Mesangiocapillary (membrane-proliferative) glomerulonephritis

Mesangiocapillary (membranoproliferative) glomerulonephritis - a variant of glomerulonephritis with a progressive course is very rare.

[1], [2], [3], [4], [5]

Epidemiology

Morphologically characterized by the proliferation of mesangial cells, creating lobularity of the glomeruli ("lobular nephritis"), and thickening or two-contouring of the capillary wall - due to the penetration (interposition) of mesangial cells. According to the location and nature of electron-dense deposits, three (sometimes four) types of mesangiocapillary nephritis are distinguished, which are identical clinically and differ slightly in laboratory data and in the results of transplantation. Most often there are types I and II. In type I, immune deposits are localized under the endothelium and in the mesangial region of the glomeruli (subendothelial or classical mesangiocapillary glomerulonephritis), in type II ("disease of dense deposits"), special osmiophilic electron-dense deposits of an unclear nature are located within the basal membrane.

The frequency among other types of glomerulonephritis in the 70's was 10-20%; in recent years in Europe and North America, mesangiocapillary glomerulonephritis has become less common (5-6%).

[6], [7], [8], [9], [10], [11]

Causes of the mesangiocapillary (membrane-proliferative) glomerulonephritis

The causes of mesangiocapillary glomerulonephritis are divided into viral and bacterial infections. Often, mesangiocapillary type I glomerulonephritis develops with infection with HBV, but recently special attention is paid to the connection of mesangiocapillary glomerulonephritis type I with HCV. In 50-60% of patients with type I mesangiocapillary glomerulonephritis, infected with HCV, cryoglobulins are detected. Cases associated with streptococcal infection, infective endocarditis, as well as the development of mesangiocapillary glomerulonephritis in schistosomiasis, pulmonary tuberculosis, and malaria are described.

Along with the idiopathic form, mesangiocapillary glomerulonephritis is detected in systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren's syndrome, ulcerative colitis, sarcoidosis, lymphomas, neoplasms, etc.

Genetic factors may play a role in the development of mesangiocapillary glomerulonephritis. Family cases of the disease in siblings are described, as well as in several generations.

A feature of mesangiocapillary glomerulonephritis is hypocomplexemia with a decrease in the level of C3 and / or C4 components, which is especially often detected in type II. Hypokomplementemia is caused by a violation of the synthesis and catabolism of complement, as well as the presence in the serum of the blood of a special immunoglobulin - C3-nephritic factor directed against C3-convertase.

Mesangiocapillary glomerulonephritis (often of type II) is sometimes combined with partial lipodystrophy (a disease that also occurs with hypocomplexemia).

More often men of young age are ill, and also children (the age is younger at type I). In the elderly it is rare.

[12]

Symptoms of the mesangiocapillary (membrane-proliferative) glomerulonephritis

Symptoms of mesangiocapillary (membranoproliferative) glomerulonephritis are the same for all morphological variants: haematuria (10-20% transient macrohematuria), pronounced proteinuria and nephrotic syndrome (often with elements of acute phthisis), decreased renal function. Mesangiocapillary glomerulonephritis is responsible for 10% of cases of nephrotic syndrome in adults and 5% in children. Arterial hypertension  is observed often, sometimes it is severe.

The combination of nephrotic syndrome with hematuria and hypertension should always be alarming regarding the possibility of mesangiocapillary nephritis. Possible  anemia  (which is associated with the presence of activated complement on the surface of erythrocytes). At type II describe a kind of retinopathy (diffuse bilateral symmetrical lesions of yellow color).

Mesangiocapillary (membranoproliferative) glomerulonephritis often begins with acute nephritic syndrome with sudden development of  hematuria, pronounced proteinuria, edema and hypertension; in this case mistakenly diagnose acute nephritis. Almost in 1/3 of patients, the disease may manifest as a rapidly progressive renal failure with a "half moon" in the kidney biopsy.

Because of the frequent combination of mesangiocapillary glomerulonephritis with infections and systemic diseases, in each case careful search of concomitant pathology is necessary.

The course of the process is steadily progressing, spontaneous remissions are rare. Mesangiocapillary glomerulonephritis is one of the most unfavorable forms; in the absence of treatment, terminal renal failure develops in 10 years in almost 50%, in 20 years - in 90% of patients. According to J.St. Cameron et al. (1983), 10-year survival of patients with nephrotic syndrome was 40%, patients without nephrotic syndrome - 85%. As a special feature of the flow of mesangiocapillary glomerulonephritis, there is a "gradual" progression and a relatively sudden deterioration in kidney function in individual patients. Clinically poor prognostic signs are the presence of nephrotic syndrome, diastolic hypertension, decreased kidney function and the detection of serological signs of HCV and HBV infection. The level of complement has no prognostic value. Mesangiocapillary glomerulonephritis, especially type II, often recurs in the graft.

