Min Jun1, Toshiaki Ohkuma1, Sophia Zoungas1,2, Stephen Colagiuri3, Giuseppe Mancia4, Michel Marre5,6,7, David Matthews8, Neil Poulter9, Bryan Williams10, Anthony Rodgers1, Vlado Perkovic1, John Chalmers11, Mark Woodward1,12,13. 1. The George Institute for Global Health, UNSW Sydney, Sydney, Australia. 2. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 3. Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Sydney Medical School, University of Sydney, Sydney, Australia. 4. Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy. 5. INSERM, UMR S1138, Centre de Recherche des Cordeliers, Paris, France. 6. Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. 7. Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. 8. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. 9. International Centre for Circulatory Health, Imperial College, London, U.K. 10. Institute of Cardiovascular Sciences, University College London (UCL) and National Institute of Health Research UCL Hospitals Biomedical Research Centre, London, U.K. 11. The George Institute for Global Health, UNSW Sydney, Sydney, Australia chalmers@georgeinstitute.org.au. 12. The George Institute for Global Health, University of Oxford, Oxford, U.K. 13. Department of Epidemiology, Johns Hopkins University, Baltimore, MD.
Abstract
OBJECTIVE: To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13-1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75-0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS: Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
OBJECTIVE: To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13-1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75-0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS: Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
Authors: Toshiaki Ohkuma; Min Jun; John Chalmers; Mark E Cooper; Pavel Hamet; Stephen Harrap; Sophia Zoungas; Vlado Perkovic; Mark Woodward Journal: Clin J Am Soc Nephrol Date: 2019-06-03 Impact factor: 8.237
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