What is proliferative glomerulonephritis? Proliferative glomerulonephritis: symptoms, causes and treatment methods
Glomerulonephritis is a disease infectious nature, which manifests itself as bilateral inflammation of the glomeruli of the kidneys. Especially often develops after streptococcal bacterial infections (scarlet fever, tonsillitis, pharyngitis, etc.).
Glomeruli are structures in the kidneys that are made up of tiny blood vessels. The nodes of these vessels help in filtering the blood and removing excess fluid. If the glomeruli are damaged, your kidneys will fail, which can lead to renal failure. Conditions in which the glomeruli become damaged are called glomerulonephritis (GN).
Glomerulonephritis is serious illness, which can be life-threatening and requires immediate treatment. Proliferative glomerulonephritis manifests itself with signs that are characterized by high permeability of the glomerular membrane.
Causes of development of proliferative glomerulonephritis
The kidneys can be called a kind of “sewage system” of the human body. When blood enters this paired organ, its path lies along to the smallest vessels directly into the renal glomeruli. Next, primary urine is formed through three main processes: filtration, reabsorption and secretion. All the liquid leaks through the glomerular membranes, and primary urine remains in the capsule itself.
What diseases are accompanied by glomerulonephritis:
1. Kidney failure (chronic).
2. Proteinuria (when protein is present in the urine).
3. Hematuria (presence of red blood cells in the urine).
All these diseases are characterized by increased permeability of the glomerular membranes (glomerular membrane). The diagnosis of “proliferative glomerulonephritis” occurs when all of the above diseases are combined and cause proliferation of the renal glomeruli and enlargement of the membrane. This process is called proliferation, in which the capsule is completely filled with capillary loops.
The mechanism that causes the disorder is still unknown, but is thought to be an immune system response, as inflammation of the glomerulus triggers the release of antibodies. The disorder usually causes nephrotic syndrome (loss of protein in the urine and swelling of the body). This may present as acute, chronic, or rapidly progressive glomerulonephritis, and may progress to chronic renal failure.
Signs of proliferative glomerulonephritis
The main symptoms that characterize this disease:
Also, if you notice a brown coating on the tongue, a smell reminiscent of ammonia from the mouth, and the skin has become yellowish, you need to urgently seek medical help.
What treatments are possible for glomerulonephritis?
One of the first directions of therapy is to control high blood pressure. Your doctor may prescribe blood pressure medications, including:
Groups of angiotensin-converting enzyme inhibitors:
Angiotensin receptor blockers:
- losartan,
- irbesartan,
- valsartan.
Other medications, such as corticosteroids, may be prescribed to reduce the response if your immune system is attacking the kidneys.
You will also need to change your diet. Reduce the amount of protein, salt and potassium in your foods. Watch how much liquid you drink. In addition, it may be recommended nutritional supplements with calcium and diuretics to reduce swelling.
MEMBRANOSAL-PROLIFERATIVE GLOMERULONEPHRITIS honey.
Membranoproliferative glomerulonephritis is a chronic glomerulonephritis characterized by mesangial cell proliferation, thickening of the glomerular capillary wall, increased mass of the mesangial matrix, and low serum complement levels. Frequency. 41% of cases of idiopathic nephrotic syndrome 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 lobulated), as well as thickening of the basement membrane. This thickening reflects the fact that new basement membranes are forming. This duplication of basement membranes is visible under electron microscopy and some special methods preparation of 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, moderate swelling of the mesangium 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. 7aGlucocorticoids are ineffective
Cytostatics
Cyclophosphamide - monthly pulse therapy (1,000 mg/day IV) for 1-2 years
Cyclosporine 3-5 mg/kg/day
NSAIDs
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 glomerulonephritisLobular glomerulonephritis
Mesangiocapillary glomerulonephritis
See also, Mesangio-proliferative glomerulonephritis, Nephrotic syndrome,. Berger disease, Chronic nephritic syndrome, Rapidly progressive nephritic syndrome, Acute nephritic syndrome ICD N00.-N08. Glomerular diseases
Directory of diseases. 2012 .
