. Hydrochlorothiazide should not be used (impairs renal function); Caution is necessary with potassium-sparing diuretics (risk of hyperkalemia), guanethidine and minoxidil (sharp retention of sodium ions and decreased GFR).

TREATMENT OF SEPARATE MORPHOLOGICAL FORMS

For any form of chronic glomerulonephritis, bed rest, diet, symptomatic therapy(described above), if possible, eliminate the etiological factor (infection, tumor). Features of the treatment of individual morphological forms mainly relate to pathogenetic immunosuppressive therapy.

MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS

In slowly progressing variants, including in patients with IgA nephropathy with episodes of gross hematuria and minimal proteinuria, there is no need for immunosuppressive therapy. In patients with a higher risk of progression (severe proteinuria or nephrotic syndrome, hypertension), GC is prescribed at 1 mg/kg/day for 2-3 months; in case of relapses, therapy is intensified with cytostatics. It is possible to use three- and four-component schemes. However, the effect of active immunosuppressive therapy on long-term prognosis (duration of preservation of renal function) in this form of glomerulonephritis remains unclear.

MEMBRANO-PROLIFERATIVE (MESANGIOCAPILLARY) GLOMERULONEPHRITIS

There is no convincing data on the advantage of any pathogenetic method of treating this form of glomerulonephritis. The importance of treatment is undeniable background disease. Hypertension control is necessary; preference is given to ACE inhibitors. In the presence of nephrotic syndrome and decreased renal function, combined therapy with GC and cyclophosphamide orally or in the form of pulses for at least 6 months is justified, possibly with the addition of antiplatelet agents (dipyridamole) and anticoagulants (warfarin, phenindione).

MEMBRANOSAL GLOMERULONEPHRITIS

Regarding the use of immunosuppressive therapy, the opinion is ambiguous. Many believe that immunosuppressants should only be used in patients with high proteinuria and/or renal failure to prevent its progression, but there are also supporters early use"aggressive" approaches. With GC monotherapy, remission cannot be achieved; better results are achieved with the combined use of GC and cytostatics, for example, according to the Ponticelli scheme with monthly alternation of methylprednisolone and chlorambucil. There is information about the successful use of pulse therapy with cyclophosphamide 1 g intravenously monthly for membranous glomerulonephritis. Nevertheless, due to frequent spontaneous remissions, it is necessary to weigh the benefits and harms of treatment with cytostatics in each specific situation. Today, it seems appropriate for patients with membranous glomerulonephritis without nephrotic syndrome (with its possible complications) And normal function kidneys, prescribe ACE inhibitors for antiproteinuric and nephroprotective purposes.

GLOMERULONEPHRITIS WITH MINIMAL CHANGES

Glomerulonephritis with minimal changes is treated with GCs. 90% of children and 50% of adults with this form of glomerulonephritis develop remission within 8 weeks of treatment with prednisolone. Prednisolone in adults is prescribed 1-1.5 mg/kg for 4 weeks, then 1 mg/kg every other day for another 4 weeks. When the duration of treatment is increased to 20-24 weeks, remission occurs in 90% of adult patients. Immunosuppressants - cyclophosphamide 2-3 mg/kg/day or chlorambucil 0.1-0.2 mg/kg/day are used in cases where GCs in an adequate dose are ineffective, and also if after long-term use they cannot be canceled due to relapses.

If attempts to prevent relapses of nephrotic syndrome using alkylating agents are unsuccessful, cyclosporine is prescribed at 3-5 mg/kg/day (for children 6 mg/m2). The treatment is long-term, the dose of the drug begins to be reduced no earlier than 6-12 months after achieving remission; the minimum maintenance dose (usually 2.5-3.0 mg/kg) is sometimes taken even for 2 years. During treatment with cyclosporine, its concentration in the blood should be monitored. The occurrence of complications (hypertension, hyperkalemia, increase in serum creatinine level by 30% of the initial level or more) requires dose adjustment or discontinuation of the drug. The lack of effect from treatment with cyclosporine with sufficient concentration in the blood is assessed after 3-4 months of use, after which the drug is discontinued.

FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Immunosuppressive treatment is not effective enough. A decrease in the severity of proteinuria is noted in 20-40% of cases with 8-week treatment with GC, the effectiveness increases to 70% with a duration of therapy of 16-24 weeks. Patients with nephrotic syndrome are prescribed prednisolone 1-1.2 mg/kg daily for 3-4 months, then every other day for another 2 months, after which the dose is gradually reduced until the drug is completely discontinued. The effectiveness of cytostatics (cyclophosphamide, cyclosporine) is approximately 50-60%; with the combined use of cytostatics with GCs, the frequency of subsequent exacerbations decreases. Cyclophosphamide can be used orally at 2-3 mg/kg/day or as pulse therapy intravenously at 1000 mg/day once a month. In case of resistance to GC, preference is given to cyclosporine (orally 3-5 mg/kg/day), remission is achieved in 25-50% of patients.

FIBRILLARY IMMUNOTACTOID GLOMERULONEPHRITIS

Treatment for fibrillar-immunotactoid glomerulonephritis has not been developed. Data have been obtained on the effectiveness of kidney transplantation.

FIBROPLASTIC GLOMERULONEPHRITIS

The diffuse form of fibroplastic glomerulonephritis is a contraindication rather than an indication for active immunosuppressive therapy, since the resolution of sclerotic processes does not occur, and the resulting side effects of the drugs are quite serious.

TREATMENT OF CHRONIC GLOMERULONEPHRITIS ACCORDING TO CLINICAL FORMS

Performed when it is impossible to perform a kidney biopsy. In front of everyone clinical forms First of all, it is necessary to influence the etiological factor, if it can be established (infection, tumors, drugs). Even when obtaining data from a morphological study of kidney tissue clinical criteria Assessing the severity and prognosis of glomerulonephritis is important for choosing adequate therapy.

CHRONIC GLOMERULONEPHRITIS WITH ISOLATED URINARY SYNDROME

In the latent form (without hypertension and unchanged renal function), active immunosuppressive therapy is not indicated; carry out regular monitoring with monitoring of blood pressure and creatinine levels in the blood. For proteinuria more than 1 g/day, ACE inhibitors are prescribed.

HEMATURIC FORM

The inconsistent effect of prednisolone and cytostatics is noted. Patients with isolated hematuria or hematuria combined with slight proteinuria are recommended long-term use ACE inhibitors (even with normal blood pressure) and dipyridamole.

HYPERTENSIVE FORM

An indispensable rule is the correction of hypertension, primarily with ACE inhibitors. It is necessary to strive to reduce blood pressure to 120-125/80 mm Hg. During exacerbations (especially of the acute nephritic syndrome type), cytostatics are used as part of a three-component regimen. GK can sometimes be prescribed as monotherapy at a dose of 0.5 mg/kg/day (in terms of prednisolone) orally or at the same dose as part of combination regimens.

NEPHROTICA FORM OF CHRONIC GLOMERULONEPHRITIS

The nephrotic form of chronic glomerulonephritis is considered an indication for the administration of prednisolone (methylprednisolone) orally and in the form of “pulse therapy,” cytostatics, antiplatelet agents and anticoagulants. Diuretics and antihyperlipidemic drugs are used.

CHRONIC GLOMERULONEPHRITIS OF MIXED TYPE

Chronic glomerulonephritis mixed type are treated actively using three- or four-component regimens. Antihypertensive drugs and diuretics are used.

SPA TREATMENT

Basic healing factor- exposure to dry and warm climates.

Indications: latent form of glomerulonephritis, hematuric form without gross hematuria, hypertensive form with blood pressure not higher than 180/105 mmHg, nephrotic form in remission.

Contraindications: exacerbation of glomerulonephritis, severe renal dysfunction, high hypertension, gross hematuria. Initial manifestations Chronic renal failure is not considered a contraindication for spa treatment.

DISPANSERIZATION

Patients with chronic glomerulonephritis should be under constant supervision of a physician (nephrologist). The rules for medical examination for chronic glomerulonephritis are developed taking into account clinical classification.

