Acute kidney injury (AKI) is a serious and under-recognized side effect of antimicrobial therapies that can prolong hospitalization, lead to development of chronic kidney disease, and increase in-hospital mortality.  CPCE researchers are investigating the pharmacoepidemiology and clinical pharmacology of nephrotoxic antimicrobials in children. We are looking at the role(s) of novel kidney biomarkers during antimicrobial therapy as means to promote early detection of AKI and improve estimation of patients’ kidney function.

This body of research seeks to improve the safety and effectiveness of antimicrobials in children by identifying risk factors for AKI in children receiving antimicrobial therapies. Utilizing research methodologies from epidemiology and clinical pharmacology, we look at the impact of dosing, antibiotic combinations, and patients’ underlying characteristics to determine the best drugs for individual patients.

Results of a recent study found that urinary biomarkers can be used to improve estimation of antibiotic drug clearance in children. A recently accepted abstract reports that vancomycin and piperacillin-tazobactam may increase the risk of AKI in children when used in combination. 

What’s Next: Work is underway to compare the ability of a novel kidney biomarker, cystatin C, to estimate vancomycin clearance in critically ill children compared to serum creatinine, the biomarker currently used in clinical practice.

Funding: The Children’s Hospital of Philadelphia

Please contact Kevin Downes, MD, attending physician and assistant professor of pediatrics, for more information about this line of research.

Antimicrobial-associated Acute Kidney Injury Published Research

Downes KJ, Cowden C, Laskin BL, Huang Y-S, Gong W, Bryan M, Fisher BT, Goldstein SL, Zaoutis TE. Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children. JAMA Pediatr. 2017:e173219.

Downes KJ, Goldstein SL, Vinks AA. Increased Vancomycin Exposure and Nephrotoxicity in Children: Therapeutic Does Not Mean Safe. J Pediatric Infect Dis Soc. 2016 Mar;5(1):65-7.

Downes KJ, Patil NR, Rao MB, Koralkar R, Harris WT, Clancy JP, Goldstein SL, Askenazi DJ. Risk factors for acute kidney injury during aminoglycoside therapy in patients with cystic fibrosis. Pediatr Nephrol. 2015 Oct;30(10):1879-88. 

Downes KJ, Rao MB, Kahill L, Nguyen H, Clancy JP, Goldstein SL. Daily serum creatinine monitoring promotes earlier detection of acute kidney injury in children and adolescents with cystic fibrosis. J Cyst Fibros. 2014 Jul;13(4):435-41.