Cisplatin-induced nephrotoxicity in childhood cancer: comparison between two countries

Background Various definitions used to describe cisplatin nephrotoxicity potentially lead to differences in determination of risk factors. This study evaluated incidence of kidney injury according to commonly used and alternative definitions in two cohorts of children who received cisplatin. Methods This retrospective cohort study included children from Vancouver, Canada (one center), and Mexico City, Mexico (two centers), treated with cisplatin for a variety of solid tumors. Serum creatinine-based definitions (KDIGO and Pediatric RIFLE (pRIFLE)), electrolyte abnormalities consisted of hypokalemia, hypophosphatemia and hypomagnesemia (based on NCI-CTCAE v5), and an alternative definition (Alt-AKI) were used to describe nephrotoxicity. Incidence with different definitions, definitional overlap, and inter-definition reliability was analyzed. Results In total, 173 children (100 from Vancouver, 73 from Mexico) were included. In the combined cohort, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity compared to pRIFLE and KDIGO criteria (82.7 vs. 63.6 vs. 44.5%, respectively). Nephrotoxicity and all electrolyte abnormalities were significantly more common in Vancouver cohort than in Mexico City cohort except when using KDIGO definition. The most common electrolyte abnormalities were hypomagnesemia (88.9%, Vancouver) and hypophosphatemia (24.2%, Mexico City). The KDIGO definition provided highest overlap of cases in Vancouver (100%), Mexico (98.6%), and the combined cohort (99.4%). Moderate overall agreement was found among Alt-AKI, KDIGO, and pRIFLE definitions (kappa = 0.18, 95% CI 0.1-0.27) in which KDIGO and pRIFLE showed moderate agreement (kappa = 0.48, 95% CI 0.36-0.60). Conclusions Compared to pRIFLE and KDIGO criteria, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity. pRIFLE is more sensitive to detect not only actual kidney injury but also patients at risk of cisplatin nephrotoxicity, while KDIGO seems more useful to detect clinically significant kidney injury.

Automated summary

This study evaluated the incidence of kidney injury in children who received cisplatin using different definitions. The Alt-AKI criteria detected more cases of nephrotoxicity compared to pRIFLE and KDIGO criteria. pRIFLE was more sensitive at detecting actual kidney injury and patients at risk, while KDIGO was better at detecting clinically significant kidney injury.