Kidney Disease and Hematopoietic Stem Cell Transplantation

Abstract

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with hematologic malignancies and certain solid tumors and nonmalignant hematologic conditions. Both AKI and CKD occur commonly after HSCT and are associated with significant morbidity and mortality. AKI and CKD in this setting may result from direct effects of the transplant or be caused by pretransplant bone marrow conditioning regimens and/or nephrotoxic agents administered in the post-transplant period. In this article, we review the epidemiology, risk factors, etiologies, pathophysiology, diagnosis, prevention, and treatment of post-HSCT AKI and CKD, with special attention to recent advances in this fast-moving and evolving field.

Figure 1

Kidney injury after hematopoietic-cell transplantation. From N Engl J Med, Sangeeta Hingorani, M.D., M.P.H., Renal Complications of Hematopoietic. Cell Transplantation, 374, 2256–2267. Copyright © (2016) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. CLS, capillary leak syndrome; GVHD, graft-versus-host disease; SOS/VOD, sinusoidal obstruction syndrome/veno-occlusive disease.

Figure 2

Risk factors for EISs. *Particularly for breast cancer, lymphomas other than Hodgkin lymphoma, POEMs, multiple sclerosis. ^TBI-based and busulfan-based. **Systemic, BK virus, CMV, parvovirus B19, adenovirus. Refs. ,,,,,–. aGVHD, acute graft-versus-host disease; CMV, cytomegalovirus; CNI, calcineurin inhibitor; ECOG, Eastern Cooperative Oncology Group; EIS, endothelial injury syndrome; GCSF, granulocyte colony-stimulating factor; HSCT, hematopoietic stem cell transplantation; INR, international normalized ratio; mTOR, mammalian target of rapamycin; MA, myeloablative; NMA, nonmyeloablative; POEMs, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes syndrome; PS, performance status; TA-TMA, transplant-associated thrombotic microangiopathy; TBI, total body irradiation.

Figure 3

Histology of TA-TMA. (A) Glomerulus with features of acute TMA including endothelial swelling, red blood cell fragmentation, karyorrhexis, and associated mesangiolysis (hematoxylin and eosin stain, original magnification 400×, scale bar=20 µm). (B) Glomerulus with features of chronic TMA including mesangiolysis and double contour formation (Jones methenamine silver stain, original magnification 400×, scale bar=20 µm). TA-TMA, transplant-associated thrombotic microangiopathy; TMA, thrombotic microangiopathy.

Figure 4

Evolution of acute TA-TMA to chronic TA-TMA and progression to CKD. LDH, lactate dehydrogenase; MODS, multiorgan dysfunction syndrome; PBS, peripheral blood smear.