The Forgotten Anion: Serum Chloride and Its Association with All-Cause Mortality Across Chronic Kidney Disease and Dialysis—A Systematic Review and Meta-Analysis

Background: Chloride is the principal extracellular anion but is seldom used in risk assessment in kidney disease, where attention centres on sodium and potassium. Individual cohorts have linked abnormal serum chloride to mortality, but the evidence has not been synthesised. Methods: We searched PubMed, OpenAlex, the Web of Science Core Collection and Embase (to 13 July 2026) for longitudinal observational studies reporting a multivariable-adjusted association between serum chloride and all-cause (primary) or cardiovascular (secondary) mortality in adults with chronic kidney disease (CKD) or on maintenance dialysis. Adjusted hazard ratios (HRs) were pooled using DerSimonian–Laird random-effects models; studies on incompatible continuous scales were summarised narratively. Risk of bias was assessed using QUIPS, the Newcastle–Ottawa Scale, and GRADE. Results: Seven cohort studies (10,692 participants) were included. In the primary pool of three categorical studies, hypochloraemia was associated with higher all-cause mortality (pooled-adjusted HR 2.46; 95% CI 1.79–3.38; τ2 = 0; I2 = 0%). Two haemodialysis cohorts modelling chloride continuously reported associations in the same direction but on different scales and were not pooled; one younger peritoneal-dialysis cohort showed the opposite direction. Certainty was low to very low. Conclusions: Serum chloride may carry prognostic information, but its direction appears context- and modality-dependent, causality remains unproven, and it is not yet a validated risk-stratification marker.