title: Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy.
abstract: BACKGROUND
  Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus.
  
  
  METHODS
  Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial.
  
  
  RESULTS
  Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine ( P = 0.048), but not control ( P = 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed.
  
  
  CONCLUSIONS
  Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptor-blocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies.
authors.affiliation: Department of Nephrology, Monash Medical Centre, Victoria, Australia. bob.atkins@med.monash.edu.au <bob.atkins@med.monash.edu.au>
authors.forename: Robert C
authors.initials: RC
authors.lastname: Atkins
authors.forename: Esther M
authors.initials: EM
authors.lastname: Briganti
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunsicker
authors.forename: Gregory
authors.initials: G
authors.lastname: Braden
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Champion de Crespigny
authors.forename: Giacomo
authors.initials: G
authors.lastname: DeFerrari
authors.forename: Paul
authors.initials: P
authors.lastname: Drury
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Wiegmann
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051437:Renal Insufficiency / Q000209:etiology* / Q000517:prevention & control; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001713:Biphenyl Compounds; D013777:Tetrazoles; D017311:Amlodipine; D000077405:Irbesartan