Renal Complications after Hematopoietic Stem Cell Transplantation: Role of Graft-Versus-Host Disease in Renal Thrombotic Microangiopathy

Abstract

Hematopoietic stem cell transplantation (HSCT) is a widely accepted treatment for mainly hematopoietic disorders. Recent advances in transplantation techniques have increased the number of long-time survivors with chronic kidney disease (CKD). The presence of CKD affects outcomes and is associated with high mortality rates. Therefore, physicians treating transplant survivors should consider renal complications and optimize management of patients with CKD after HSCT. The pathology of CKD after HSCT is affected by many factors, and the causes of renal thrombotic microangiopathy (TMA) are diverse and complicated. We have treated patients who underwent allogeneic HSCT and developed latestage renal TMA possibly associated with graft-versus-host disease (GVHD). Administration of immunosuppressive drugs, such as calcineurin inhibitors, is typically reduced in patients with TMA. However, if renal TMA is caused by renal GVHD, the use of immunosuppressive drugs should be increased, contradicting conventional thinking. On the basis of previous findings and our own observations, we review the pathology of renal complications after HSCT and focus on the role of GVHD in the development of renal TMA.

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation

“…Transplantation-associated-thrombotic microangiopathy (TA-TMA) is another complication of HCT associated with a substantial risk of mortality ( 88 ). It typically develops subacute or chronically ( 89 ), and can also lead to AKI ( 60 ). Vascular endothelial damage associated with transplantation results in thrombus formation and fibrin deposition in the capillaries and small arteries, microangiopathic hemolytic anemia, and consumptive thrombocytopenia ( 88 ).…”

“…The Kidney is the most vulnerable organ to TA-TMA ( 62 , 89 ). Renal TA-TMA presents as both AKI and CKD ( 62 , 89 ) and is often accompanied by hypertension, proteinuria, and a decreased GFR ( 89 ).…”

“…The Kidney is the most vulnerable organ to TA-TMA ( 62 , 89 ). Renal TA-TMA presents as both AKI and CKD ( 62 , 89 ) and is often accompanied by hypertension, proteinuria, and a decreased GFR ( 89 ). The histopathology of renal TA-TMA is characterized by fibrin deposition in the glomeruli, narrowing of the capillary lumen, presence of fragmented red blood cells, basement membrane duplication, mesangiolysis, and edema of the endothelium ( 89 , 92 ).…”

“…Several clinical studies have shown an association between TA-TMA and aGVHD ( 93 , 94 ), but these were retrospective studies confounded by the use of CNIs ( 88 ). Nevertheless, clinical studies have suggested that vascular endothelial cells are targeted by donor T cells ( 95 ), and some studies suggest that TA-TMA may be caused by GVHD of the vascular endothelium ( 89 , 96 , 97 ).…”

ACUTE RENAL DISORDER IN PATIENTS WITH ACUTE LEUKEMIA AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: A SERIES OF CLINICAL CASES

“…Причины развития ОПП у больных с острым лейкозом в условиях ТГСК многофакторны и во многом зависят от тяжести посттрансплантационных осложнений. Известно, что тяжелые осложнения, которые реципиенты ТГСК переживают после трансплантации, имеют опосредованное влияние на функции почек, такие как острая реакция «трансплантат против хозяина», сердечно-сосудистая патология, инфекционные осложнения [6][7][8]. Кроме того, реципиенты ТГСК подвергаются поэтапному длительному приему химиотерапевтических препаратов, обладающих нефротоксическим эффектом [9].…”