NGAL and KIM-1 as early biomarkers of cisplatin-associated nephrotoxicity.

Abstract

e24080 Background: Cisplatin can cause renal injury in one-third of the patients. After the uptake by tubular renal cells cisplatin causes TNF-a immediate inflammation and death of tubular cell, ischemia and vascular damage on the kidney, which results in glomerular filtration rate (GFR) decrease (Toyuz et al, 2019). Serum creatinine is increased at the time of approximately 50% of nephrons are damaged. The identification of predictors and early markers of renal damage will make it possible to identify a high-risk group and monitor renal damage (Touyz, 2018). NGAL is activated immediately after ischemic or direct toxic damage to the kidneys in the distal segments of the nephron (Schmidt-Ott et al, 2007; Mishra). KIM-1 is an early marker of proximal tubule damage (Prasaja et al, 2015). Both NGAL and KIM-1 demonstrated their role of renal damage biomarkers in contrast-induced acute kidney injury. The goal of this study was to assess NGAL and KIM-1 as biomarkers of early nephrotoxicity induced by cisplatin and to assess their role as risk factors. Methods: The study included 50 patients who received cisplatin. Nephrotoxicity was determined as a decrease in GFR to < 60 ml/min/1.73 m2 at 8 weeks from the initiation of therapy. The levels of KIM-1 and NGAL in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of primary clinical and laboratory parameters. ROC-analysis was used to assess sensitivity and specificity of markers. Results: The decrease of GFR less then < 60 ml/min/1.73 m2 at 8 weeks was observed in 11 (22%) of patients. There were no signs of increase of blood pressure in 8 weeks of observation. Serum creatinine increased clinically significant in 8 weeks after the start of therapy. The level of NGAL and KIM-1 rapidly increased in 1 week after the start of therapy (p < 0.001) which is shown in Table. The unfavorable predictor of nephrotoxicity was a 1-week increase of urine NGAL and KIM-1: OR 8.37; 95%CI 4.64-95.84; p = 0.001. Both NGAL and KIM-1 demonstrated high sensitivity, specificity and area under the curve (AUC) – both 0.69 as early biomarkers of nephrotoxicity assessed after 8 weeks from the start of therapy. Conclusions: An increase of KIM-1 and NGAL observed earlier then serum creatinine increase. Elevation in 1 week after the initiation of therapy can predict nephrotoxicity with high specificity and sensitivity. At the same time an early increase in the concentrations of KIM-1 and in the urine is the independent risk factors for cisplatin-induced nephrotoxicity. [Table: see text]