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Table 4 Anemia correction studies

From: Erythropoiesis stimulating agents and reno-protection: a meta-analysis

Reference Study Location ESA Duration of Therapy Comparator Arm Subjects (Total and # in groups) Starting vs Achieved Hb High(H) or low(L) Hb Group (g/dL) Other Renal Outcomes
Abraham 1990 [38] Hennepin County Medical Center Minneapolis Minn (USA) Epoetin α (50–150 U/Kg 3X/w) to raise Hct to 37% vs 29%. 8–12 weeks to raise Hct then patients received ESA Placebo (unspecified) N = 8: ESA(4), control(4) L: 9.3 vs 9.7
H: 10.7 vs 12.3
After 18 weeks there was no difference in the 1/sCr curves and no difference in protein excretion
Clyne 1992 [39] Karolinska Hospital, Danderyd Hospital Stockholm (Sweden) Epoetin β (300 U/kg) 1X/week to raise Hb from 8.6 to 11.7 g/dL 12 weeks Placebo (unspecified) N = 22: ESA(12), control(10) L: 9.3 vs 9.4
H: 8.7 vs 11.3
No change in eGFR in either group. No significant difference in change in sCr
Kleinman 1989 [40] Valley Presbyterian hospital, Van Nuys California (USA) ESA (100 U/kg, 3x/week) to raise hct from 28 to 38–40% 12 weeks Placebo (unspecified) N = 14: ESA(7), control(7) L: 9.4 vs 9.4
H: 9.4 vs 11.9
No difference in sCr or change in sCr
Kuriyama 1997 [41] Saiseikai Central hospital, Tokyo Japan Epoetin β (6000 U/week) to raise hct from 25.5 to 35.5% 36 weeks No ESA N = 108: ESA(42), control(66) L: 9.3 vs 8.4
High Hb control
12.0 vs 10.7
H: 9.0 vs 11.8
Time to a doubling in sCr significantly slower in the ESA group.
Lim 1989 [42] University of Iowa Hospitals’ Renal Clinic, Iowa (USA) ESA (50, 100, or 150 U/kg 3X/week) 8 weeks Placebo (unspecified) N = 13: ESA(11), control(2) L: 9,0 vs 12.7
H: 9.0 vs 8.0
No change in renal function over 2 months in ESA group
Lim 1990 [43] University of Iowa Hospitals’ Renal Clinic, Iowa (USA) Epoetin α 3X/week, later switched to 1X/week to raise Hct from 28 to 36% 11.8 ± 6.8 months (range 2.8-23.8) No ESA N = 20: ESA(10), control(10) L: 11.0 vs 9.0
H: 9.3 vs 12.0
The rate of change in sCr was similar over 12 months
Revicki 1995 [18] USA Epoetin α (50 U/kg, 3X/week) then titrated to increase Hct from 27 to 35%. 48 weeks No ESA N = 83: ESA(43), control(40) L: 8.9 vs 8.6
H: 8.9 vs 10.5
No difference in change in eGFR after 48 weeks, no difference in time to dialysis
Akizawa 2011 [44] Japan Darbepoetin alfa (30 ug 1X/week) to target Hb 11–13 g/dL. 48 weeks rHuEpo (~4000 U/week) to maintain Hb at 9–11 g/dL. All received at least one dose of ESA N = 321: High Hb (161), Low Hb (160) L: 9.2 vs 10.1
H: 9.2 vs 11.9
No difference in 2 years decline in eGFR
Cianciaruso 2008 [45] Italy Epoetin α (2000 U 1x/week) to maintain Hb at 12–14 g/dL 12 months No ESA unless Hb dropped below 9 g/dL. 2/49 received ESA N = 95: High Hb (46), Low Hb (49) L: 11.7 vs 11.4
H: 11.6 vs 12.4
No significant difference in eGFR or sCr
Drueke 2006 [46] 94 centers 22 countries Epoetin β to raise Hb to a target of 13–15 g/dL. Median was 5000 U 1X/week 48 months Hb targeted to >10.5 g/dL. ESA only if Hb dropped below 10.5 g/dL. 67% received ESA during the study. Median 2000 U 1X/week N = 603: High Hb (301), Low Hb (302) L: 11.6 vs 11.4
H: 11.6 vs 13.5
No significant difference in the last eGFR value before initiation of dialysis. Time to initiation of dialysis was shorter in the high Hb group at 18 months (P = 0.03).
