Background
Methods
Study population
Laboratory analysis
Statistical analysis
Results
Patient characteristics
Variables | Variables | |||||
---|---|---|---|---|---|---|
Clinical characteristics | Laboratory measurements | Median | (Interquartile range) | |||
Age | 68.9 | ± | 11.3 | Complete blood cell count | ||
Sex (women/men) | 50 | / | 135 | White blood cell count. ×103/mL | 5.9 | (4.9 - 7.0) |
Body mass index, kg/m2
| 23.3 | ± | 3.1 | Hemoglobin, g/dL | 13.5 | (12.4 - 14.7) |
Systolic blood pressure, mmHg | 128.2 | ± | 19.5 | Platelet count. ×104/mL | 20.1 | (17.2 - 25.3) |
Cardiovascular disease | Blood chemistry | |||||
Ischemic heart disease, n (%) | 124 | (67.0) | Total protein, g/dL | 6.9 | (6.6 - 7.4) | |
Arrhythmia, n (%) | 43 | (23.2) | Albumin, g/dL | 4.0 | (3.8 - 4.2) | |
Cardiomyopathy, n (%) | 22 | (11.9) | Alanine aminotransferase, IU/L | 19 | (14–27) | |
NYHA class III/IV, n (%) | 16 | (8.6) | Blood urea nitrogen, mg/dL | 17 | (14–21) | |
Aortic aneurysm, n (%) | 10 | (5.4) | Serum creatinine, mg/dL | 0.88 | (0.74 - 1.08) | |
Peripheral artery disease, n (%) | 19 | (10.3) | eGFR. mL/min/1.73 m2
| 49.5 ± 15.0 | ||
Valvular heart disease, n (%) | 7 | (3.8) | C-reactive protein, mg/dL | 0.10 | (0.04 - 0.45) | |
Smoking status | B-type natriuretic peptide, pg/mL | 49.4 | (22.3 - 123.4) | |||
Never, n (%) | 69 | (37.3) | Corrected calcium, mg/dL | 9.1 | (8.8 - 9.4) | |
Former, n (%) | 89 | (48.1) | Inorganic phosphate, mg/dL | 3.3 ± 0.5 | ||
Current, n (%) | 27 | (14.6) | FGF23, pg/mL | 46.9 | (33.7 - 67.8) | |
α-Klotho, pg/mL | 343 | (218–474) | ||||
Medication | ||||||
ACE inhibitors/ARB, n (%) | 96 | (51.9) | Urine chemistry | |||
Beta blockers, n (%) | 72 | (38.9) | Albumin, g/dL | 8.7 | (4.5 - 34.0) | |
Calcium channel blockers, n (%) | 84 | (45.4) | Creatinine, mg/dL | 74.8 | (42.9 - 126.4) | |
Aldosterone antagonist, n (%) | 8 | (4.3) | Albumin/creatinine ratio, mg/g | 12.9 | (6.6 - 34.4) | |
Sulfonylurea, n (%) | 16 | (8.6) | Calcium/creatinine ratio, mg/g | 0.07 | (0.04 - 0.12) | |
DPP4 inhibitors, n (%) | 28 | (15.1) | Phosphate/creatinine ratio, mg/g | 0.49 ± 0.21 | ||
Insulin, n (%) | 15 | (8.1) | Fractional excretion of calcium, % | 0.73 | (0.42 - 1.12) | |
Loop, n (%) | 32 | (17.3) | TRP, % | 86.1 ± 6.7 | ||
Thiazide, n (%) | 15 | (8.1) | TmP/GFR, mg/dL | 2.9 | (2.5 - 3.5) | |
Statin, n (%) | 96 | (51.9) |
eGFR ≥60 mL/min/m2
| eGFR 30–60 mL/min/m2
| eGFR <30 mL/min/m2
| |||||
---|---|---|---|---|---|---|---|
Variables | (n = 44) | (n = 124) | (n = 17) | P value | |||
eGFR, mL/min/1.73 m2
| 69.2 ± 8.7 | 45.9 ± 8.4 | 25.6 ± 8.4 | <0.001 | |||
Urine albumin creatinine ratio | 10 | (7–55) | 13 | (6–27) | 75 | (10–196) | 0.036 |
Serum cCa, mg/dL | 9.1 | (8.8 - 9.5) | 9.1 | (8.7 - 9.3) | 9.1 | (8.7 - 9.3) | 0.508 |
