title: Safety of enhanced renin-angiotensin-aldosterone system inhibition with aliskiren in nondiabetic patients with chronic kidney disease.
abstract: BACKGROUND
  Various methods of combination renin-angiotensin-aldosterone system blockade help achieve more potent antiproteinuric effects, but may be associated with higher risk of side effects. Therapies involving direct renin inhibitor, aliskiren, may promote renal fibrosis by stimulating (pro)renin receptor due to increased renin levels.
  
  
  OBJECTIVE
  The aim of the study was to compare the effects of combination treatment with angiotensin receptor blockers, telmisartan (80 mg/d) and aliskiren (300 mg/d) with those of combination treatment with 80 mg/d telmisartan and mineralocorticoid receptor blocker (50 mg/d eplerenone) and telmisartan (160 mg/d) alone on the urinary excretion of transforming growth factor β1 (TGF‑β1), renal function, and serum potassium levels.
  
  
  METHODS
  A randomized open-label controlled cross-over study was performed in 18 white patients (7 women and 11 men; mean age, 42.4 ±1.9 years) with proteinuric nondiabetic chronic kidney disease and estimated glomerular filtration rate of 85.2 ±4.6 ml/min.
  
  
  RESULTS
  The urinary excretion of TGF‑β1 was stable despite a significant increase in plasma renin levels after treatment with telmisartan and aliskiren. There were no differences in renal function and serum potassium levels between the compared treatments. Moreover, there were no episodes of hypotension or acute renal impairment.
  
  
  CONCLUSIONS
  Combination therapy with telmisartan and aliskiren may be safe in young nondiabetic patients with normal renal function at low vascular risk. This treatment may be an alternative for a subset of patients in whom standard RAA system blockade is ineffective.
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland. slizak@gumed.edu.pl
authors.forename: Sławomir
authors.initials: S
authors.lastname: Lizakowski
authors.forename: Leszek
authors.initials: L
authors.lastname: Tylicki
authors.forename: Przemysław
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Marcin
authors.initials: M
authors.lastname: Renke
authors.forename: Beata
authors.initials: B
authors.lastname: Sulikowska
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Heleniak
authors.forename: Rafał
authors.initials: R
authors.lastname: Donderski
authors.forename: Rafał
authors.initials: R
authors.lastname: Bednarski
authors.forename: Milena
authors.initials: M
authors.lastname: Przybylska
authors.forename: Jacek
authors.initials: J
authors.lastname: Manitius
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D004232:Diuretics / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012720:Severity of Illness Index; D000077333:Telmisartan; D016896:Treatment Outcome
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D004232:Diuretics; D005650:Fumarates; C446481:aliskiren; D000077333:Telmisartan