Clotrimazole troches induce supratherapeutic blood levels of sirolimus and tacrolimus in an allogeneic hematopoietic cell-transplant recipient resulting in acute kidney injury

OBJECTIVE The purpose of this study was to compare acute kidney injury (AKI)–related outcomes of patients who received aminophylline in addition to standard of care with matched historical controls who received standard of care alone. METHODS This was a single center, retrospective, historical control cohort study that included patients treated for AKI. Patients who received aminophylline from January 2017 to June 2018 were matched for age, sex, primary diagnosis, and hematopoietic cell transplant history in a 1:2 ratio to historical controls treated for AKI from July 2015 to September 2016. The primary outcome was improvement in AKI stage at 5 and 10 days from treatment initiation. RESULTS Twenty-seven patients who received aminophylline were matched to 54 historical controls. Fifty-eight patients (72%) had recently undergone hematopoietic cell transplant. At day 5, improvement in AKI stage was observed in 56% of patients in each group (p = 1.0); at day 10, improvement in AKI stage was observed in 75% of patients in the aminophylline group vs 70% of historical controls (p = 0.76). By day 10, serum creatinine levels had returned to baseline in 21% of patients in the aminophylline group and 34% of patients in the control group (p = 0.37). CONCLUSIONS Findings of this study demonstrated no difference in the rate of AKI resolution or in the proportion of patients with resolved AKI when aminophylline was added to standard of care for the treatment of AKI in this pediatric hematology/oncology population.

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

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.19801220 ◽

2021 ◽

pp. CJN.19801220

Author(s):

Matthew Abramson ◽

Victoria Gutgarts ◽

Junting Zheng ◽

Molly Maloy ◽

Josel Ruiz ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Lower Risk ◽

Kidney Injury ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Hematopoietic Stem

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.

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