American Diabetes Association
CANonEGFRslope_05222023_supplemental.pdf (253.32 kB)

Cardiovascular autonomic neuropathy and risk of kidney function decline in type 1 and type 2 diabetes: findings from the PERL and ACCORD cohorts 

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posted on 2023-07-19, 19:06 authored by Yaling Tang, Lynn Ang, Mamta Jaiswal, Brendan R. Dillon, Nazanene H. Esfandiari, Hetal S. Shah, Cathie Spino, 5 Cindy Plunkett, Bruce A. Perkins, Rodica Pop Busui, Alessandro Doria

Previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among persons 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 the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N=7,973). Baseline CAN was ascertained using ECG-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss ≥-5 ml/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed effect, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 (95%CI [-1.93, -0.37], P= 4.0x10-3) ml/min/1.73m2/year in PERL and 0.34 (95%CI [-0.49, -0.19], P= 6.3x10-6) ml/min/1.73m2/year in ACCORD. This translated in 2.11 (95% CI [1.23-3.63], P=6.9x10-3) and 1.39 (95% CI [1.20-1.61], P=1.1x10-5) 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 (HR=2.60, 95%CI [1.15-5.45], p=0.02 in PERL and HR=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 develop new therapies to prevent kidney function decline in patients with diabetes.  


Y.T. was supported by a Mary K. Iacocca Senior Fellowship. L.A. was supported by the JDRF Center of Excellence at the University of Michigan. M.J. was supported by American Diabetes Association Post-doctoral Fellowship 1-16-PDF-051. R.P.B. was supported by grants R01DK107956, U01DK119083,1U01 DK0945157, R01DK116723, and the JDRF Center of Excellence at the U of Michigan. A.D. was supported by grant P30DK036836 (Enrichment Core of the Diabetes Research Center at the Joslin Diabetes Center) and R01DK126799. The PERL clinical trial was supported by grants from NIDDK (R03-DK-094484, R34-DK-097808, UC4-DK-101108, P30-DK-036836, and P30-DK-020572), JDRF (17-2012-377), the National Center for Advancing Translational Sciences (UL1-TR-002494, UL1-TR- 001422, UL1-TR-002556, UL1-TR-002319, and UL1-TR- 001105), and the National Institute on Aging (Claude Pepper Center grant number, P30-AG-024824). The ACCORD clinical trial was funded by the 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, and IAA-Y1-HC-1010); by other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; and by General Clinical Research Centers. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.