title: Lisinopril pharmacokinetics and erythropoietin requirement in haemodialysis patients.
abstract: 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.
  
  
  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.
authors: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Wolfgang
authors: W
authors: Winnicki
authors: Anna
authors: A
authors: Prehslauer
authors: Josef
authors: J
authors: Kletzmayr
authors: Harald
authors: H
authors: Herkner
authors: Gere
authors: G
authors: Sunder-Plassmann
authors: Martin
authors: M
authors: Brunner
authors: Walter H
authors: WH
authors: Hörl
authors: Guerkan
authors: G
authors: Sengoelge
mesh_terms: D000740:Anemia / Q000139:chemically induced*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003430:Cross-Sectional Studies; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D017706:Lisinopril / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006397:Hematinics; D017706:Lisinopril