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Association of serum chloride level with mortality and cardiovascular events in chronic kidney disease: the CKD-ROUTE study

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Abstract

Background

Electrolyte abnormalities, particularly dysnatremia, are independent predictors of adverse outcome in individuals with and without renal failure. However, the association of serum chloride level (Cl−) with mortality or risk of cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear.

Methods

This prospective cohort study included 923 pre-dialysis CKD G2–G5 patients among the participants of the CKD Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers. The primary outcome was a composite of overall death and CV events, and the secondary outcome was overall death. Data were analyzed using the Cox hazards model with adjustment for potential confounders.

Results

Median Cl− was 106.0 mEq/L at enrollment [quartile (Q) 1: ≤103.9, n =  207; Q2: 104.0–105.9, n =  207; Q3: 106.0–108.0, n =  289; Q4: ≥108.1, n = 220]. During a median follow-up of 33 months, there were 98 CV events, 66 deaths, and 154 composite outcomes. The hazard ratio (HR) for the composite outcome was higher for Q1 than Q3 [HR 1.72; 95 % confidence interval (CI) 1.08–2.72; P =  0.022]. As a continuous variable in a subset of patients whose Cl− was ≤106.0 mEq/L, higher Cl− was associated with lower risk of the composite outcome (HR 0.93; 95 % CI 0.87–0.99; P = 0.023). HR for all-cause mortality was also higher for Q1 than Q3 (HR 2.48; 95 % CI 1.22–5.03; P =  0.012).

Conclusion

Low Cl− was associated with increased mortality and risk of CV events in pre-dialysis CKD patients. Cl− may be an additional prognostic indicator in CKD.

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Authors and Affiliations

  1. Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan

    Shintaro Mandai, Soichiro Iimori, Shotaro Naito, Hiroaki Kikuchi, Eisei Sohara, Tomokazu Okado, Sei Sasaki, Tatemitsu Rai & Shinichi Uchida

  2. Department of Nephrology, Tokyo Kyosai Hospital, 2-3-8 Nakameguro, Meguro-ku, Tokyo, 153-8934, Japan

    Eiichiro Kanda & Katsuyuki Oi

  3. Department of Nephrology, Nitobe Memorial Nakano General Hospital, 4-59-16 Chuo, Nakano, Tokyo, 164-0011, Japan

    Yumi Noda

  4. JA Toride Medical Center, 2-1-1 Hongo, Toride, Ibaraki, 302-0022, Japan

    Masanobu Akazawa

  5. Department of Nephrology, Tsuchiura Kyodo General Hospital, 11-7 Manabeshinmachi, Tsuchiura, Ibaraki, 300-0053, Japan

    Takayuki Toda

Authors
  1. Shintaro Mandai
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  2. Eiichiro Kanda
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  14. Shinichi Uchida
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Correspondence to Eiichiro Kanda.

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Mandai, S., Kanda, E., Iimori, S. et al. Association of serum chloride level with mortality and cardiovascular events in chronic kidney disease: the CKD-ROUTE study. Clin Exp Nephrol 21, 104–111 (2017). https://doi.org/10.1007/s10157-016-1261-0

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  • DOI: https://doi.org/10.1007/s10157-016-1261-0

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