title: Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes.
abstract: 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.
authors.affiliation: Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
authors.forename: Linda H
authors.initials: LH
authors.lastname: Ficociello
authors.forename: Betsy E
authors.initials: BE
authors.lastname: Ostrander
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Silva
authors.forename: Janice
authors.initials: J
authors.lastname: Weinberg
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000503:physiopathology*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000209:etiology
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins