Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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 m² on two consecutive visits), and subclinical cardiovascular disease.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00360893 NCT00360815.

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.

Figure 1.

Transitions in albuminuria status observed during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. The figure depicts the four albuminuria categories examined in primary analyses and the observed numbers of transitions between categories. Of 1441 participants included, 1373 entered the DCCT with normoalbuminuria and 68 entered the DCCT with persistent microalbuminuria. During subsequent follow-up, 355 participants with normoalbuminuria at baseline developed persistent microalbuminuria, 171 participants with persistent microalbuminuria regressed to persistent normoalbuminuria, and 180 participants developed macroalbuminuria. Some participants were observed to undergo multiple transitions in albuminuria status over time and were included in multiple counts in the figure. AER, albumin excretion rate.