Kidney disease and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

Abstract

OBJECTIVE Kidney disease manifests clinically as elevated albumin excretion rate (AER), impaired glomerular filtration rate (GFR), or both, and is a cause of substantial morbidity and mortality in type 1 diabetes (T1D). The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study tested whether intensive diabetes therapy (INT) aimed at lowering glucose concentrations as close as safely possible to the normal range reduces the risks of kidney disease and other diabetes complications. RESEARCH DESIGN AND METHODS In the DCCT, 1,441 participants with T1D were randomly assigned to INT or conventional diabetes therapy (CON) for a mean duration of 6.5 years. Subsequently, participants have been followed for 18 years in the ongoing observational EDIC. Standardized longitudinal measurements of AER, estimated GFR, and blood pressure were made throughout the DCCT/EDIC. RESULTS During the DCCT, INT reduced the risks of incident microalbuminuria (AER ≥40 mg/24 h) and macroalbuminuria (AER ≥300 mg/24 h) by 39% (95% CI 21-52%) and 54% (29-74%), respectively. During EDIC years 1-8, participants previously assigned to DCCT INT continued to experience lower rates of incident microalbuminuria and macroalbuminuria, with risk reductions of 59% (39-73%) and 84% (67-92%), respectively. Beneficial effects of INT on the development of impaired GFR (sustained estimated GFR <60 mL/min/1.73 m(2)) and hypertension became evident during combined DCCT/EDIC follow-up, with risk reductions of 50% (18-69%) and 20% (6-21%), respectively, compared with CON. CONCLUSIONS In the DCCT/EDIC, INT resulted in clinically important, durable reductions in the risks of microalbuminuria, macroalbuminuria, impaired GFR, and hypertension.

Figure 1

Cumulative incidence of impaired GFR (sustained estimated GFR <60 mL/min/1.73 m²) by DCCT treatment group, accounting for death as a competing risk. Reproduced with permission from de Boer et al. (12).

Figure 2

Cumulative incidence of hypertension (two consecutive study visits with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or the use of antihypertensive medications) by DCCT treatment assignment. Reproduced with permission from de Boer et al. (14).

Figure 3

Cumulative incidence of persistent microalbuminuria (AER ≥30 mg/24 h on two consecutive study visits) in the DCCT/EDIC, by duration of T1D and DCCT treatment assignment. Reproduced with permission from de Boer et al. (15).

Figure 4

Cumulative incidence of long-term renal outcomes after the development of persistent microalbuminuria (AER ≥30 mg/24 h on two consecutive study visits, defining time 0) among 325 participants in the DCCT/EDIC. Normoalbuminuria (AER <30 mg/24 h on two consecutive study visits), macroalbuminuria (AER ≥300 mg/24 h), impaired GFR (estimated GFR <60 mL/min/1.73 m² on two consecutive study visits), and ESRD are evaluated as parallel outcomes and are not mutually exclusive. Reproduced with permission from de Boer et al. (15).