Long-term Assessment of NSAID Prescriptions and Potential Nephrotoxicity Risk in Adult Kidney Transplant Recipients

Background. Nonsteroidal anti-inflammatory drug (NSAID) use is recommended to be avoided in kidney transplantation, with a paucity of studies assessing their safety within this population. This study aims to use a large cohort of Veterans Affairs (VA) kidney transplantation recipients to assess the risk of acute kidney injury (AKI) with NSAID use. Methods. This is a 10-year longitudinal cohort study of adult kidney transplant recipients retrospectively followed in the VA system from 2001 to 2010 that assessed for risk of AKI with NSAID prescriptions. NSAID prescriptions, patient characteristics, and estimated glomerular filtration rates were abstracted from the VA comprehensive electronic health record. NSAID exposure was assessed by duration, dosage, and type. AKI events were defined by >= 50% decrease in estimated glomerular filtration rate. Risk was estimated using longitudinal multivariable generalized logistic regression model. Results. About 5100 patients were included with a total of 29 980 years of follow-up; 671 NSAID prescriptions in 273 (5.4%) patients (2.24 per 100 patient-y) with 472 (70%) high dose were identified. High-dose NSAID prescriptions were associated with 2.83 (95% confidence interval [CI], 1.55-5.19; P < 0.001) higher odds of AKI events within a given year; low dose was not associated with AKI (odds ratio, 1.93; 95 % CI, 0.95-6.02; P = 0.256). One 7-day NSAID course was associated with 5% higher odds of increasing AKI events, whereas chronic use (>= 180 d) was associated with 3.25 (95% CI, 1.78-5.97; P < 0.001) higher odds of AKI. Conclusions. Prescriptions for NSAIDs were uncommon in this cohort but were associated with a significant increase in the risk of AKI, which was impacted by higher NSAID dose and longer NSAID durations.