Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss of ≥5 mL/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed-effects, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 mL/min/1.73 m2/year (95% CI −1.93 to −0.37; P = 4.0 × 10−3) in PERL and 0.34 mL/min/1.73 m2/year (95% CI −0.49 to −0.19; P = 6.3 × 10−6) in ACCORD. This translated to 2.11 (95% CI 1.23–3.63; P = 6.9 × 10−3) and 1.39 (95% CI 1.20–1.61; P = 1.1 × 10−5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (hazard ratio 2.60 [95% CI 1.15–5.45], P = 0.02, in PERL and hazard ratio 1.54 [95% CI 1.28–1.84], P = 3.8 × 10−6, in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help with development of new therapies to prevent kidney function decline in patients with diabetes. Article Highlights: Cardiovascular autonomic neuropathy is a strong and independent predictor of rapid kidney function decline in both type 1 and type 2 diabetes. Autonomic nervous system dysfunction may serve as a novel target to develop new therapies to prevent kidney function loss in diabetes. Electrocardiogram-derived indices of cardiovascular autonomic neuropathy might be useful, when added to known clinical risk factors, to improve the identification of patients at high risk of rapid kidney function loss and select them for intensive preventive treatments. [ABSTRACT FROM AUTHOR]