Key result
Higher-target ESA therapy cuts mortality ~64% and preserves eGFR in kidney transplant recipients.
Why the study?
Retrospective studies suggest an association between erythropoiesis-stimulating agents and increased mortality in renal transplant recipients. Whether erythropoiesis-stimulating agent therapy alters the impaired large artery stiffness and endothelial function contributing to high cardiovascular morbidity in these patients was unknown.
Meta-Analysis (n=38,233)
Yes
Answers are grounded in this paper and cite their sources.
May support higher hemoglobin targets with ESA in kidney transplant recipients; hypothesis-generating and requires confirmation in larger trials.
BACKGROUND/AIMS: Recent retrospective studies suggest an association of therapy with erythropoiesis-stimulating agents (ESAs) and increased mortality in renal transplant recipients (RTR). Large artery structure and function are significantly impaired in RTR which contributes to their high cardiovascular morbidity and could be altered by erythropoietin. We aimed to examine the influence of ESA therapy on large artery stiffness and endothelial function in RTR. METHODS: 63 RTR with chronic allograft dysfunction and renal anemia were randomized to a group receiving darbepoetin alfa (Dar) and a control group (Co). At baseline and after 8 months of treatment (cumulative Dar dose 11.1 µg/kg b.w.) brachial and common carotid artery distensibility coefficients, aortic pulse wave velocity, brachial artery flow-mediated and nitroglycerin-mediated vasodilation were measured as well as the following biomarkers of vascular function: vWF, sVCAM, sICAM, E-selectin, t-PA and PAI-1. RESULTS: 23 patients in the Dar group and 17 patients in the Co group were available for per-protocol analysis. Hemoglobin increased significantly from 10.9 to 12.6 g/dl after 8 months in the Dar group, whereas it remained stable at 11.3 g/dl in the Co group. Effects on large artery stiffness, endothelial function and biomarkers of vascular function did not differ significantly between the two groups. CONCLUSION: Therapy with Dar during 8 months did not significantly impact parameters of large artery stiffness and endothelial function in RTR. These data suggest that therapy with erythropoietin does not deteriorate arterial stiffness and endothelial function in RTR.
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Bartels et al. (2012) conducted a meta-analysis in Posttransplant anemia in kidney transplant recipients (n=38,233). Erythropoiesis-stimulating agent (ESA) therapy targeting higher hemoglobin levels vs. ESA therapy maintaining a low target hemoglobin level (mean 11.37 ± 1.45 g/dL) or no ESA treatment was evaluated on Mortality (death) in late ESA therapy targeting high vs low hemoglobin levels (OR 0.36, 95% CI 0.14 to 0.89, p=0.040). ESA therapy targeting higher hemoglobin levels preserved eGFR (WMD 3.65 mL/min/1.73 m2, p=0.013) and reduced mortality (OR 0.36, 95% CI 0.14-0.89, p=0.040) in kidney transplant recipients.
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