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)