Article Figures & Data
Figures
- Figure 1.
Distribution of baseline serum phosphate in the study population.
- Figure 2.
Cumulative incidence of ESRD alone and in combination with doubling serum creatinine in patients stratified according to serum phosphate quartiles. I/II quartile: < 3.45 mg/dl. III quartile: 3.45 to 4.00 mg/dl. IV quartile: > 4.00 mg/dl.
Tables
- Table 1.
Main clinical and biochemical characteristics of study patients according to serum phosphate quartiles
1st and 2nd Phosphate Quartiles P 3rd Phosphate Quartile P 4th Phosphate Quartile P Ramipril (n = 81) Placebo (n = 85) Ramipril (n = 48) Placebo (n = 44) Ramipril (n = 36) Placebo (n = 37) Age (years) 51 ± 13 52 ± 12 0.55 48 ± 14 49 ± 16 0.92 46 ± 13 45 ± 15 0.63 Male sex, n (%) 68 (84%) 72 (84.7%) 0.89 36 (75%) 30 (68.2%) 0.47 28 (77.8%) 18 (50.0%) 0.01 Urinary sodium (mEq/24 h) 98 ± 39 89 ± 47 0.25 85 ± 36 88 ± 40 0.74 75 ± 27 78 ± 41 0.71 Urinary urea (mg/24 h) 1067 ± 583 984 ± 470 0.35 1017 ± 428 1010 ± 449 0.94 811 ± 392 844 ± 230 0.69 On treatment with Ca supplements, n (%) 2 (2.5%) 2 (2.4%) 0.96 1 (2.1%) 0 (0%) 0.34 0 (0%) 1 (2.7%) 0.32 On treatment with Vit. D analogs, n (%) 1 (1.2%) 1 (1.2%) 0.97 2 (4.2%) 2 (4.5%) 0.93 5 (13.9%) 2 (5.4%) 0.22 Smokers, n (%) 19 (23.5%) 10 (11.8%) 0.05 8 (16.7%) 9 (20.5%) 0.64 10 (27.8%) 7 (18.9%) 0.37 Diabetes, n (%) 4 (4.9%) 5 (5.9%) 0.79 6 (12.5%) 5 (11.4%) 0.87 3 (8.3%) 2 (5.4%) 0.62 Cholesterol (mg/dl) 241 ± 56 240 ± 53 0.96 236 ± 53 248 ± 62 0.34 258 ± 109 250 ± 55 0.71 Albumin (g/dl) 3.9 ± 0.5 3.9 ± 0.5 0.70 3.9 ± 0.5 3.9 ± 0.4 0.78 3.6 ± 1.2 3.8 ± 0.4 0.53 Glucose (mg/dl) 104 ± 26 105 ± 34 0.89 116 ± 55 110 ± 47 0.57 98 ± 23 105 ± 38 0.34 Calcium (mg/dl) 9.1 ± 1.4 9.3 ± 1.0 0.53 9.4 ± 0.5 9.4 ± 0.6 0.71 9.2 ± 0.6 9.1 ± 0.6 0.85 Phosphate (mg/dl) 2.8 ± 0.5 2.9 ± 0.4 0.07 3.8 ± 0.2 3.7 ± 0.2 0.36 4.6 ± 0.6 4.5 ± 0.4 0.15 Hemoglobin (g/dl) 14.2 ± 1.3 14.0 ± 1.7 0.55 13.7 ± 2.0 12.9 ± 1.6 0.04 12.6 ± 1.9 12.2 ± 1.7 0.38 Systolic pressure (mmHg) 145 ± 22 146 ± 17 0.86 147 ± 15 145 ± 18 0.56 146 ± 18 148 ± 19 0.69 Diastolic pressure (mmHg) 91 ± 11 91 ± 12 0.72 91 ± 14 87 ± 10 0.13 89 ± 11 91 ± 11 0.58 Mean arterial pressure (mmHg) 109 ± 14 110 ± 13 0.77 110 ± 13 107 ± 11 0.20 108 ± 12 110 ± 11 0.57 Urinary protein (g/24 h) 2.3 (1.3–3.7) 3.0 (1.5–4.3) 0.11 2.7 (1.5–4.0) 2.6 (1.4–3.9) 0.57 3.8 (2.2–7.8) 4.0 (2.0–6.6) 0.61 Iohexol GFR (ml/min/1.73m2) 52 ± 20 47 ± 17 0.05 45 ± 20 40 ± 17 0.15 35 ± 16 31 ± 13 0.27 1st and 2nd quartiles, serum phosphate <3.45 mg/dl; 3rd phosphate quartile, 3.45–4.00 mg/dl; 4th phosphate quartile, >4.00 mg/dl. Data are expressed mean ± SD or as percent frequency, as appropriate.
