title: Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis.
abstract: BACKGROUND
  Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined.
  
  
  METHODS
  We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone.
  
  
  RESULTS
  Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
  
  
  CONCLUSIONS
  In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.
authors.affiliation: Department of Nephrology, School of Medicine, Second University of Naples, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Iodice
authors.forename: Mario M
authors.initials: MM
authors.lastname: Balletta
authors.forename: Roberto
authors.initials: R
authors.lastname: Minutolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Giannattasio
authors.forename: Stefano
authors.initials: S
authors.lastname: Tuccillo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bellizzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Amora
authors.forename: Giorgio
authors.initials: G
authors.lastname: Rinaldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Signoriello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: Luca
authors.initials: L
authors.lastname: De Nicola
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D003404:Creatinine / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000188:drug therapy*; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D017257:Ramipril / Q000008:administration & dosage*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; D000077405:Irbesartan; D017257:Ramipril