Mesangioproliferative glomerulonephritis

Mesangioproliferative glomerulonephritis is characterized by the proliferation of mesangial cells, the expansion of mesangium, the deposition of immune complexes in mesangium and under the endothelium.

Mesangioproliferative glomerulonephritis is a fairly frequent morphological type of glomerulonephritis, responding (unlike previous variants) to all the criteria of glomerulonephritis as an immunoinflammatory disease. The main symptoms of mesangioproliferative glomerulonephritis: proteinuria, hematuria, in some cases - nephrotic syndrome, arterial hypertension. The course of mesangioproliferative glomerulonephritis is relatively favorable. In our early observations, 10-year survival (before terminal renal failure) was 81%. Currently, there is a tendency to identify different clinical and morphological options, depending on the class of immunoglobulins that prevail in glomerular deposits.

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

Causes and pathogenesis of IgA-nephropathy

The causes and pathogenesis of IgA-nephropathy are intensively studied. One hypothesis suggests an abnormal glycosylation of IgA, which leads to its deposition in the glomeruli and causes activation of leukocytes and cascade of inflammation.

As possible etiological factors, viral (and other infectious), food and endogenous antigens are discussed. Among the viruses, the possible role of respiratory viruses, cytomegalovirus and the Epstein-Barr virus is being studied . UHF-irradiation of the tonsils (possibly, stimulating ARVI) causes a worsening of urine tests, especially in those patients who had a history of macrohematuria.

There are reports of the etiological role of mycotoxin. It is believed that mycotoxin, entering the intestines and disrupting the immune system of the mucosa, can be the cause of IgA-H in humans.

Among the food antigens in some patients, the role of gluten has been proven. In the serum of patients with IgA-H, titers of IgA-AT were increased to gliadin and other food proteins. The role of endogenous antigens, including hit-shock proteins, is possible.

Genetic factors also matter. Associations between lgA-nephritis and HLA-BW35, as well as with HLA-DR4-antigen are described. Family cases are possible. There is evidence of a link between the progression of IgA-H and the polymorphism of the ACE gene.

Kidney damage is characterized by focal or diffuse mesangioproliferative glomerulonephritis or other types of proliferative glomerulonephritis. At present, there is a tendency to refer to IgA-H and other morphological types of glomerulonephritis with kidney deposition of IgA. Morphologically the activity of IgA-H is assessed by the same signs as the activity of other morphological types.

[6], [7], [8], [9], [10], [11], [12],

Symptoms of IgA Nephropathy

Symptoms of IgA nephropathy develop at a young age, more often in men. In 50% of patients, recurrent macrohematuria occurs in febrile respiratory illnesses in the first days or even hours of illness ("synpharyngitis macrohematuria"), less often after other diseases, vaccination or severe physical exertion. Often, macrohematuria is accompanied by inefficient dull pain in the lower back, transient hypertension, sometimes with fever. Episodes of macrohematuria can be with transient oliguric acute renal failure, presumably caused by congestion of tubules by erythrocyte cylinders.

In most cases, these episodes pass without a trace, but patients described in whom after acute renal failure the function of the kidney was not completely restored.

In other patients, IgA-nephritis is latent, with microhematuria, often with small proteinuria. In 15-50% of patients (usually older age and / or with microhematuria) in later stages, nephrotic syndrome (in our observations in 25% of patients) may join, in 30-35% - arterial hypertension. Among our patients with microhematuria, systemic signs were frequently noted: arthralgia, myalgia, Raynaud's syndrome, polyneuropathy, hyperuricemia.

IgA-nephropathy

The main place among the variants of mesangioproliferative glomerulonephritis is occupied by glomerulonephritis with the deposition in the glomeruli of immunoglobulin A-IgA-nephritis, IgA-nephropathy (IgA-H), Berger's disease. It was described by J. Berger et al. In 1967 as a recurrent benign hematuria. In subsequent years, with prolonged follow-up, it was found that in 20-50% of adult patients, kidney function worsens over time. Now it is considered as a persistent or slowly progressing disease.

Currently, the framework of IgA-H is expanding significantly. In this group, a number of researchers include other types of jade, in which IgA is detected in the glomeruli. At the same time, the terms "IgA-nephritis" or more often "IgA-nephropathy" are gradually beginning to be replaced with the term "Mesangioproliferative glomerulonephritis", although it is mentioned that IgA-H belongs to a large group of mesangioproliferative nephritis, including glomerulonephritis with C3 and IgG deposits, and glomerulonephritis with IgM deposits.

The problem is complicated by the vagueness of the relationship between IgA-H and hemorrhagic vasculitis (purpura Schonlein-Henoch), which also increases serum IgA, and IgA deposits are found in the kidneys, and it is therefore assumed that IgA-H is a mono-organ form of hemorrhagic vasculitis.

The incidence of IgA nephritis among other types of glomerulonephritis is approximately 30% in Asia and 10-12% in Europe and Australia. In some countries (Japan), IgA-nephritis has prevailed (25-50%) among all cases of chronic glomerulonephritis. According to our clinic, it was detected in 12.7% of 1218 morphologically confirmed cases of glomerulonephritis (8.5% of all biopsies).

Diagnosis of IgA-nephropathy

In the serum of blood in 35-60% of patients the content of IgA is increased, its polymeric forms predominate. The degree of increase in IgA does not reflect the clinical course of the disease and does not affect the prognosis. Serum also reveals high titers of IgA-containing immune complexes, which in some cases contain antibodies against bacterial, viral and food antigens. Complement whey is usually normal.

Differential diagnosis of IgA-nephropathy is carried out with urolithiasis, kidney tumors, with IgA-nephritis in hemorrhagic vasculitis and chronic alcoholism, with Alport syndrome, disease of thin basal membranes.

