title: Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study.
abstract: In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.
  
  
  
  We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2on two consecutive visits), and subclinical cardiovascular disease.
  
  
  
  At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification.
  
  
  
  In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.
authors: Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington.
authors: Ian H
authors: IH
authors: de Boer
authors: Biostatistics Center, The George Washington University, Rockville, Maryland.
authors: Xiaoyu
authors: X
authors: Gao
authors: Biostatistics Center, The George Washington University, Rockville, Maryland.
authors: Patricia A
authors: PA
authors: Cleary
authors: Biostatistics Center, The George Washington University, Rockville, Maryland.
authors: Ionut
authors: I
authors: Bebu
authors: Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington.|Biostatistics Center, The George Washington University, Rockville, Maryland.|Division of Endocrinology, Metabolism & Molecular Medicine, Northwestern University, Chicago, Illinois.|Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.|Dalla Lana School of Public Health, Hospital for Sick Children, Toronto, Ontario, Canada.|Division of Endocrinology and Metabolism, University of Toronto and University Health Network, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota; and.|Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: John M
authors: JM
authors: Lachin
authors: Division of Endocrinology, Metabolism & Molecular Medicine, Northwestern University, Chicago, Illinois.
authors: Mark E
authors: ME
authors: Molitch
authors: Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Trevor
authors: T
authors: Orchard
authors: Dalla Lana School of Public Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Andrew D
authors: AD
authors: Paterson
authors: Division of Endocrinology and Metabolism, University of Toronto and University Health Network, Toronto, Ontario, Canada.
authors: Bruce A
authors: BA
authors: Perkins
authors: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota; and.
authors: Michael W
authors: MW
authors: Steffes
authors: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Bernard
authors: B
authors: Zinman
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000652:urine*; D000787:Angina Pectoris / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D059168:Carotid Intima-Media Thickness; D003324:Coronary Artery Disease / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D062645:Percutaneous Coronary Intervention / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology*; D020521:Stroke / Q000453:epidemiology; D061205:Vascular Calcification / Q000453:epidemiology*; D055815:Young Adult
keywords: albumins; albuminuria; cardiovascular disease; cardiovascular diseases; carotid intima-media thickness; chronic kidney disease; coronary vessels; diabetes; diabetes mellitus, type 1; diabetes mellitus, type 2; disease progression; kidney; progression of chronic renal failure; renin-angiotensin system; risk