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 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 first step to recognizing drug induced kidney disease and developing strategies to prevent and manage this condition.

Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China

“…Drug‐induced hepatotoxicity was diagnosed according to the criteria of drug‐induced liver disorders in which aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels more than three times the upper limit of normal were considered to have hepatotoxicity . Chronic kidney injury was diagnosed as persistence of hematuria, proteinuria, or/and casts for more than 90 days . As you can see in Figure , the diagram of study enrollment is shown.…”

Nephrotoxicities

“…Because NGAL and tobramycin use a similar transport receptor (megalin), these results suggest that other biomarkers may also be predictive of disordered pharmacokinetics for other medications depending on their respective transport physiologies. Finally, a recent combined adult and pediatric international multicenter initiative has been aimed at assessing genetic predisposition to medication-associated AKI by using genome-wide association studies 22 .…”

Drug-associated acute kidney injury: who’s at risk?

“…A panel of international pediatric and adult nephrologists and pharmacists developed a standardized description of the phenotype for drug-associated kidney disease in hospitalized patients [36]. The four general categories include AKI, glomerular disorders, nephrolithiasis and tubular dysfunction, and underlying mechanisms can either be dose-dependent or dose-independent (as in acute interstitial nephritis) [36].…”

“…The four general categories include AKI, glomerular disorders, nephrolithiasis and tubular dysfunction, and underlying mechanisms can either be dose-dependent or dose-independent (as in acute interstitial nephritis) [36]. The authors concede that multi-drug exposures and concurrent AKI risk factors make the use of these criteria challenging.…”