Evaluation of Urinary α-Glutathione-S-Transferase (α-GST) as a Marker of Early Cisplatin Induced Kidney Injury

Abstract

Abstract-Cisplatin is a very effective chemotherapeutic, but the risk of nephrotoxicity frequently hinders the use of its higher dose. This study was designed as a prospective observational cohort study to evaluate the efficacy of urinary renal tubular enzyme α-Glutathione-s-transferase(α-GST) for predicting kidney injury in cisplatin treated cancer patients. Venous blood samples were collected from all the patients, before the administration of cisplatin (baseline), and at 12h, 24h, 48h and 20days after cisplatin infusion and a random urine sample was collected before and at 2h , 6h, 12h, 24h and 48h after cisplatin administration. Serum creatinine was estimated by Jaffe's method using commercial reagent kit and α -GST was estimated in all the urine samples by colorimetric kinetic assay using NBD-Cl. There was a 20.5% incidence of acute kidney injury after cisplatin administration based on AKIN criteria. The mean urinary α-Glutathione S Transferase levels at different time intervals show a clear temporal rise, especially from 2hrs after cisplatin administration, till 12hrs and at a slower rate thereafter. The AUC of >0.8 for α-GST in all the timed urine samples after cisplatin administration indicated its good performance in predicting kidney injury. Urinary levels of proximal tubular enzyme, α-GST is found to be useful in predicting early kidney injury induced by cisplatin.

Assessment Standards

“…Our unpublished experience with aGST has been that IHC does not correlate well with urine concentrations. In spite of that experience, aGst has been identified in proximal tubules (Bauchet et al 2011) and clinically linked to cisplatin-induced, proximal tubular injury (Saleena et al 2012), and it would be interesting to see if results similar to those obtained with Kim-1 could be derived with aGST. Undoubtedly, there will be no universal method for all biomarkers or all cellular biomarkers.…”