Evaluation of urinary tubular enzymes for the detection of early kidney injury due to cisplatin chemotherapy

Abstract

This study was designed to evaluate the efficacy of urinary renal tubular cell specific enzymes α-Glutathione-s-transferase(α-GST) and Gamma glutamyl transpeptidase (GGT) for predicting kidney injury in cisplatin treated cancer patients. The urinary levels of these enzymes, studied in a timely manner may help in identifying patients who may benefit from early interventions. Methods: After obtaining Institutional ethical clearance, venous blood samples were collected from all the patients, before the adminsitration of cisplatin (baseline), and at 12 hours, 24 hours, 48 hours and 20days after cisplatin infusion and a random urine sample was collected before and at 2 hrs , 6 hrs, 12 hrs, 24hrs and 48hrs after cisplatin administration. Serum creatinine was estimated by Jaffe‘s method using commercial reagent kit. α –GST and GGT was estimated in all the urine samples by colorimetric kinetic assay using NBD-Cl and Glycylglycine respectively. Results: There was a 20.5% incidence of acute kidney injury after cisplatin administration as suggested by a significant rise in the serum creatinine levels(≥0.3mg/dL) within the first 48 hours. The mean urinary α-GST 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 GGT levels showed a steep increase upto 6 hours before gradually declining over the next 48 hours after cisplatin administration among patients who eventually developed AKI. Conclusion: Urinary levels of proximal tubular enzymes, α-GST and GGT are useful in predicting early kidney injury induced by cisplatin. As the test method is simple and cheaper, the estimation of α-GST in random urine samples may be particularly useful for identifying patients with high risk of AKI.