Treatment of the mesangiocapillary (membrane-proliferative) glomerulonephritis

Treatment of mesangiocapillary glomerulonephritis is still insufficiently developed. A number of proposed approaches do not have sufficient justification, and many authors seem contentious. Adverse prognostic signs - the presence of nephrotic syndrome and impaired renal function from the very beginning of the disease. In patients with nephrotic syndrome, 10-year renal survival is no more than 50%.

It should be remembered about the possibility of secondary forms of mesangiocapillary glomerulonephritis, which require other therapeutic approaches: mesangiocapillary glomerulonephritis in chronic infections (including HBV and HCV virus infection), cryoglobulinemia, and various forms of plasma cell discourses. In these diseases, antibacterial therapy, alpha-interferon, plasmapheresis, or chemotherapy can be indicated.

In other patients, if idiopathic mesangiocapillary glomerulonephritis is confirmed, the following approaches are recommended.

Treatment of mesangiocapillary glomerulonephritis without nephrotic syndrome

Patients with proteinuria less than 3 g / day and normal CF in active treatment do not need; with hypertension is important strict control of blood pressure, preferably ACE inhibitors; with large proteinuria and decreased CF, it is possible to use prednisolone and cytostatics or a combination of aspirin and dipyridamole.

Treatment of mesangiocapillary glomerulonephritis with nephrotic syndrome

Corticosteroids / corticosteroids and cytotoxic agents

At the first attack of a nephrotic syndrome and normal function of kidneys it is possible to begin with corticosteroids [1 mg / (kghsut) for 2 months]. In this case, the results are better in children who have the greatest experience of prolonged steroid therapy.

When the combination of corticosteroids with cytostatics results are better. R. Faedda et al. (1994), in 19 patients with glucocorticoids (initially methylprednisolone pulses, then prednisolone inwards) and cyclophosphamide on average for 10 years followed by observation (7.5 years), remission was noted in 15 of 19 patients (40% of the patients developed gonadal failure); a part of patients had relapses, which were also inferior to co-therapy. In our group of 28 patients with mesangiocapillary glomerulonephritis receiving cytostatics (cyclophosphamide, chlorbutin or azathioprine) in combination with prednisolone, 10-year renal survival was 71%, which is significantly higher than that usually observed in untreated nephrotics with mesangiocapillary glomerulonephritis. In another study, of the 9 seriously ill mesangiocapillary glomerulonephritis treated with cyclophosphamide pulses, the best results (100% renal survival after 7 years) were recorded in 4 patients with a high index of morphological activity (> 4) who received at least 6 g of the drug for 6 months. At the same time, in 5 patients with the same activity index, but less actively treated (who received less than 6 g of the drug), renal survival was less than 50%.

In this regard, with a pronounced nephrotic syndrome or nephrotic syndrome with a declining renal function, it is better to begin immediately with a combination of corticosteroids and cytostatics (the latter can be in the form of cyclophosphamide pulses).

[13], [14], [15], [16], [17], [18], [19]

Cytotoxic drugs, anticoagulants and antiplatelet agents

In uncontrolled studies, a combination of cytostatics, anticoagulants and antiplatelet agents produced good results. In a controlled study evaluating the effects of cyclophosphamide, dipyridamole and warfarin, no significant effect on proteinuria and progression of renal failure was observed. In another controlled trial, dipyridamole (225 mg / day) and aspirin (975 mg / day) in patients with type I mesangiocapillary glomerulonephritis slowed the rate of progression during the first 4 years, but by the 10th year these differences between treated and untreated patients were erased (renal survival rate, respectively, 49 and 41%).

[20], [21], [22], [23]

Cyclosporin

Data on the use of cyclosporine in mesangiocapillary glomerulonephritis are very limited. In uncontrolled studies, cyclosporine [4-6 mg / (kg x 105)] combined with low doses of prednisalone caused a moderate decrease in proteinuria. However, due to the potential nephrotoxicity and increased hypertension, cyclosporine in patients with mesangiocapillary glomerulonephritis is not widely used at present.

[24], [25], [26], [27], [28], [29], [30], [31]