Background

Tacrolimus is a cornerstone for graft-versus-host disease prophylaxis (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo-SCT) ,despite its known nephrotoxic potential. While ACEi and ARBs can induce or exacerbate acute kidney injury (AKI) , their impact on AKI incidence and adverse renal outcomes with concurrent tacrolimus use is unclear. This study aimed to evaluate the incidence of AKI and other renal complications associated with the combined use of ACEi/ARBs and tacrolimus.

Methodology

A retrospective analysis conducted utilizing the TriNetX Research Network identified cancer patients aged 18 years or older from 2015-2024 who underwent Allo-SCT and commenced Tacrolimus therapy. Patients were categorized into two distinct cohorts: those who received concomitant ACE/ARBs and those who did not. Six-month outcomes were evaluated in individuals without antecedent renal events. The cohorts were compared using 1:1 propensity score matching, with adjustments made for age, sex, race, comorbidities, baseline left ventricular ejection fraction (LVEF), Tacrolimus serum levels, and medication history. The primary endpoints assessed were AKI and proteinuria; secondary endpoints encompassed the requirement for renal replacement therapy and alterations in LVEF at the six-month mark.

Results

A cohort of 13,311 patients who underwent Allo-SCT and initiated tacrolimus therapy was identified. Of these, 3,100 patients received concomitant ACEis or ARBs with tacrolimus, while 10,211 did not. Following propensity score matching, each group comprised 2,565 patients. The incidence of AKI was notably higher in the group treated with ACEi or ARBs concurrently with tacrolimus (35% vs 31%, p = 0.0342, HR = 1.14). Proteinuria was also significantly more prevalent in this group (25% vs 17%, p < 0.0001, HR = 1.5). While the requirement for renal replacement therapy was marginally lower in the ACEi or ARB group (3.4% vs 4.0%), this difference did not achieve statistical significance (p = 0.0697). LVEF at six months post-transplant was significantly reduced in the ACEi or ARB group (56% vs 58%, p = 0.0307); however, the change from baseline LVEF was not statistically significant (p = 0.76), potentially attributable to limited availability of follow-up LVEF data.

Conclusion

Our study suggests that the use of ACEi/ARBs in Allo-SCT patients taking Tacrolimus for GVHD significantly increased the risk of early AKI and proteinuria. Although propensity score matching was used to balance baseline characteristics, some residual confounding may remain due to clinical factors influencing the prescribing of ACEi/ARBs. Despite this, the observed increase in renal complications suggests careful consideration should be taken when using ACEi/ARBs in these patient groups, focusing on alternative hypertensive regimens

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2025
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