title: Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.
abstract: BACKGROUND
  Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD).
  
  
  METHODS
  In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline.
  
  
  RESULTS
  ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia.
  
  
  CONCLUSIONS
  In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored.
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Hanna
authors: H
authors: Fröhlich
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Christoph
authors: C
authors: Nelges
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Tobias
authors: T
authors: Täger
authors: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors: Vedat
authors: V
authors: Schwenger
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Rita
authors: R
authors: Cebola
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Johannes
authors: J
authors: Schnorbach
authors: Castle Hill Hospital of the University of Hull, Kingston upon Hull, United Kingdom.
authors: Kevin M
authors: KM
authors: Goode
authors: Castle Hill Hospital of the University of Hull, Kingston upon Hull, United Kingdom.
authors: Syed
authors: S
authors: Kazmi
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Hugo A
authors: HA
authors: Katus
authors: National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, United Kingdom.
authors: John G F
authors: JG
authors: Cleland
authors: Castle Hill Hospital of the University of Hull, Kingston upon Hull, United Kingdom.
authors: Andrew L
authors: AL
authors: Clark
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Electronic address: Lutz.Frankenstein@med.uni-heidelberg.de.
authors: Lutz
authors: L
authors: Frankenstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D003920:Diabetes Mellitus; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006947:Hyperkalemia / Q000453:epidemiology; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*; D012189:Retrospective Studies; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists