Cyclosporine-induced remission of relapsing nephrotic syndrome in children Amir Tejani, MD, Khalid Butt, MD, Howard Trachtman, MD, M. Suthanthiran, MD, C, J. Rosenthal, MD, and M. R. Khawar, MD From the Renal Division, Department of Pediatrics, and the Departments of Surgery and Medicine, State University of New York Health Science Center at Brooklyn and The Rogosin Institute We treated 20 steroid-resistant or steroid-dependent nephrotic patients with oral cyclosporine for 8 weeks; they had been treated previously with cyclo- phosphamide or chlorambucil. Cyclosporine was started at 7 mg/kg/d and titrated to maintain a serum level of '100 to 200 ng/mL. Of 20 patients, 14 had a complete remission and the remaining six had a reduction in their proteinuria. By life table analysis, 40% of the responders show a sustained remission of up to a year. Pretherapy levels of interleukin 2, measured in 10 patients, were normal or supranormal in eight, six of whom were treatment responders; two patients with low levels of interleukin 2 were both nonresponders. Cyclosporine can be used to induce a remission in relapsing nephrotic patients, and short-term cyclosporine therapy does not produce nephrotoxic effects. (J PEDIATR 1987;411(6, part 2):1056-62) Current knowledge of the pathogenesis of glomerulone- phritis is limited. Circulating immune complexes, Zin situ complexes) and antibodies to the basement membrane antigens 3 have been involved in the pathogenesis of differ- ent types of glomerulonephritis. In other primary glomer- ular disease, such as minimal-change nephrotic syndrome and focal segmental glomerulosclerosis, there is little evidence to support classic immunologic mechanisms. This scarcity of immunologic involvement in nephrotic syn- drome suggests that capillary permeability in such patients may be altered by nonimmunologic stimuli. On contact with a specific antigen, sensitized lympho- cytes secrete a number of highly active lymphokines. It is postulated that these lymphokines lead to alterations in the glomerular anionic sites, resulting in the albuminuria of the nephrotic state. 4 Several lymphokines have been iden- tified in patients with the nephrotic syndrome. Eyres et al. 5 using a leukocyte migration test, demonstrated that patients with nephrotic syndrome have evidence of T cell sensitization. Lagrue et al. 6 identified the presence of a Reprint requests: Arnir Tejani, MD, Renal Division, Department of Pediatrics, SUNY Health Sciences Center, 450 Clarkson Ave., Box 49, Brooklyn, NY 11203. lymphokine in the supernatant of lymphocytes taken from patients with the nephrotic syndrome. The presence of a serum factor to account for the altered T cell function has been suggested on the basis of a reduction of mitogen- stimulated blast transformation of lymphocytes.7 Published data s suggest that factors present in the serum of nephrotic patients during relapse suppress T cell func- tion. A circulating factor designated lymphocytotoxin has been isolated? Plasma from patients with relapsing IL-2 lnterleukin 2 FSGS FoCal segmental glornerulosclerosis CsA Cyclosporine nephrotic syndrome inhibited autologous lymphocyte response to mitogen stimulation. 9 Reduction of reactive T lymphocytes, as measured by E rosette formation during relapses, has been shown) ~ Recently, Schnaper et al. H and Schnaper and Aune 12 identified another lymphokine in the blood and urine of nephrotic patients, which they designated as soluble immune response suppressor. They postulated that this factor, released by activated suppressor T cells, may account for the immunosuppressed state associated with 1056