VA NEPHRON-D: Diabetes iN Nephropathy Study
Condition: Kidney Disease; Nephropathy; Type 2 Diabetes
MeSH terms: Kidney Diseases; Diabetes Mellitus, Type 2
Intervention: losartan; lisinopril
Intervention description: 50 or 100mg/day; 10, 20 or 40 mg/day
Intervention MeSH terms: Losartan; Lisinopril
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 1448.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: kidney disease; nephropathy; type 2 diabetes; hyperkalemia; acute kidney injury

Summary:

      Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. The
      overall rate of ESRD secondary to diabetes has risen 68% since 1992. Medications that block
      the renin angiotensin system have been shown to decrease the progression of diabetic
      nephropathy. The use of an angiotensin receptor blocker (ARB) has been shown to decrease the
      risk of progression of kidney disease in two studies of individuals with Type 2 diabetes and
      proteinuria. Despite the use of an ARB, the incidence of renal failure remained high in the
      treated group in both studies. The combination of an angiotensin converting enzyme inhibitor
      (ACEI) and ARB can lead to more complete blockade of the renin angiotensin system. In
      diabetic kidney disease, combination therapy has been shown to decrease proteinuria in
      short-term studies. Although there are encouraging results for improvement in proteinuria
      there are no data on progression of kidney disease for the use of combination of ACEI and ARB
      therapy in patients with diabetes. In addition, there could be an increased risk of serious
      hyperkalemia in individuals with diabetes who receive combination ACEI and ARB. The
      investigators therefore propose a randomized double blind multi-center clinical trial to
      assess the effect of combination of ACEI and ARB in patients with diabetes and proteinuria on
      progression of kidney disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes

          -  Albuminuria >300mg/gram creatinine

          -  Stage 2 or 3 CKD (eGFR 30 to <90 mg/min/1.73m*2 )

          -  Able to give informed consent

          -  Telephone contact available

        Exclusion Criteria:

          -  History of intolerance to ACEI or ARB

          -  Serum potassium level >5.5 meq/L

          -  Receiving sodium polystyrene sulfonate (Kayexalate)

          -  Pregnancy, breast feeding, planning to become pregnant or sexually active and not
             using birth control

          -  Renal transplant recipient

          -  Suspected non-diabetic kidney disease

          -  Inability to discontinue current use of ACEI/ARB combination

          -  Current use of Lithium

          -  Severe (end-stage) comorbid disease

          -  Prisoner

          -  Age <18

          -  Estimated glomerular filtration rate (GFR) <30 or >=90 ml/min/1.73m*m

          -  HbA1c >10.5%

          -  Patient refusal

          -  Participation in a concurrent interventional study

          -  Blood pressure >180/95

          -  Unwilling to stop any proscribed medications after enrollment