HDCN Article Review/Hyperlink

Gregory MJ, Smoyer WE, Sedman A, Kershaw DB, Valentini RP, Johnson K, Bunchman TE

Long-term cyclosporine therapy for pediatric nephrotic syndrome: a clinical histological analysis

J Am Soc Nephrol (Apr) 7:543-549 1996

This is a study of children with idiopathic nephrotic syndrome who were treated with a combination of cyclosporine and alternate-day steroids for 6-53 months (mean 22). In 12 of 22 patients, a precyclosporine biopsy was performed as was a second biopsy at 12-41 months, mean 21 months, later. They found that in 2 patients, 17%, there was increase in interstitial fibrosis and tubular atrophy suggesting cyclosporine nephrotoxicity. Cyclosporine trough levels were maintained between 70 and 120 ng/ml. This low toxicity rate is the most important finding in this study.

The response rate in patients with steroid resistant nephrotic syndrome, 13 of 15, is more difficult to interpret. Most pediatric nephrologists have several frustrating steroid resistant patients with unremitting focal segmental glomerulosclerosis (FSGS). The present study showed that 3 or 3 steroid resistant patients with FSGS responded to cyclosporine and alternate day prednisone. The authors defined steroid resistance as patients who have not entered remission after at least 8 weeks of daily prednisone therapy. There is mounting evidence that cyclosporine should not be instituted until at least 6 months of daily prednisone has been administered. Many "steroid resistant" patients become steroid sensitive if prednisone is continued longer than 8 weeks. Therefore, it is difficult to interpret the high remission rate the authors observed in patients who were treated with cyclosporine and labeled steroid resistant in this study. Many of these patients might have benefitted from longer term steroid therapy.

Again, a major contribution of this study is the serial biopsy material in 12 patients, which suggested a low incidence of cyclosporine nephrotoxicity. Don Moel, M.D., Loyola University at Chicago School of Medicine