See what "MEMBRANOSE-PROLIFERATIVE GLOMERULONEPHRITIS" is in other dictionaries:
membranous-proliferative glomerulonephritis- (g. membranosoproliferativa; synonym: G. mesangioproliferative, G. hypocomplementary persistent) pathomorphological type of chronic G., characterized by a combination of signs of membranous and proliferative G. ... Big Medical Dictionary
Glomerulonephritis- I Glomerulonephritis (lat. glomerulus glomerulus + nephritis [s] (Nephritis)) bilateral diffuse immune inflammation of the kidneys with predominant damage to the glomeruli, see Nephritis. II Glomerulonephritis (glomerulonephritis; glomerulo (Glomerul) + Nephritis; syn... Medical encyclopedia
Honey. Membranous glomerulonephritis is a glomerulonephritis with diffuse thickening of the basement membranes of the glomerular capillaries (partly due to Ig deposition), clinically characterized by a gradual onset of nephrotic syndrome and a long... ... Directory of diseases
glomerulonephritis hypocomplementary persistent- (g. hypocomplementaria persistens) see Membranous proliferative glomerulonephritis... Big Medical Dictionary
mesangioproliferative glomerulonephritis- (g. mesangioproliferativa) see Membranous proliferative glomerulonephritis... Big Medical Dictionary Directory of diseases
Honey. Acute nephritic syndrome is characterized by the sudden onset of hematuria and proteinuria, signs of azotemia (decreased glomerular filtration rate), retention of salts and water in the body, and arterial hypertension. Etiology ... ... Directory of diseases
Honey. Chronic nephritic syndrome is a syndrome that accompanies a number of diseases of different etiologies, characterized by diffuse glomerular sclerosis leading to chronic renal failure, clinically manifested by proteinuria, cylindruria, hematuria and arterial... ... Directory of diseases
The term was first used in 1958 by Kark et al. and then included in the classifications of Fiaschi et al. (1959); Blainer et al. (1960), etc. However, from the very beginning this term suffered from uncertainty. Some believe that membranous-proliferative glomerulonephritis is a simple combination of proliferative and membranous changes (it was stated above that “true membranous glomerulonephritis” is not accompanied by cellular proliferation); the existence of focal and diffuse forms of membranous-proliferative glomerulonephritis is also allowed (Fiaschi et al., 1959; V.V. Serov, 1973, etc.). The difficulty lies in the fact that some researchers still attribute any thickening of the basement membranes of capillaries - focal or diffuse - to membranous glomerulonephritis (Schwartz et al., 1970). However, there is a form of glomerulonephritis for which the combination of diffuse thickening of the basement membranes of the capillaries with proliferation of glomerular cells is characteristic. In this case, lobulation is usually expressed in the glomeruli. Such changes were first described by Allen in 1951 as lobular glomerulonephritis (which, in particular, gave rise to a debate about the thickness of the basement membranes in lobular glomerulonephritis). Subsequently, it was shown that diffuse thickening of the basement membranes in combination with diffuse proliferation of mesangial and endothelial cells of the glomeruli can be used as a criterion for membranous proliferative glomerulonephritis, characterized by morphological features and a unique clinical picture (Burkholder et al., 1970; West and McAdams, 1970; B. N. Tsibel, 1972).
Rice. 14. Membranous proliferative glomerulonephritis (biopsy).
Lobularity of the glomerulus, an increased number of cells, thickened capillary basement membranes along the periphery of the lobules. Hematoxylin-eosin staining, UV. 300.
Rice. 15. Membranous proliferative glomerulonephritis (biopsy).
Diffuse thickening of the basement membranes of capillaries, most of which do not perceive silver. The thickened mesangial skeleton is intensely silvered. Impregnation according to Jones-Mowry. Uv. 1300.
The glomeruli usually have a lobular structure (Fig. 14) and in this respect resemble lobular glomerulonephritis (Mandalenakis et al., 1971). The number of cells is increased by 2-2.5 times, most of them are located in the centers of the lobules. The basement membranes of the capillaries are thickened, look like homogeneous ribbons and are stained pink with hematoxylin-eosin, yellow with picrofuchsin, and red with the PAS reaction. When using some other stains, a significant change in the tinctorial properties of the basement membranes is detected, which is not found in any other lesions of the glomeruli. When stained with azocarmine, basement membranes, as a rule, do not perceive aniline blue and are stained red with azocarmine. However, the most clear change in the tinctorial properties of the basement membranes is found during silvering using the Jones method or its modifications. Basal membranes do not perceive silver and are stained with an additional dye (for example, orange G). At the same time, thickened and disintegrated mesangial fibers are silvered quite intensely (Fig. 15). This change in the tinctorial properties of the basement membranes can serve as a clear differential feature membranous proliferative glomerulonephritis (Burkholder et al., 1970; West and McAdams, 1970).
