Received November 8, 2006
Accepted on February 14, 2007

ORIGINAL ARTICLES

Determinants of Progression from Microalbuminuria to Proteinuria in Patients Who Have Type 1 Diabetes and Are Treated with Angiotensin-Converting Enzyme Inhibitors

Linda H. Ficociello ^*, Bruce A. Perkins ^*, Kristen H. Silva ^*, Dianne M. Finkelstein , Halina Ignatowska-Switalska ^||, Zbigniew Gaciong ^||, L. Adrienne Cupples , Ann Aschengrau ^¶, James H. Warram ^*, and Andrzej S. Krolewski ^*1

*Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, and ¶School of Public Health, Boston University, Boston, Massachusetts; Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada; and ||Division of Internal Medicine and Hypertension, Warsaw Medical University, Warsaw, Poland

¹ To whom correspondence should be addressed. E-mail: andrzej.krolewski{at}joslin.harvard.edu.

	Abstract

The aims of this study were to assess the frequency and determinants of (1) treatment with angiotensin-converting enzyme inhibitors (ACE-I) and (2) progression to proteinuria in the presence of ACE-I treatment in patients with type 1 diabetes and microalbuminuria. A clinic-based cohort study of patients with type 1 diabetes was begun in 1991. The patients who were included in this study (n = 373) are the cohort members who received a diagnosis of microalbuminuria during a 2-yr baseline observation and were followed for 10 yr with frequent assessments of urinary albumin excretion and biennial examinations. Progression to proteinuria occurred when the median urinary albumin excretion during a 2-yr interval exceeded 299 µg/min. During the decade-long study, the proportion of patients who had a history of microalbuminuria and were treated with ACE-I rose from 17 to 67%. Patients who started this treatment had (on average) higher BP, higher urinary albumin excretion, and longer diabetes duration than those who did not. Microalbuminuria often progressed to proteinuria (6.3/100 person-years) in those who were treated. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors of this progression. Although treatment with ACE-I increased during the past decade, it was not completely effective, because microalbuminuria progressed to proteinuria in many treated patients. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors for progression while on ACE-I treatment. The mechanisms that are responsible for the frequent failure of ACE-I to prevent progression of microalbuminuria to proteinuria in a clinical setting are not clear.