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

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

Treatment of ANCA-associated vasculitides with kidney damage has 3 phases: remission induction, maintenance therapy and treatment of exacerbations. The best results were obtained with cyclophosphamide in combination with glucocorticoids.

• Induction of remission.
  • For the induction of remission, pulse therapy with methylprednisolone 500-1000 mg intravenously for 3 days is used, followed by the appointment of prednisolone by mouth at a dose of 1 mg / kg of body weight per day for a period of at least 1 month. Then the dose of prednisolone is gradually reduced to maintenance: by 6 months of treatment - 10 mg / day.
  • Cyclophosphanum is prescribed in the form of pulse therapy 800-1000 mg intravenously once a month monthly orally at a dose of 2-3 mg / kg body weight per day (150-200 mg / day) for 4-6 months.
  • At the initial stage of treatment, one-stage "pulse" therapy with methylprednisolone and cyclophosphamide is justified. Doses of the drug depend on the severity of the patient's condition, the severity of renal failure: methylprednisolone is prescribed in a dose of not more than 500 mg intravenously for 3 days, cyclophosphamide - 400-600 mg intravenously once in patients with severe arterial hypertension, electrolyte disorders, with glomerular filtration rate less than 30 ml / min, in patients prone to developing infections and cytopenia. Intervals between conducting sessions of pulse therapy in such situations should be reduced to 2-3 weeks.
• Supportive treatment of Wegener's granulomatosis.
  • If after 6 months of treatment, remission of the disease is achieved, the dose of cyclophosphamide is reduced to a maintenance dose (100 mg / day), which the patient takes for at least 1 year. An alternative option of maintenance therapy is the replacement of cyclophosphamide with azathioprine at a dose of 2 mg / kg body weight per day.
  • The optimal duration of treatment with cytostatics is not determined. In most cases, therapy can be limited to 12 months and, if clinico-laboratory remission is achieved, 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 small. Therefore, when remission is achieved, treatment with cytostatics is recommended to continue for another 12-24 months, which significantly reduces the risk of exacerbations. Both modes of administration of cyclophosphamide (in the form of pulse therapy and ingestion) 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 remissions is less in patients who received treatment with ultra-high doses of drugs intravenously, and therefore after several sessions of pulse therapy, it is advisable to switch to cyclophosphamide ingestion.
  • The role of plasmapheresis in the treatment of "low-immune" ANCA-associated vasculitis is unclear. It is believed that with Wegener's granulomatosis plasmapheresis is indicated in cases of rapid development of renal insufficiency (creatinine concentration in the blood of more than 500 μmol / L) and the presence of potentially reversible changes in the kidney biopsy. It is recommended to conduct 7-10 sessions of plasmapheresis with the replacement of 4 l of plasma for 2 weeks. The lack of a positive effect in these terms makes further application of the method impractical.
• Treatment of exacerbations. Despite full treatment at the onset of the disease, 40% of patients develop exacerbations on average 18 months after discontinuation of therapy. Usually, the same lesions are noted at the same time as in the beginning of the disease, but it is also possible to involve new organs. Exacerbation of glomerulonephritis is manifested by microhematuria and impaired renal function. It is not recommended to consider fluctuations of 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 exacerbations treatment, it is suggested to conduct an ANCA titer study in dynamics. According to different authors, the ANCA titer increases when the disease worsens in 25-77% of patients, but ANCA titres should not be used as a decisive factor in determining indications for the resumption of immunosuppressive therapy or its abolition, since in some patients the exacerbation is not accompanied by an increase in ANCA titers , and the persistence of high titres was noted in individuals with a clear clinical remission.

Renal Replacement Therapy

Almost 20% of patients with Wegener's granulomatosis need hemodialysis at the time of diagnosis. Half of them have hemodialysis - 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 which of the patients with immunosuppressive treatment of Wegener's granulomatosis, conducted in parallel, will lead to the restoration of kidney function and the disappearance of the need for hemodialysis. In the future, most of these patients in a period of several months to 3-4 years develop terminal chronic renal failure. Patients with Wegener's granulomatosis, who undergo hemodialysis due to terminal chronic renal failure, usually do not have extrarenal signs of vasculitis activity and do not need supportive immunosuppressive therapy, nevertheless, in some cases, exacerbations of the disease develop, which serves as an indication for the resumption of active treatment with glucocorticoids and cytostatics, whose regimen is adjusted depending on the mode of hemodialysis.

Kidney transplantation is currently performed in a small number of patients with Wegener's granulomatosis.