Renoprotection in Early Diabetic Nephropathy in Pima Indians
Condition: Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Intervention: Losartan; Placebo
Intervention description: 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.
Intervention MeSH terms: Losartan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 170.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Angiotensin II Receptor Antagonist; Therapeutic Trial; Glomerular Filtration Rate; Kidney Biopsy; Non-Insulin Dependent Diabetes Mellitus

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Volunteers from the Gila River Indian Community who meet the eligibility criteria will be
        invited to participate.

        To be eligible for participation in the study, subjects must meet the following criteria:

          -  Aged 18-65.

          -  Diagnosis of type 2 diabetes greater than or equal to 5 years.

          -  Serum creatinine concentration less than to 1.4 mg/dl.

          -  Serum potassium concentration less than or equal to 5.5 milliequivalents (mEq)/L.

          -  At least 2 of 3 weekly screening urinary albumin-to-creatinine ratios less than 300
             mg/g. All screening tests are to be within 3 months of enrollment.

          -  Willingness, after receiving a thorough explanation of the study, to participate.

        EXCLUSION CRITERIA:

        Subjects will be excluded for the following reasons:

          -  Clinically significant disorders of the liver, cardiovascular disease, cerebrovascular
             disease, peripheral vascular disease, pulmonary diseases, renal-urinary disorders,
             gastrointestinal disorders, or hematocrit levels less than or equal to 30 percent in
             women or less than or equal to 35 percent in men.

          -  Renovascular or malignant hypertension; uncontrolled hypertension despite treatment
             with three antihypertensive drugs; or hypertension that is being treated with
             antihypertensive medicines and the primary care physician or the patient refuses to
             adopt the blood pressure treatment regimen outlined in the study protocol.

          -  Hematuria of unknown etiology.

          -  Chronic debilitating disorders with or without treatment that would interfere with the
             assessment of kidney function or that might reduce the chances of survival for a
             sufficient length of time to evaluate efficacy of treatment.

          -  Currently receiving a drug regimen that includes: steroids, immunosuppressants, or
             investigational new drugs.

          -  Pregnancy. Women of childbearing potential must have a negative pregnancy test prior
             to entry and every three months during the study.

          -  Evidence of inability to empty the bladder.

          -  Hypersensitivity to angiotensin-converting enzyme inhibitors (ACEi), ARBs, or iodine.

          -  Bleeding disorders, since kidney biopsies could not be performed safely in these
             individuals.

          -  Massive obesity with body mass index greater than or equal to 45 kg/m(2).

          -  Non-diabetic renal disease.

          -  Conditions that are likely to interfere with informed consent or compliance with the
             protocol.