Table 6.
Changes in other mineral metabolism and kidney function parameters over 12 months in the COMBINE trial
| Trt | (Na) Observed Concentrationsb | Adjusted Estimates of Treatment Effectsc |
P Value versus p-p | ||
|---|---|---|---|---|---|
| Baseline | Month 3 | Month 12 | Change per Yeard (95% CI) | ||
| 24 h urine phosphate-to-creatinine, mg/g | |||||
| N-L | (53) 448±114 | (47) 369±145 | (36) 413±162 | −32.3 (−76.5 to 11.9) | 0.13 |
| N-p | (51) 484±126 | (42) 451±128 | (38) 461±121 | −26.5 (−64.8 to 11.8) | 0.15 |
| p-L | (50) 463±98 | (47) 367±121 | (41) 400±118 | −60.0 (−101.0 to −19.0) | 0.009 |
| p-p | (51) 461±120 | (45) 449±128 | (43) 478±130 | 10.7 (−22.3 to 43.7) | — |
| PTH, pg/mle | |||||
| N-L | (53) 92.5 [35.0, 222.0] | (48) 97.5 [31, 238] | (41) 108 [48, 209] | 4.4% (−11.6% to 20.6%) | 0.29 |
| N-p | (50) 109.5 [42.0, 184.8] | (46) 77.0 [35, 264] | (40) 85 [33, 241] | −0.1% (−13.6% to 13.5%) | 0.10 |
| p-L | (50) 105.3 [40.8, 240.3] | (47) 85.0 [49, 246] | (42) 90 [41, 223] | 2.4% (−10.2% to 15.2%) | 0.15 |
| p-p | (51) 101.0 [47.0, 218.0] | (46) 100.0 [50, 245] | (45) 111 [53, 298] | 15.4% (3.4% to 27.4%) | — |
| Serum calcium, mg/dl | |||||
| N-L | (53) 9.50±0.49 | (49) 9.69±0.50 | (41) 9.64±0.52 | 0.04 (−0.09 to 0.16) | 0.39 |
| N-p | (51) 9.44±0.43 | (47) 9.65±0.45 | (41) 9.65±0.59 | 0.18 (0.04 to 0.32) | 0.02 |
| p-L | (50) 9.48±0.46 | (47) 9.59±0.51 | (44) 9.55±0.54 | 0.04 (−0.06 to 0.15) | 0.29 |
| p-p | (51) 9.50±0.51 | (46) 9.48±0.51 | (46) 9.46±0.53 | −0.03 (−0.13 to 0.06) | — |
| eGFR, ml/min per 1.73 m2 | |||||
| N-L | (53) 31.6±7.5 | (49) 30.8±8.1 | (41) 31.5±9.6 | −1.67 (−3.71 to 0.38) | 0.56 |
| N-p | (51) 31.8±7.9 | (47) 29.9±9.0 | (41) 29.2±8.8 | −3.76 (−5.53 to −2.00) | 0.29 |
| p-L | (50) 32.2±7.4 | (47) 31.6±9.0 | (44) 31.7±10.2 | −0.80 (−2.35 to 0.75) | 0.16 |
| p-p | (51) 32.3±9.1 | (46) 30.2±10.7 | (46) 29.3±12.1 | −2.45 (−4.14 to −0.77) | — |
| Urine ACR, mg/ge | |||||
| N-L | (53) 100 [12, 1123] | (47) 83 [10, 2030] | (41) 125 [15, 1182] | 54.0% (22.1% to 86.8%) | 0.14 |
| N-p | (51) 56 [8, 1341] | (45) 104 [7, 3380] | (39) 101 [9, 2680] | 63.0% (34.0% to 92.6%) | 0.04 |
| p-L | (50) 176 [10, 1789] | (48) 309 [7, 2398] | (44) 252 [16, 2697] | 26.7% (−3.1% to 57.3%) | 0.85 |
| p-p | (51) 181 [9, 1387] | (46) 195 [6, 1896] | (42) 123 [8, 2452] | 22.9% (−2.4% to 48.7%) | — |
| Fractional excretion of phosphate | |||||
| N-L | (53) 25.4±7.8 | (47) 22.3±9.7 | (36) 24.2±10.0 | −0.45 (−2.75 to 1.85) | 0.18 |
| N-p | (51) 26.4±8.2 | (42) 27.5±10.1 | (38) 28.4±12.0 | 2.04 (−1.17 to 5.26) | 0.85 |
| p-L | (50) 25.5±6.2 | (47) 21.6±7.8 | (41) 23.2±9.4 | −2.07 (−4.58 to −0.43) | 0.03 |
| p-p | (51) 27.2±10.9 | (45) 27.7±10.7 | (43) 29.6±11.3 | 1.68 (−0.45 to 3.82) | — |
Trt, randomized treatment group; p-p, nicotinamide placebo/lanthanum carbonate placebo; 95% CI, 95% confidence interval; N-L, nicotinamide active/lanthanum carbonate active; N-p, nicotinamide active/lanthanum carbonate placebo; p-L, nicotinamide placebo/lanthanum carbonate active; —, reference category.
Descriptive statistics for observed concentrations and estimated treatment effects derived using all available data.
Data are mean±SD for all variables except PTH and urine ACR, which are shown as median [10th, 90th percentiles].
Results of mixed-effects analyses controlling for the baseline level of the factor analyzed, sex, eGFR, and clinical center.
Twelve-month changes were composed from the average of any participant slopes from the chronic phase (months 3–12) and any participant slopes from the acute phase (baseline to month 3), weighting by the two periods’ relative duration.
FGF23 and urine ACR values were log-transformed before analysis. Estimated treatment effects expressed as percentage change per month (from baseline) in the geometric mean.