Acute kidney injury in patients with systemic sclerosis participating in hematopoietic cell transplantation trials in the United States

Abstract

Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc.

Copyright © 2011 American Society for Blood and Marrow Transplantation. All rights reserved.

Figures

Figure 1

PAS stained section of renal biopsy from patient 6. The glomerulus has duplication of the basement membrane (arrowhead), segmental collapse of capillary loops and mesangiolysis. An adjacent longitudinally oriented arteriole (arrow) has a small residual eccentric lumen nearly obliterated by myointimal matrix. PAS stain, 40× optic

Figure 2

A and B Autopsy kidney from patient 8 with scleroderma renal crisis. 2A. Interlobular arteriole with severe luminal narrowing from “onion skin-like” myointimal hyperplasia. H&E 40× optic 2B, the shrunken glomerulus has collapse of capillary loops with focal necrosis of endothelial cell (arrowhead). A contiguous afferent arteriole has fibrinoid necrosis (arrow) within the thickened intimal layer. H&E 40× optic

Figure 2

A and B Autopsy kidney from patient 8 with scleroderma renal crisis. 2A. Interlobular arteriole with severe luminal narrowing from “onion skin-like” myointimal hyperplasia. H&E 40× optic 2B, the shrunken glomerulus has collapse of capillary loops with focal necrosis of endothelial cell (arrowhead). A contiguous afferent arteriole has fibrinoid necrosis (arrow) within the thickened intimal layer. H&E 40× optic