Dynamics of urinary kim-1 as a biomarker of acute kidney injury in cancer patients undergoing cisplatin-based chemotherapy

Abstract

Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI). The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment. Material and Methods . The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value. Results . According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m 2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mg uCr ) in 3 patients (15.8 %; median 2.1 ng/mg uCr ); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mg uCr ; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mg uCr ; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mg uCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051). Conclusion . An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.