Sara N Salerno1, Yuting Liao2, Wesley Jackson3, Rachel G Greenberg4, Cameron J McKinzie2, Ashley McCallister2, Daniel K Benjamin5, Matthew M Laughon3, Keia Sanderson6, Reese H Clark7, Daniel Gonzalez8. 1. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC. 2. Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC. 3. Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC. 4. Department of Pediatrics, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Durham, NC. 5. Department of Economics, Clemson University, Clemson, SC. 6. Department of Medicine-Nephrology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC. 7. MEDNAX Center for Research, Education, Quality and Safety, Sunrise, FL. 8. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: daniel.gonzalez@unc.edu.
Abstract
OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in infants exposed to nephrotoxic drug combinations admitted to 268 neonatal intensive care units managed by the Pediatrix Medical Group. STUDY DESIGN: We included infants born at 22-36 weeks gestational age, ≤120 days postnatal age, exposed to nephrotoxic drug combinations, with serum creatinine measurements available, and discharged between 2007 and 2016. To identify risk factors associated with a serum creatinine definition of AKI based on the Kidney Disease: Improving Global Outcomes criteria, we performed multivariable logistic and Cox regression adjusting for gestational age, sex, birth weight, postnatal age, race/ethnicity, sepsis, respiratory distress syndrome, baseline serum creatinine, and duration of combination drug exposure. The adjusted odds of AKI were determined relative to gentamicin + indomethacin for the following nephrotoxic drug combinations: chlorothiazide + ibuprofen; chlorothiazide + indomethacin; furosemide + gentamicin; furosemide + ibuprofen; furosemide + tobramycin; ibuprofen + spironolactone; and vancomycin + piperacillin-tazobactam. RESULTS: Among 8286 included infants, 1384 (17%) experienced AKI. On multivariable analysis, sepsis, lower baseline creatinine, and duration of combination therapy were associated with increased odds of AKI. Furosemide + tobramycin and vancomycin + piperacillin-tazobactam were associated with a decreased risk of AKI relative to gentamicin + indomethacin in both the multivariable and Cox regression models. CONCLUSIONS: In this cohort, infants receiving longer durations of nephrotoxic combination therapy had an increased odds of developing AKI.
OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in infants exposed to nephrotoxic drug combinations admitted to 268 neonatal intensive care units managed by the Pediatrix Medical Group. STUDY DESIGN: We included infants born at 22-36 weeks gestational age, ≤120 days postnatal age, exposed to nephrotoxic drug combinations, with serum creatinine measurements available, and discharged between 2007 and 2016. To identify risk factors associated with a serum creatinine definition of AKI based on the Kidney Disease: Improving Global Outcomes criteria, we performed multivariable logistic and Cox regression adjusting for gestational age, sex, birth weight, postnatal age, race/ethnicity, sepsis, respiratory distress syndrome, baseline serum creatinine, and duration of combination drug exposure. The adjusted odds of AKI were determined relative to gentamicin + indomethacin for the following nephrotoxic drug combinations: chlorothiazide + ibuprofen; chlorothiazide + indomethacin; furosemide + gentamicin; furosemide + ibuprofen; furosemide + tobramycin; ibuprofen + spironolactone; and vancomycin + piperacillin-tazobactam. RESULTS: Among 8286 included infants, 1384 (17%) experienced AKI. On multivariable analysis, sepsis, lower baseline creatinine, and duration of combination therapy were associated with increased odds of AKI. Furosemide + tobramycin and vancomycin + piperacillin-tazobactam were associated with a decreased risk of AKI relative to gentamicin + indomethacin in both the multivariable and Cox regression models. CONCLUSIONS: In this cohort, infants receiving longer durations of nephrotoxic combination therapy had an increased odds of developing AKI.
Authors: Keia R Sanderson; Bradley Warady; William Carey; Veeral Tolia; Marcella H Boynton; Daniel K Benjamin; Wesley Jackson; Matthew Laughon; Reese H Clark; Rachel G Greenberg Journal: J Pediatr Date: 2021-11-16 Impact factor: 4.406
Authors: Tamara van Donge; Anne Smits; John van den Anker; Karel Allegaert Journal: Int J Environ Res Public Health Date: 2021-01-14 Impact factor: 3.390