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.