Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Background and objectives Acute kidney injury (AKI) is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of non-relapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft-versus-host disease (GVHD) regimens. To date, GVHD and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre/post-hematopoietic transplant risk factors in a large recent cohort. Design, setting, participants, and measurements We performed a single-center retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014-2017. We defined AKI and CKD based on KDIGO criteria and estimated GFR using CKD-EPI equation. We assessed AKI pre/post-hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using Chi-squared test. AKI was treated as a time-dependent variable in relation to non-relapse mortality. Results Incidence of AKI by day-100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced intensity conditioning carried higher AKI risk compared to myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and CNI nephrotoxicity. Kidney replacement therapy was initiated in 21/616 (3%) of whom 9/21 (43%) recovered and 5/21 (24%) survived to hospital discharge. T-cell depleted transplants, higher baseline albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73/345) of patients after 12 months. Non-relapse mortality was higher in those with AKI (HR 2.77, 95% CI: 1.8-4.27). Conclusions AKI post-hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to CNIs. T cell depleted hematopoietic cell transplants and higher albumin had lower risk of AKI. Forty-three percent of patients requiring KRT recovered kidney function. Prospective studies are needed to further assess modification of these risk factors.

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation

“…Factors known to contribute to the risk of AKI after HCT include pre-treatment factors such as being female ( 21 ), age 55 years or older ( 22 ), and underlying conditions such as diabetes ( 23 ), hypertension ( 21 ), and chronic kidney disease (CKD) ( 24 ). Risk factors for AKI associated with HCT include TBI conditioning ( 22 ), use of a calcineurin inhibitors (CNIs) for GVHD prevention ( 23 , 25 , 26 ), and use of MTX for GVHD prophylaxis ( 22 , 23 ). Post-transplant stay in an intensive care unit ( 21 ) and the need for mechanical ventilation ( 27 ) are also risk factors.…”

“…Most of the renal injury after HCT is thought to be caused by nephrotoxic drugs, particularly CNIs given for GVHD prophylaxis ( 34 ). CNIs can cause both AKI and CKD ( 61 ); however, CNIs serum concentration does not always correlate with the severity of AKI ( 26 ). CNIs cause AKI through a variety of mechanisms.…”

Incidence and Risk Factors for Acute Kidney Injury after Allogeneic Stem Cell Transplantation: A Prospective Study

“…Although the prognosis of patients undergoing HSCT has improved in recent years, a meta-analysis of 36 cohort studies found that AKI incidence after HSCT remained high throughout the years, affecting more than half of the patients [ 3 ]. As such, a proper assessment of the risk factors associated with AKI occurrence in the HSCT population is of extreme importance, since HSCT patients’ prognosis may be additionally improved by addressing the modifiable ones.…”

“…Although several studies approached the subject of AKI following HSCT, most of them were performed in a retrospective manner [ 3 , 4 , 5 ]. As well, the literature provides inconsistent evidence on the relationship between AKI and calcineurin inhibitors (CNI) overdosing [ 4 , 5 ].…”

Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram

“…As the severity of renal failure increases, the mortality rate of AKI patients also increases, accounting for more than 80% of patients requiring RRT 5 . The incidence of non-recurring deaths in AKI patients is high (HR 2.77, 95% CI 1.8–4.27) 6 . The study found that the cumulative mortality rate of the non-malignant disease AKI group within 100 days after HSCT was significantly higher than that of the non-AKI group (44.4% vs. 0%, p = 0.003) 7 .…”