FK 506 in the management of nephrotic syndrome after renal transplantation.

N EPHROTIC syndrome developing after renal trans-plantation has many etiologies. Recurrent focal scle-rosing glomerulonephritis is' ane of the leading causes.! Other etiologies include: (1) transplant glomerulopathy; (2) chronic rejection; (3) de novo membranous glomerulone-phritis (ON); and (4) other recurrent glomerulonephropa-thies (membranoproliferative glomerulonephritis [MPGN] , systemic lupus erythematosus [SLE], diabetes, etc).2 The important treatment goals for these patients are to control the metabolic consequences of nephrotic syndrome and delay or prevent progression of renal failure. None of these diseases has been successfully treated after transplantation with the therapies conventionally used for native kidney ON. After a dramatic improvement in proteinuria in a patient with de novo focal segmental glomerulosclerosis (FSGS). we embarked on a limited pilot trial to determine if FK 506 might be helpful in managing these patients. 3 Because this was a probing effort. no patient with post-transplant nephrotic syndrome was eliminated from consideration. This diverse group of histological lesions might reproduce the immunologic mediators of the primary disease that developed in the patient's native kidneys or initiate a wholly different set of immune processes that result in a totally different form of GN. 4 Posttransplant glomerulopathies may provide a unique opportunity to investigate the determinants of glomerular injury. patients with posttransplant nephrotic syndrome were converted from cyclosporine A (eyA) to FK 506. Approximately half the patients were initially transplanted at the University of Pittsburgh; the remainder were referred to the University of Pittsburgh specifically for management of the nephrotic syndrome with FK 506. The criteria for entry into this study were serum creatinine (Ser) <6.0 and the presence of nephrotic range proteinuria. Baseline graft biopsies were performed in all cases. Immunosuppression Protocols All patients were receiving eyA and prednisone immunosuppres-sion; most also received imuran. eyA was stopped 24 hours or the evening prior (12 hours) to conversion if no rejection was noted on baseline biopsies. The initial conversion FK 506 dose was .3 mglkgld given in two divided doses. After approximately six patients, the dose of FK 506 was lowered to .2 mglkgld in divided doses. This reduction in dosage was primarily due to significant nephrotoxicity and other symptoms of excessive FK 506 therapy. The starting dose was later lowered to .15 mglkgld twice per day if rejection was absent at the time of conversion. If moderate rejection was present on pretreatment biopsies, a dose of .2 to .3 mglkgld given twice was used. One patient with moderate …