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Association of Serum Chloride Concentration With All-Cause and Cardiovascular Mortality in Patients Undergoing
Tomoya Hamashoji1, Shoji Tsuneyoshi1, Kazuhiro Okamura1
1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Insights
Low serum chloride levels in peritoneal dialysis (PD) patients are linked to higher risks of death from all causes and cardiovascular events. This suggests serum chloride may be a valuable marker for assessing mortality risk in PD patients.
Area of Science:
- Nephrology
- Clinical Chemistry
- Epidemiology
Background:
- Low serum chloride concentration is associated with mortality in chronic kidney disease (CKD) patients undergoing hemodialysis.
- Evidence linking serum chloride to mortality in peritoneal dialysis (PD) patients, particularly maintenance PD patients, is limited, often stemming from incident cohorts.
Purpose of the Study:
- To investigate the independent association between serum chloride concentration at registry enrollment and all-cause and cardiovascular mortality in maintenance PD patients.
- To determine if serum chloride levels can serve as a prognostic marker for mortality risk in this population.
Main Methods:
- A multicenter retrospective cohort study was conducted using data from the Fukuoka Peritoneal Dialysis Registry (F-PDR) in Japan (2011-2020).
- 1,049 maintenance PD patients with PD duration of at least 90 days were analyzed.
- Serum chloride concentration was categorized into tertiles, and Cox proportional hazards models were used for analysis, with multivariable adjustments and multiple imputation for missing covariates.
Main Results:
- Over a median follow-up of 731 days, 17.1% of patients died (179 total), with 5.6% (59 patients) from cardiovascular causes.
- Compared to the highest tertile (>99 mmol/L), the lowest tertile (<96 mmol/L) of serum chloride was independently associated with significantly higher risks of all-cause mortality (HR, 2.59; 95% CI, 1.55-4.34).
- The lowest serum chloride tertile was also linked to a substantially increased risk of cardiovascular mortality (HR, 3.33; 95% CI, 1.28-8.66).
Conclusions:
- Lower serum chloride concentration is independently associated with increased risks of all-cause and cardiovascular mortality in maintenance PD patients.
- Serum chloride may serve as a useful and accessible biomarker for risk stratification and predicting mortality in patients undergoing PD.
- Further research is warranted to explore the mechanisms underlying this association and its clinical implications.
Rationale & Objective:
Low serum chloride concentration is linked to mortality in chronic kidney disease and hemodialysis, but evidence in peritoneal dialysis (PD) has largely come from incident cohorts. We evaluated whether serum chloride concentration at registry enrollment is independently associated with all-cause and cardiovascular mortality among maintenance PD patients.
Study Design:
Multicenter retrospective cohort study.
Setting & Participants:
The Fukuoka Peritoneal Dialysis Registry (F-PDR) enrolled PD patients from 20 centers in Japan (2011-2020). Enrollment in this cohort study was not restricted to the time of PD initiation. After excluding patients with PD duration <90 days at F-PDR enrollment, 1,049 maintenance PD patients were analyzed.
Exposure:
Serum chloride concentration at registry enrollment, categorized into tertiles (T1 <96, T2 96-99, and T3 >99 mmol/L).
Outcomes:
All-cause mortality (primary) and cardiovascular mortality (secondary).
Analytical Approach:
Cox proportional hazards models estimated HR and 95% CI with multivariable adjustment including serum sodium and other prespecified covariates. Missing covariates were handled with multiple imputation.
Results:
Over a median follow-up of 731 days, 179 patients (17.1%) died, including 59 (5.6%) from cardiovascular causes. In the fully adjusted model, compared with T3 (>99 mmol/L), T1 (<96 mmol/L) was associated with higher risks of all-cause mortality (HR, 2.59; 95% CI, 1.55-4.34) and cardiovascular mortality (HR, 3.33; 95% CI, 1.28-8.66).
Limitations:
Observational design with potential residual confounding. Serum chloride and covariates were measured only at registry enrollment. Serum bicarbonate was unavailable. Generalizability may be limited.
Conclusions:
In maintenance PD patients, lower serum chloride concentration was independently associated with increased all-cause and cardiovascular mortality risks, suggesting serum chloride may be a useful marker for risk assessment.
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