(B-296) Risk of Acute Kidney Injury Associated with Nephrotoxic Burden: A Systematic Review of Observational Studies

Background: Acute kidney injury (AKI) remains a critical health concern, affecting approximately 20% of hospitalized patients. Nephrotoxic drugs contribute in up to 30% of AKI cases, with evidence suggesting a significantly higher risk when multiple nephrotoxins are administered concurrently.

Objectives: This systematic review aims to consolidate existing evidence on nephrotoxic burden and its association with AKI in non-critically ill hospitalized patients. Specifically, we evaluated studies that define nephrotoxic burden, propose measurement methodologies, and assess the risk of AKI linked to the concurrent administration of three or more nephrotoxins.

Methods: In accordance with PRISMA guidelines, we conducted a systematic review of observational studies that assessed nephrotoxic burden or the risk of AKI with concurrent nephrotoxic drug use in hospitalized patients. A comprehensive search was conducted across PubMed, Embase, Scopus, Web of Science, and Semantic Scholar with no restriction on the publication date. Studies involving patients with chronic kidney disease or those on dialysis were excluded. Extracted data included study characteristics, nephrotoxic burden assessment, and AKI risk estimates. The National Heart, Lung, and Blood Institute (NHLBI) Study Quality Assessment Tools were used to assess the study quality.

Results: A total of 10 observational studies met the inclusion criteria, comprising both adult and pediatric hospitalized patients. Two studies proposed methods for quantifying nephrotoxic burden: one introduced "medication exposure intensity," measuring the number of concomitant nephrotoxic drugs administered, while another applied the "nephrotoxic drug-days" approach, assigning a score based on the number of nephrotoxic drugs received per day. Both methods highlighted the significance of simultaneous nephrotoxin administration in determining burden.
Findings consistently demonstrated that an increased nephrotoxic burden was associated with a higher risk of AKI. One study reported an odds ratio of 1.2 (95% CI: 1.04-1.38, p = 0.015) per unit increase in burden score. Two studies found that increases in medication exposure intensity were linked to a 1.34 to 1.7-fold higher odds of AKI (95% CI: 1.09-1.65, P=0.01; 95% CI: 1.04-2.9, P= 0.03). Seven additional studies examined AKI risk associated with the concurrent administration of 3 or more nephrotoxins, reporting odds ratios ranging from 1.4 to 2.8. According to NHLBI, three studies were rated as good, six as fair, and one as poor due to a high risk of bias.

Conclusions: This review reinforces the significance of nephrotoxic burden as a major risk factor for AKI, suggesting a pattern of increased AKI incidence with higher cumulative nephrotoxin exposure. There is a need to implement nephrotoxin stewardship programs to mitigate AKI risk in hospitalized patients.