Development and multi-cohort validation of a sarcopenia-inflammation index for predicting all-cause mortality in patients with chronic kidney disease.

PURPOSE: Sarcopenia and chronic systemic inflammation frequently co-occur in chronic kidney disease (CKD), collectively driving poor prognosis. Yet current clinical practice lacks an integrated metric to quantify their combined prognostic impact. This study aimed to develop and validate a novel Sarcopenia-Inflammation (SI) Index for predicting all-cause mortality in CKD patients. METHODS: This prospective multi-cohort study utilized the C-OPTION cohort (N = 539) as both the discovery and primary validation dataset. To assess cross-population generalizability across distinct ethnic groups and healthcare settings, the SI Index was further evaluated in two large population-representative datasets: NHANES (N = 1,731) and CHARLS (N = 2,625). The SI Index was constructed as a weighted linear combination of sarcopenia status and inflammatory markers derived from multivariate Cox regression coefficients. Predictive performance was evaluated using time-dependent ROC curves, C-index, and AIC/BIC. Incremental prognostic value, 10-fold cross-validation, and subgroup analyses were performed to confirm model robustness. RESULTS: Among 4,895 CKD patients, multivariate Cox regression identified sarcopenia (HR: 4.582-5.947) and high inflammatory status (HR: 1.43-2.41) as independent mortality determinants with additive effects (interaction p > 0.05). The SI Index was established as: 1.522 × Sarcopenia + 1.300 × Abnormal Muscle Traits + 0.880 × High Inflammation. External validation demonstrated superior prognostic discrimination over single-dimension markers, elevating the C-index from 0.623-0.684 (sarcopenia alone) and 0.557-0.584 (inflammation alone) to 0.657-0.741. Incorporating the SI Index into a base clinical model significantly improved C-index from 0.565-0.726 to 0.729-0.768 (all p < 0.001), with optimal AIC/BIC. Associations remained robust across subgroups stratified by age, sex, comorbidities, and renal function, and 10-fold cross-validation confirmed model stability. CONCLUSION: The SI Index is a potent, reproducible prognostic tool that integrates muscle decline and systemic inflammation to enhance all-cause mortality prediction in CKD, providing a quantitative basis for identifying high-risk patients and guiding personalized intervention strategies.