The Value of Urinary NGAL, KIM-1, and IL-18 Measurements in the Early Detection of Kidney Injury in Oncologic Patients Treated with Cisplatin-Based Chemotherapy.

ABSTRACT

Cisplatin is still a widely used anticancer drug characterized by significant nephrotoxicity. Acute kidney injury (AKI), diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, has limitations, including a delayed increase in creatinine. We determined the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in diagnosing AKI according to the KDIGO criteria in patients treated with cisplatin. We recruited 21 subjects starting cisplatin-based chemotherapy (Cisplatin-based group) and 11 treated with carboplatin-based chemotherapy or 5-fluorouracil regimens (non-cisplatin-based group). Blood and urine samples were collected during four subsequent cycles of chemotherapy (68 and 38 cycles, respectively). AKI occurred in four patients in the cisplatin-based group (5.9% of 68 cisplatin-based chemotherapy cycles). Among them, three urinary markers were increased by over 100% in two cases, two in one case and one in another. A doubling of at least one investigated parameter was observed more frequently during cisplatin-based chemotherapy (80.3% vs. 52.8%; OR = 3.65, 95% CI 1.49-8.90; p < 0.01). The doubling of at least one new urinary AKI marker was more common in patients receiving cisplatin and frequently was not associated with overt AKI. Thus, a subclinical kidney injury detected by these markers occurs more frequently than deterioration in kidney function stated with creatinine changes.