Treatment with IFN-{alpha}, -{beta}, or -{gamma} is associated with collapsing focal segmental glomerulosclerosis

Abstract

Background and objectives: Treatment with IFN is rarely associated with nephrotic syndrome and renal biopsy findings of minimal-change disease or FSGS.

Design, setting, participants, & measurements: We report 11 cases of collapsing FSGS that developed during treatment with IFN and improved after discontinuation of therapy.

Results: The cohort consists of seven women and four men with a mean age of 48.2 yr. Ten of the 11 patients were black. Six patients were receiving IFN-alpha for hepatitis C virus infection (n = 5) or malignant melanoma (n = 1), three were receiving IFN-beta for multiple sclerosis, and two were treated with IFN-gamma for idiopathic pulmonary fibrosis. After a median and mean [corrected] duration of therapy of 4.0 and 12.6 months, respectively, patients presented with acute renal failure (mean creatinine 3.5 mg/dl) and nephrotic-range proteinuria (mean 24-hour urine protein 9.7 g). Renal biopsy revealed collapsing FSGS with extensive foot process effacement and many endothelial tubuloreticular inclusions. Follow-up was available for 10 patients, all of whom discontinued IFN. At a mean of 23.6 months, nine of 10 patients had improvement in renal function, including one with complete remission and two with partial remission. Among the seven patients with available data, mean proteinuria declined from 9.9 to 3.0 g/d. Four of the seven patients were treated with immunosuppression, and there was no detectable benefit.

Conclusions: Collapsing FSGS may occur after treatment with IFN-alpha, -beta, or -gamma and is typically accompanied by the ultrastructural finding of endothelial tubuloreticular inclusions. Optimal therapy includes discontinuation of IFN.

Figure 1.

Pathologic findings. (A) A glomerulus with collapsing FSGS exhibits global wrinkling and retraction of the glomerular basement membranes and diffuse swelling and proliferation of overlying visceral epithelial cells (Jones methenamine silver). (B) In this glomerulus with collapsing FSGS, some of the podocytes are detached from the glomerular basement membrane and lie free within the urinary space (periodic acid Schiff). (C) On ultrastructural evaluation, visceral epithelial cells exhibit microvillous transformation and complete foot process effacement. An endothelial TRI is present. (D) At high magnification, an endothelial TRI is seen. Magnifications: ×400 in A and B; ×5000 in C; ×8000 in D.

Figure 2.

Temporal relationship among serum creatinine, proteinuria, and use of IFN in patient 9.