To evaluate abnormalities of renal morphology associated with long-term cyclosporine therapy, we obtained percutaneous renal biopsy specimens from 17 patients who had been treated for autoimmune uveitis with cyclosporine for an average of two years. For comparison, we also analyzed renal biopsy specimens from patients with idiopathic hematuria who had not received cyclosporine. The atrophic and sclerosing glomerular and tubulointerstitial lesions in the specimens were assessed to derive a chronicity index. The specimens from the patients treated with cyclosporine showed a significantly higher chronicity index than those from the controls (P less than 0.00005). All patients who had received cyclosporine had interstitial fibrosis, tubular atrophy, or both. A good functional predictor of the abnormalities in renal morphology was the length of time that a patient's serum creatinine had exceeded the base-line value by more than 50 percent. Chronic pathologic alterations were seen even in patients who had normal renal function at the time of the biopsy. In conjunction with sequential measurements of renal function, renal biopsy may have an important role in defining the type and degree of nephrotoxicity that can develop in patients receiving long-term cyclosporine therapy for autoimmune disease.
SummaryNephrotic syndrome (NS) is an extremely rare complication of myeloablative allogeneic haematopoietic cell transplantation (HCT) that usually occurs in association with chronic graft-versus-host disease (C-GVHD). We observed an unexpectedly high incidence of NS in a cohort of 163 consecutive patients undergoing non-myeloablative HCT from a related human leucocyte antigen-compatible donor. Seven patients developed NS at a median 318 d post-transplant (range 119-1203 d; cumulative incidence 6AE1%). The median age at onset of NS was 46 years (range 33-59 years); three of the seven patients had no evidence of C-GVHD while four had accompanying limited C-GVHD. At diagnosis, median proteinuria was 16AE5 g/24 h (range 3-24 g/ 24 h). Renal biopsy was performed in four cases and revealed membranous nephropathy. NS was not always associated with other symptoms of C-GVHD, and in contrast to previous reports, usually did not improve with the re-initiation of aggressive immunosuppression, resulting in progressive renal failure necessitating dialysis in three of seven cases. Membranous nephropathy resulting in NS is a previously unrecognised and clinically significant complication of non-myeloablative HCT.
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