Acute Kidney Injury and CKD Associated with Hematopoietic Stem Cell Transplantation

Abstract

Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%–73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy.

Onconephrology: The intersections between the kidney and cancer

“…For example, from 10% up to 73% of patients post-HSCT develop AKI, with 5% requiring renal replacement therapy and up to 60% developing CKD as a direct consequence of the AKI episode. 63 Patients with severe AKI who required renal replacement therapy and who recovered were at highest risk for progression to CKD. The severity of AKI is a strong predictor of progression to CKD.…”

“…62 HSCT is also associated with TMA. 62,63 TMA can present with AKI, new or acute worsening of hypertension, proteinuria, and active urinary sediment. AKI is often severe and may ultimately require dialysis.…”

“…AKI is often severe and may ultimately require dialysis. 62,63 Kidney histology reveals endothelial cell swelling, fibrin thrombi within capillary loops and arterioles, fragmented red blood cells, mesangioysis, and thickened arterioles and glomerular capillaries. 62,63 Certain cancers, especially when metastatic, more frequently cause TMA compared with others-these include mucinous gastric cancers, ovarian cancers, lymphomas, and acute myeloid leukemias.…”

“…62,63 Kidney histology reveals endothelial cell swelling, fibrin thrombi within capillary loops and arterioles, fragmented red blood cells, mesangioysis, and thickened arterioles and glomerular capillaries. 62,63 Certain cancers, especially when metastatic, more frequently cause TMA compared with others-these include mucinous gastric cancers, ovarian cancers, lymphomas, and acute myeloid leukemias. 64 More recently, cancers associated with a monoclonal gammopathy, including plasma cell dyscrasias and B-cell lymphoproliferative disorders, were recognized as being associated with TMA.…”

KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantation

“…[4][5][6] In patients treated with hematopoietic cell transplantation, there are several unique causes of both AKI and CKD. 7 The risk of AKI can be potentiated by several factors: dehydration due to vomiting, diarrhea, obstruction of the urinary tract, fluid and electrolyte disturbances, contrast agent administration, nonsteroidal anti-inflammatory drugs, nephrotoxic antibiotics, and renal toxicity of chemotherapeutic or targeted drugs. [4][5][6] The incidence of AKI in patients with high-grade hematological malignancy has been estimated to be as high as 68.5% using RIFLE criteria (risk, injury, failure, loss of function, end-stage kidney disease [ESKD]), with >90% of cases resulting from hypoperfusion, acute tubular necrosis, TLS, nephrotoxins, or hemophagocytic lymphohistiocytosis.…”