Serum inorganic phosphate, mg/dL | 3.40 | (3.10 - 3.70) | 3.30 | (2.90 - 3.70) | 3.30 | (3.00 - 3.65) | 0.546 |
Urine calcium creatinine ratio, mg/g | 0.11 | (0.07 - 0.17) | 0.07 | (0.04 - 0.11) | 0.03 | (0.01 - 0.05) | <0.001 |
Fractional excretion of calcium, % | 0.81 | (0.48 - 1.30) | 0.72 | (0.42 - 1.05) | 0.46 | (0.17 - 0.89) | 0.041 |
Urine phosphate creatinine ratio, mg/g | 0.50 ± 0.23 | 0.49 ± 0.20 | 0.39 ± 0.15 | 0.149 | |||
TRP, % | 90.1 ± 4.9 | 85.5 ± 6.2 | 80.2 ± 8.6 | <0.001 | |||
TmP/GFR, mg/dL | 3.3 | (2.8 - 4.2) | 2.8 | (2.5 - 3.4) | 2.6 | (2.2 - 3.2) | <0.001 |
FGF23, pg/mL | 41.2 | (29.4 - 62.3) | 47.0 | (35.3 - 67.9) | 66.4 | (45.6 - 111.3) | 0.009 |
α-Klotho, mg/dL | 425 | (254–539) | 351 | (224–473) | 211 | (163–286) | 0.001 |
UACR <30 mg/g cr | UACR 30–300 mg/g cr | UACR ≥300 mg/g cr | |||||
---|---|---|---|---|---|---|---|
Variables | (n = 135) | (n = 40) | (n = 10) | P value | |||
eGFR, mL/min/1.73 m2
| 51 ± 14 | 48 ± 17 | 39 ± 17 | 0.039 | |||
Urine albumin creatinine ratio | 9 | (5–15) | 76 | (51–154) | 1241 | (719–2045) | <0.001 |
Serum cCa, mg/dL | 9.1 | (8.8 - 9.4) | 9.3 | (8.8 - 9.5) | 9.3 | (8.8 - 9.5) | 0.530 |
Serum inorganic phosphate, mg/dL | 3.30 | (2.90 - 3.70) | 3.30 | (2.90 - 3.50) | 3.65 | (3.30 - 3.98) | 0.042 |
Urine calcium creatinine ratio | 0.07 | (0.04 - 0.12) | 0.07 | (0.03 - 0.15) | 0.07 | (0.02 - 0.10) | 0.789 |
Fractional excretion of calcium, % | 0.73 | (0.43 - 1.06) | 0.71 | (0.36 - 1.50) | 0.74 | (0.38 - 1.33) | 0.984 |
Urine phosphate creatinine ratio | 0.47 ± 0.19 | 0.52 ± 0.23 | 0.59 ± 0.25 | 0.088 | |||
TRP, % | 87.2 ± 5.7 | 84.0 ± 8.0 | 80.6 ± 9.6 | 0.001 | |||
TmP/GFR, mg/dL | 3.0 | (2.6 - 3.5) | 2.7 | (2.2 - 3.4) | 2.9 | (2.6 - 3.5) | 0.186 |
FGF23, pg/mL | 46.8 | (34.3 - 67.0) | 44.1 | (29.9 - 68.5) | 58.3 | (47.0 - 86.3) | 0.330 |
α-Klotho, mg/dL | 345 | (223–468) | 330 | (200–474) | 358 | (218–589) | 0.736 |
Correlation between serum FGF23/α-Klotho and eGFR/UACR and other calcium phosphate metabolism-related factors
Total study population | eGFR ≥60 mL/min/m2
| eGFR <60 mL/min/m2
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Log (FGF23) | Log (α-Klotho) | Log (FGF23) | Log (α-Klotho) | Log (FGF23) | Log (α-Klotho) | |||||||
Log (FGF23) | - | −0.14 | 0.064 | - | −0.23 | 0.138 | - | −0.10 | 0.256 | |||
Log (α-Klotho) | −0.14 | 0.064 | - | −0.23 | 0.138 | - | −0.10 | 0.256 | - | |||
Log (cCa) | 0.22 | 0.003 | 0.06- | 0.444 | 0.13 | 0.395 | 0.09 | 0.553 | 0.26 | 0.002 | 0.05 | 0.559 |
Inorganic phosphate | 0.23 | 0.002 | 0.05 | 0.509 | 0.11 | 0.469 | −0.25 | 0.104 | 0.27 | 0.001 | −0.01 | 0.934 |
Log (urine Ca/cr) | −0.15 | 0.039 | 0.22 | 0.003 | −0.23 | 0.134 | −0.05 | 0.735 | −0.09 | 0.311 | 0.26 | 0.002 |
Log (FEca) | −0.15 | 0.045 | 0.15 | 0.037 | −0.25 | 0.106 | −0.04 | 0.786 | −0.10 | 0.247 | 0.19 | 0.021 |