For the first time, such changes in basement membranes in nephrotic syndrome were observed by Jones (1957) and attributed them to the evolution of membranous glomerulonephritis. However, as the observations of other authors and our own studies show, these changes are also found in cases with a clinical duration of the disease of several months, and the spiny projections characteristic of membranous glomerulonephritis do not occur for any duration of the disease. Mandalenakis et al indicate a predominant proliferation of mesangial cells and an increase in the mesangial matrix in this form of glomerulonephritis, due to which lobulation becomes distinct in the glomeruli. (1971); Michael et al. (1971); West and McAdams (1970); Burkholder et al. (1970). The essence of changes in basement membranes and the pathogenesis of membranous proliferative glomerulonephritis seem unclear. The disease occurs predominantly in adolescence and is characterized by nephrotic syndrome, a long, relatively benign course with spontaneous remissions, low levels of serum complement, and lack of effect from steroid and immunosuppressive therapy (West and McAdams, 1970). Burkholder et al. (1970) found deposits in basement membranes of IgG- and IgM-globulin. On the contrary, Holland and Benett (1972) found predominantly βIC-globulin deposits in the basement membranes, and only a small amount of IgG. The authors doubt the immune nature of this form of glomerulonephritis and note the discrepancy constantly low level complement to long-term remissions during the course of the disease. In this regard, the evolution of morphological changes in the glomeruli is of interest. Herdman et al. (1970) observed a decrease in the thickness of basement membranes during repeated biopsy in the case of membranous proliferative glomerulonephritis. During repeated biopsy with clinical remission, we established not only a decrease in the thickness of the basement membranes, but also the partial formation of new ones with the restoration of their tinctorial properties. The process occurred with the participation of podocytes and was accompanied by a decrease in the number of mesangial cells to normal (Fig. 16). These changes may correspond to clinical remission of the disease. Perhaps complement fixation causes the destruction of the capillary basement membranes' own glycoproteins and the infiltration of the membranes with plasma glycoproteins; The tinctorial properties of the deposited protein differ from membranes.
Rice. 16. Repeated biopsy of the same patient as in Fig. 15, taken after 2 years.
The capillary membranes are much thinner compared to the previous study, in some places they are indistinguishable from normal ones, some of them are silvered. The mesangial skeleton is also much thinner. Impregnation and increase are the same,
what is in fig. 15.
Restoring tinctorial properties is only possible with restoration of the membrane itself. The disease is characterized by a relatively long course, but gradually the glomeruli can hyalinize and renal failure develops (Jones, 1957; Mandalenakis et al., 1971). The tinctorial properties of the membrane, characteristic of this form of glomerulonephritis, are preserved in the remaining glomeruli and can be used for differential diagnosis and on sectional material. Changes in the tubules correspond to the phase of the disease - with nephrotic syndrome, protein and lipids can accumulate in the epithelium of the proximal convoluted tubules; with renal failure, tubular atrophy and nephron desolation are noted.
Differential diagnosis V early stages diseases, when proliferation is less pronounced, is carried out with membranous glomerulonephritis. The only reliable diagnostic sign is the loss of argyrophilia by the basement membranes with silvering according to Jones - Mowry in the case of membranous proliferative glomerulonephritis and the presence of silvering spines on a somewhat thinned membrane in membranous glomerulonephritis. In later stages of the disease, in the presence of a pronounced lobular structure of the glomeruli, proliferation and thickening of the membranes, differentiation is carried out with lobular glomerulonephritis. And in this case, a reliable sign is the ratio of basement membranes to silver. In lobular glomerulonephritis, argyrophilia of the basement membranes with silvering according to Jones - Mowry is always preserved or increases as the basement membranes thicken, while in membranous-proliferative glomerulonephritis, the affinity of the membranes for silver is completely or partially (in cases of membrane restoration) lost *.
* To obtain satisfactory results when silvering, the thickness of paraffin sections should not exceed 3 microns.
