Original ArticlesChronic Kidney Disease

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

Sankar D. Navaneethan, Jesse D. Schold, Susana Arrigain, Stacey E. Jolly, Edgard Wehbe, Rupesh Raina, James F. Simon, Titte R. Srinivas, Anil Jain, Martin J. Schreiber and Joseph V. Nally
CJASN October 2011, 6 (10) 2395-2402; DOI: https://doi.org/10.2215/CJN.03730411

Article Figures & Data

Figures

  • Figure 1.
    Figure 1.

    Flow chart showing how patients were selected for this analysis from the electronic-health-record-based registry. CKD, chronic kidney disease; eGFR, estimated GFR.

  • Figure 2.
    Figure 2.

    Kaplan–Meier survival curve based on serum bicarbonate levels among chronic kidney disease patients.

  • Figure 3.
    Figure 3.

    Associations (log hazard and 95% confidence interval) between all-cause mortality and baseline serum bicarbonate levels. Model adjusted for age, gender, African-American race, body mass index, diabetes, hypertension, hyperlipidemia, malignancy, congestive heart failure, cerebrovascular disease, and coronary artery disease at chronic kidney disease diagnosis and estimated GFR, use of renin-angiotensin system blockers and diuretics, hemoglobin and albumin.

  • Figure 4.
    Figure 4.

    Hazard ratio and 95% confidence interval (CI) of all-cause mortality associated with low serum bicarbonate levels among select subgroups. eGFR, estimated GFR.

Tables

  • Table 1.

    Characteristics of patients serum bicarbonate levels measured at CKD diagnosis

    VariableaNot Measured (n = 2400)Low Bicarbonate (<23 mmol/L) (n = 5796)Normal Bicarbonate (23–32 mmol/L) (n = 35,301)High Bicarbonate (>32 mmol/L) (n = 652)
    Ageb (mean [SD])73.7 (9.8)68.9 (13.8)72.3 (11.5)71.9 (12.2)
    eGFRb (mean [SD])47.0 (10.0)42.3 (12.2)48.3 (9.7)46.4 (10.9)
    eGFR stage
        Stage 3a (GFR 45 to 59 [%])63.848.169.763.7
        Stage 3b (GFR 30 to 44 [%])28.032.424.226.5
        Stage 4 (GFR 15 to 29 [%])8.219.56.19.8
    Male gender (%)52.649.645.543.3
    African American (%)8.918.512.216.1
    Diabetes (%)12.927.722.621.6
    Hypertension (%)79.387.689.784.8
    Coronary artery disease (%)14.820.923.226.1
    Cerebrovascular disease (%)7.89.39.58.6
    Congestive heart failure (%)2.59.18.621.9
    Malignancy (%)29.226.123.623.2
    Hyperlipidemia (%)72.971.779.575.2
    COPD (%)6.37.89.020.1
    Smoking (%)
        nonsmoker84.083.588.786.5
        smoker9.010.27.07.7
        missing information7.06.34.35.8
    BMI kg/m2 (%)
        <18.50.961.81.11.2
        18.5 to 24.923.824.323.128.1
        25 to 29.934.532.835.628.5
        30 to 34.919.720.321.115.6
        35 to 39.99.19.48.812.1
        > 404.76.95.89.2
        missing information7.44.54.35.2
    Albumin (g/dl)b (mean [SD])4.0 ± 0.514.0 ± 0.534.2 ± 0.414.1 ± 0.48
    Hemoglobin (g/dl) (mean [SD])12.9 ± 1.812.1 ± 2.013.0 ± 1.712.8 ± 1.9

    • Overall serum bicarbonate groups <23, 23 to 32, and >32 significantly different with P < 0.001 for all variables except cerebrovascular disease. The chi-squared test was used to assess categorical variables and ANOVA used for continuous variables. CKD, chronic kidney disease; eGFR, estimated GFR; COPD, chronic obstructive pulmonary disease; BMI, body mass index.

    • a Chi-squared test, P < 0.05, unless otherwise noted, comparing patients with serum bicarbonate measured versus all those not measured.

    • b t-test, P < 0.05, comparing patients with serum bicarbonate measured versus all those not measured.

  • Table 2.

