Rituximab Use in Nephrotic Syndrome

Abstract

Yasir Sharba, Sadiqe Jabar AL-Muhana and Rafal Riayadh AL-Dikeli

Background: Nephrotic syndrome may be caused by primary (idiopathic) renal disease or by a variety of secondary causes. Patients present with marked edema, proteinuria, hypoalbuminemia, and often hyperlipidemia. Treatment of most patients should include fluid and sodium restriction, oral or intravenous diuretics, and angiotensin-converting enzyme inhibitors. Adults with nephrotic syndrome may benefit from corticosteroid treatment. The treatment of patients with the steroid-resistant nephrotic syndrome (SRNS) and steroid-dependent nephrotic syndrome (SDNS) is challenging. On the basis of suggestions that B lymphocytes are crucial in the pathogenesis of the nephrotic syndrome, rituximab (a monoclonal antibody against CD20 antigen) is used in treatment of these patients.

Aim of study: To evaluate the role of rituximaband mycophenolic acid in treatment of patientswith steroid-resistant (SRNS) and steroid-dependent nephrotic syndrome (SDNS), whom not respond or relapse after calcineurin inhibitor (CNI) (tacrolimus or cyclosporine) had been used.

Patients and methods: Case series study was done between 2012 - 2015 in AL-Sadder Teaching Hospital Nephrology Center and record 40 patients with different age groups, males and females with different histopathological types (Minimal Change Glomerulonephritis, Focal Segmental Glomerulosclerosis, Mesengeo Prolifrative Glomerulonephritis). These patients were taking prednisilone and\or calcineurin inhibitor (tacrolimus “prograf”) or (cyclosporine “sandimmune”), and they get either Steroid Dependent Nephrotic Syndrome or Steroid Resistant Nephrotic Syndrome with frequent admission more than four time per year. To these patients we start rituximab intravenous infusion monthly for at least six months with the use of steroid and mycophenolate mofetil during these six months. The patients followed up for 3-12 months after initiation of rituximab by different investigations and the patients were classified according to their response into complete, partial and no response. After one year stop rituximab treatment, follow the patients clinically and by investigations for (1-2) years to determine which patients get relapse.

Results: Majority (80%) of patients with nephrotic syndrome who had good response to rituximab were younger age group < 15 years. Better response to rituximab associated with Minimal Change Glomerulonephritis. There was significant reduction in blood urea, serum creatinine, urine (protein/creatinine) ratio and serum cholesterol. Serum albumin was significant elevated. Response to rituximab was not significantly associated with gender or steroid response. Majority of patients with good response not relapse and need more time for follow up. Relapsing after stopping rituximab not significantly associated with age, gender, histopathological type and steroid response.

Conclusion: Rituximab and mycophenolate mofetil used in steroid-resistant nephrotic syndrome to get ride from side effects of calcineurine inhibitor (tacrolimus or cyclosporine). Rituximab and mycophenolate mofetil used in steroid-dependent nephrotic syndrome after calcineurine inhibitorto get ride from side effects of steroid. Improvement in renal function is result from stopping of calcineurine inhibitor (nephrotoxic drugs) and/or from rituximab and mycophenolate mofetil. Cost of rituximab is less than the cost that needed if the patients had frequent admissions to the hospital or developed renal failure and ended with dialysis.

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