Cardiovascular autonomic neuropathy (CAN) has been shown to predict progressive kidney function decline among persons with type 1 diabetes. We aimed to determine whether CAN has a similar effect on kidney function decline in type 2 diabetes (T2D). To this end, we investigated the association between measures of CAN obtained at baseline and GFR decline during a 5-year follow-up among T2D participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. CAN was defined as ECG-derived heart rate variability indices being below the 5th percentile of the normal distribution (standard deviation of all normal-to-normal R-R intervals [SDNN] <8.2 ms and root mean square of successive differences between normal-to-normal R-R intervals [rMSSD] <8.0 ms). eGFR slopes were estimated by linear regression among participants with ≥3 eGFR measurements during follow up. Of the 6,805 ACCORD participants who had valid measures of CAN and eGFR slope, 1,327 (19.5%) had evidence of CAN at baseline. CAN independently predicted a steeper eGFR decline during follow-up (beta=-0.44 ml/min/1.73m2/year, P=0.0007); 24.6% of participants with CAN at baseline experienced subsequent eGFR loss ≥5 ml/min/1.73m2 per year as compared to 18.6% of participants without CAN (OR=1.39 [1.18 - 1.64], P<0.0001, after adjustment for age, sex, duration of diabetes, BMI, HbA1c, eGFR, urinary albumin-creatinine ratio, and positive CVD history at baseline). Consistent with these findings, in a time-to-event analysis, baseline CAN was associated with a 40% increase in the risk of experiencing a ≥40% eGFR loss during follow-up (adjusted HR=1.40 [1.20-1.63], P<0.0001).

In summary, CAN was an independent predictor of kidney function loss in T2D participants. Further studies are needed to understand whether this association reflects a shared etiology of CAN and diabetic kidney disease or a direct deleterious effect of autonomic nervous system alterations on kidney function.


Y. Tang: None. C. Bueno junior: None. H. Shah: None. L. Ang: None. R. Pop-busui: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Averitas Pharma, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Nevro Corp., Regenacy. A. Doria: None.


National Heart, Lung, and Blood Institute N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at