Lisinopril pharmacokinetics and erythropoietin requirement in haemodialysis patients

Eur J Clin Invest. 2012 Oct;42(10):1087-93. doi: 10.1111/j.1365-2362.2012.02699.x. Epub 2012 Jul 28.


Background: There is ongoing controversy whether angiotensin-converting enzyme inhibitors (ACE-I) contribute to anaemia by causing hyporesponsiveness to erythropoiesis-stimulating agents (ESA). However, it is unknown whether or not plasma levels or area under the curve (AUC) of ACE-I are associated with responsiveness to ESA therapy.

Materials and methods: We examined the association between lisinopril AUC, lisinopril plasma levels and ESA requirements that was assessed using an ESA index [(ESA IU/week/body weight kg)/(haemoglobin g/dL)]. After screening 184 haemodialysis patients, 14 fulfilled the inclusion criteria, mainly long-term use of oral lisinopril in the upper end of dosage range for this population with stable haemoglobin levels and intravenous ESA therapy. Lisinopril plasma levels were measured at eight different time points (predialysis, immediate post-dialysis and hourly for 6h thereafter; AUC1), and the seven post-dialysis lisinopril plasma levels were used for calculation of AUC2.

Results: The mean ESA index of all patients was 27·90±25·84 (IU/week/kg)/(g/dL). Average lisinopril AUC1 was 1212·48±1209·75 [mg*h/L], whereas AUC2 averaged 947·67±977·07 [mg*h/L]. Two patients (14%) had no detectable lisinopril plasma levels, indicating their noncompliance. There was no association between ESA index and AUC or plasma levels of lisinopril at any time point for all 14 or for the 12 compliant patients.

Conclusions: Our study shows that long-term, high-dose lisinopril therapy has no effect on ESA responsiveness. Thus, avoidance or a dose reduction of ACE-I in dialysis patients will not necessarily lead to reduced ESA requirements and costs.

MeSH terms

  • Anemia / chemically induced*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / blood
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics*
  • Area Under Curve
  • Cross-Sectional Studies
  • Female
  • Hematinics / therapeutic use*
  • Humans
  • Kidney Failure, Chronic / therapy
  • Lisinopril / adverse effects
  • Lisinopril / blood
  • Lisinopril / pharmacokinetics*
  • Male
  • Middle Aged
  • Renal Dialysis*


  • Angiotensin-Converting Enzyme Inhibitors
  • Hematinics
  • Lisinopril