Abstract | BACKGROUND/AIMS: METHODS: This was a randomized, double-masked, placebo-controlled study performed in 690 patients with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg for 2-4 years. The primary end point was the time to doubling of serum creatinine; the secondary end points included evaluations of proteinuria, kidney function, and retinopathy. RESULTS: Serum creatinine doubled in 26% (61/236) of the placebo-treated patients and in 20% (91/454) of those who received pimagedine (p = 0.099). The estimated glomerular filtration rate decreased more slowly in the pimagedine-treated patients with a 36-month decrease from baseline of 6.26 ml/min/1.73 m(2) as compared with 9.80 ml/min/1.73 m(2) in the placebo-treated patients (p = 0.05), and pimagedine reduced the 24-hour total urinary proteinuria. (The mean reduction from baseline at month 36 was 732 mg/24 h at the low dose and 329 mg/24 h at the high dose as compared with 35 mg/24 h in the placebo group; p </= 0.001.) Fewer pimagedine-treated patients with baseline and end point evaluations (31/324; 10%) as compared with those receiving placebo (16%; 28/179) experienced a three-step or greater progression of the retinopathy (Early Treatment of Diabetic Retinopathy Study) score (p = 0.030). Three patients receiving high-dose pimagedine but none receiving low-dose treatment developed glomerulonephritis. CONCLUSIONS: While this study did not demonstrate a statistically significant beneficial effect of pimagedine on the progression of overt nephropathy resulting from type 1 diabetes, it is noteworthy in providing the first clinical proof of the concept that inhibiting advanced glycation end product formation can result in a clinically important attenuation of the serious complications of type 1 diabetes mellitus.
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Authors | W Kline Bolton, Daniel C Cattran, Mark E Williams, Sharon G Adler, Gerald B Appel, Kenneth Cartwright, Peter G Foiles, Barry I Freedman, Philip Raskin, Robert E Ratner, Bruce S Spinowitz, Frederick C Whittier, Jean-Paul Wuerth, ACTION I Investigator Group |
Journal | American journal of nephrology
(Am J Nephrol)
2004 Jan-Feb
Vol. 24
Issue 1
Pg. 32-40
ISSN: 0250-8095 [Print] Switzerland |
PMID | 14685005
(Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2004 S. Karger AG, Basel |
Chemical References |
- Enzyme Inhibitors
- Glycation End Products, Advanced
- Guanidines
- pimagedine
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Topics |
- Adult
- Albuminuria
(prevention & control)
- Blood Pressure Determination
- Diabetes Mellitus, Type 1
(complications, drug therapy, physiopathology)
- Diabetic Nephropathies
(drug therapy, etiology, physiopathology)
- Disease Progression
- Dose-Response Relationship, Drug
- Double-Blind Method
- Enzyme Inhibitors
(therapeutic use)
- Female
- Glomerular Filtration Rate
- Glycation End Products, Advanced
(antagonists & inhibitors)
- Guanidines
(therapeutic use)
- Humans
- Male
- Prospective Studies
- Treatment Outcome
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