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Published in: Clinical and Experimental Nephrology 2/2019

Open Access 01-02-2019 | Original article

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

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

Published in: Clinical and Experimental Nephrology | Issue 2/2019

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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.
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Literature
1.
go back to reference 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;54:270–7.CrossRefPubMedPubMedCentral 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;54:270–7.CrossRefPubMedPubMedCentral
2.
go back to reference 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;62:670–8.CrossRefPubMedPubMedCentral 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;62:670–8.CrossRefPubMedPubMedCentral
3.
go back to reference 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;73:192–9.CrossRefPubMed 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;73:192–9.CrossRefPubMed
4.
go back to reference 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;65:1031–40.CrossRefPubMed 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;65:1031–40.CrossRefPubMed
5.
go back to reference 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;20:2075–84.CrossRefPubMedPubMedCentral 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;20:2075–84.CrossRefPubMedPubMedCentral
6.
go back to reference 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;79:356–62.CrossRefPubMed 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;79:356–62.CrossRefPubMed
7.
go back to reference 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;12:80–7.CrossRefPubMedPubMedCentral 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;12:80–7.CrossRefPubMedPubMedCentral
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference Nihon Jinzo Gakkai. Evidence-based clinical practice guideline for CKD. Nihon Jinzo Gakkaishi. 2013;55(5):585–860. Nihon Jinzo Gakkai. Evidence-based clinical practice guideline for CKD. Nihon Jinzo Gakkaishi. 2013;55(5):585–860.
10.
go back to reference 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):1101–7.CrossRefPubMed 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):1101–7.CrossRefPubMed
11.
go back to reference Abramowitz MK1, Hostetter TH, Melamed ML. The serum anion gap is altered in early kidney disease and associates with mortality. Kidney Int. 2012;82:701–9.CrossRefPubMedPubMedCentral Abramowitz MK1, Hostetter TH, Melamed ML. The serum anion gap is altered in early kidney disease and associates with mortality. Kidney Int. 2012;82:701–9.CrossRefPubMedPubMedCentral
12.
go back to reference 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;303:854–8.CrossRefPubMed 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;303:854–8.CrossRefPubMed
13.
go back to reference 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;6:2814–21.CrossRefPubMedPubMedCentral 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;6:2814–21.CrossRefPubMedPubMedCentral
14.
go back to reference 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;53:982–92.CrossRef 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;53:982–92.CrossRef
15.
go back to reference Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.CrossRef Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.CrossRef
16.
go back to reference Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef
17.
go back to reference 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;8:371–81.CrossRefPubMedPubMedCentral 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;8:371–81.CrossRefPubMedPubMedCentral
18.
go back to reference Havlin J, Matousovic K, Schück O. Sodium-chloride difference as a simple parameter for acid–base status assessment. Am J Kidney Dis. 2017;69:707–8.CrossRefPubMed Havlin J, Matousovic K, Schück O. Sodium-chloride difference as a simple parameter for acid–base status assessment. Am J Kidney Dis. 2017;69:707–8.CrossRefPubMed
19.
go back to reference SD W, Pearson J, PA G, AL S. RB L. The fall of the serum anion gap. Arch Intern Med. 1990;150:311–3.CrossRef SD W, Pearson J, PA G, AL S. RB L. The fall of the serum anion gap. Arch Intern Med. 1990;150:311–3.CrossRef
20.
go back to reference Dobre M, Rahman M, Hostetter TH. Current status of bicarbonate in CKD. J Am Soc Nephrol. 2015;26:515–23.CrossRefPubMed Dobre M, Rahman M, Hostetter TH. Current status of bicarbonate in CKD. J Am Soc Nephrol. 2015;26:515–23.CrossRefPubMed
21.
go back to reference Nath KA, Hostetter MK, Hostetter TH. Increased ammoniagenesis as a determinant of progressive renal injury. Am J Kidney Dis. 2017;17:654–7.CrossRef Nath KA, Hostetter MK, Hostetter TH. Increased ammoniagenesis as a determinant of progressive renal injury. Am J Kidney Dis. 2017;17:654–7.CrossRef
22.
go back to reference Bishop ML, Fody EP, Schoeff LE. Clinical Chemistry: Techniques, Principles, Correlations. 7th ed. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins; 2010. Bishop ML, Fody EP, Schoeff LE. Clinical Chemistry: Techniques, Principles, Correlations. 7th ed. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins; 2010.
23.
go back to reference Kraut JA, Kurtz I. Metabolic acidosis of CKD: Diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005;45:978–93.CrossRefPubMed Kraut JA, Kurtz I. Metabolic acidosis of CKD: Diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005;45:978–93.CrossRefPubMed
Metadata
Title
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
Authors
Yuichi Maruta
Takeshi Hasegawa
Etsuko Yamakoshi
Hiroki Nishiwaki
Fumihiko Koiwa
Enyu Imai
Akira Hishida
Publication date
01-02-2019
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 2/2019
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-018-1631-x

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