Wegener's granulomatosis and kidney damage

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

Epidemiology

Wegener's granulomatosis affects men and women of any age with almost equal frequency. The literature contains descriptions of the disease in children under 2 years of age and people over 90 years of age, but the average age of patients is 55-60 years. In the United States, the disease is more often detected in representatives of the white race than in African Americans. The incidence of Wegener's granulomatosis, long considered a casuistically rare disease, has been rapidly increasing in recent years: in the early 1980s, the incidence of this form of systemic vasculitis, according to epidemiological studies conducted 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 United States, the incidence rate is 3 cases per 100,000 population.

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Causes Wegener's granulomatosis

Wegener's granulomatosis was first described in 1931 by H. Klinger as an unusual form of nodular polyarteritis. In 1936, F. Wegener identified this 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 signs: granulomatous inflammation of the respiratory tract, necrotizing vasculitis, and glomerulonephritis.

The exact cause of Wegener's granulomatosis has not been established. It is assumed that there is a connection between the development of Wegener's granulomatosis and infection, 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 entry of an antigen (possibly of viral or bacterial origin) through the respiratory tract. A higher frequency of exacerbations of the disease is also known in carriers of Staphylococcus aureus.

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Pathogenesis

In recent years, a key role in the pathogenesis of Wegener's granulomatosis has been attributed to anti-neutrophil cytoplasmic antibodies (ANCA). In 1985, FJ Van der Woude et al. first demonstrated that ANCA are detected with high frequency in patients with Wegener's granulomatosis and suggested their diagnostic significance in this form of systemic vasculitis. Later, ANCA were found in other forms of small vessel vasculitis (microscopic polyangiitis and Churg-Strauss syndrome), which is why this group of diseases began to be called ANCA-associated vasculitis.

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Symptoms Wegener's granulomatosis

The onset of Wegener's granulomatosis often occurs as a flu-like syndrome, the development of which is associated with the circulation of proinflammatory 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, migrating 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.

The symptoms of Wegener's granulomatosis, as with other small vessel vasculitis, are distinguished by significant polymorphism associated with frequent damage to the vessels of the skin, lungs, kidneys, intestines, and peripheral nerves. The frequency of these organ manifestations varies with different forms of small vessel vasculitis.

Diagnostics Wegener's granulomatosis

Diagnosis of Wegener's granulomatosis reveals a number of non-specific laboratory changes: increased ESR, neutrophilic leukocytosis, thrombocytosis, normochromic anemia, and in a small percentage of cases, eosinophilia. Dysproteinemia with increased globulin levels is characteristic. Rheumatoid factor is detected in 50% of patients. The main diagnostic marker of Wegener's granulomatosis is ANCA, the titer of which correlates with the degree of vasculitis activity. Most patients are found to have c-ANCA (to proteinase-3).

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Treatment Wegener's granulomatosis

In the natural course without 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 cytostatic drugs, the 5-year survival rate was 38%.

With the use of immunosuppressive therapy, the prognosis of Wegener's granulomatosis has changed: the use of aggressive therapeutic regimens allows achieving an effect in 90% of patients, of which 70% experience complete remission with restoration of renal function or its stabilization, disappearance of hematuria and extrarenal signs of the disease.

Forecast

The prognosis of Wegener's granulomatosis is determined primarily by the severity of lung and kidney damage, the time of onset and the treatment regimen. Before the use of immunosuppressive drugs, 80% of patients died within the first year of the disease. Survival was less than 6 months. Monotherapy with glucocorticoids, suppressing the activity of vasculitis and damage to the upper respiratory tract, increased the life expectancy of patients, but was ineffective in kidney and lung damage. Adding cyclophosphamide to therapy made it possible to achieve remission in more than 80% of patients with pulmonary-renal syndrome in the context of Wegener's granulomatosis.

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

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

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