CX3CR1-T280M polymorphism and end-stage renal disease development in chronic kidney disease

Chronic kidney disease (CKD) is a major global health concern driven by hypertension and diabetes, with genetic factors playing a key role in its pathogenesis. CX3CR1, the sole known receptor for the chemokine fractalkine, and its polymorphisms T280M and V249I have been implicated in the progression of several chronic diseases. This prospective observational study investigates the role of the CX3CR1 T280M polymorphism in CKD progression to end-stage disease. We included 121 CKD patients with varying renal insufficiency severity. Patients were stratified by CX3CR1-T280M genotype: Group 1 wild-type (T/T, 71.9%) and Group 2 carriers of the mutated allele (T/M or M/M, 28.1%). The primary outcome was kidney replacement therapy (KRT) initiation over 18 years. Cox proportional hazards univariate analysis was used for survival assessment. The M allele for CX3CR1 is associated with higher baseline serum creatinine levels, consistent with previous cross-sectional studies. During follow-up, KRT was initiated in 26 patients (17.2% in Group 1, 32.3% in Group 2). Survival analysis showed a significant association between the CX3CR1-T280M polymorphism and CKD progression (HR 2.28, 95% CI: 1.04–4.98, p 0.039). This study confirms the role of the CX3CR1-T280M polymorphism in determining prognosis in CKD patients, particularly in predicting the risk of a critical outcome such as initiation of KRT.