Table 6.
Multivariate Cox regression analysis of composite renal endpoints
| Factors | No. of patients | No. of patients with renal endpoints (%) | HR (95% CI) | p value | |
|---|---|---|---|---|---|
| Hb level at 3 months after the start of darbepoetin administration | < 11 g/dL | 2380 | 1066 (44.8) | Ref | |
| ≥ 11 g/dL | 1093 | 432 (39.5) | 0.731 (0.604–0.884) | 0.0013 | |
| Sex | Male | 2412 | 1071 (44.4) | Ref | |
| Female | 2032 | 742 (36.5) | 0.634 (0.536–0.749) | < 0.0001 | |
| Age (years) | < 65 | 999 | 580 (58.1) | Ref | |
| ≥ 65 to < 75 | 1195 | 558 (46.7) | 0.794 (0.652–0.967) | 0.0216 | |
| ≥ 75 | 2250 | 675 (30.0) | 0.669 (0.547–0.819) | < 0.0001 | |
| Diabetes | No | 2567 | 942 (36.7) | Ref | |
| Yes | 1877 | 871 (46.4) | 1.186 (1.004–1.401) | 0.0444 | |
| Transfusion | No | 4047 | 1631 (40.3) | Ref | |
| Yes | 364 | 176 (48.4) | 1.424 (1.062–1.910) | 0.0183 | |
| Baseline systolic blood pressure (mmHg) | < 130 | 1519 | 512 (33.7) | Ref | |
| ≥ 130 to < 140 | 851 | 366 (43.0) | 1.468 (1.181–1.824) | 0.0005 | |
| ≥ 140 | 1480 | 751 (50.7) | 1.434 (1.186–1.734) | 0.0002 | |
| Baseline eGFR (mL/min/1.73 m2) | < 15 | 1791 | 1082 (60.4) | 3.227 (2.245–4.639) | < 0.0001 |
| 15 to < 30 | 1729 | 544 (31.5) | 1.344 (0.926–1.951) | 0.1204 | |
| ≥ 30 | 538 | 95 (17.7) | Ref | ||
| Baseline urine protein (mg/dL) | Continuous quantity | 2033 | 882 (43.4) | 1.001 (1.001–1.001) | < 0.0001 |
| Dose of darbepoetin administered per week | < Median | 2220 | 741 (33.4) | Ref | |
| ≥ Median | 2224 | 1072 (48.2) | 1.514 (1.282–1.790) | < 0.0001 | |
| Concurrent use of antihypertensive agent | No | 650 | 175 (26.9) | Ref | |
| Yes | 3794 | 1638 (43.2) | 1.654 (1.158–2.360) | 0.0056 | |
Patients in the effectiveness analysis set regarding Hb levels and eGFR who received darbepoetin for more than 3 months and did not develop any of the endpoints (50% reduction in eGFR, initiation of dialysis, and kidney transplantation) evaluated within 3 months of darbepoetin administration were included in this analysis (n = 4444)
The following variables were selected as explanatory variables: Hb level at 3 months after the start of darbepoetin administration, sex, age, body mass index, history, diabetes, previous treatment with recombinant human erythropoietin, transfusion, baseline systolic blood pressure, baseline eGFR, increase rate of Hb level during darbepoetin administration for 4 weeks, baseline urine protein (spot urine), dose of darbepoetin administered per week, antihypertensive agent, antithrombotic agent, and lipid-lowering agent
Time (days) to composite renal endpoints (either 50% reduction in eGFR, initiation of dialysis, or kidney transplantation)
CI confidence interval, eGFR estimated glomerular filtration rate, Hb hemoglobin, HR hazard ratio
P values for trend (Wald chi-square test [type 3]) were p = 0.0004 for age, p = 0.0002 for baseline systolic blood pressure, and p < 0.0001 for baseline eGFR
The median (25, 75 percentiles) of darbepoetin dose administered per week was 15.4 (10.3, 23.2) µg