Steroid-resistant nephrotic syndrome due to renal-limited thrombotic microangiopathy and membranous nephropathy after allogeneic hematopoietic stem cell transplantation successfully treated with calcineurin inhibitors

Abstract

Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown. Herein, we report three cases of renal-limited TMA after allo-HSCT that presented with nephrotic syndrome, in which renal biopsy showed TMA and concurrent membranous nephropathy. All patients were refractory to glucocorticoid monotherapy and the addition of CNIs led to complete remission of nephrotic syndrome. Renal-limited TMA after allo-HSCT may present as nephrotic syndrome with distinct pathophysiological features from renal-limited TMA in non-allo-HSCT recipients. Previous reports have suggested that renal-limited TMA after allo-HSCT is associated with renal graft-versus-host disease, and thus optimizing immunosuppressive therapy, including CNI treatment, may be useful. CNI treatment may be an option even in the presence of renal-limited TMA after allo-HSCT accompanied by concurrent membranous nephropathy.

Keywords: Calcineurin inhibitors; Hematopoietic stem cell transplantation; Membranous nephropathy; Nephrotic syndrome; Transplantation-associated thrombotic microangiopathy.