. Latent And hematuric form. Frequency of visits - 2 times a year. Observed parameters: body weight, blood pressure, fundus, urine analysis according to Nechiporenko, general analysis and blood electrolytes, proteinogram, protein content in daily urine, concentration of creatinine in blood serum, urea, Reberg-Tareev test. Kidney ultrasound every year. In case of hematuria, the patient is referred for consultation to a urologist.

. Hypertensive form- the same research methods, but observation must be carried out once every 1-3 months.

. Nephrotic And mixed form. The volume of research is the same, the frequency of observation is once every 1-2 months. Special attention it is necessary to pay attention to the severity of edema syndrome and the electrolyte composition of the blood in connection with the use of diuretics.

Exacerbation of any form of chronic glomerulonephritis is considered an indication for hospitalization. In case of temporary disability (more than 2 months) without reversal of the symptoms of the disease, it is necessary to resolve the issue of disability.

FORECAST

Mesangioproliferative glomerulonephritis. Proteinuria reaching the threshold of nephrotic syndrome has an unfavorable prognostic value. IgA nephropathy has a benign course in most cases, but 20-40% of patients reach terminal stage CRF. Unfavorable prognostic factors for IgA nephropathy: older age, male gender, proteinuria above the nephrotic threshold (3.5 g/day), impaired renal function at the onset of the disease, biopsy detection of extracapillary “crescents” or glomerular hyalinosis, interstitial fibrosis.

Membranous glomerulonephritis. Nephrotic syndrome with membranous glomerulonephritis disappears spontaneously in 40% of patients, recurs in 40% and proceeds continuously with the slow development of chronic renal failure in 20% of patients. Unfavorable prognostic factors: male gender, old age, persistent hypertension, severe proteinuria and hyperlipidemia, deterioration of renal function, late recognition of the paraneoplastic genesis of glomerulonephritis. Complications include renal vein thrombosis and pulmonary embolism.

Membrane-proliferative (mesangiocapillary) glmerulonephritis generally has an unfavorable prognosis, since with this form pathogenetic therapy ineffective. High risk factors for progression include renal failure at the time of diagnosis, age over 50 years, hypertension, and detection of extracapillary cellular “crescents” in the glomeruli of the kidneys.

Glomerulonephritis With minimal changes prognosis is assessed favorably. Spontaneous remissions are observed in 30-40% of children, but in adulthood they are much more rare.

Focal segmental glomerulosclerosis. Unfavorable prognostic factors indicating the possibility of rapid progression include hypertension in combination with persistent treatment-resistant nephrotic syndrome and thrombotic complications.

Fibrillar-immunotactoid glomerulonephritis progresses to end-stage chronic renal failure over 1-10 years.

Fibroplastic glomerulonephritis - a step to secondary shriveled kidney and chronic renal failure; there is no reverse development of fibroplastic changes.

Pregnant with glomerulonephritis constitute a risk group for complications during pregnancy and childbirth.

Membranous-proliferative glomerulonephritis - MPGN (mesangiocapillary glomerulonephritis, mixed membranous and proliferative glomerulonephritis, chronic hypocomplementary glomerulonephritis) is characterized by nephrotic syndrome with hematuria and (or) arterial hypertension or nephritic or isolated urinary syndrome with specific morphological changes. Often found in teenagers.

Pathomorphology. According to the WHO classification, there are 3 types of membranous-proliferative glomerulonephritis, based on ultrastructural changes:

Type 1 - classic, with subendothelial deposits and unchanged basement membrane;

Type 2 - with intramembranous deposits (or disease of dense deposits);

Type 3 - with pronounced structural changes in the basement membrane, as well as subepithelial and subendothelial deposits.

All three types of the disease are characterized by the presence of endothelial mesangial proliferation and the deposition of immune deposits.

Pathogenesis. Membranous proliferative glomerulonephritis is an immune complex disease. In pathogenesis, the leading role is given to circulating and fixed immune complexes with activation of the complement system along the classical and alternative pathways, activation of the vascular-platelet, coagulation units of hemostasis with the formation of microthrombi in the capillaries of the glomerulus.

