Metabolically unhealthy obesity is a novel risk factor for cisplatin- associated nephrotoxicity in patients with bladder cancer: a retrospective cohort study

Abstract

Abstract Purpose Cisplatin-associated nephrotoxicity limits chemotherapy in bladder cancer patients. Obesity defined by body mass index (BMI) has yielded conflicting findings regarding the prediction of nephrotoxicity, possibly due to metabolic heterogeneity within the obese population. This study explored whether metabolically unhealthy obesity (MUO) independently predicts cisplatin-related nephrotoxicity. Methods A total of 332 Bladder cancer patients receiving cisplatin-based chemotherapy were retrospectively analyzed. Four metabolic phenotypes were defined according to BMI and the number of metabolic abnormalities. Cisplatin-associated nephrotoxicity was defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Univariate and multivariate logistic regression were used to identify risk factors. Results A cohort of 332 cisplatin-treated bladder cancer patients was analyzed, and the incidence of cisplatin-associated nephrotoxicity was 31.0%. Baseline obesity, Eastern Cooperative Oncology Group (ECOG) status, hypoalbuminemia and neutrophil-to-lymphocyte ratio (NLR) were significantly different between patients with and without nephrotoxicity. Multivariate analysis identified overall obesity as an independent risk factor for nephrotoxicity (OR = 2.319, 95%CI:1.236–4.350, P = 0.009). Stratified metabolic-phenotype analysis demonstrated that only MUO independently predicted higher nephrotoxicity risk (OR = 4.618, 95%CI:1.897–11.261, P = 0.001). In line with this finding, MUO patients showed a more prominent post-chemotherapy creatinine elevation relative to Metabolically healthy obesity (MHO) patients ( P = 0.027), whereas creatinine change was similar between non-obese and obese subjects ( P = 0.281). Conclusion Metabolically-unhealthy obesity is an independent associated factor for cisplatin-associated nephrotoxicity in bladder cancer patients. Metabolic-phenotype evaluation may facilitate early risk stratification before cisplatin chemotherapy.