Consensus Obtained for the Nephrotoxic Potential of 167 Drugs in Adult Critically Ill Patients Using a Modified Delphi Method

Abstract

Introduction: The approach to evaluating nephrotoxins in studies of drug-associated acute kidney injury varies. Some studies use a list of under ten drugs for evaluation whereas others include over 100 drugs. Drugs are typically assigned a binary classification, nephrotoxic or not nephrotoxic. This oversimplifies the nephrotoxic potential of the drugs under investigation.

Objective: This study aimed to assign a nephrotoxin potential for 167 drugs used in the adult critical care setting.

Methods: A three-round, international, interdisciplinary, web-based modified-Delphi study was used to evaluate nephrotoxins used in adult critically ill patients. Twenty-four international experienced clinicians were identified through the Acute Disease Quality Initiative group and professional affiliations. Included individuals represented the fields of intensive care, nephrology, and pharmacy. One hundred and fifty-nine medications were identified from the literature, with eight additional medications added after the first round, for a total of 167 medications. The primary outcome was consensus achieved for nephrotoxicity ratings. Scores were evaluated each round to determine if a consensus was met.

Results: Our nephrotoxin potential index rating indicated that 20 drugs were nephrotoxicity probable or probable/definite per consensus. Nephrotoxic potential was assessed based on the standard use of medications in intensive care and the following consensus scores: 0 = no nephrotoxic potential, 1 = possible nephrotoxic potential, 2 = probable nephrotoxic potential, 3 = definite nephrotoxic potential.

Conclusions: The nephrotoxin potential index rating allows for prioritization of targeted drugs with greater nephrotoxic potential for institutional nephrotoxin stewardship programs. Furthermore, the nephrotoxin potential index rating provides homogeneity for research and guidance on detailed assessments by severity for each drug.

Fig. 1

Delphi method flowchart. The Delphi process was between March 2020 and April 2021. A total of three rounds were completed. Unless otherwise listed, all parameters from the previous round were carried forward for the following round

Fig. 2

Consensus nephrotoxicity ratings by medication therapeutic class. Numeric ratings corresponding to each nephrotoxicity category are as follows: 0 = “No Potential”; 0.5 = “Unlikely to Possible”; 1.0 = “Possible”; 1.5 = “Possible to Probable”; 2.0 = “Probable”; 2.5 = “Probable to Definite”; 3.0 = “Definite” (no medication received a 3 rating). An interactive version of this figure is available as Electronic Supplementary Material