Renal biomarkers predict nephrotoxicity after paraquat

Klintean Wunnapuk, Xin Liu, Philip Peake, Glenda Gobe, Zoltan Endre, Jeffrey E. Grice, Michael S. Roberts, Nicholas A. Buckley

Paraquat is a widely used herbicide which has been involved in many accidental and intentional deaths. Nephrotoxicity is common in severe acute paraquat poisoning. We examined seven renal injury biomarkers, including cystatin-C, kidney injury molecule-1, β2-microglobulin, clusterin, albumin, neutrophil gelatinase-associated lipocalin and osteopontin, to develop a non-invasive method to detect early renal damage and dysfunction and to compare with the conventional endogenous marker creatinine. Male Wistar rats were dosed orally with four different doses of paraquat, and the biomarker patterns in urine and plasma were investigated at 8, 24 and 48h after paraquat exposure. By Receiver Operating Characteristic analysis, urinary kidney injury molecule-1 was the best marker at predicting histological changes, with areas under the Receiver Operating Characteristic curve of 0.81 and 0.98 at 8 and 24h (best cut-off value>0.000326μg/ml), respectively. Urinary kidney injury molecule-1, urinary albumin and urinary Cystatin-C elevations correlated with the degree of renal damage and injury development. Further study is required to compare biomarkers changes in rats with those seen in human poisoning.