Renal Complications of Hematopoietic-Cell Transplantation

Abstract

ach year, approximately 50,000 patients worldwide undergo hematopoietic-cell transplantation. This procedure, which is used to treat a wide range of malignant and nonmalignant diseases, may involve either a myeloablative or reduced-intensity conditioning regimen; the use of alternative allogeneic donors (i.e., haploidentical or mismatched donors); cells from bone marrow, cord blood, or peripheral-blood stem cells; and new immunomodulatory agents to prevent graft-versus-host disease (GVHD) 1 (Table 1). Despite the overall improvement in outcomes after hematopoietic-cell transplantation, kidney injury remains a frequent complication and contributes to the morbidity and mortality associated with the procedure. 2-11 The onset of acute kidney injury and chronic kidney disease, which affect from 10 to 70% of transplant recipients, 2,7,12,13 varies from days after transplantation to months or years afterward. Acute injury is generally indicated by elevated levels of serum creatinine up to 100 days after transplantation, and chronic injury by elevated levels at or after 100 days. Acute kidney injury that persists for 3 months or longer is usually reclassified as chronic kidney disease. The overall health of the patient at the time of transplantation is generally assessed with use of a hematopoietic-cell transplantation-specific comorbidity index that includes the serum creatinine level. 14 In this index, which includes 17 categories of organ dysfunction, scores for organ-specific coexisting conditions range from 0 to 3, with higher scores indicating a greater severity of the condition. The risk categories are not fixed and can vary according to conditioning regimens. Scores on the comorbidity index range from 0 to 12. Higher scores on the index (the weighted sum of all the scores for organ-specific conditions and other pretransplantation characteristics) indicate a greater risk of death that is not associated with relapse. In general, patients with a score of 0 are considered to be at low risk of death that is not associated with relapse, those with a score of 1 or 2 are considered to be at intermediate risk, and those with a score of 3 or greater are considered to be at high risk. A score of 1 or more is correlated with a risk of acute post-transplantation kidney injury. 3 Such kidney injury may be caused by conditioning chemotherapy, total-body irradiation, nephrotoxic agents, infections, the hepatic sinusoidal obstruction syndrome (previously called veno-occlusive disease of the liver), transplantation-associated thrombotic microangiopathy, and GVHD. 3-7,15-19 This article reviews the causes, diagnosis, and management of complications and disorders of the kidney after hematopoietic-cell transplantation. Definition a nd Epidemiol ogy of K idne y Injur y Acute kidney injury after transplantation was initially defined as a doubling of the baseline serum creatinine level within the first 100 days after transplantation.

Thrombotic Microangiopathy With Granulomatosis Interstitial Nephritis in an Allogenic Bone Marrow Transplant Patient: A Case Report and Review of the Literature

“…According to a recent report, kidney-biopsy specimens obtained from patients with TMA showed mesangiolysis and loss of endothelial cells with occlusion of capillary lumens with fibrin, as was the case for our patient [13]. According to one institution's study of 67 patients, kidney specimens often demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, arteriosclerosis, and rarely membranous nephropathy [25].…”

“…Chronic kidney disease is estimated to impact 15-20% HSCT recipients [22]. Acute injury is considered to occur when serum creatinine levels are elevated up to 100 days after transplantation, whereas chronic injury represents injury at or after that [13]. This was the case for our patient who presented with a decline in renal function, more than a year after her transplant.…”

“…While renal failure can be due to chemotherapy, radiation, fluid loss TMA in a BMT Patient J Hematol. 2017;6(2-3):52-58 secondary to diarrhea or vomiting, sepsis, or nephrotoxicity secondary to calcineurin inhibitors and antimicrobials, there are BMT-specific reasons such as marrow infusion toxicity, hepatic veno-occlusive disease, TMA, and GvHD [12,13].…”

“…This includes discontinuing potentially toxic agents such as calcineurin inhibitors and sirolimus, prescribing adequate antimicrobial treatment, and maintaining adequate renal function using renal replacement therapy [4]. Whereas some clinicians discontinue calcineurin inhibitors and opt for switching to mycophenolate mofetil, sirolimus or both, some patients have experienced resolution of their TMA when given increasing doses of calcineurin inhibitors [13]. Furthermore, aggressively managing hypertension, another risk factor for CKD and TA-TMA, is imperative as 70% of children and adults develop hypertension within the first 2 years of their HSCT [13].…”

Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

“…[3][4][5][6] However, GvHD as a severe inflammatory disease may also indirectly cause nephropathy. 7 The exact etiology of renal dysfunction after BMT often remains unclear, because no renal biopsy is taken in most cases. However, AKI is a risk factor for developing chronic kidney disease (CKD) and is associated with increased morbidity and mortality.…”