Table 2.
Effects of subcutaneous titrated dosages of erythropoietin in patients not on dialysis on progression to renal replacement therapy
| Reference (study design) | Level of renal function; trial duration | No. of pts | Treatment regimen | Endpoint | Outcome |
| Dean et al. [55] (retrospective) | eGFR 30–59 mL/min/1.73 m2 (n = 71) eGFR <29 mL/min/1.73 m2 (n = 51) Hb = 10–11.9 g/dL or 8.0–9.9 g/dL |
122 Only pts with ≥8 EPO doses included | EPO (Hb targets, doses not specified | Change in least-squares slope of inverse serum creatinine clearance vs time before and after EPO | Baseline eGFR 30–59 ml/min/1.73 m2: Pre-EPO rate, dL/mg/yr: -0.0981 (95% CI, -0.12, -0.07) Post-EPO rate, dL/mg/yr: -0.0692 (95% CI, -0.09, -0.04) Weighted mean difference, dL/mg/yr: 0.0454 (95% CI, 0.0150, 0.0757) Baseline eGFR <29 ml/min/1.73 m2: Pre-EPO rate, dL/mg/yr: -0.0899 (95% CI, -0.12, -0.06) Post-EPO rate, dL/mg/yr: -0.0416 (95% CI, -0.06, -0.02) Weighted mean difference, dL/mg/yr: 0.0493 (95% CI, 0.0272, 0.0679) Overall: Pre-EPO rate, dL/mg/yr: -0.0937 (95% CI, -0.11, -0.08) Post-EPO rate, dL/mg/yr: -0.0569 (95% CI, -0.07, -0.04) Weighted mean difference, dL/mg/yr: 0.0475 (95% CI, 0.0272, 0.0679) P < 0.05 |
| CREATE study [61] (r) | eGFR 15–35 mL/min/1.73 m2, Hb 11.0–12.5 g/dL;3 yrs | 300 | EPO to 13–15 g/dL | Time to dialysis (secondary) eGFR also assessed | Change of mean eGFR from baseline: Year 1: High-Hb group -3.6 ± 6.7 mL/min Low-Hb group -3.1 ± 5.3 mL/min Time to dialysis was significantly shorter in high-Hb group (P = 0.3) |
| 300 | EPO to 10.5–11.5 g/dL | ||||
| Gouva et al. [58] (r, mc) | SrCr 2–6 mg/dL (eGFR not given), Hb 9.0–11.6 g/dL;22.5 mo | 45 | Early EPO to Hb≥3 g/dL | Composite of doubling of baseline SrCr, renal replacement or death | Composite endpoint: Early EPO pts, 29% Deferred EPO pts, 53%; P = 0.0078 Renal replacement: Early EPO pts, 22% Deferred EPO pts, 42%; P = 0.011 |
| 43 | Deferred EPO when Hb<9.0 g/dL | ||||
| Jungers et al. [59] (c-cs) | Predialysis (CrCl ≤15 mL/min) pts (eGFR not given); 24 mo | 20 (Hb<10 g/dL) | EPO to 11.5 g/dL | Change-from-baseline rate of decline in creatinine clearance, time to dialysis | Rate of change in creatinine clearance, mL/min/1.73 m2/month: EPO group: Baseline -0.36 ± 0.16 End of study -0.26 ± 0.15 (P < .05) Standard care group: Baseline -0.55 ± 0.48 End of study -0.57 ± 0.44 Time to dialysis: EPO group 16.2 ± 11.9 mo Standard care group 10.6 ± 6.1 mo (P < 0.01). |
| 43 (Hb>10 g/dL) | Standard care | ||||
| Kuriyama et al. [79] (r) | SrCr 2–4 mg/dL (eGFR not given), Hematocrit<30%;28 mo median follow-up | 31 | Standard care | Doubling of baseline SrCr | Doubling of baseline SrCr EPO, 52% of pts Standard care, 84% of pts Nonanemic control, 60% of pts Progression to dialysis: EPO, 33% of pts Standard care, 65% of pts (P = 0.008) Nonanemic control, 37% of pts |
| 42 | EPO to Hct 33–35% | ||||
| SrCr 2–4 mg/dL, Hematocrit>30%;28 mo median follow-up | 35 | Nonanemic control | |||
| Rossert et al. [66] (r, mc, uncontrolled)a | Iothalamate GFR 25–60 mL/min; 40 mo | 108 | EPO for Hb 14–15 g/dL (men) and 13–14 g/dL (women) | Change-from-baseline GFR as estimated by iohexol clearance | GFR change: High Hb group -0.058 mL/min/1.73 m2 Low Hb group -0.081 mL/min/1.73 m2. No significant difference between groups |
| 133 | PRN EPO for Hb 11–12 g/dL | ||||
| Silverberg et al. [46] (nr) | Cockcroft-Gault eGFR decline >1 mL/min per mo; 11.8 mo | 84 (NIDDM) | EPO to Hb 12.5 g/dL + IV Iron PRN | SrCr and CrCl (secondary endpoints) | GFR decline halted in both groups |
| 95 (no NIDDM) |
a Because of labeling changes for EPO, this study terminated after 7.4 and 8.3 months of maintenance in the high and low Hb group, respectively.
c-cs = case-control study; CHF = congestive heart failure;CrCl = creatinine clearance; db = double-blind; EPO = epoetin; (e)GFR = (estimated) glomerular filtration rate; Hct = hematocrit; mc = multicenter; IV = intravenous; mo = months; NIDDM = noninsulin-dependent diabetes mellitus; nr = nonrandomized; PLA = placebo; PRN = as required; pts = patients; r = randomized; SrCr = serum creatinine; wks = weeks.