Clinical picture. The disease is characterized by pronounced variability in its onset, course, and rate of progression to chronic renal failure.

Treatment. In the treatment of glomerulonephritis, a four-component regimen or prednisolone therapy is used in an alternating regimen (for several years).

Combination therapy with prednisone, cyclophosphamide, dipyridamole, and anticoagulants for up to 4 years improves the prognosis of membranous proliferative glomerulonephritis in children and adults. For MPGN, alkylating cytostatics are used (usually cyclophosphamide 2-2.5 mg/kg/day for 12-24 weeks), DNA transcription inhibitors (cyclosporine A, Neoral 3.5-7 mg/kg/day for 6-12 months), antimetabolites ( azathioprine 2-2.5 mg/kg/day 6-12 months).

In 1992, P. Tarshish published a report from the international ISKDS group on the results of treatment of idiopathic MPGN with prednisolone at a dose of 40 mg/m2 (every other day) in an alternating regimen. It has been shown that long-term treatment with prednisolone at a dose of 40 mg/m2 every other day improves the outcome of MPGN types 1 and 3, but does not lead to improvement in type 2.

J. Berstein and S. Andreoli proposed a protocol for the treatment of membranous proliferative glomerulonephritis type 1: pulse therapy with methylprednisolone 30 mg/kg (maximum dose 1.5 g) every other day (6 infusions) in combination with oral prednisolone 2 mg/kg ( maximum dose 60 mg) lasting 12-66 months.

Demonstrated effectiveness combination therapy MPGN with prednisolone and azathioprine (6-12 months), followed by a transition to alternating prednisolone for several years.

With high activity of MPGN with an extracapillary component, synchronous pulse therapy with methylprednisolone and plasmapheresis is indicated, followed by 4-component therapy (prednisolone + cytostatic + anticoagulants + antiplatelet agents) or prednisolone therapy in an alternating mode. With progression to chronic renal failure, plasmapheresis is indicated.

Course and prognosis. Chronic course MPGN becomes recurrent, persistent or progressive. The prognosis of MPGN is questionable.

Membranous - proliferative glomerulonephritis(MPGN, mesangiocapillary glomerulonephritis) is a glomerulonephritis characterized by mesangial proliferation and thickening of the glomerular basement membrane. Statistical data. 5-20% of all cases of glomerulonephritis, from 30 to 40% of cases of nephrotic syndrome in children and adults. Men and women get sick equally often.

Code by international classification diseases ICD-10:

• N00.2

Causes

Etiology. It can be idiopathic and secondary (with SLE, cryoglobulinemia, infection, damage to the glomeruli by drugs and toxins).

Pathomorphology. There are three (sometimes four) MPGN type. All forms are characterized by proliferation of mesangial cells, an increase in the volume of the mesangial matrix, and thickening of the basement membrane. Type I (idiopathic) is characterized by an intact basement membrane, subendothelial immune deposits, and positive immunofluorescence in the regarding IgG, C1q, C4, C2 and properdin. Type II (dense deposit disease) - intramembranous deposits and positive immunofluorescence for IgG, C3 and properdin. Type III - combined signs of membranous glomerulonephritis (fragmentation of the basement membrane) and type I MPGN. Type IV - subendothelial and subepithelial deposits.

Symptoms (signs)

Clinical picture. Nephrotic syndrome is a mixed form (with arterial hypertension, erythrocyturia, azotemia). In 1/3 of patients, rapidly progressive renal failure develops with edema and severe arterial hypertension.

Diagnostics

Laboratory data. Hypocomplementemia.

Diagnostic tactics. Mixed form nephrotic syndrome with relatively rapid development of renal failure is always suspicious for MPGN. The diagnosis is verified by biopsy.

Treatment

TREATMENT

Diet (see Chronic glomerulonephritis).

Treatment of the primary disease (HBV and HCV infections, etc.).

