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Original ArticlesMineral Metabolism and Bone Disease
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Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction

Antonio Bellasi, Marcora Mandreoli, Leopoldo Baldrati, Matteo Corradini, Pierpaolo Di Nicolò, Giulio Malmusi and Antonio Santoro
CJASN April 2011, 6 (4) 883-891; DOI: https://doi.org/10.2215/CJN.07810910
Antonio Bellasi
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Marcora Mandreoli
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Leopoldo Baldrati
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Matteo Corradini
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Pierpaolo Di Nicolò
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Giulio Malmusi
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Antonio Santoro
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  • Figure 1.
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    Figure 1.

    (A) Overall likelihood of experiencing the composite end point according to quartile of serum phosphorus. (B) The HR of experiencing the composite end point according to serum phosphorous levels adjusted for age, case mix, hemoglobin, total calcium, uric acid and ACE inhibitors, vitamin D, and calcium salts use. The solid line represents the HR according to serum phosphorous level; the grey area represents the 95% CI.

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    Figure 2.

    Association between hyperphosphatemia (serum phosphorus ≥4.3 mg/dl) and the composite outcome (death or progression to ESRD) in different CKD-NDD subgroups. Here are depicted the HR associated with hyperphosphatemia compared with the reference group (serum phosphorus ≥3.3 but <3.8 mg/dl) in different stages of CKD, age category, sex, and diabetes status. All results are adjusted for the case mix and hemoglobin, total calcium, uric acid, ACE inhibitors, vitamin D, and calcium salts use.

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    Figure 3.

    Overall likelihood of progression to end-stage renal disease and dialysis inception according to the serum phosphorous quartile.

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    Figure 4.

    Overall likelihood of all causes of death according to the serum phosphorous quartile.

Tables

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    Table 1.

    Demographic, clinical, and laboratory characteristics of the entire study cohort and according to quartiles of phosphorus

    VariableOverall (n = 1716)Quartiles of Serum PhosphorusP Trend
    P < 3.3 mg/dl (n = 382)P ≥ 3.3 mg/dl and < 3.8 mg/dl (n = 426)P ≥ 3.8 mg/dl and < 4.3 mg/dl (n = 479)P ≥ 4.3 (n = 429)
    Demographic variables
        age (years)70.0 (13.6)72.0 (11.3)71.6 (12.8)69.6 (13.9)67.2 (15.2)<0.001
        male gender (%)66.284.368.561.453.1<0.001
    Clinical variables
        hypertension (%)96.396.197.19696.20.78
        diabetes mellitus (%)29.020.225.234.034.80.001
        COPD (%)11.612.912.811.19.90.47
        CVD (%)36.739.839.435.732.60.10
        CKD (%)
            stage 337.037.130.823.78.3<0.001
            stage 446.617.025.032.825.2<0.001
            stage 516.23.610.823.362.4<0.001
    Laboratory variables
        phosphorus (mg/dl)3.9 (2.13)2.9 (0.3)3.5 (1.4)4.0 (0.16)5.2 (3.9)<0.001
        calcium (mg/dl)9.0 (0.93)9.1 (1.0)9.0 (0.9)9.0 (0.9)8.8 (0.9)0.006
        iPTH (ng/ml)178 [73 to 178]98 [68 to 169]119 [71 to 185]117 [75 to 203]173 [96 to 334]<0.001
        hemoglobin (mg/dl)12.5 (3.3)13.2 (1.7)12.6 (1.6)12.2 (5.7)11.6 (1.6)<0.001
        total cholesterol (mg/dl)192 (42)191 (41)191 (40)193 (45)193 (43)0.91
        HDL cholesterol (mg/dl)51.9 (15)49.5 (13)51.4 (14)53.1 (16)53.8 (16)0.01
        triglycerides (mg/dl)149 (81)155 (83)140 (74)152 (83)149 (81)0.09
        uric acid (mg/dl)6.3 [5.2 to 7.4]6.3 [5.6 to 7.4]6.2 [5.6 to 7.4]6.3 [5.1 to 7.3]6.2 [5.2 to 7.6]0.55
        glucose (mg/dl)108 (38)106 (34)107 (41)112 (42)105 (34)0.08
        creatinine (mg/dl)2.3 [1.8 to 3.1]1.9 [1.6 to 2.3]2.0 [1.7 to 2.7]2.4 [1.8 to 2.9]3.2 [2.3 to 4.4]<0.001
        GFR (mg/min per 1.73 m2)25 [18 to 34]32 [25 to 40]28 [21 to 36]24 [18 to 32]17 [12 to 24]<0.001
    Concomitant medications
        calcium salts15.96.49.414.632.5<0.001
        vitamin D16.19.813.516.723.9<0.001
        ARB31.732.131.333.529.90.71
        ACE inhibitors46.747.249.047.443.30.39
        other hypertensive medications24.519.425.024.728.50.03
    • Data are expressed as mean (standard deviation) or median [IQR] when appropriate. ARB, Angiotensin Receptor Blockers.