Gouva 2004 [47] Greece Epoetin α (50 U/kg 1x/week) to raise Hb from 9–11.6 g/dL to a Hb target of 13 g/dL Treatment time was a median of 22.5 months (range 16–24) No ESA for a median of 12 months (range 7–19), then no ESA unless Hb dropped below 9 g/dL. N = 88: High Hb(45), Low Hb(43) L: 10.1 vs 10.3
H: 10.1 vs 12.9
No difference in sCr
Levin 2005 [48] Canada Epoetin α (2000 U 1X/week) to raise and maintain Hb at 12.0–14.0 g/dL 24 months Low Hb (<11 g/dL), 16/74 received ESA N = 172: High Hb(85) Low Hb(87) L: 11.7 vs 11.4
H: 11.8 vs 12.8
No difference in creatinine clearance. Change in eGFR slower in the treatment group (not significant)
MacDougall 2007 [49] United Kingdom Epoetin α (1000 U 2X/week) to maintain Hb at 11.0 g/dl. Total was 190,000 U 3 years No ESA until Hb dropped below 9 g/dL (55/132 received ESA; total 152,000 U N = 197: High Hb(65), Low Hb(132) L: 10.9 vs 10.5
H: 10.8 vs 11.0
No difference in time to dialysis, creatinine clearance, change in creatinine clearance or death.
Pfeffer 2009 [50] 623 sites in 24 countries Darbepoetin alfa 0.75 mcg/kg (Q2W and switched to QM); to increase Hb from 10.4 to 12.5 g/dL. 48 months; median duration of 29 months No ESA until Hb dropped below 9 g/dL, 46% received 1 or more doses of ESA N = 4038. High Hb(2012), low Hb(2026) L:10.4 vs 10.6
H: 10.5 vs 12.5
No difference in the renal composite endpoint
Ritz 2007 [51] 64 centers in 16 countries Epoetin β (2000 U/week) to a target Hb of 13–15 g/dL. 15 months Hb target of 10.5–11.5 g/dL. 13/82 patients received ESA N = 172: High Hb(89), Low Hb(83) L: 11.7 vs 12.1
H: 11.9 vs 13.5
No effect on the rate of decrease in creatinine clearance, change in eGFR or urine protein
Roger 2004 [52] Australia and New Zealand Epoetin α 1X/week to increase Hb from 10 to 13 g/dL 24 months ESA if Hb below 9 g/dL, 8/78 received ESA N = 155: High Hb(75), Low Hb(80) L: 11.2 vs 11.0
H: 11.2 vs 12.2
No difference eGFR or creatinine clearance at 2 years
Rossert 2006 [53] 93 centers in 22 countries Epoetin α (25–100 U/kg 1X/week) to a Hb target of 13–15 g/dL. Median dose was 4,514 IU/week 4 months Hb stabilization then 7.4 months maintenance (high Hb) or 8.3 months (low Hb) Hb target of 11–12 g/day. 65/195 received at least 1 ESA dose. Ave dose 2,730 IU/week (333–7667) N = 390: High Hb(195), Low Hb(195) L: 11.5 vs 11.7
H: 11.6 vs 13.9
No significant differences in rates of decrease in eGFR
Singh 2006 [54] 130 sites in USA Epoetin α 1x/week to achieve Hb target of 13.5 g/dL. Ave 11,215 U/week Median duration 16 months; 661 patients (46.2%) completed 36 months Target Hb of 11 g/dL (709/717 received ESA) Ave dose 6276 U/week N = 1432: High Hb (715), Low Hb (717) L: 10.1 vs 11.3
H: 10.1 vs 12.6
No difference in hospitalization for RRT
Villar 2011 [55] 15 centers in France ESA to target a Hb of 13–14.9 g/dL. Mean weekly ESA dose 6028 ± 6729 IU 24 months Target Hb of 11–12.9 g/dL. Mean dose 1558 ± 1314 UI/week N = 89: High Hb (46), Low Hb (43) L: 11.5 vs 11.9
H: 11.4 vs 13.2
No difference in proteinuria or decline in eGFR (2 years)