Phenotype-specific association of C-reactive protein-to-lymphocyte ratio with incident proteinuric CKD versus isolated eGFR decline: a real-world retrospective cohort study

Background Residual kidney risk persists in hypertensive patients despite guideline-directed blood pressure (BP) management. Whether systemic inflammation is preferentially associated with the development of distinct early chronic kidney disease (CKD) phenotypes remains uncertain. Methods This retrospective cohort study included 5,904 hypertensive patients with preserved baseline kidney function. The primary exposure was the C-reactive protein-to-lymphocyte ratio (CLR). Outcomes assessed were incident proteinuric CKD, isolated estimated glomerular filtration rate (eGFR) decline, and any incident CKD. Phenotype-specific associations were evaluated using multivariable cause-specific Cox models. We additionally assessed the additive interaction between CLR and BP control, and evaluated the incremental predictive value of CLR beyond traditional risk factors. Results During a median follow-up of 34.1 months, 598 participants developed proteinuric CKD, 89 developed isolated eGFR decline, and 728 developed any incident CKD. Higher CLR was independently associated with proteinuric CKD (per 1-SD: HR 1.14, 95% CI 1.05–1.24; highest vs lowest quartile: HR 1.46, 95% CI 1.15–1.85) and any incident CKD (per 1-SD: HR 1.13, 95% CI 1.05–1.22), but not with isolated eGFR decline (per 1-SD: HR 1.05, 95% CI 0.85–1.29). A significant additive interaction emerged between high CLR and uncontrolled BP (RERI 0.30), synergistically amplifying renal risk. Adding CLR to traditional risk models significantly improved risk reclassification (NRI 0.083, P = 0.008). Conclusions In hypertensive patients, elevated CLR preferentially predicts new-onset proteinuria over isolated eGFR decline. As an accessible biomarker for renal risk stratification, CLR can identify patients requiring vigilant proteinuria surveillance and comprehensive management, particularly those with uncontrolled BP.