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Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes

Toshiharu Ninomiya^*, Vlado Perkovic^*, Bastiaan E. de Galan^*,, Sophia Zoungas^*, Avinesh Pillai^*, Meg Jardine^*, Anushka Patel^*, Alan Cass^*, Bruce Neal^*, Neil Poulter, Carl-Erik Mogensen, Mark Cooper^||, Michel Marre^¶, Bryan Williams^**, Pavel Hamet, Giuseppe Mancia, Mark Woodward^*,, Stephen MacMahon^*, John Chalmers^* on behalf of the ADVANCE Collaborative Group

*George Institute for International Health, University of Sydney, Sydney, Australia;
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands;
International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom;
Medical Department M, Aarhus University Hospital, Aarhus Sygehus, Aarhus C, Denmark;
^||Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute, Melbourne, Australia;
^¶Service d'Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat–Claude Bernard, Paris, France;
**Department of Cardiovascular Sciences, University of Leicester School of Medicine, Leicester, United Kingdom;
Research Centre, Centre hospitalier de l'Université de Montréal, Montreal, Canada;
Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; and
Mount Sinai School of Medicine, New York, New York

Correspondence: Dr. Vlado Perkovic, George Institute for International Health, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW 2050, Australia. Phone: +61-2-9993-4523; Fax: +61-2-9993-4502; E-mail: vperkovic{at}george.org.au

Received for publication December 16, 2008. Accepted for publication March 5, 2009.

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m² at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673