Renal function mediates the association between neutrophil percentage-to-albumin ratio and survival in cancer survivors: a large cross-sectional study.

Background: Cancer survivors face heightened mortality risks due to recurrence, comorbidities, and insufficient prognostic tools. The neutrophil percentage-to-albumin ratio (NPAR), integrating inflammation and nutrition, has shown prognostic value in cancers but lacks validation in survivor populations. Objective: To assess the predictive efficacy of NPAR on mortality in cancer survivors and to explore the mediating role of renal function. Methods: Data from NHANES (2003-2018) were used to analyse 3,134 cancer survivors. Cox models assessed the association of NPAR with all-cause, cancer-specific, and non-cancer mortality. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of NPAR. Restricted cubic splines assessed non-linear associations, while mediation analysis quantified the role of renal function. The external validation study was conducted between January 2016 and December 2018, involving an additional 985 cancer patients recruited from a tertiary hospital in China. Results: This study demonstrated that each 1-unit increase in NPAR was associated with a 10% increase in the risk of all-cause mortality, a 6% increase in the risk of cancer-related mortality, and a 12% increase in the risk of non-cancer mortality. This dose-dependent association remained robust in multivariable-adjusted models. RCS analyses further revealed a nonlinear relationship between NPAR and risk of death, with a steep inflection point in risk of all-cause mortality when NPAR exceeded 12.84. ROC analysis showed that NPAR had an AUC of 0.608 for all-cause mortality, outperforming the systemic immune-inflammation index (SII). Finally, mediation analyses elucidated renal impairment as a key pathway through which NPAR affects prognosis: 23.08% of the NPAR-mediated risk of all-cause mortality was driven by a decline in eGFR, and 21.97% of the risk of non-cancer mortality was attributable to worsening renal function. In real-world data analysis, NPAR has also been demonstrated to correlate positively with all-cause mortality, cancer-specific mortality, and non-cancer-specific mortality among cancer patients. Conclusion: NPAR is a robust prognostic biomarker for mortality in cancer survivors, mediated in part by renal dysfunction. These findings highlight the clinical utility of NPAR and the need for interventions targeting the inflammation-nutrition-kidney pathways.