Original Investigation Pathogenesis and Treatment of Kidney Disease| Volume 64, ISSUE 4, P534-541, October 01, 2014

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)


      Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear.

      Study Design

      Retrospective cohort study.

      Setting & Participants

      5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine−cystatin C equation.


      Serum bicarbonate concentrations.


      Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year).


      Average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR.


      Cause of metabolic acidosis cannot be determined in this study.


      Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m2.

      Index Words

      To read this article in full you will need to make a payment


      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Moranne O.
        • Froissart M.
        • Rossert J.
        • et al.
        Timing of onset of CKD-related metabolic complications.
        J Am Soc Nephrol. 2009; 20: 164-171
        • Kraut J.A.
        • Kurtz I.
        Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment.
        Am J Kidney Dis. 2005; 45: 978-993
        • Nath K.A.
        • Hostetter M.K.
        • Hostetter T.H.
        Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3.
        J Clin Invest. 1985; 76: 667-675
        • Navaneethan S.D.
        • Schold J.D.
        • Arrigain S.
        • et al.
        Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease.
        Clin J Am Soc Nephrol. 2011; 6: 2395-2402
        • Raphael K.L.
        • Wei G.
        • Baird B.C.
        • 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
        • Yaqoob M.M.
        Acidosis and progression of chronic kidney disease.
        Curr Opin Nephrol Hypertens. 2010; 19: 489-492
        • Shah S.N.
        • Abramowitz M.
        • Hostetter T.H.
        • Melamed M.L.
        Serum bicarbonate levels and the progression of kidney disease: a cohort study.
        Am J Kidney Dis. 2009; 54: 270-277
        • Kovesdy C.P.
        • Anderson J.E.
        • Kalantar-Zadeh K.
        Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD.
        Nephrol Dial Transplant. 2009; 24: 1232-1237
        • Menon V.
        • Tighiouart H.
        • Vaughn N.S.
        • et al.
        Serum bicarbonate and long-term outcomes in CKD.
        Am J Kidney Dis. 2010; 56: 907-914
        • Bild D.E.
        • Bluemke D.A.
        • Burke G.L.
        • et al.
        Multi-Ethnic Study of Atherosclerosis: objectives and design.
        Am J Epidemiol. 2002; 156: 871-881
        • Inker L.A.
        • Schmid C.H.
        • Tighiouart H.
        • et al.
        Estimating glomerular filtration rate from serum creatinine and cystatin C.
        N Engl J Med. 2012; 367: 20-29
        • Shlipak M.G.
        • Katz R.
        • Kestenbaum B.
        • et al.
        Rapid decline of kidney function increases cardiovascular risk in the elderly.
        J Am Soc Nephrol. 2009; 20: 2625-2630
        • Park M.
        • Shlipak M.G.
        • Katz R.
        • et al.
        Subclinical cardiac abnormalities and kidney function decline: the Multi-Ethnic Study of Atherosclerosis.
        Clin J Am Soc Nephrol. 2012; 7: 1137-1144
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Block G.
        • Woods M.
        • Potosky A.
        • Clifford C.
        Validation of a self-administered diet history questionnaire using multiple diet records.
        J Clin Epidemiol. 1990; 43: 1327-1335
        • Mayer-Davis E.J.
        • Vitolins M.Z.
        • Carmichael S.L.
        • et al.
        Validity and reproducibility of a food frequency interview in a multi-cultural epidemiology study.
        Ann Epidemiol. 1999; 9: 314-324
        • Gutierrez O.M.
        • Katz R.
        • Peralta C.A.
        • et al.
        Associations of socioeconomic status and processed food intake with serum phosphorus concentration in community-living adults: the Multi-Ethnic Study of Atherosclerosis (MESA).
        J Ren Nutr. 2012; 22: 480-489
        • Scialla J.J.
        • Anderson C.A.
        Dietary acid load: a novel nutritional target in chronic kidney disease?.
        Adv Chronic Kidney Dis. 2013; 20: 141-149
        • Lutsey P.L.
        • Jacobs Jr., D.R.
        • Kori S.
        • et al.
        Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: the MESA Study.
        Br J Nutr. 2007; 98: 397-405
        • Mahajan A.
        • Simoni J.
        • Sheather S.J.
        • Broglio K.R.
        • Rajab M.H.
        • Wesson D.E.
        Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.
        Kidney Int. 2010; 78: 303-309
        • de Brito-Ashurst I.
        • Varagunam M.
        • Raftery M.J.
        • Yaqoob M.M.
        Bicarbonate supplementation slows progression of CKD and improves nutritional status.
        J Am Soc Nephrol. 2009; 20: 2075-2084
        • Goldenstein L.
        • Driver T.H.
        • Fried L.F.
        • et al.
        Serum bicarbonate concentrations and kidney disease progression in community-living elders: the Health, Aging, and Body Composition (Health ABC) Study.
        Am J Kidney Dis. 2014; 64: 542-549
        • Warnock D.G.
        Uremic acidosis.
        Kidney Int. 1988; 34: 278-287
        • Frassetto L.A.
        • Morris Jr., R.C.
        • Sebastian A.
        Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline.
        Am J Physiol. 1996; 271: F1114-F1122
        • Abramowitz M.K.
        • Hostetter T.H.
        • Melamed M.L.
        Association of serum bicarbonate levels with gait speed and quadriceps strength in older adults.
        Am J Kidney Dis. 2011; 58: 29-38
        • Foley R.N.
        • Wang C.
        • Ishani A.
        • Collins A.J.
        NHANES III: influence of race on GFR thresholds and detection of metabolic abnormalities.
        J Am Soc Nephrol. 2007; 18: 2575-2582
        • Remer T.
        • Manz F.
        Potential renal acid load of foods and its influence on urine pH.
        J Am Diet Assoc. 1995; 95: 791-797
        • Kirschbaum B.
        Spurious metabolic acidosis in hemodialysis patients.
        Am J Kidney Dis. 2000; 35: 1068-1071