Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients

Paolo Lopedote; Elisabetta Xue; Julie Chotivatanapong; Emily C Pao; Chiara Wychera; Ann E Dahlberg; Laurel Thur; Laura Roberts; Kelsey Baker; Ted A Gooley; Sangeeta Hingorani; Filippo Milano

doi:10.3389/fonc.2023.1186503

Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients

Front Oncol. 2023 May 16:13:1186503. doi: 10.3389/fonc.2023.1186503. eCollection 2023.

Authors

Affiliations

¹ Department of Medicine, St. Elizabeth's Medical Center, Boston University, Boston, MA, United States.
² Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
³ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
⁴ Department of Pediatrics, University of Washington, Seattle, WA, United States.

Abstract

Introduction: Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT.

Methods: Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI.

Results: We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01).

Discussion: AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.

Keywords: acute kidney injury (AKI); allogenic stem cell transplantation; bilirubin; chronic kidney disease (CKD); cord blood transplantation (CBT); graft versus host disease (GVHD); steroid.