NGAL and KIM-1 – early urinary biomarkers of nephrotoxicity mediated by cisplatin: Observational study

Background. Cisplatin is widely used in modern oncological practice. Despite high efficacy treatment with cisplatin is conjugated with high risk of nephrotoxicity. Approximately one third of patients develop renal disfunction after first injection of cisplatin. In clinical practice serum creatinine elevation is used as a marker of renal damage, which is observed after failure of 50% of kidney function. That is why the finding of early biomarker of nephrotoxicity is still an issue. NGAL and KIM-1 are markers of renal damage, the predictive value of which has been described in cardiac surgery and resuscitation practice: an increase in the concentration of these markers in urine precedes the development of renal damage, both ischemic and direct toxic.

Aim. To evaluate the role of NGAL and KIM-1 in urine as early markers of cisplatin nephrotoxicity.

Materials and methods. The study included 50 patients treated with cisplatin in combination with fluoropyrimidines or paclitaxel. Prior to treatment and over a period of 8 weeks, the Friedman test was used to assess blood pressure, plasma creatinine, potassium, urea levels, daily proteinuria, urine NGAL and KIM-1 levels, and glomerular filtration rate (GFR). ROC analysis was used to assess the prognostic significance of NGAL and KIM-1 in the development of nephrotoxicity.

Results. There was a statistically significant increase in the level of urea (χ²=17.7; df 4, p=0.001), potassium (χ²=42; df 4, p<0.001), a decrease in GFR (χ²=32.3; df 4, p<0.001), the appearance of proteinuria (χ²=50.4; df 4, p<0.001). The concentration of NGAL and KIM-1 increased already one week after the start of cisplatin therapy, reaching a maximum by 8 weeks (χ²=200; df 4, p<0.001). The appearance of NGAL at a concentration of 10.743 ng/ml and KIM-1 at a concentration of 182.4 pg/ml in the first week after administration of cisplatin allows predicting the development of nephrotoxicity by the 8th week with high sensitivity (90.91%) and specificity (94.87%), AUC 0.96.

Conclusion. The appearance of NGAL and KIM-1 in urine already in the first week of treatment allows predicting the development of nephrotoxicity – a decrease in GFR of less than 60 ml/min by the 8th week of therapy with high sensitivity and specificity. Both biomarkers can be considered early prognostically significant.