139 - Amlodipine and Calcineurin Inhibitor Induced Nephrotoxicity Following Allogeneic Hematopoietic Stem Cell Transplant

Abstract

Background: Previous studies, primarily in the renal transplant population, have suggested that calcium channel blockers (CCBs) may protect against calcineurin inhibitor (CNI)-induced nephrotoxicity. However, this has not been evaluated in the hematopoietic stem cell transplant population. Methods: We reviewed data from 350 consecutive patients who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2006 and 2016 at a single institution to determine whether patients receiving amlodipine for hypertension had improved renal outcomes compared to patients who did not receive amlodipine. Subject data included up to one year from the initiation of a CNI. Results: Patients in the amlodipine group (n = 130) received 76 median days treatment with amlodipine and experienced a lesser median decline in creatinine clearance (CrCl) at predefined time points through day 180, as determined by a 2-tailed Mann-Whitney U-test. This trend remained through day 360 but did not reach statistical significance. At day 30, change in CrCl was -17.4 mL/min in the amlodipine cohort and -33.8 mL/min in the control group (P < .001). At day 180, median change in CrCl was -40.9 and -50.6 mL/min respectively (P = .005). A mixed-effects logistic regression model was used for multivariate analysis and found supra-therapeutic CNI levels (P < .0001), older age (P = .0006), past medical history of hypertension (P = .0171), and the use of antihypertensive medications other than amlodipine (P < .0001) correlated to a greater CrCl decline. For our secondary endpoint, we found that patients receiving amlodipine had a significantly lower risk of being hospitalized with acute kidney injury (AKI) (Figure 1). Probabilities of hospitalization were estimated utilizing the Kaplan-Meier method. Curves were compared and hazard-ratios calculated using log-rank tests. Hospitalization with AKI kidney injury occurred in 7.7% (10/130) of patients in the amlodipine cohort and 16.4% (36/220) of patients in the control group (P = .0218). Multivariate analysis found supratherapeutic CNI levels to also be an independent risk factor for hospitalization with AKI (P = .004). Patients receiving amlodipine were older (P = .005) and more likely to have a greater BMI (P = .0021), a greater baseline systolic and diastolic blood pressure (P < .0001), a lower baseline creatinine clearance (P = .016), and a past history of diabetes mellitus (P = .013) and hypertension (P < .0001) . Also, a higher rate of supratherapeutic CNI levels was found in the amlodipine cohort. Conclusion: Overall, we found more favorable renal outcomes in the amlodipine group despite holding greater baseline risks for renal decline compared to the control group. Our data support the use of amlodipine for hypertension in the allo-HSCT population and provide evidence suggesting that CCBs protect against CNI-induced nephrotoxicity.