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    Table 2.

    Association between hyperphosphatemia and the composite outcome (death or progression to ESRD) in the study cohort

    VariableOverall (n = 1716)
    Age-AdjustedCase Mix ModelaCox Full Modelb
    HR95% CIPHR95% CIPHR95% CIP
    P < 3.3 mg/dl0.640.42 to 0.960.030.750.49 to 1.140.180.780.51 to 1.190.25
    P ≥ 3.3 and < 3.8RefRefRef
    P ≥ 3.8 and < 4.31.290.91 to 1.810.140.980.69 to 1.390.940.930.66 to 1.330.72
    P ≥ 4.34.012.93 to 5.47<0.0012.321.64 to 3.27<0.0012.041.44 to 2.90<0.001
    • ↵a Case mix: age + gender, eGFR, history of diabetes mellitus, history of hypertension, and history of COPD and CVD.

    • ↵b Full model: age + case mix + hemoglobin, total calcium, uric acid and ACE inhibitors, vitamin D, and calcium salts use.

    • View popup
    Table 3.

    Predictors of the composite end point, progression to ESRD, and all-cause mortality

    VariableComposite End PointProgression to ESRDAll-Cause Mortality
    HR95% CIPHR95% CIPHR95% CIP
    Demographics
        age (per 1 year)1.011.00 to 1.020.0030.990.98 to 1.000.191.091.06 to 1.11<0.001
        men versus women1.401.06 to 1.830.011.360.96 to 1.910.071.851.15 to 2.990.01
    Clinical variables
        diabetes1.200.93 to 1.550.151.310.94 to 1.840.101.410.93 to 2.140.10
        hypertension1.860.67 to 5.150.221.940.58 to 6.440.273.150.42 to 23.50.26
        COPD1.100.73 to 1.640.630.880.46 to 1.660.690.910.49 to 1.710.97
        CVD0.910.68 to 1.210.810.960.64 to 1.430.851.160.74 to 1.820.50
    Laboratory variables
        serum phosphate (mg/dl)
        P < 3.30.780.51 to 1.190.250.610.30 to 1.240.170.740.43 to 1.280.29
        P ≤ 3.3 and < 3.8RefRefRefRefRefRefRefRefRef
        P ≥ 3.8 and < 4.30.930.66 to 1.330.721.360.84 to 2.180.200.640.36 −1.140.13
        P ≥ 4.32.041.44 to 2.90<0.0012.881.77 to 4.67<0.0012.491.44 to 4.320.001
        eGFR (ml/min)0.940.91 to 0.97<0.0010.880.86 to 0.91<0.0010.970.95 to 0.990.02
        hemoglobin (>12.4 g/dl)0.720.55 to 0.940.010.760.53 to 1.100.150.750.50 to 1.120.16
        calcium (mg/dl)0.880.74 to 1.040.150.750.61 to 0.920.0051.010.78 to 1.310.90
        total cholesterol (mg/dl)0.990.99 to 1.000.400.990.99 to 1.000.301.000.99 to 1.000.99
        uric acid (mg/dl)1.010.99 to 1.020.361.000.93 to 1.080.861.000.99 to 1.020.16
    Concomitant medications
        ACE inhibitor use1.010.78 to 1.290.930.850.60 to 1.180.341.180.80 to 1.750.31
        ARBs use1.361.03 to 1.780.021.340.95 to −1.900.091.240.88 to 2.090.16
        vitamin D use1.110.81 to 1.500.491.390.96 to 2.030.081.390.83 to 2.930.20
        calcium salts use1.361.03 to 1.810.021.170.82 to 1.660.371.260.77 to 2.050.33
    • ARB, Angiotensin Receptor Blockers.

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Clinical Journal of the American Society of Nephrology: 6 (4)
Clinical Journal of the American Society of Nephrology
Vol. 6, Issue 4
1 Apr 2011
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Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction
Antonio Bellasi, Marcora Mandreoli, Leopoldo Baldrati, Matteo Corradini, Pierpaolo Di Nicolò, Giulio Malmusi, Antonio Santoro
CJASN Apr 2011, 6 (4) 883-891; DOI: 10.2215/CJN.07810910

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Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction
Antonio Bellasi, Marcora Mandreoli, Leopoldo Baldrati, Matteo Corradini, Pierpaolo Di Nicolò, Giulio Malmusi, Antonio Santoro
CJASN Apr 2011, 6 (4) 883-891; DOI: 10.2215/CJN.07810910
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