Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria

George Jerums, Terri J. Allen, Duncan J. Campbell, Mark E. Cooper, Richard E. Gilbert, Jeremy J. Hammond, Jan Raffaele, Con Tsalamandris

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Abstract

The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm Hg. Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 ± 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 μg/min; nifedipine, 59 μg/min; and placebo, 66 μg/min. During the first 3 years, 7 of the perindopriltreated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 μg/min for perindopril, 122 μg/min for nifedipine, and 112 μg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 ± 1.8 mL/min/1.73 m2/y), but not in the other two groups (perindopril, -1.0 ± 1.2 mL/min/1.73 m2/y; placebo, -1.3 ± 1.1 mL/min/1.73 m2/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20/μg/min) in normotensive patients with type I diabetes and microalbuminuria.

Original languageEnglish
Pages (from-to)890-899
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume37
Issue number5
DOIs
Publication statusPublished - 1 Jan 2001
Externally publishedYes

Keywords

  • Albumin excretion rate (AER)
  • Angiotensin-converting enzyme (ACE) inhibition
  • Calcium channel blockade
  • Diabetic nephropathy
  • Glomerular filtration rate (GFR)
  • Microalbuminuria
  • Type 1 diabetes

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