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Abstract: TH-PO230

Recombinant Erythropoietin Reduces Endothelium-Mediated Vasodilation in Patients with CKD – A Prospective Controlled Study

Session Information

Category: Anemia and Iron Metabolism

  • 202 Anemia and Iron Metabolism: Clinical

Authors

  • Sun, Zoe Dong yang, University of Cambridge, Cambridge, United Kingdom
  • Selvarajah, Viknesh, University of Cambridge, Cambridge, United Kingdom
  • Hubsch, Annette, University of Cambridge, Cambridge, United Kingdom
  • Pritchard, Nicholas R., Cambridge University Hopitals NHS Foundation Trust, Cambridge, United Kingdom
  • Cheriyan, Joseph, University of Cambridge, Cambridge, United Kingdom
  • Wilkinson, Ian, University of Cambridge, Cambridge, United Kingdom
  • Hiemstra, Thomas F., University of Cambridge, Cambridge, United Kingdom
Background

Recombinant erythropoietin (rhEPO) is used for the treatment of CKD-associated anaemia, despite the hypertension and cardiovascular risks. Postulated mechanisms include endothelial dysfunction. Given the emergence of non-rhEPO treatments, elucidating the vascular effects of rhEPO in CKD-associated anaemia is important for comparative studies with non-rhEPO treatments.

Methods

We conducted a single centre open-label prospective non-randomised matched-control study in pre-dialysis rhEPO-naïve patients with CKD (n=12) and matched-healthy controls (n=12) to assess the effect of rhEPO on endothelial function (NCT02987465). Forearm blood flow responses to intra-arterial acetylcholine (ACh endothelium-dependent vasodilator), noradrenaline (NA) and BQ123 (ETA receptor antagonist) were assessed using venous occlusion plethysmography in CKD patients before and 6-weeks after rhEPO and in controls at baseline. Blood pressure, blood parameters and aortic stiffness (carotid-femoral pulse-wave velocity PWV) were measured. The primary outcome was change in log-transformed forearm blood flow compared using mixed-effects ANOVA.

Results

Baseline characteristics were similar between CKD patients and controls (age±SD 65±16 vs 64±16 years, male 83% vs male 83%). Although median eGFR (16, IQR 13-25 vs 83, IQR 78-90 ml/min, p<0.001) and haemoglobin (Hb 97±11 g/L vs 140±9 g/L, p<0.001) were lower, mean arterial pressure (110±21 vs 92±9 mmHg, p=0.02) and PWV (11.5±4.8 vs 8.3±2.2 m/s, p=0.04) were higher in patients with CKD. Response to ACh did not differ significantly between CKD patients and controls at baseline. In the CKD group, rhEPO increased haemoglobin (Hb) to 110 ± 17g/L (p<0.001) after 6 weeks, and reduced endothelium-dependent vasodilation by 23% (95% CI, 5% to 40%, p=0.009). The response to BQ123 did not differ after rhEPO treatment (-5%, 95% CI, -13% to 2%, p=0.15), but there was a greater vasoconstrictor response to NA (10%, 95% CI, 2% to 17%, p=0.01). Blood pressure and arterial stiffness did not change significantly after rhEPO.

Conclusion

Endothelium-dependent vasodilation is impaired after rhEPO treatment in patients with CKD, and NA-induced vasoconstriction is enhanced, suggesting possible mechanisms for rhEPO-associated hypertension and adverse cardiovascular outcomes.

Funding

  • Commercial Support