Wegener's granulomatosis and kidney damage

Wegener's granulomatosis is a granulomatous inflammation of the respiratory tract with necrotic vasculitis of small and medium-sized vessels, combined with necrotizing glomerulonephritis.

Epidemiology

Wegener's granulomatosis is affected almost at the same frequency by both men and women of any age. In the literature there are descriptions of the disease in children under 2 years and persons over 90 years, but the average age of patients is 55-60 years. In the United States, the disease is more often found in representatives of the white race than in African Americans. The frequency of Wegener's granulomatosis, which has long been considered a casuistically rare disease, is rapidly growing in recent years: in the early 1980s, the incidence of this form of systemic vasculitis, according to epidemiological studies in the UK, was 0.05-0.07 cases per 100 000 population , in the period from 1987 to 1989 - 0.28 cases per 100 000 population, and from 1990 to 1993 - 0.85 cases per 100 000 population. In the US, the incidence is 3 cases per 100 000 population.

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

Causes of the wegener's granulomatosis

Wegener's granulomatosis was first described in 1931 by N. Klinger as an unusual form of nodular polyarteritis. In 1936 F. Wegener identified the disease as an independent nosological form, and in 1954 G. Godman and J. Churg formulated modern clinical and morphological criteria for diagnosis, including a characteristic triad of symptoms: granulomatous airway inflammation, necrotizing vasculitis and glomerulonephritis.

The exact cause of Wegener's granulomatosis is not established. We assume a connection between the development of Wegener's granulomatosis and infection, which is indirectly confirmed by the facts of frequent onset and exacerbation of the disease in the winter-spring period, mainly after respiratory infections, which is associated with the ingestion of an antigen (possibly of viral or bacterial origin) through the respiratory tract. There is also a higher frequency of exacerbations of the disease in carriers of  Staphylococcus aureus.

[5], [6], [7], [8], [9]

Pathogenesis

In the pathogenesis of Wegener's granulomatosis, antineutrophilous cytoplasmic antibodies (ANCA-Anti-Neu-trophil Cytoplasmatic Antibodies) have played a key role in recent years. In 1985, FJ Van der Woude et al. First showed that ANCA were detected with high frequency in patients with Wegener's granulomatosis, and suggested their diagnostic significance in this form of systemic vasculitis. Later, ANCA were detected in other forms of vasculitis of small vessels (microscopic polyangiitis and Cherdja Strauss syndrome), and this group of diseases was called ANCA-associated vasculitis.

[10], [11], [12], [13], [14], [15], [16], [17],

Symptoms of the wegener's granulomatosis

The onset of Wegener's granulomatosis often occurs in the form of an influenza-like syndrome, the development of which is associated with the circulation of pro-inflammatory cytokines, possibly produced as a result of a bacterial or viral infection preceding the prodromal period of the disease. At this time, most patients have typical symptoms of Wegener's granulomatosis: fever, weakness, malaise, migratory arthralgia in both large and small joints,  myalgia, anorexia, weight loss.

The prodromal period lasts about 3 weeks, after which the main clinical signs of the disease appear.

Symptoms of Wegener's granulomatosis, as in other vasculitis of small vessels, are distinguished by significant polymorphism associated with frequent damage to the vessels of the skin, lungs, kidneys, intestines, peripheral nerves. With different forms of vasculitis of small vessels, the frequency of these organ manifestations is different.

Diagnostics of the wegener's granulomatosis

Diagnosis of Wegener's granulomatosis reveals a number of nonspecific laboratory changes: an increase in ESR, neutrophilic leukocytosis, thrombocytosis, normochromic anemia, in a small percentage of cases of eosinophilia. Characteristic of disproteinemia with an increase in the level of globulins. In 50% of patients, rheumatoid factor is detected. The main diagnostic marker of Wegener's granulomatosis is the ANCA, whose titer correlates with the degree of vasculitis activity. In most patients, c-ANCA (to proteinase-3) is detected.

[18], [19], [20], [21], [22], [23]

Treatment of the wegener's granulomatosis

With natural course in the absence of therapy, ANCA-associated vasculitis has an unfavorable prognosis: before the introduction of immunosuppressive drugs into clinical practice, 80% of patients with Wegener's granulomatosis died in the first year of the disease. In the early 1970s, before the widespread use of cytotoxic drugs, the 5-year survival rate was 38%.

With the use of immunosuppressive therapy, the prediction of Wegener's granulomatosis has changed: the use of aggressive therapeutic regimens makes it possible to achieve the effect in 90% of patients, 70% of them note complete remission with restoration of kidney function or its stabilization, disappearance of hematuria and extrarenal signs of the disease.

Forecast

The prediction of Wegener's granulomatosis is determined primarily by the severity of the lung and kidney damage, the period of onset and the regimen of therapy. Before the use of immunosuppressive drugs 80% of patients died during the first year of the disease. Survival was less than 6 months. Monotherapy with glucocorticoids, the suppressive activity of vasculitis and upper respiratory tract damage, increased the life expectancy of patients, but proved ineffective in the defeat of the kidneys and lungs. Addition of cyclophosphamide to the therapy allowed to achieve remission in more than 80% of patients with pulmonary-renal syndrome within Wegener's granulomatosis.

Prognostic factors for ANCA-associated vasculitis are the level of blood creatinine before treatment and hemoptysis. Hemoptysis is an unfavorable prognostic sign for the patient's survival, and the concentration of blood creatinine in the onset of the kidney process is the determining risk factor for the development of chronic renal insufficiency. In patients with a creatinine concentration in the blood of less than 150 μmol / L, 10-year renal survival is 80%. The main morphological factor of a favorable prognosis is the percentage of normal glomeruli in the kidney biopsy.

The main causes of death of patients with Wegener's granulomatosis in the acute phase of the disease are generalized vasculitis, severe renal failure, infections.

[24], [25]