    Factors associated with low serum bicarbonate and high serum bicarbonate at CKD diagnosis

    EffectModel 1 (n = 37,346)Model 2 (n = 32,623)
    Low Bicarbonate (<23 mmol/L) OR (95% CI)PHigh Bicarbonate (>32 mmol/L) OR (95% CI)P
    Age quintiles<0.010.09
        62.4 to 70.1 versus 18 to 62.40.72 (0.66, 0.79)0.79 (0.61, 1.02)
        70.2 to 76.4 2 versus 18 to 62.40.63 (0.58, 0.70)0.71 (0.55, 0.93)
        76.4 to 82.3 versus 18 to 62.40.57 (0.52, 0.63)0.82 (0.63, 1.06)
        82.3 to 104 versus 18 to 62.40.50 (0.45, 0.55)0.73 (0.56, 0.96)
    Male gender1.32 (1.23, 1.40)<0.010.94 (0.79, 1.11)0.46
    African-American race versus others1.24 (1.14, 1.35)<0.011.09 (0.86, 1.37)0.49
    BMI group (kg/m2)0.17<0.01
         <18.5 versus 18.5 to 24.91.28 (1.00, 1.63)0.82 (0.40, 1.68)
        25 to 29.9 versus 18.5 to 24.90.96 (0.89, 1.04)0.71 (0.57, 0.88)
        30 to 34.9 versus 18.5 to 24.90.96 (0.87, 1.05)0.67 (0.51, 0.86)
        35 to 39.9 versus 18.5 to 24.90.94 (0.84, 1.07)1.17 (0.88, 1.56)
        40+ versus 18.5 to 24.90.88 (0.77, 1.02)1.16 (0.83, 1.62)
        missing versus 18.5 to 24.91.03 (0.87, 1.21)0.97 (0.65, 1.46)
    eGFR (per 10-ml/min per 1.73 m2 increase)0.66 (0.64, 0.67)<0.010.92 (0.85, 0.998)0.046
    Diabetes1.20 (1.11, 1.29)<0.010.79 (0.64, 0.98)0.03
    Hypertension1.03 (0.93, 1.14)0.540.71 (0.56, 0.90)0.04
    Hyperlipidemia0.79 (0.73, 0.85)<0.010.84 (0.69, 1.03)0.10
    Coronary artery disease0.94 (0.87, 1.02)0.121.13 (0.92, 1.38)0.25
    Congestive heart failure0.82 (0.73, 0.91)<0.012.57 (2.08, 3.16)<0.01
    COPD0.88 (0.78, 0.98)0.0192.52 (2.05, 3.09)<0.01
    Smoking<0.010.77
        yes versus no1.38 (1.24, 1.54)0.92 (0.67, 1.27)
        missing versus no1.28 (1.12, 1.47)1.10 (0.75, 1.60)
    Hb per 1 g/dl increase0.83 (0.82, 0.85)<0.011.01 (0.96, 1.06)0.83
    Albumin per 1 mg/dl increase0.79 (0.74, 0.84)<0.010.71 (0.59, 0.86)<0.01

    • Model was additionally adjusted for the year of inclusion in the registry. CKD, chronic kidney disease; OR, odds ratio; CI, confidence interval; BMI, body mass index; eGFR, estimated glomerular filtration rate; COPD, chronic obstructive pulmonary disease.

  • Table 3.

    Associations between serum bicarbonate levels and all-cause mortality among chronic kidney disease patients

    Bicarbonate GroupUnadjusted HR [95% CI] (n = 41,445)Model A HR [95 %CI] (n = 41,445)Model B HR [95 %CI] (n = 37,687)Model C HR [95% CI] (n = 37,687)
    <23 mmol/L versus 23 to 32 mmol/L1.65 (1.56, 1.75)1.75 (1.65, 1.85)1.35 (1.27, 1.44)1.23 (1.16, 1.31)
    >32 mmol/L versus 23 to 32 mmol/L2.12 (1.86, 2.42)2.08 (1.83, 2.37)1.76 (1.54, 2.02)1.74 (1.52, 2.00)

    • Model A adjusted for age, gender, and race. Model B adjusted variables included in Model A, plus body mass index, diabetes, hypertension, hyperlipidemia, malignancy, congestive heart failure, cerebrovascular disease, coronary artery disease, chronic obstructive pulmonary disease, history of angiotensin-converting enzyme/angiotensin receptor blocker prescription, history of diuretic prescription at chronic kidney disease diagnosis, and hemoglobin and albumin. Model C adjusted variables included in Model B, plus baseline estimated GFR. HR, hazard ratio; CI, confidence interval.

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Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease
Sankar D. Navaneethan, Jesse D. Schold, Susana Arrigain, Stacey E. Jolly, Edgard Wehbe, Rupesh Raina, James F. Simon, Titte R. Srinivas, Anil Jain, Martin J. Schreiber, Joseph V. Nally
CJASN Oct 2011, 6 (10) 2395-2402; DOI: 10.2215/CJN.03730411
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