Immunosuppressive therapy.. GCs are usually ineffective.. For proteinuria<3 г/сут и нормальной СКФ иммунодепрессивная терапия не показана.. При нефротическом синдроме: преднизолон в дозе 1 мг/кг внутрь или в сочетании с циклофосфамидом (хлорамбуцилом, азатиоприном) ежедневно в течение 2 мес или в виде пульсов 1 р/мес в течение 1-2 лет.. 3 - компонентная схема: цитостатики, антикоагулянты и антиагреганты (дипиридамол в дозе 400-600 мг/сут или ацетилсалициловая кислота в дозе 250-320 мг/сут); тем не менее преимущества в контролируемых исследованиях не доказаны.. Циклоспорин 3-5 мг/кг/сут в сочетании с низкими дозами преднизолона (данные неконтролируемых исследований).

Flow. Progressive to chronic renal failure, remissions are rare. The 10-year survival rate is no more than 50%, the prognosis is better with type I. Recurrence of the disease is possible in the transplanted kidney.

Reduction. MPGN is membranous proliferative glomerulonephritis.

ICD-10. N00.2 Acute nephritic syndrome, diffuse membranous glomerulonephritis

Page 15 of 60

Membranous-proliferative glomerulonephritis (mesangiocapillary glomerulonephritis)
Membranous proliferative glomerulonephritis (MPGN) is a chronic diffuse form of proliferative glomerulonephritis with specific histological and immunological changes and electron microscopic findings. changes in the kidneys can be caused by some unrelated systemic disorders (for example, lipodystrophy, a1-antitrypsin deficiency, congenital absence of the C2 component of the complement system), but usually MPGN acts as a primary disease. Its two types are well known: I and II. Clinically they are not distinguishable. Renal manifestations include nephrotic syndrome, acute nephritis, nephrosonephritis, asymptomatic proteinuria, rapidly progressive (crescentic) glomerulonephritis, chronic renal failure, or recurrent gross hematuria. Hypertension and azotemia are usually prominent. Despite the fact that the specific etiology is unknown, changes in the kidneys are caused by immunological mechanisms: type I is characterized by a typical pathway of activation of the complement system with the deposition of an immune complex, type II is characterized by an alternative pathway of activation with the nephrotic factor S3 detected in the serum. Girls get sick more often than boys, usually in adolescence or young adulthood. Both types are differentiated according to histological, immunological and electron microscopic examination. The histological picture in both types is significantly the same: the glomeruli increase in size, the mesangial cells proliferate quite uniformly, and the capillary walls thicken. There may be a marked increase in the amount of matrix with a tendency for the glomeruli to become lobulated. Epithelial crescentic formations often appear. In the initial stage, neutrophilic infiltration of the glomeruli is possible.
In type I, subendothelial accumulations and interposition of the mesangial matrix between the endothelium and the basement membrane lead to thickening of the capillary walls, giving the appearance of a double loop. In type II, thickening of the capillary walls occurs as a result of the deposition of dense refractive masses in the basement membrane itself, giving it a ribbon-like appearance. Electron microscopic examination reveals electron-dense masses in the middle part of the basement membrane, replacing and expanding the dense plate. The same masses are found in the mesangium, glomerular capsule and tubular basement membrane. Type II MPGN is sometimes called dense disease
deposits or with dense intramembrane deposits. Some authors distinguish type III of the disease with contiguous subepithelial and subendothelial deposits that destroy the basement membrane and cover the lamina densa.
The results of immunological studies indicate some differences in the manifestations of type I; The most common of these include granular deposits containing IgG, IgM, C3, Clq and C4 along peripheral loops with variable fluorescence of mesangial structures. In many patients, accumulations of properdin and S3 occur. In contrast, patients with type II MGPN show large accumulations of SZ in round, tuberous deposits within the mesangium and very little, if any, in intramembranous deposits; properdin is usually not found.
Serum complement in type I is represented by a reduced amount of Clq and C4 and a variable decrease in the amount of C3, on the basis of which the classical pathway of activation of the complement system is assumed, while in type II there is a constant decrease in the amount of this component, which is associated with an alternative activation pathway; Clq and C4 levels remain within normal limits. Nephritic factor S3 is detected more often than in type I.
Type I is 2-3 times more common than type II, which can develop in patients with lipodystrophy. Type II is more likely to recur in the transplanted kidney. Girls more often than boys suffer from the idiopathic form of the disease, which first appears in adolescence or early adolescence. Almost 1/3 of patients with MPGN have nephrotic syndrome, although this accounts for less than 10% of children suffering from it; In some patients, the picture of acute nephrosonephritis is expressed, and in the rest, massive hematuria, asymptomatic proteinuria and chronic progressive renal failure occasionally appear. Proteinuria is not selective. Hypertension and a decrease in GFR are noted in approximately 1/3 of patients, almost 10% develop renal failure within 2 years and the long-term prognosis should be approached with great caution, since in half of the cases the disease progresses and within 10 years can develop into chronic renal disease failure. There is no consensus regarding the treatment of patients.
Prednisone (an alternative high-dose regimen), dipyridamole, anticoagulants, and antimetabolic agents may be used. The results obtained by the authors of this section indicate that the rate of progression of the disease can be reduced and the patient’s condition will improve if he is treated early (in the acute stage) with azathioprine and prednisone every other day and treatment is continued for several years. For patients with end-stage renal failure, the most optimal solution is a kidney transplant; Although the disease may spread to the transplanted kidney, it may not be accompanied by significant clinical manifestations.