Chronic glomerulonephritis is a chronic immune inflammatory disease of the kidneys with long-term persistent or recurrent urinary syndrome (proteinuria and/or hematuria) and a 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
Clinical forms* |
Latent (chronic glomerulonephritis with isolated urinary syndrome) |
Hematuric |
Hypertensive |
Nephrotic |
Mixed (nephrotic syndrome in combination with hypertension) |
Phases |
Exacerbation |
Remission |
Stages chronic renal insufficiency |
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 forms. 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
Mesangioproliferative glomerulonephritis |
IgA nephropathy (it is considered as a monosyndromic variant of adult hemorrhagic vasculitis), chronic viral hepatitis B, Crohn's disease, Sjögren's syndrome, ankylosing spondylitis, gastrointestinal adenocarcinomas |
Membrane-proliferative (mesangiocapillary) glomerulonephritis |
Idiopathic Secondary to SLE, cryoglobulinemia, chronic viral (hepatitis C virus) or bacterial infections, damage to the glomeruli of drugs by toxins |
Membranous glomerulonephritis |
Cancers of the lung, intestines, stomach, breast and kidney (paraneoplastic glomerulonephritis), non-Hodgkin's lymphoma, leukemia, SLE (lupus glomerulonephritis), viral hepatitis B, syphilis, filariasis, malaria, schistosomiasis, exposure to drugs (gold and mercury preparations, penicillamine) |
Glomerulonephritis With minimal changes |
Acute respiratory infections, vaccinations; sometimes occurs after the manifestation of an atopic phenotype (associated with HLA B12 Ag), when taking NSAIDs, rifampicin or interferon alfa; Fabry disease, diabetes mellitus, lymphoproliferative pathology (Hodgkin's lymphoma). In most cases the cause remains unknown |
Focal segmental glomerulosclerosis |
Idiopathic Secondary: sickle cell anemia, renal transplant rejection, cyclosporine toxicity, surgical excision of part of the renal parenchyma, chronic vesicoureteral reflux, heroin use; congenital (nephron dysgenesis, late stages Fabry disease) defects; HIV infection (collapsing nephropathy) |
Fibrillar-immunotactoid glomerulonephritis |
Often associated with lymphoproliferative diseases (chronic lymphocytic leukemia, Hodgkin's lymphoma) |
Fibroplastic glomerulonephritis |
Outcome of most glomerulopathies |
PATHOGENESIS
The same mechanisms are involved in the development and maintenance of immune inflammation as in acute glomerulonephritis. After the initiating damaging factors are triggered, the cells of the inflammatory infiltrate and the cells of the glomerulus secrete various mediators. Complement activation occurs, 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 a key role in the processes of accumulation and changes in the structure of the extracellular matrix, which end in sclerosis of the glomerulus.
However for further progression glomerulonephritis are important and non-immune factors.
Changes in hemodynamics (intraglomerular hypertension and hyperfiltration) occupy a leading place among non-immune mechanisms of progression of chronic glomerulonephritis. An increase in intraglomerular pressure is facilitated by systemic hypertension, adaptive hypertrophy and hyperfunction of the remaining nephrons, a concomitant decrease in the tone of arterioles (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 tissues of the nephron. 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 a 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.
There was a direct correlation between the progression of chronic glomerulonephritis and the presence of tubulointerstitial changes. In their development great importance give proteinuria, primarily with the release of albumin and transferrin. Excessively filtered proteins cause activation and release of vasoactive and inflammatory factors by tubular epithelium 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 response, marked 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 is the pathological basis of renal failure, has played an important role in the development of a nephroprotective strategy (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 of kidney damage. In the early stages of obesity, a state of relative oligonephronia develops (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. Most probable cause 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. Immune deposits are not found. 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 (focal changes) are involved in the process, sclerosis of individual segments occurs in them (segmental changes); the remaining glomeruli are intact. In the pathogenesis of focal segmental glomerulosclerosis, humoral permeability factors, as well as molecular mechanisms, are important. 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, inhibitors of cyclin-dependent kinase p21 and p27 are considered as 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. If 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 study reveals proteinuria (no more than 1-2 g / day), microhematuria, leukocyturia, cylindruria (hyaline and erythrocyte cylinders). The relative density of urine is not changed. Possibly primary latent and secondary latent course(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 the urine - microhematuria and usually unexpressed 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. Hypertension 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 the tone of the sympathetic division of the autonomic nervous system. Antidiuretic hormone is released and the synthesis of atrial natriuretic factor is inhibited. The combination of neurohumoral mechanisms leads to 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 of 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 increased risk 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).
Except large quantity 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 kidney disease” (CKD) has been proposed. 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. Characterized by episodes of gross hematuria with pain in lumbar region associated with nasopharyngeal or gastrointestinal infections. Unlike acute post-infectious glomerulonephritis, the time of onset kidney symptoms coincides with the influence 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 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 with 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. Hypertension is an important component of the 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. Symptoms of chronic renal failure are considered an additional sign.