Disease of thin basal membranes (benign familial hematuria) is a disease with a good prognosis, taking place with microhematuria; usually inherited by an autosomal dominant type; there are no deposits of IgA in the kidneys; for the final confirmation of the diagnosis, it is necessary to measure the thickness of the GBM at electron microscopy, which is 191 nm for thin membrane disease, and 326 nm for IgA-H.

The course of IgA-H is relatively favorable, especially in patients with macrogemuria. Renal insufficiency develops in 10-15 years in 15-30% of patients, progresses slowly.

Factors worsening the prognosis for IgA-nephropathy:

• pronounced microhematuria;
• pronounced proteinuria;
• arterial hypertension;
• kidney failure;
• severity of morphological changes (sclerosis of glomeruli, interstitium);
• deposition of IgA in the walls of peripheral vessels;
• male;
• older age at the onset of the disease.

L. Frimat et al. (1997) in a prospective study identified 3 main clinical factors of poor prognosis: males, daily proteinuria level above 1 g and serum creatinine level more than 150 mmol / l.

IgA-H often recurs in the transplant, in 50% of recipients - within 2 years. However, when transplanting a cadaveric kidney, graft survival is better than with other kidney diseases. It is not recommended to transplant from HLA-identical siblings.

[13], [14], [15]

Treatment of mesangioproliferative glomerulonephritis and lgA-nephropathy

Currently, the treatment of mesangioproliferative glomerulonephritis and IgA-nephropathy has not been developed. This can partly be explained by the large variability in the outcomes of the disease (terminal renal failure develops only in some patients, with varying rates) and the difficulty of predicting the prognosis in each individual patient, even with the already established clinical and morphological prognostic factors. Most of the studies to date that concluded that proteinuria decreased or stabilized function as a result of therapy are based either on individual observations or retrospective data analysis.

Elimination of foci of infection, tonsillectomy

The effectiveness of other measures aimed at preventing exacerbations of infection, namely the removal of the foci of infection (tonsillectomy) and prolonged therapy with antibiotics, is still debated. Tonsillectomy does reduce the number of episodes of macrogematuria, and sometimes also proteinuria and IgA level in serum. There is evidence of a possible inhibitory effect of tonsillectomy on the progression of the kidney process. In connection with this, tonsillectomy can be recommended to patients with frequent exacerbations of tonsillitis.

Some authors believe that the short-term treatment with antibiotics of acute respiratory or gastrointestinal infections is justified, especially when the infection provokes episodes of macrohematuria.

[16], [17], [18], [19]

Glucocorticosteroids and cytotoxic agents

Evidence of a significant effect of immunosuppressants (glucocorticoids or their combination with cytostatics) on the course of slowly progressing forms of the disease is not.

A large multicenter Italian study evaluating the effectiveness of glucocorticoids (alternating regimen) in patients with a high risk of progression - a proteinuria level of 1-3.5 g / day, confirmed a decrease in proteinuria and stabilization of kidney function.

In our observations, cytostatic therapy was effective in 59% of patients with mesangioproliferative glomerulonephritis. In a randomized prospective study, the efficacy of pulse therapy with cyclophosphamide was the same as for oral administration, but there were significantly fewer side effects.

Cyclophosphamide, dipyridamole, warfarin (phenylin)

This three-component method (cyclophosphamide for 6 months, the remaining 2 drugs for 3 years) in a controlled study from Singapore reduced proteinuria and stabilized kidney function. However, a 5-year follow-up assessment of patients in the Singapore study did not reveal any difference in the rate of progression of renal failure in the treated and untreated patients.

Cyclosporine in a dose of 5 mg / kghs) in a randomized trial reduced proteinuria, serum IgA concentration and expression of interleukin-2 receptors on T-cells. V. Chabova et al. (1997) treated with cyclosporine A 6 patients with IgA-nephropathy with proteinuria more than 3.5 g / day (average 4.66 g / day) and creatinine level less than 200 μmol / l; proteinuria decreased after 1 month to 1.48 and after 12 months to 0.59 g / day. Complications: hypertension (4 patients), hypertrichosis (2 patients), vomiting (1 patient). In our studies, cyclosporin A caused remission in 4 of 6 patients with resistant or steroid-dependent PGMN with nephrotic syndrome.

Fish oil containing omega-3-polyunsaturated fatty acids (suppressing the synthesis of inflammatory prostaglandins) was ineffective in patients with IgA nephritis in three controlled studies and slowed the progression of renal failure in one controlled trial in patients with moderately impaired function (creatinine <3 mg %), who received fish oil for 12 g / day for 2 years.

Thus, based on the severity of the prognosis of different variants of IgA-nephropathy, the following therapeutic approaches can be recommended:

• patients with isolated hematuria (especially with episphanting macrogematuria), small proteinuria (<1 g / day) and normal renal function, aggressive therapy is not indicated. ACE inhibitors (for nephroprotective purposes), dipyridamole may be prescribed;
• patients with a risk of progression (proteinuria> 1 g for 24 h, hypertension, normal or moderately reduced renal function or morphological signs of disease activity) may be prescribed:
  • ACE inhibitors: prolonged use even at normal arterial pressure;
  • cod liver oil: 12 g / day for 2 years (effectiveness is still doubtful);
  • corticosteroids: taking prednisolone orally every other day, starting at 60 mg / day for 3 months with a gradual decrease in dose;
• Patients with severe proteinuria (> 3 g / day) or nephrotic syndrome are shown active therapy - glucocorticoids, cytostatics (including in the form of CPA-pulse therapy).

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