Chronic glomerulonephritis, characterized by proliferation of mesangial cells, thickening of the wall of the glomerular capillaries, increased mass of the mesangial matrix, and low levels of complement in the serum. Frequency. 41% of cases of idiopathic nephrotic syndrome are in children and 30% of cases in adults. Men and women are affected equally.

Etiology. Membranous-proliferative glomerulonephritis can be idiopathic and secondary (with SLE, cryoglobulinemia, chronic viral or bacterial infection, damage to the glomeruli by drugs, toxins, metabolites).

Pathomorphology.

There are three types of pathological changes in membranous proliferative glomerulonephritis. All forms are characterized by proliferation of mesangial cells and an increase in the volume of the mesangial matrix (the capillary glomerulus becomes lobed), as well as thickening of the basement membrane. This thickening reflects the fact that new basement membranes are forming. This doubling of the basement membranes is visible under electron microscopy and some special methods of preparing the material (for example, during impregnation with silver salts). In this case, mesangial cells find themselves between the new and old basement membranes

Type I (idiopathic) is characterized by an intact glomerular basement membrane, subendothelial and mesangial deposits, significant mesangial swelling and positive immunofluorescence for IgG, Clq, C4, C2 and properdin

Type II (dense deposit disease) is characterized by the presence of intramembranous and subepithelial deposits (tubercles) in 50% of cases, mesangial deposits, mild mesangial swelling and positive immunofluorescence for IgG, C3 and properdin

Type III is characterized by signs of true membranous glomerulonephritis and membranous proliferative glomerulonephritis type I.

Clinical picture

Symptoms are variable. Rapid progression to renal failure with edema and severe hypertension (acute nephritis)

Hypocomplementemia, the degree of which can serve as a guide to determine disease activity.

Treatment:

Diet No. 7a

Glucocorticoids are ineffective

Cytostatics

Cyclophosphamide - monthly pulse therapy (1,000 mg/day IV) for 1-2 years

Cyclosporine 3-5 mg/kg/day

Indomethacin 150 mg/day long-term

Antiplatelet agents for a long time

Dipyridamole 400-600 mg/day

Acetylsalicylic acid 250-320 mg/day

Surgical treatment - kidney transplantation; however, recurrence of the disease is also possible in the transplanted kidney. Flow. In 50% of cases, chronic glomerulonephritis with end-stage chronic renal failure develops within 10 years.

Synonyms

Hypocomplementary persistent glomerulonephritis

Lobular glomerulonephritis

Mesangiocapillary glomerulonephritis

see also

Glomerular diseases, membranous glomerulonephritis, minimal change disease, mesangio-proliferative glomerulonephritis, focal glomerulosclerosis, nephrotic syndrome, malignant nephrosclerosis. Berger's disease, Chronic nephritic syndrome, Rapidly progressive nephritic syndrome, Acute nephritic syndrome ICD N00.-N08. Glomerular diseases

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Flight of the soul
After fifty comes the time when you find true freedom.

