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Microalbuminuria and the Risk for Early Progressive Renal Function Decline in Type 1 Diabetes

Bruce A. Perkins^*,, Linda H. Ficociello^*, Betsy E. Ostrander^*, Kristen H. Silva^*, Janice Weinberg, James H. Warram^*, and Andrzej S. Krolewski^*,,||

^* Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston University School of Public Health, Harvard School of Public Health, ^|| Department of Medicine, Harvard Medical School, Boston, Massachusetts; and Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada

Address correspondence to: Dr. Andrzej S. Krolewski, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. Phone: 617-732-2668; Fax: 617-732-2667; E-mail: andrzej.krolewski{at}joslin.harvard.edu

Received for publication August 17, 2006. Accepted for publication January 18, 2007.

This study aimed to establish the time of initiation and the determinants of renal function decline in type 1 diabetes. Until now, such decline has been assumed to be a late-occurring event associated with proteinuria. A total of 267 patients with normoalbuminuria and 301 patients with microalbuminuria were followed for 8 to 12 yr. Linear trends (slopes) in GFR were estimated by serial measurement of serum cystatin C. Cases of early renal function decline were defined by loss in cystatin C GFR that exceeded –3.3%/yr, a threshold that corresponds to the 2.5th percentile of the distribution of GFR slopes in an independent nondiabetic normotensive population. Cases of early renal function decline occurred in 9% (mean slope –4.4; range –5.9 to –3.3%/yr) of the normoalbuminuria group and 31% (mean slope –7.1; range –23.8 to –3.3%/yr) of the microalbuminuria group (P < 0.001). Risk for early renal function decline depended on whether microalbuminuria regressed, remained stable, or progressed, rising from 16 to 32 and 68%, respectively (P < 0.001). In multivariate analysis, risk for decline was higher after age 35 yr or when glycosylated hemoglobin exceeded 9% but did not vary with diabetes duration, smoking, BP, or angiotensin-converting enzyme inhibitor treatment. Contrary to the existing paradigm of diabetic nephropathy, progressive renal function decline in type 1 diabetes is an early event that occurs in a large proportion of patients with microalbuminuria. Together with testing for microalbuminuria, clinical protocols using cystatin C to diagnose early renal function decline and track response to therapeutic interventions should be developed.

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