SYNDROME DIAGNOSIS
NEPHROTICA SYNDROME
Nephrotic syndrome is most often observed in glomerulonephritis with minimal changes, membranous glomerulonephritis (both primary and secondary), focal segmental glomerulosclerosis, diabetic glomerulosclerosis, and 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 in urinary sediment occurs, in addition to chronic glomerulonephritis, with diabetic nephropathy and 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) damage to the glomeruli 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 of more often "large" proteinuria associated with multiple myeloma with the presence of paraprotein in the blood (hyperproteinemia). There is also benign proteinuria (occurs with a febrile reaction, hypothermia, emotional stress, accompanies heart failure and obstructive sleep apnea syndrome). The term "benign" reflects a favorable prognosis for kidney function. Orthostatic proteinuria occurs only in vertical position; it is commonly seen in adolescents, may be constant or intermittent, and has a favorable prognosis.
. Leukocyturia with glomerulonephritis, it often has the character of lymphocyturia (more than 20% of leukocytes in the urinary sediment are lymphocytes).
KIDNEY BIOPSY
Needle 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.
An increase in venous pressure in the systemic circulation - with 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 DIAGNOSIS
Chronic glomerulonephritis must be differentiated from chronic pyelonephritis, acute glomerulonephritis, nephropathy of pregnancy, 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 background pathology (chronic inflammation, primarily rheumatoid arthritis; multiple myeloma; Mediterranean familial fever). 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), scanty 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 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;
Reduction of edema;
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 trends in nephrology in recent years is the development of nephroprotective therapy aimed at inhibiting the progression of kidney diseases by influencing the common 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 ACTIVITIES
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 caution must be observed in the event of acute respiratory diseases or exacerbation of chronic foci of infection (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 against the background simultaneous administration drugs essential amino acids and their keto analogues (for example, "Ketosteril" 10-12 tablets per day). For nephrotic syndrome, a hypocholesterol diet and food containing polyunsaturated fatty acids (sea fish, sunflower oil) are rational.
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 high probability development of 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 questionable. For membrano-proliferative glomerulonephritis and focal segmental glomerulosclerosis, GCs are less effective. Two routes of administration of HA are used.
◊ Orally: average dose is 1 mg/kg/day in terms of prednisolone (usually it is 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 until completely cancelled).
◊ Pulse therapy involves intravenous drip administration 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 of glomerulonephritis with high the risk of 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 when using them (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 from these groups of drugs are used as part of combination regimens for hypertensive 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 intake of table salt to 3-5 g / day and observe bed rest with 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 initiation of 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 stenosis renal arteries.
◊ 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 EDEMAS
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, and symptomatic therapy (described above) are prescribed, if possible, the etiological factor (infection, tumor) is eliminated. 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 treating the underlying disease is undeniable. Hypertension control required; 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 be used only in patients with high proteinuria and/or renal failure to prevent its progression, but there are also advocates for the early use of “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 they cannot be discontinued after long-term use 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 baseline and 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 more of a contraindication than an indication for active immunosuppressive therapy, since resolution of sclerotic processes does not occur, and emerging side effects drugs are quite serious.
TREATMENT OF CHRONIC GLOMERULONEFRITIS ACCORDING TO CLINICAL FORMS
Carried out 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 for assessing the severity and prognosis of glomerulonephritis are important for choosing adequate therapy.
CHRONIC GLOMERULONEPHRITIS WITH ISOLATED URINARY SYNDROME
In the latent form (without hypertension and unchanged kidney 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 associated with mild proteinuria are recommended long-term use of 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 of mixed type is treated actively using three- or four-component regimens. Antihypertensive drugs and diuretics are used.
SPA TREATMENT
The main healing factor is exposure to a dry and warm climate.
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 of chronic renal failure are 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 have been developed taking into account the 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. With hematuria, the patient is referred for a consultation with 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 studies is the same, the frequency of observation is 1 time in 1-2 months. Particular attention should be paid 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 regression of 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 in most cases a benign course, but 20-40% of patients reach the end stage of chronic renal failure. Unfavorable prognostic factors for IgA nephropathy: elderly 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 spontaneously disappears in 40% of patients, recurs in 40% and proceeds continuously with slow development of CRF in 20% of patients. Unfavorable prognostic factors: male gender, advanced age, persistent hypertension, severe proteinuria and hyperlipidemia, deterioration of renal function, late recognition of 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 is a step towards a secondary wrinkled 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.