A new beginning
There is nothing worse than sitting still as if life is over. This is the worst thing you can think of: sitting and doing nothing.

When there are more advantages
I was recently diagnosed with glaucoma and prescribed eye drops. You know, these drops made my eyelashes thicker. You need to see the positive sides in everything.

Sugar wrinkles
Anti-aging creams won't help if you eat a lot of sugar. Wrinkles occur from sweets, wine and white bread, pasta and even fruit. But there is also good news. Quitting sugar gives incredibly quick results. For those who change their diet, the skin brightens and smoothes out within a few days.

1041 rub

The book by a candidate of medical sciences, a doctor with many years of practical experience by O.I. Eliseeva, introduces methods of cleansing and restoring the human body, recommends certain cleansing options according to diseases, age and taking into account contraindications. The manual can be used at home for preventive and therapeutic purposes.

For a wide range of readers.

237 rub

The book presents modern approaches to the use of various classes of antimicrobial drugs: antibacterial, antituberculosis, antifungal, antiviral, antiprotozoal, anthelmintic. Their clinical and pharmacological characteristics and features of use for various infections are considered.

For doctors of various specialties (therapists, surgeons, obstetricians-gynecologists, clinical pharmacologists, bacteriologists, etc.), teachers, graduate students, residents and students of medical universities.

715 rub

Runny nose, otitis, sore throat - these diseases are probably familiar to everyone. Incorrect treatment not only does not bring relief, but can also transform an ordinary disease into a chronic form. Are you “hooked” on drops for a runny nose? Is your child being asked to have their adenoids or tonsils removed? Does any ear pain qualify as otitis media and require immediate use of antibiotics? Book 9 of the "ADR" series is the most complete guide to diseases of the ENT organs. It will completely change your understanding of the modern method of treating ear, nose and throat, will help you, together with your doctor, choose the right treatment and, if possible, abandon antibiotics and outdated “barbaric” procedures.

234 rub

The book puts forward a theory about the causes of cancer and a hypothesis about the origin of life on Earth. A fundamentally new assessment of the essence of dissymmetry in living organisms is given. It has been proven that 80% of water and 16% of protein that we are made of are its “habitat”, and these 96% live their own special life, but in collaboration with biochemistry and genetics. Hence, cancer is considered as a kind of living organism, not just as a pathology, but as something global, going beyond the framework of known biology, in connection with space, mathematics and physics.
The connection between living beings and their crystalline past has been established. Microcrystals were found in the blood plasma of healthy and cancerous animals. The symmetry of these crystals is most likely cubic. According to the author, dissymmetry and polarization are inherent not only in living matter, they are characteristic of all phenomena and laws of the Universe. It has been established that anisotropy dominates in living objects; due to it, cells feed, purify and divide. The predominance of isotropy in tissues leads to old age, disease and cancer.
The treatment developed by Dr. Kutushov, based on this theory, is dissymmetrizing (anisotropic) therapy, not only pathogenetic, but primarily etiotropic treatment. According to the author and many volunteer patients who underwent treatment using the method of M.V. Kutushov, this type of therapy is harmless and effective.
Practical results of treatment obtained over 12 years prove its advantages over many existing approaches in modern oncology and confirm the correctness of the put forward theory.

86 rub

The reference book contains tables and diagrams relating to diagnostics, differential diagnosis, therapeutic and preventive measures for diseases of internal organs, cardiology, pulmonology, endocrinology, rheumatology, allergies, rheumatic diseases, diseases of the gastrointestinal tract, liver, pancreas, kidneys.

For general practitioners, family doctors, cardiologists, rheumatologists, endocrinologists, gastroenterologists, pulmonologists, nephrologists, hematologists and other doctors, as well as teachers, interns, residents and senior students of higher medical universities.

1340 rub