Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study

Yuichi Maruta, Takeshi Hasegawa, Etsuko Yamakoshi, Hiroki Nishiwaki, Fumihiko Koiwa, Enyu Imai, Akira Hishida, Yuichi Maruta, Takeshi Hasegawa, Etsuko Yamakoshi, Hiroki Nishiwaki, Fumihiko Koiwa, Enyu Imai, Akira Hishida

Abstract

Background: Metabolic acidosis, which reduces serum bicarbonate levels, contributes to the progression of chronic kidney disease (CKD). The difference between sodium and chloride (Na-Cl) may theoretically predict serum bicarbonate levels. This study aimed to evaluate serum Na-Cl level as a risk factor for renal function decline among patients who participated in the chronic kidney disease Japan cohort (CKD-JAC) study.

Methods: The association between low Na-Cl concentration (< 34 mmol/L) and composite renal function decline events (any initiation of renal replacement therapy or 50% decline in estimated glomerular filtration rate) was evaluated among 2143 patients with CKD stage G3a-4. Using Cox regression analysis, hazard ratios (HRs) were estimated after adjusting for the following covariates: age, sex, diabetes mellitus, diabetic nephropathy, cardiovascular disease, anemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, loop diuretics, cigarette smoking, body mass index, serum albumin, systolic blood pressure, urine albumin-to-creatinine ratio, and CKD stage.

Results: Composite renal function decline events were observed in 405 patients (18.9%) over the 4-year follow-up period. Low serum Na-Cl level (< 34 mmol/L) was independently associated with a greater risk for composite renal function decline events (HR 1.384; 95% confidence interval [CI], 1.116-1.717). Subgroup analyses identified that the association between low Na-Cl level and composite renal function decline events was stronger among patients with CKD stage G4 and those with anemia.

Conclusions: Our investigation suggests that Na-Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia.

Keywords: Acid–base disorder; Bicarbonate; CKD; Electrolyte; Metabolic acidosis.

Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest. Financial disclosure: TH has consulted for and received lecture fees from Kyowa Hakko Kirin; and FK has received speaker honoraria and a support grant from Kyowa Hakko Kirin. The other authors have nothing to declare.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 2007578 in Showa University Fujigaoka Hospital) and with the 1964 Helsinki declaration as amended in 2000.

Figures

Fig. 1
Fig. 1
Participant enrollment
Fig. 2
Fig. 2
Associations of evaluated variables with composite renal function decline events in Japanese patients with CKD stage G3a-4. Composite renal function decline event: any initiation of renal replacement therapy or a 50% decline in the eGFR from baseline; DM diabetes mellitus, CVD cardiovascular disease, ACEIs angiotensin-converting enzyme inhibitors, ARBs angiotensin receptor blockers, BMI body mass index, SBP systolic blood pressure, UACR urine albumin-to-creatinine ratio, Hb hemoglobin

References

    1. Shah SN, Abramowitz M, Hostetter TH, Melamed ML. Serum bicarbonate levels and the progression of kidney disease: a cohort study. Am J Kidney Dis. 2009;54:270–277. doi: 10.1053/j.ajkd.2009.02.014.
    1. Dobre M, Yang W, Chen J, Drawz P, Hamm LL, Horwitz E, et al. Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the chronic renal insufficiency cohort (CRIC) study. Am J Kidney Dis. 2013;62:670–678. doi: 10.1053/j.ajkd.2013.01.017.
    1. Phisitkul S, Hacker C, Simoni J, Tran RM, Wesson DE. Dietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptors. Kidney Int. 2008;73:192–199. doi: 10.1038/sj.ki.5002647.
    1. Eustace JA, Astor B, Muntner PM, Ikizler TA, Coresh J. Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney Int. 2004;65:1031–1040. doi: 10.1111/j.1523-1755.2004.00481.x.
    1. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009;20:2075–2084. doi: 10.1681/ASN.2008111205.
    1. Raphael KL, Wei G, Baird BC, Greene T, Beddhu S. Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans. Kidney Int. 2011;79:356–362. doi: 10.1038/ki.2010.388.
    1. Jeong J, Kwon SK, Kim HY. Effect of bicarbonate supplementation on renal function and nutritional indices in predialysis advanced chronic kidney disease. Electrolyte Blood Press. 2014;12:80–87. doi: 10.5049/EBP.2014.12.2.80.
    1. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150. doi: 10.1038/kisup.2012.73.
    1. Nihon Jinzo Gakkai Evidence-based clinical practice guideline for CKD. Nihon Jinzo Gakkaishi. 2013;55(5):585–860.
    1. Imai E, Matsuo S, Makino H, Watanabe T, Akizawa T, Nitta K, et al. Chronic kidney disease Japan cohort (CKD-JAC) study: design and methods. Hypertens Res. 2008;31(6):1101–1107. doi: 10.1291/hypres.31.1101.
    1. Abramowitz MK1, Hostetter TH, Melamed ML. The serum anion gap is altered in early kidney disease and associates with mortality. Kidney Int. 2012;82:701–709. doi: 10.1038/ki.2012.196.
    1. Gabow PA, Kaehny WD, Fennessey PV, Goodman SI, Gross PA, Schrier RW. Diagnostic importance of an increased serum anion gap. N Engl J Med. 1980;303:854–858. doi: 10.1056/NEJM198010093031505.
    1. van Hoeven KH, Joseph RE, Gaughan WJ, McBride L, Bilotti E, McNeill A, et al. The anion gap and routine serum protein measurements in monoclonal gammopathies. Clin J Am Soc Nephrol. 2011;6:2814–2821. doi: 10.2215/CJN.07380711.
    1. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in japan. Am J Kidney Dis. 2009;53:982–992. doi: 10.1053/j.ajkd.2008.12.034.
    1. Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.
    1. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. doi: 10.1080/01621459.1999.10474144.
    1. Goraya N, Simoni J, Jo CH, Wesson DE. A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate. Clin J Am Soc Nephrol. 2013;8:371–381. doi: 10.2215/CJN.02430312.
    1. Havlin J, Matousovic K, Schück O. Sodium-chloride difference as a simple parameter for acid–base status assessment. Am J Kidney Dis. 2017;69:707–708. doi: 10.1053/j.ajkd.2016.12.019.
    1. SD W, Pearson J, PA G, AL S. The fall of the serum anion gap. Arch Intern Med. 1990;150:311–313. doi: 10.1001/archinte.1990.00390140057012.
    1. Dobre M, Rahman M, Hostetter TH. Current status of bicarbonate in CKD. J Am Soc Nephrol. 2015;26:515–523. doi: 10.1681/ASN.2014020205.
    1. Nath KA, Hostetter MK, Hostetter TH. Increased ammoniagenesis as a determinant of progressive renal injury. Am J Kidney Dis. 2017;17:654–657. doi: 10.1016/S0272-6386(12)80344-1.
    1. Bishop ML, Fody EP, Schoeff LE. Clinical Chemistry: Techniques, Principles, Correlations. 7. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins; 2010.
    1. Kraut JA, Kurtz I. Metabolic acidosis of CKD: Diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005;45:978–993. doi: 10.1053/j.ajkd.2005.03.003.

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