title: High doses of irbesartan offer long-term kidney protection in cases of established diabetic nephropathy.
abstract: BACKGROUND
  Hypothetically, the greater the blockade of angiotensin AT1 receptors from ultra-high doses of angiotensin receptors blockers (ARB), the greater the expected renoprotection effects. The aim of our study was to evaluate the effects of ultra-high doses of irbesartan on proteinuria and renal function in diabetics with established or overt diabetic nephropathy (ODN).
  
  
  METHODS
  Ours was a prospective, non-randomised 3-year follow-up study, using a multifactorial therapeutic approach based on irbesartan 600mg daily. Demographic variables, anthropometric data, and biochemical parameters were comparatively analysed at the beginning and end of the study. Forty patients (75% with type 2 diabetes) were included, average age 57.1 +/- 10, 29 male (72.5%).
  
  
  RESULTS
  SBP (157.6 +/- 27mm Hg vs 130.1 +/- 14mm Hg) and DBP (88.8 +/- 10mm Hg vs 76.2 +/- 8mm Hg) decreased significantly at the end of follow-up (P<.001). Serum creatinine increased by only 0.17mg/dl, although this was a statistically significant difference (P<.05). Proteinuria markedly decreased from 2.64 +/- 1.99 to 0.98 +/- 1.18 (P<.0001), i.e. 59.2%. Twenty-five percent of patients had normal albuminuria at the end of the follow-up period. Lipid profiles significantly improved. No patients withdrew from the study due to side effects, and serum potassium did not change significantly over the course of the study. Except for BMI and HbA1c, all other therapeutic targets set out by ADA recommendations improved significantly.
  
  
  CONCLUSIONS
  The treatment of ODN with ultra-high doses of irbesartan was highly effective and safe in reducing proteinuria and slowing the progressive course to ESRD.
authors.affiliation: Hospital Regional Universitario Carlos Haya, Málaga, Spain. sirosru@yahoo.es
authors.forename: Silvia
authors.initials: S
authors.lastname: Ros-Ruiz
authors.forename: Pedro
authors.initials: P
authors.lastname: Aranda-Lara
authors.forename: Juan C
authors.initials: JC
authors.lastname: Fernández
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Martínez-Esteban
authors.forename: Cristina
authors.initials: C
authors.lastname: Jironda
authors.forename: Pilar
authors.initials: P
authors.lastname: Hidalgo
authors.forename: Domingo
authors.initials: D
authors.lastname: Hernández-Marrero
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan