PUK1 Comparing Serum Creatinine to Stress/Damage Biomarkers for Early Detection of Drug-Associated Acute Kidney Injury: A Systematic Review

Abstract

Approximately 18-26% of acute kidney injury (AKI) cases are associated with a drug related cause. Nephrotoxin drug administration is one of the greatest risk factors for AKI in hospitalized patients in the United States. Current diagnostic practices utilize serum creatinine and urinary output as the primary biomarkers for assessing kidney function Unfortunately, this can lead to delayed detection due to a 24-36 hour lag in serum creatinine rise after an injurious event. This study explores the clinical utility of several kidney damage biomarkers, including NGAL, KIM-1, Interleukin-18, b2-microglobulin, FABP, and [TIMP-2][IGFBP7], for the purpose of early recognition of risk/ongoing drug-induced acute kidney injury (D-AKI) in comparison to serum creatinine. A systematic review of publications in PubMed, Cochrane Library, Embase, and Cinhal between January 2013 and December 2020 was conducted following PRISMA reporting guidelines utilizing Rayyan software. Eligible articles included patients with D-AKI, assessed a kidney stress/damage for the biomarkers of interest s, conducted a comparison to serum creatinine, and measured the time to biomarker rise following drug exposure . The search produced 4,523 citations. Forty-three articles were selected for preliminary screening and 20 articles were included for final review. Preliminary results show a significant rise in NGAL and KIM-1 attributable to D-AKI 12-24 hours prior to a rise in serum creatinine. Availability of data meeting the inclusion criteria for the other biomarkers are lacking. Preliminary results support the utility of these novel kidney biomarkers for the use in early detection of D-AKI. We are still in the early stages of understanding the clinical applications of stress/damage kidney biomarkers specific to D-AKI.