Next-generation biomarkers for detecting kidney toxicity

Abstract

There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.The kidney is a major site of organ damage caused by drug toxicity. This frequently manifests during drug development and/or in standard clinical care. Nephrotoxicity resulting from drug exposure has been estimated to contribute to 19-25% of all cases of acute kidney injury (AKI, the currently preferred term for the clinical disorder formerly called acute renal failure) in critically ill patients 1 . Given the societal cost of nephrotoxicity and the insensitivity of current methods to detect it, sensitive methods for prediction of toxicity in preclinical studies and identification of injury in humans are extremely important for patient safety in clinical practice and in all stages of the drug-development process. It is in the interest of patients, physicians, the drug industry and health regulatory bodies to prevent new nephrotoxic drugs from entering the market or, when the medical need dictates use of such an agent, to be able to identify early and best manage nephrotoxicity.This article discusses the purview of the first effort of the PSTC-a collaboration of the biotech and pharmaceutical industry, the US Food and Drug Administration (FDA; Rockville, MD), the European Medicines Agency (EMEA; London, UK) and academia-to facilitate the qualification of renal biomarkers for safety in drug development. It brings together expertise from a variety of disciplines to organize and/or create evidentiary datasets to present to the regulatory agencies for qualification decision-making. Although this first

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“…The exposures we employed were based on our previous studies (Godman et al 2010a, b;Fuller et al 2013) and approximated an extended clinical HBOT treatment course. We tested a number of the urinary biomarkers (Bonventre et al 2010;Waring and Moonie 2011;Deverajan 2011), and the data revealed evidence of a protective function of HBOT.…”

Early markers of obesity-related renal injury in childhood

“…Examples of biomarkers for renal injury are proteins, lipids, microRNAs, genomic, metabolomic, or proteomic patterns, imaging determinations, electrical signals, and cells present on a urinalysis. A partial list of candidate markers for kidney injury is present in Table 1 with the corresponding sites along the nephron [7]. Legacy kidney biomarkers include serum creatinine (sCr), blood urea nitrogen (BUN), urinary albumin/protein, and volume excretion.…”

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