Renoprotection in Early Diabetic Nephropathy in Pima Indians
Condition: Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Study type: Interventional
Phase: Phase 3

Summary: 
      This investigation is a randomized, double-blinded, placebo-controlled clinical trial in
      adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine
      ration less than 30 mg/g) or microalbuminuria (albumin-to-creatinine ration = 30-299 mg/g) to
      test the hypothesis that blockade of the renin-angiotensin system with the angiotensin
      receptor blocker (ARB) losartan can prevent or further attenuate the development and
      progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are
      receiving standard diabetes care.

      One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes
      for at least 5 years, serum creatinine concentrations less than 1.4 mg/dl, and no evidence of
      non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion
      at baseline and other 78 had microalbuminuria. Subjects in each albumin excretion group were
      randomized to treatment with either the angiotensin II receptor antagonist, losartan, or
      placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and
      fractional clearances of albumin and IgG will be made initially, at one month, and at
      12-month intervals from baseline thereafter. A kidney biopsy was performed after six years in
      111 subjects. Morphometric analysis of renal biopsies was used to determine differences in
      glomerular structure between treatment groups.
    

Detailed description: 
      This investigation is a randomized, double-blinded, placebo-controlled clinical trial in
      adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine
      ratio < 30 mg/g) or microalbuminuria (albumin-to-creatinine ratio = 30-299 mg/g) to test the
      hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor
      blocker (ARB) losartan can prevent or further attenuate the development and progression of
      early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving
      standard diabetes care.

      One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes
      for at least 5 years, serum creatinine concentrations < 1.4 mg/dl, and no evidence of
      non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion
      at baseline and the other 78 had microalbuminuria. Subjects in each albumin excretion group
      were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or
      placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and
      fractional clearances of albumin and immunoglobulin G (IgG) were made initially, at one
      month, and at 12-month intervals from baseline thereafter. A kidney biopsy was be performed
      after six years in 111 subjects. Morphometric analysis of renal biopsies was used to
      determine differences in glomerular structure between treatment groups.

      The major outcome measure was a decline in GFR to less than or equal to 60 ml/min or to half
      the baseline value in subjects that enter the study with a GFR of < 120 ml/min. Other
      measures of renoprotection were assessed, including group differences in 1) change in albumin
      excretion, 2) change in serum creatinine concentration, and 3) glomerular morphology in all
      subjects as outlined above.
    

Intervention name(s): Losartan; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Treatment with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop.; Treatment with placebo corresponding to each dose of losartan.
Other intervention name(s): Cozaar; MK-954; DuP 753
Intervention MeSH terms: Losartan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Angiotensin II Receptor Antagonist; Therapeutic Trial; Glomerular Filtration Rate; Kidney Biopsy; Non-Insulin Dependent Diabetes Mellitus