Amy K Mottl1, John B Buse2, Faramarz Ismail-Beigi3, Ronald J Sigal4, Carolyn F Pedley5, Vasilios Papademetriou6, Debra L Simmons7, Lois Katz8, Josyf C Mychaleckyj9, Timothy E Craven10. 1. University of North Carolina Kidney Center and amy_mottl@med.unc.edu. 2. University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 3. Division of Endocrinology, Case Western Reserve University, Cleveland, Ohio. 4. Division of Endocrinology and Metabolism, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 5. General Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina. 6. Division of Cardiology, Veterans Affairs and Georgetown Medical Centers, Washington, DC. 7. Division of Endocrinology, Veterans Affairs Medical Center, Salt Lake City, Utah. 8. Veterans Affairs New York Harbor Healthcare System, New York, New York. 9. Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia; and. 10. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Abstract
BACKGROUND AND OBJECTIVES: In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. RESULTS: There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). CONCLUSIONS: In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.
RCT Entities:
BACKGROUND AND OBJECTIVES: In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. RESULTS: There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). CONCLUSIONS: In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.
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