Urine phosphate creatinine ratio | 0.07 | 0.348 | 0.03 | 0.728 | −0.09 | 0.544 | −0.13 | 0.411 | 0.12 | 0.153 | 0.08 | 0.363 |
Percent TRP | −0.14 | 0.064 | 0.11 | 0.124 | 0.15 | 0.331 | 0.03 | 0.858 | −0.14 | 0.099 | 0.08 | 0.331 |
Log (TmP/GFR) | 0.07 | 0.355 | 0.04 | 0.634 | 0.17 | 0.276 | −0.13 | 0.385 | 0.10 | 0.247 | 0.04 | 0.638 |
Linear regression analysis
Univariate model | Stepwise multivariate model | |||||
---|---|---|---|---|---|---|
Predictors | Std β | (95% confidence interval) | P value | Std β | (95% confidence interval) | P value |
dependent variable: Log(FGF23) | ||||||
Sex (male = 1) | −0.02 | (−0.17 - 0.12) | 0.741 | |||
Age | 0.21 | (0.07 - 0.35) | 0.004 | 0.16 | (0.01 - 0.30) | 0.034 |
eGFR | −0.21 | (−0.35 - -0.07) | 0.004 | −0.16 | (−0.34 - -0.02) | 0.027 |
Log(UACR) | 0.13 | (−0.01 - 0.28) | 0.077 | |||
Log(cCa) | 0.24 | (0.10 - 0.38) | 0.001 | 0.21 | (0.07 - 0.35) | 0.003 |
Inorganic phosphate | 0.23 | (0.09 - 0.37) | 0.002 | 0.19 | (0.05 - 0.33) | 0.007 |
Dependent variable: log(α-Klotho) | ||||||
Sex (male = 1) | 0.00 | (−0.14 - 0.15) | 0.955 | |||
Age | −0.14 | (−0.28 - 0.01) | 0.064 | |||
eGFR | 0.24 | (0.10 - 0.39) | 0.001 | 0.24 | (0.10 - 0.39) | 0.001 |
Log(UACR) | −0.01 | (−0.15- 0.14) | 0.931 | |||
Log(cCa) | −0.03 | (−0.18 - 0.12) | 0.680 | |||
Inorganic phosphate | −0.05 | (−0.19 - 0.10) | 0.509 |
eGFR ≥60 mL/min/m2
| eGFR <60 mL/min/m2
| ||||||||
---|---|---|---|---|---|---|---|---|---|
Univariate model | Univariate model | Stepwise multivariate model | |||||||
Predictors | Std β | (95% confidence interval) | P value | Std β | (95% confidence interval) | P value | Std β | (95% confidence interval) | P value |
Dependent varialble: log(FGF23) | |||||||||
Sex (male = 1) | 0.05 | (−0.26 - 0.36) | 0.743 | −0.10 | (−0.27 - 0.06) | 0.227 | |||
Age | 0.08 | (−0.23 - 0.39) | 0.589 | 0.23 | (0.07-0.39) | 0.006 | 0.24 | (0.08 - 0.39) | 0.003 |
eGFR | −0.02 | (−0.34 - 0.29) | 0.874 | −0.19 | (−0.35 - -0.02) | 0.025 | |||
Log(UACR) | −0.05 | (−0.36 - 0.26) | 0.742 | 0.18 | (0.01 - 0.34) | 0.037 | |||
Log(cCa) | 0.22 | (−0.08 - 0.52) | 0.150 | 0.24 | (0.08 - 0.40) | 0.004 | 0.21 | (0.06 - 0.37) | 0.008 |
Inorganic phosphate | 0.11 | (−0.20 - 0.42) | 0.469 | 0.27 | (0.10 - 0.43) | 0.001 | 0.21 | (0.05 - 0.37) | 0.011 |
Dependent variable: log(α-Klotho) | |||||||||
Sex (male = 1) | 0.11 | (−0.20 - 0.42) | 0.474 | 0.02 | (−0.14 - 0.19) | 0.794 | |||
Age | −0.17 | (−0.48 - 0.14) | 0.269 | −0.09 | (−0.15 - 0.19) | 0.794 | |||
eGFR | 0.09 | (−0.22 - 0.40) | 0.564 | 0.24 | (0.08 - 0.40) | 0.004 | 0.24 | (0.08 - 0.40) | 0.004 |
Log(UACR) | −0.09 | (−0.40 - 0.22) | 0.551 | 0.02 | (−0.15 - 0.18) | 0.844 | |||
Log(cCa) | 0.00 | (−0.31 - 0.31) | 0.995 | −0.03 | (−0.20 - 0.13) | 0.685 | |||
Inorganic phosphate | −0.19 | (0.52 - 0.13) | 0.237 | −0.01 | (−0.17 - 0.16) | 0.934 |