title: Aliskiren and perindopril reduce the levels of transforming growth factor-β in patients with non-diabetic kidney disease.
abstract: BACKGROUND
  It is highly likely that the rise in plasma prorenin and plasma renin during renin inhibitor treatment is induced at least as much by the fall in blood pressure (BP) as it is by the negative feedback of angiotensin II. This could potentially be harmful because high levels of renin and prorenin may stimulate the (pro)renin receptor, thus inducing profibrotic effects. To further understand this relationship, the influence of aliskiren on the urinary excretion of transforming growth factor-β1 (TGF-β1) and procollagen III N-terminal propeptide (PIIINP) was evaluated in patients with nondiabetic kidney diseases.
  
  
  METHODS
  Aliskiren 300 mg and perindopril 10 mg, were each individually administered for 12 weeks separated by a placebo period in a cross-over, randomized, double-blinded pilot study.
  
  
  RESULTS
  A 1,131% (P < 0.001) and 628% (P < 0.001) increase in plasma renin concentration was observed after the aliskiren and perindopril therapies, respectively, as compared to the placebo. Aliskiren and perindopril increased prorenin concentrations as compared to the placebo by 100% (P < 0.01) and 52.4% (P = 0.53), respectively. The TGF-β1 excretion was lower after tested therapies compared to the placebo (55.0 ± 7.56 vs. 56.21 ± 8.56 vs. 85.79 ± 14.11 pg/mg creatinine; P = 0.016); without differences between aliskiren and perindopril. PIIINP excretion did not differ between treatments.
  
  
  CONCLUSIONS
  The study shows that both aliskiren and perindopril suppress TGF-β1 in patients with chronic kidney diseases. This effect was observed despite significant increases in the renin and prorenin concentrations. Further studies involving histological assessments are required to elucidate the exact impact of these agents on renal fibrosis.
authors.affiliation: Department of Nephrology, Transplantation and Internal Medicine, Medical University of Gdansk, Gdansk, 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: Marcin
authors.initials: M
authors.lastname: Renke
authors.forename: Przemysław
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Heleniak
authors.forename: Maja
authors.initials: M
authors.lastname: Sławińska-Morawska
authors.forename: Ewa
authors.initials: E
authors.lastname: Aleksandrowicz-Wrona
authors.forename: Sylwia
authors.initials: S
authors.lastname: Małgorzewicz
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D020913:Perindopril / Q000627:therapeutic use*; D010865:Pilot Projects; D011347:Procollagen / Q000097:blood; D012083:Renin / Q000097:blood; D016212:Transforming Growth Factor beta / Q000652:urine*; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; C041876:procollagen Type III-N-terminal peptide; C446481:aliskiren; D003404:Creatinine; D012083:Renin; D020913:Perindopril