Membrane-proliferative GN- a heterogeneous group of diseases that have mixed nephritic and nephrotic features and morphological characteristics. They are mainly found in children. Cause of membrane-proliferative glomerulonephritis- deposition of immune complexes, which is idiopathic or secondary to systemic pathology. Diagnosis of membrane-proliferative glomerulonephritis confirmed by the kidneys. The prognosis is usually unfavorable. Treatment of membrane-proliferative glomerulonephritis includes antiplatelet drugs and glucocorticoids.
Membrane-proliferative GN is a group of immune-mediated disorders characterized histologically by thickening of the BM and proliferative changes on light microscopy. There are three types, each of which can have primary or secondary causes. Primary forms occur in children and young adults aged 8–30 years and are responsible for 10% of all cases of NS in children, while secondary forms tend to affect adults over 30 years of age. Men and women get sick equally often; Familial cases of some types of the disease are known. Genetic factors are thought to play a role, at least in some cases.
The type accounts for 80-85% of cases. It usually occurs secondary to systemic immune diseases, chronic infectious processes, malignant neoplasms and other disorders.
The type is 15-20%. It is likely an autoimmune disease in which gG autoantibodies bind the C3 convertase, rendering the latter resistant to inactivation; Immunofluorescent staining reveals SZ around dense inclusions and in the mesangium.
A type is considered to be a type-like disorder. The cause is unknown but may be related to immune complex deposition. gG autoantibodies against terminal complement components were detected in 70% of patients.
Symptoms of membrane-proliferative glomerulonephritis
Symptoms correspond to those in nephrotic syndrome in 60-80% of cases. Symptoms of nephritic syndrome are presented in 15-20% of cases and types and more often with the type of disease. At the time of diagnosis, 30% of patients have hypertension, and 20% have hypertension. Arterial hypertension often develops even before the glomerular filtration rate decreases. Patients with this type of disease have a high incidence of ocular disorders, which ultimately impair vision.
Diagnosis of membrane-proliferative glomerulonephritis
The diagnosis is based on the results of a kidney biopsy. Serum complement profiles are more often altered in membrane-proliferative GN than in other glomerular diseases and are of diagnostic value; hypocomplementemia is multifactorial in origin and is considered a disease marker rather than a cause. With the type of disease, the concentration of S3 is often reduced than C4 at the time of diagnosis, then it decreases during observation, but ultimately returns to normal. The content of SZ decreases more often and more intensely depending on the type of disease. In type, the concentration of C3 is reduced, and C4 remains normal. Nephritic factor S3 is found in 80% of patients with the type and in some patients with the GN type. Nephritic terminal complement factor is detected in 20% of the type, in rare cases of the type and 70% of cases of the type of disease.
Serological tests are mandatory to clarify the secondary causes of GN type. Clinical analysis blood obtained during diagnosis demonstrates normochromic non-normocytic, often disproportionate to the stage, and thrombocytopenia of consumption.
Prognosis and treatment of membrane-proliferative glomerulonephritis in children
Membrane-proliferative type GN often progresses slowly. The type progresses noticeably faster. In general, the long-term prognosis is unfavorable. End-stage renal disease develops in 50% of patients within 3-5 years and in 75% within 10 years; after 5 years, only 25% of patients maintained normal renal function. Spontaneous remission occurs in less than 5% of patients. Membrane-proliferative type GN recurs in 30% of cases after transplantation; the type recurs in 90% of cases.
Specific therapy is probably not indicated for patients with non-nephrotic range proteinuria because the disease usually progresses slowly. Children with “nephrotic range” proteinuria are prescribed prednisolone 2.5 mg/kg orally once a day every other day for a year, followed by a maintenance dose of 20 mg every other day for 3-10 years, which can stabilize renal function. However, glucocorticoids can cause growth retardation and hypertension. In adults, dipyridamole with acetylsalicylic acid for a year appears to stabilize renal function after 3-5 years of onset, but after 10 years there is no difference from placebo. Long-term therapy may be required.
Additional methods of treatment of membrano-proliferative glomerulonephritis include interferon-2 for pathology associated with, and plasmapheresis with glucocorticoids for concomitant severe cryoglobulinemia or rapidly progressing GN. ACE inhibitors may reduce proteinuria and help control hypertension.
