Kidney injury in the murine models of hematopoietic stem cell transplantation

Abstract Acute graft-versus-host disease (GVHD) affects different organs, including the skin, liver and gastrointestinal tract. Although kidneys are not among the organs commonly known to be the target of acute GVHD, kidney damage is frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have studied the effect of bone marrow transplant (BMT) on the kidneys in different murine models of GVHD. We found that glomerular damage in the kidneys is a common pathologic finding in mice after BMT. The histopathologic features of glomeruli damage included mesengiolysis, mesangial proliferation and edema, subendothelial and endothelial thickening, splitting of capillary walls in glomeruli, narrowing and collapsing of capillary lumens, fibrinoid necrosis of afferent arterioles, intimal hyperplasia, and microthrombi. These pathologic features are similar to those detected in kidneys of patients with thrombotic microangiopathy (TMA) after allo-HSCT. We have previously shown that activation of the complement system plays a role in the GVHD-induced tissue injury in mice. In the current study, we showed the presence of complement activation products in the kidney specimens of mice after BMT. We also showed that complement deficiency reduced the extent and severity of post-BMT glomerular damage in mice. We concluded that BMT in mice is associated with glomerular injury and tubulointerstitial nephritis, and that kidney damage is at least partially mediated by activation of the complement system.