Table 2.
Comparison of Biomarkers During Follow-Up According to Development of End-Stage Renal Disease
| Comparison of Biomarkers in those that develop ESRD (n=668) vs. Not (n=3,370) | |||||||
|---|---|---|---|---|---|---|---|
| Time Prior to ESRD/Modified End of Follow-up | P-values | ||||||
| Biomarker | 3 years | 2 years | 1 year | Time of ESRD/mEnd of Follow-up | Estimated Time of Divergencea | Equality | Interaction |
| Placebo Group | |||||||
| ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ||||
| Hemoglobin (g/dL) | 10.4 vs 10.3; p=0.10 | 10.3 vs 10.5; p=0.001 | 10.2 vs 10.7; p<0.001 | 9.5 vs 10.9; p<0.001 | 2.1 years | <0.001 | <0.001 |
| Darbepoetin (Mean Dose in mcg/month) | 1.3 vs 3.9; p=0.019 | 3.2 vs 3.4; p=0.82 | 7.4 vs 3.3; p<0.001 | 18.5 vs 3.8; p<0.001 | 1.4 years | <0.001 | <0.001 |
| Darbepoetin Dose Difference ([ESRD – non-ESRD] in mcg/month) | −2.6 | −0.2 | +4.1 | +14.7 | 1.4 years | <0.001 | <0.001 |
| Ferritin (mcg/L)b | 147 vs 105; p<0.001 | 148 vs 114; p<0.001 | 172 vs 132; p<0.001 | 204 vs 153; p<0.001 | >3 years | <0.001 | 0.36 |
| Transferrin Saturation (%) | 24.9 vs 22.6; p=0.007 | 24.5 vs 24.0; p=0.3 | 26.1 vs 25.2; p=0.07 | 24.3 vs 26.0; p=0.014 | N/A | <0.001 | <0.001 |
| CRP (mg/L)b, c | 3.7 vs 3.0; p=0.05 | 3.9 vs 3.2; p=0.007 | 3.9 vs 3.5; p=0.06 | 5.8 vs 3.7; p<0.001 | 0.6 years | <0.001 | 0.006 |
| Darbepoetin Group | |||||||
| ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ESRD vs. not (P-difference) | ||||
| Hemoglobin (g/dL) | 11.2 vs 11.4; p=0.05 | 11.7 vs 11.8; p=0.036 | 11.9 vs 12.1; p<0.001 | 11.5 vs 12.5; p<0.001 | 1.6 years | <0.001 | <0.001 |
| Darbepoetin (Mean Dose in mcg/month) | 131 vs 136; p=0.42 | 138 vs 148; p=0.08 | 162 vs 161; p=0.95 | 232 vs 177; p=<0.001 | 0.6 years | <0.001 | <0.001 |
| Darbepoetin Dose Difference ([ESRD – non-ESRD] in mcg/month) | −5 | −10 | +1 | +55 | 0.6 years | <0.001 | <0.001 |
| Ferritin (mcg/L)b | 92 vs 78; p<0.001 | 119 vs 98; p<0.001 | 151 vs 122; p<0.001 | 179 vs 150; p=0.005 | >3 years | 0.002 | 0.73 |
| Transferrin Saturation (%) | 22.0 vs 20.9; p=0.3 | 25.6 vs 25.7; p=0.94 | 29.8 vs 29.8; p=0.94 | 29.5 vs 32.2; p=0.002 | 0.2 years | 0.008 | 0.005 |
| CRP (mg/L)b, c | 2.9 vs 3.2; p=0.35 | 3.5 vs 3.1; p=0.14 | 3.6 vs 3.4; p=0.41 | 5.3 vs 3.7; p<0.001 | 0.4 years | <0.001 | <0.001 |
P values refer to the difference in average biomarker concentrations between those that did and do not develop ESRD at specific time points (time of event or end of follow-up; 1 year prior; 2 years prior; or 3 years prior). Equality tests the null hypothesis that the curves are superimposable (i.e. differences in biomarkers between groups); P for Interaction tests the null hypothesis that the curves are parallel (i.e. differences in biomarker trajectories over time).
Estimated time of divergence of biomarkers of interest (developed ESRD vs. not) was defined as the latest time at which the difference in point estimates became significant at α=0.01.
Groups are summarized and compared using geometric means
Individuals with undetectable CRP (≤3 mg/L) were assumed to have a CRP=1.5 mg/L