Late Kidney Morbidity and Mortality in Hematopoietic Cell Transplant Survivors

Abstract

Increasing numbers of patients are undergoing hematopoietic cell transplantation (HCT); however, further characterization of late kidney outcomes in HCT recipients is needed. This study investigated long-term kidney outcomes in HCT survivors and compared the risk of late kidney morbidity/mortality in these survivors with that in non-HCT cancer survivors and the general population. A cohort of long-term (≥2 years) allogeneic and autologous HCT survivors treated for cancer at our institution between 1992 and 2009 (n = 1792) was compared with a non-HCT cancer cohort selected from the state cancer registry (n = 5455) matched on diagnosis, sex, and age at year of cancer diagnosis/HCT (index date). Additional comparisons were made with a matched general population sample drawn from state driver's licensing files (DOL; n = 16,340). Statewide hospital discharge codes and death registry codes (International Classification of Diseases 9/10) were used to identify cases of acute kidney failure (AKF) and chronic kidney disease (CKD) occurring ≥2 years after the index date. Cumulative incidence rates and hazard ratios (HRs; according to multivariable proportional hazard models) estimated the absolute and relative risks of AKF and CKD. Among HCT survivors, we examined the influence of additional characteristics including estimated glomerular filtration rate (eGFR) at 1-year post-HCT. The cumulative incidence rates of late kidney complications were slightly greater in the HCT survivors versus the non-HCT cancer survivors at 10 years after the index date. Both groups were more likely to experience late AKF or CKD morbidity/mortality compared with the general population (AKF: HCT, 9.4%; non-HCT, 7.7%; DOL, 1.8%; CKD: HCT, 5.7%; non-HCT, 5.0%; DOL, 1.2%). Differences between HCT survivors and non-HCT survivors were seen primarily starting 5 years after the index date, with increased hazards for late AKF (HR, 1.4; 95% confidence interval [CI], 1.1 to 1.9) and CKD (HR, 1.9; 95% CI, 1.3 to 2.8). Among allogeneic HCT survivors, the presence of hypertension at <2 years post-HCT was significantly associated with subsequent AKF (HR, 2.9; 95% CI, 1.7 to 5.0) and CKD (HR, 5.2; 95% CI, 2.7 to 10.0) at 2 to 10 years post-HCT, with similar associations seen for autologous HCT survivors. Low eGFR (<60 mL/min/1.73 m²) at 1 year post-HCT was associated with late AKF morbidity/mortality for both allogeneic (HR, 5.3; 95% CI, 2.1 to 13.2) and autologous HCT (HR, 2.7; 95% CI, 1.2 to 6.3) compared with survivors with normal eGFR (>90 mL/min/1.73 m²). Overall, the risk for hospitalization or death from AKF or CKD continued to increase with time from HCT and exceeded that of non-HCT cancer survivors at >5 years after treatment. Appropriate screening and early intervention with medication adjustments or lifestyle modifications in those with hypertension or evidence of abnormal eGFR post-HCT could potentially mitigate this risk.

Keywords: Acute kidney failure; Chronic kidney disease; Hematopoietic cell transplantation; Long-term outcomes.