Treatment of kidney damage in 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 treatment for Wegener's granulomatosis, the prognosis of this disease 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.

Since the prognosis depends on the timing of the initiation of treatment for Wegener's granulomatosis, the main principle of therapy is its early initiation, even if there are no morphological and serological data.

Treatment of ANCA-associated vasculitis with renal involvement has 3 phases: remission induction, maintenance therapy and treatment of exacerbations. The best results are obtained with treatment with cyclophosphamide in combination with glucocorticoids.

• Induction of remission.
  • To induce remission, pulse therapy with methylprednisolone is used at a dose of 500-1000 mg intravenously for 3 days, followed by prescribing prednisolone orally at a dose of 1 mg/kg of body weight per day for at least 1 month. Then the dose of prednisolone is gradually reduced to a maintenance dose: by 6 months of treatment - 10 mg/day.
  • Cyclophosphamide is prescribed as pulse therapy at 800-1000 mg intravenously once a month or orally at a dose of 2-3 mg/kg of body weight per day (150-200 mg/day) for 4-6 months.
  • At the initial stage of treatment, simultaneous "pulse" therapy with methylprednisolone and cyclophosphamide is justified. The doses of the drug depend on the severity of the patient's condition and the severity of renal failure: methylprednisolone is prescribed in a dose of no more than 500 mg intravenously for 3 days, cyclophosphamide - 400-600 mg intravenously once in patients with severe arterial hypertension, electrolyte disorders, with a glomerular filtration rate of less than 30 ml / min, in patients prone to the development of infections and cytopenia. The intervals between pulse therapy sessions in such situations should be reduced to 2-3 weeks.
• Maintenance treatment of Wegener's granulomatosis.
  • If remission of the disease is achieved after 6 months of treatment, the dose of cyclophosphamide is reduced to a maintenance dose (100 mg/day), which the patient takes for at least another year. An alternative option for maintenance therapy is replacing cyclophosphamide with azathioprine at a dose of 2 mg/kg of body weight per day.
  • The optimal duration of treatment with cytostatics has not been determined. In most cases, therapy can be limited to 12 months, and if clinical and laboratory remission is achieved, the drugs should be discontinued, after which the patient should remain under the supervision of a specialist. However, with this treatment regimen, the duration of remission is usually short. Therefore, upon achieving remission, treatment with cytostatics is recommended to be continued for another 12-24 months, which significantly reduces the risk of exacerbations. Both regimens of cyclophosphamide administration (pulse therapy and oral administration) are equally effective in suppressing the activity of vasculitis at the beginning of treatment. However, the frequency of exacerbations is higher and the duration of remission is shorter in patients treated with ultra-high doses of drugs intravenously, and therefore, after several pulse therapy sessions, it is advisable to switch to oral cyclophosphamide.
  • The role of plasmapheresis in the treatment of "poorly immune" ANCA-associated vasculitides is unclear. It is believed that in Wegener's granulomatosis, plasmapheresis is indicated in cases of rapid development of renal failure (creatinine concentration in the blood is more than 500 μmol/l) and the presence of potentially reversible changes in the kidney biopsy. It is recommended to conduct 7-10 plasmapheresis sessions with the replacement of 4 l of plasma over 2 weeks. The absence of a positive effect during this period makes further use of the method inappropriate.
• Treatment of exacerbations. Despite adequate treatment at the onset of the disease, 40% of patients develop exacerbations on average 18 months after stopping therapy. Usually, the same lesions are noted as at the onset of the disease, but involvement of new organs is also possible. Exacerbation of glomerulonephritis is manifested by microhematuria and deterioration of renal function. It is not recommended to consider fluctuations in proteinuria as a reliable sign of exacerbation, since moderate proteinuria is possible with the development of glomerulosclerosis. Treatment of Wegener's granulomatosis and exacerbations requires the same therapeutic approach that is used at the onset of the disease. To monitor the activity of Wegener's granulomatosis and timely initiation of treatment for exacerbations, it is proposed to conduct a study of the ANCA titer in dynamics. According to various authors, an increase in ANCA titers is observed during an exacerbation of the disease in 25-77% of patients, however, ANCA titers should not be used as a decisive factor in determining indications for resuming immunosuppressive therapy or its discontinuation, since in a number of patients an exacerbation is not accompanied by an increase in ANCA titers, and the persistence of high titers is noted in individuals with clear clinical remission.

Renal replacement therapy

Almost 20% of patients with Wegener's granulomatosis require hemodialysis at diagnosis. In half of them, hemodialysis is a temporary measure that can be stopped within 8-12 weeks. However, at the beginning of this type of treatment, it is almost impossible to determine in which patients, immunosuppressive treatment of Wegener's granulomatosis, carried out in parallel, will lead to restoration of kidney function and the disappearance of the need for hemodialysis. Subsequently, most of these patients develop terminal chronic renal failure within a period of several months to 3-4 years. Patients with Wegener's granulomatosis who undergo hemodialysis due to terminal chronic renal failure, as a rule, do not have extrarenal signs of vasculitis activity and do not require maintenance immunosuppressive therapy; however, in some cases, exacerbations of the disease develop, which serves as an indication for the resumption of active treatment with glucocorticoids and cytostatics, the regimen of which is adjusted depending on the hemodialysis regimen.

Kidney transplantation has now been performed in a small number of patients with Wegener's granulomatosis.