A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: Study design and patient characteristics

Ray Bain, Richard Rohde, Lawrence G. Hunsicker, Janet McGill, Sidney Kobrin, Edmund J. Lewis, John Lachin, Jay Wish, John Sheehan, Marc Pohl, Tomas Berl, Godofredo Santiago, Jacob Lemann, Samuel Blumenthal, Lee Hebert, Norris Stanley Nahman, Stanley Goldfarb, Mohammad Sikder, Roger Rodby, Andrew LeveyMark Williams, Frederick Whittier, Daniel Cattran, Stephen Lietz, Daiva Valaitis, Jesse Hano, Douglas Maxwell, Jerome Porush, Samuel Spitalewitz, Kenneth Shapiro, Sharon Adler, Nathan Tolchin, Wendy Hoy, Robert Bernstein, Laura Svetkey, Zeev Sharon, Peter Lodewick, Hugh Tildesley, Nadir Farid, Julia Breyer

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17 Scopus citations

Abstract

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion >500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) <2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (<140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a >50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean ±SD): male/female, 52%/48%; age, 35 ± 8 yr; duration of diabetes, 21 ± 7 yr; duration of proteinuria, 2.8 ± 3.3 yr; duration of retinopathy, 4.5 ± 4.1 yr; 50% of cohort presented with hypertension, duration, 4 ± 4.7 yr; blood pressure, 139/86 ± 19/12; SCr, 1.35 ± 0.44 mg/dL; GFR 78 ± 32 mL/min; BUN, 24 ± 11 mg/dL; proteinuria, 3.1 ± 3.3 g/day; cholesterol, 236 ± 50 mg/dL; total glycosylated hemoglobin, 11.1 ± 2.1%. Analysis of baseline data with entry GFR yielded the following univariate linear associations: GFR had a weak but significant inverse correlation with urine protein/creatinine ratio (r2 = 0.19), entry systolic blood pressure (-0.62 mL/min/1.73 m2/mm Hg; r2 = 0.13), age at entry (-1.2 mL/min/yr; r2 = 0.07), and serum cholesterol (r2 = 0.09). GFR was not correlated with duration of diabetes (r2 = 0.006), percentage of life as a diabetic (r2 = 0.02), or blood glycohemoglobin (r2 = 0.007). The elements of a controlled clinical trial are described. The baseline entry data confirm an association between reduced GFR and increasing hypertension, proteinuria, and cholesterolemia but not duration of diabetes, percentage of life as a diabetic, or severity of hyperglycemia.

Original languageEnglish (US)
Pages (from-to)S97-S103
JournalJournal of the American Society of Nephrology
Volume3
Issue number4 SUPPL.
StatePublished - Oct 1 1992

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Keywords

  • Angiotensin-converting enzyme inhibition
  • Captopril
  • Diabetes mellitus
  • Diabetic nephropathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Bain, R., Rohde, R., Hunsicker, L. G., McGill, J., Kobrin, S., Lewis, E. J., Lachin, J., Wish, J., Sheehan, J., Pohl, M., Berl, T., Santiago, G., Lemann, J., Blumenthal, S., Hebert, L., Nahman, N. S., Goldfarb, S., Sikder, M., Rodby, R., ... Breyer, J. (1992). A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: Study design and patient characteristics. Journal of the American Society of Nephrology, 3(4 SUPPL.), S97-S103.