Longitudinal Patterns of Ankle-Brachial Index and Their Association With Progression of CKD in Patients With Type 2 Diabetes and Elevated Body Mass Index.

Rationale & objective: Ankle-brachial index (ABI) is used to screen for vascular complications in the setting of diabetes. This study sought to examine the relationship of longitudinal ABI data and chronic kidney disease (CKD) progression in patients with type 2 diabetes mellitus (T2DM) and increased body mass index.

Study design: A post hoc analysis of the Look AHEAD (Action for Health in Diabetes) trial.

Setting & participants: This study included 3,631 participants in the Look AHEAD trial with a baseline estimated glomerular filtration rate>60mL/min/1.73m².

Exposures: Average ABI and average annual change in ABI were calculated based on annual ABI measurements during the first 4 years of the study.

Outcome: CKD progression, defined as kidney failure requiring maintenance dialysis or the occurrence of an estimated glomerular filtration rate<60mL/min/1.73m² with a decrease of≥30% versus baseline at a follow-up visit.

Analytical approach: Restricted cubic spline and Cox proportional hazards models were fit to estimate associations and to explore nonlinearity.

Results: During a median follow-up of 10.1 years, CKD progression developed in 1,051 participants. There was a reversed J-shaped relationship of CKD progression with average ABI (ABI<1.17: HR per 1-SD decrement, 1.23; 95% CI, 1.06-1.42; ABI≥1.17: HR per 1-SD increment, 1.10; 95% CI, 1.00-1.22) and average annual change in ABI (change in ABI less than-0.007: HR per 1-SD decrement, 1.37; 95% CI, 1.12-1.66; change in ABI of at least-0.007: HR per 1-SD increment, 1.13; 95% CI, 1.03-1.24).

Limitations: Observational study, potential unmeasured confounding.

Conclusions: Low and high-average ABI, even at clinically normal values, as well as decreasing and increasing average annual ABI, were associated with a higher risk of CKD progression in patients with T2DM and increased body mass index. Monitoring ABI and its changes over time may facilitate CKD risk stratification in patients with T2DM.

Plain-language summary: The ankle-brachial index (ABI) has recently become a routine screening parameter for vascular complications in patients with diabetes. In this post hoc analysis of the Look AHEAD (Action for Health in Diabetes) trial including 3,631 participants with type 2 diabetes mellitus and increased body mass index, we examined the longitudinal relationship of average ABI and annual change in ABI with chronic kidney disease progression. We observed that low and high-average ABI, even at clinically normal values, as well as decreases and increases in average annual ABI, were associated with a higher risk of chronic kidney disease progression in patients with type 2 diabetes mellitus and increased body mass index.