Details

Autor(en) / Beteiligte

• COSTACOU, Tina
• FERRELL, Robert E
• ELLIS, Demetrius
• ORCHARD, Trevor J

Titel

Haptoglobin Genotype and Renal Function Decline in Type 1 Diabetes

Ist Teil von

• Diabetes (New York, N.Y.), 2009-12, Vol.58 (12), p.2904-2909

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Haptoglobin Genotype and Renal Function Decline in Type 1 Diabetes Tina Costacou 1 , Robert E. Ferrell 2 , Demetrius Ellis 3 and Trevor J. Orchard 1 1 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania; 2 Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania; 3 Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Corresponding author: Tina Costacou, costacout{at}edc.pitt.edu . Abstract OBJECTIVE Haptoglobin (Hp) binds free Hb, inhibiting Hb-induced oxidative damage. As oxidative stress has been associated with microvascular complications, we evaluated the relationship between Hp genotype and microalbuminuria, macroalbuminuria, end-stage renal disease (ESRD), and early renal function decline in type 1 diabetes. RESEARCH DESIGN AND METHODS Participants from the Epidemiology of Diabetes Complications Study with DNA available were studied for the incidence of microalbuminuria (albumin excretion rate [AER] 20–200 μg/min), macroalbuminuria (AER >200 μg/min), ESRD (renal dialysis or transplantation), and renal function decline (a decline ≥30 ml/min per 1.73 m 2 from baseline estimated [by the Cockcroft-Gault equation] glomerular filtration rate [eGFR] in those with baseline eGFR >60 ml/min per 1.73 m 2 ). RESULTS The proportions with the Hp 2/2, 2/1, and 1/1 genotype were 43.4, 44.4, and 12.1%, respectively. During 18 years of follow-up, the incidence of eGFR decline, microalbuminuria, macroalbuminuria, and ESRD was 42.0, 40.5, 16.7, and 12.2%, respectively. No significant univariate differences were observed by Hp genotype. However, in multivariable Cox models, an ∼twofold increased risk was observed for the Hp 2/2 compared with the Hp 1/1 genotype for eGFR decline (hazard ratio 1.79 [95% CI 1.06–3.00]) and ESRD (2.74 [1.17–6.45]); no significant associations were observed for microalbuminuria or macroalbuminuria. CONCLUSIONS These data suggest that although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD. Understanding these apparent contradictory findings may provide further insight into the pathogenesis of renal disease in type 1 diabetes. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received June 11, 2009. Accepted August 17, 2009. © 2009 American Diabetes Association