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The calcineurin inhibitors (CNI) cyclosporine and tacrolimus are the most widely used immunosuppressive medications following allogeneic hematopoietic stem cell transplant (HSCT) for the prevention of graft-versus-host disease (GVHD). 1 These agents exert their effect by blocking the calcineurin/NFAT pathway in activated T cells, resulting in suppressed transcription of interleukin-2 and related cytokines ultimately reducing T-cell proliferation and activity. 2-4 CNIs are not T-cell specific, and multiple toxicities have been documented since their introduction in the 1970s and 80s. Of greatest concern is CNI-induced renal dysfunction, both acute and chronic. Acute CNI nephrotoxicity is characterized by a change in hemodynamics, primarily a result of renal afferent arteriole vasoconstriction. 4-6 Considered reversible, acute CNI nephrotoxicity is most likely mediated by an increase in vasoconstrictor factors and a decrease in vasodilator factors. 7-9 Long-term use of a CNI can lead to irreversible and progressive renal structural changes and dysfunction, known as chronic CNI nephrotoxicity. 10-12 Despite great interest in preventative strategies to mitigate CNI-induced renal toxicities, no agent has proven clearly effective. Abstract Studies in the renal transplant population have suggested calcium-channel blockers (CCBs) may protect against calcineurin inhibitor (CNI)-induced nephrotoxicity. However, this has not been evaluated in the hematopoietic stem cell transplant (HSCT) population. This retrospective study reviews data from 350 consecutive patients who underwent allogeneic HSCT to determine whether amlodipine improved renal outcomes. Subject data included up to one year from CNI initiation. Patients in the amlodipine group (n = 130) received an average of 143 days treatment with amlodipine and experienced a smaller decrease in creatinine clearance (CrCl) through day 180. At day 30, change in CrCl was −17.4 mL/min in the amlodipine cohort and −33.8 mL/min in the control (P < 0.001). At day 180, change in CrCl was −40.9 and −50.6 mL/min, respectively (P = 0.005). Incidence of hospitalization with acute kidney injury (AKI) was significantly lower in patients receiving amlodipine, 7.7% (10/132) vs 16.4% (36/220) (hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.22-0.89).Median blood pressure in the amlodipine group remained <132/78 through day 360.Our data support the use of amlodipine for hypertension in the allogeneic HSCT population and provide evidence suggesting that CCBs protect against CNI-induced nephrotoxicity. K E Y W O R D Sallogeneic hematopoietic stem cell transplantation (HSCT), calcineurin inhibitors (CNI), calcium-channel blockers (CCBs), hypertension, nephrotoxicity, renal protection

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