Phenotype standardization for drug-induced kidney disease

Abstract

Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition.

Figures

Figure 1. Onset and Duration of Drug Induced Kidney Injury

This figure conceptualizes the varying clinical presentations of drug induced nephrotoxicity drawing similarities to the KIDIGO definitions of kidney injury. Some antimicrobials can cause an acute rise in serum creatinine in relation to the start of the medication (e.g. aminoglycosides, amphotericin). Chemotherapeutic agents, such as cisplatin, cause a rise in serum creatinine that can occur beyond 7 days. Other medications have a slower onset of injury and can take months or years to be recognized clinically (e.g. tenofovir or lithium).

Figure 2. Case Vignettes of Drug Induced Kidney Injury

This figure contains two patient cases demonstrating the application of the phenotype criteria for acute kidney injury and glomerular phenotypes.