ESRD occurrence Crude Hazard ratio, 95% CI, and P-value Adjusted for confounders, gender, and systolic BP Hazard ratio, 95% CI, and P-value Phosphate (1 mg/dl) 3.30 (2.46–4.43), P < 0.001 1.84 (1.27–2.67), P = 0.001 Treatment with Ramipril (0 = no; 1 = yes) 0.48 (0.29–0.79), P = 0.004 Albumin (1 g/dl) 0.43 (0.26–0.73), P = 0.002 Hemoglobin (1 g/dl) 0.90 (0.78–1.02), P = 0.11 Iohexol GFR (1 ml/min/1.73m2) 0.94 (0.92–0.96), P < 0.001 Urinary Protein (1 g/24 h) 1.11 (1.02–1.21), P = 0.01 Gender (0 = M; 1 = F) 1.71 (0.94–3.10), P = 0.08 Systolic pressure (1 mmHg) 1.03 (1.01–1.04), P = 0.001 Combined end point (ESRD/creatinine doubling) Crude Hazard ratio, 95% CI, and P-value Adjusted for confounders, gender, and systolic BP Hazard ratio, 95% CI, and P-value Phosphate (1 mg/dl) 2.87 (2.18–3.77), P < 0.001 1.66 (1.18–2.33), P = 0.004 Treatment with Ramipril (0 = no; 1 = yes) 0.49 (0.31–0.79), P = 0.003 Albumin (1 g/dl) 0.50 (0.31–0.82), P = 0.006 Hemoglobin (1 g/dl) 0.92 (0.81–1.05), P = 0.20 Iohexol GFR (1 ml/min/1.73m2) 0.95 (0.93–0.97), P < 0.001 Urinary protein (1 g/24 h) 1.11 (1.02–1.20), P = 0.01 Gender (0 = M; 1 = F) 1.51 (0.87–2.63), P = 0.14 Systolic pressure (1 mmHg) 1.02 (1.01–1.03), P = 0.002 The approach to multivariate Cox's regression analysis is described in detail in the Methods section. Data are expressed as hazard ratio, 95% CI, and P-values.
- Table 3.
Crude incidence rate of ESRD and (a) combined renal end point, and (b) according to serum phosphate quartiles and study arms (Ramipril versus placebo)
(a) Incidence rate of end stage renal disease (ESRD) Crude Incidence Rate of ESRD Occurrence (events/100 person-years) *Crude Hazard Ratio, 95% CI, and P-value (Ramipril versus placebo) Placebo group Ramipril group First two quartiles (<3.45 g/dl) 6.9 (4.0–11.2) 0.42 (0.01–2.4) 0.13 (0.04–0.39), P < 0.0001 Third quartile (3.45–4.00 mg/dl) 13.8 (7.6–23.2) 6.5 (3.0–12.3) 0.32 (0.18–0.59), P < 0.001 Fourth quartile (> 4.00 mg/dl) 26.8 (16.1–41.7) 20.7 (11.6–34.2) 0.82 (0.44–1.55), P = 0.54 P for effect modification = 0.008 (b) Incidence rate of the combined renal end point (ESRD and doubling of serum creatinine) Crude Incidence Rate of Renal Outcomes (events/100 person-years) *Crude Hazard ratio, 95% CI, and P-value (Ramipril versus placebo) Placebo group Ramipril group First two quartiles (<3.45 g/dl) 8.8 (5.3–13.7) 1.3 (0.3–3.8) 0.15 (0.06–0.39), P < 0.0001 Third quartile (3.45–4.00 mg/dl) 18.6 (10.8–29.7) 6.7 (3.1–12.7) 0.37 (0.22–0.62), P < 0.001 Fourth quartile (> 4.00 mg/dl) 27.9 (16.8–43.8) 25.2 (14.7–40.4) 0.90 (0.49–1.66), P = 0.73 P for effect modification = 0.004 Data are incidence rate and 95% confidence intervals.
*The crude hazard ratios of Ramipril treatment for study outcomes across serum phosphate quartiles were derived by Cox models including Ramipril treatment, serum phosphate strata, and their interaction term.
- Table 4.
Interaction analysis between Ramipril treatment and serum phosphate strata for (a) ESRD alone and (b) in combination to doubling of serum creatinine levels
(a) End stage renal disease (ESRD) Adjusted for Confounders, Gender, and Systolic BP Hazard ratio, 95% CI, and P-value Treatment with Ramipril (0 = no; 1 = yes) P for interaction = 0.034 Phosphate strata [1 = I/II quartile; 2 = III quartile; 3 = IV quartile] Treatment * phosphate strata Albumin (1 g/dl) 0.46 (0.27–0.77), P = 0.003 Hemoglobin (1 g/dl) 0.89 (0.78–1.02), P = 0.10 Iohexol GFR (1 ml/min/1.73m2) 0.94 (0.92–0.96), P < 0.001 Urinary protein (1 g/24 h) 1.13 (1.04–1.23), P = 0.003 Gender (0 = M; 1 = F) 1.56 (0.85–2.85), P = 0.15 Systolic pressure (1 mmHg) 1.03 (1.01–1.04), P < 0.001 (b) ESRD/doubling of serum creatinine Adjusted for confounders, gender and systolic BP Hazard ratio, 95% CI, and P-value Treatment with Ramipril (0 = no; 1 = yes) P for interaction = 0.021 Phosphate strata [1 = I/II quartile; 2 = III quartile; 3 = IV quartile] Treatment * phosphate strata Albumin (1 g/dl) 0.53 (0.33–0.88), P = 0.01 Hemoglobin (1 g/dl) 0.91 (0.80–1.04), P = 0.17 Iohexol GFR (1 ml/min/1.73m2) 0.95 (0.93–0.96), P < 0.001 Urinary protein (1 g/24 h) 1.12 (1.04–1.21), P = 0.003 Gender (0 = M; 1 = F) 1.34 (0.76–2.36), P = 0.23 Systolic pressure (1 mmHg) 1.02 (1.01–1.04), P = 0.001 Data are expressed as hazard ratio, 95% CI, and P-values.
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Phosphate May Promote CKD Progression and Attenuate Renoprotective Effect of ACE Inhibition
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