Cardiac autonomic neuropathy as a long-term predictor of renal decline in type 1 diabetes
Aims: Diabetic kidney disease (DKD) and cardiac autonomic neuropathy (CAN) frequently coexist in type 1 diabetes and share several pathophysiological mechanisms. However, it remains unclear whether CAN independently predicts long-term renal function decline. This study investigated whether baseline CAN is associated with accelerated deterioration of kidney function and progression of diabetic kidney disease during 15 years of follow-up.
Methods: This retrospective analysis included 87 adults with type 1 diabetes enrolled between 2007 and 2010. Cardiac autonomic function was assessed at baseline using standardized cardiovascular autonomic reflex tests (CARTs), and participants were classified as having no CAN, early CAN or established CAN according to O'Brien's criteria (Br Heart J 55(4):348–54.). Renal outcomes, including estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio, were collected every four years over a 15-year follow-up. Mixed-effects models adjusted for demographic and metabolic confounders were used to determine whether CAN independently predicted renal decline.
Results: At baseline, increasing CAN severity was associated with higher KDIGO chronic kidney disease risk categories. During follow-up, participants with established CAN experienced a substantially greater decline in eGFR compared with those without CAN (14.8 vs 3.3 ml/min/1.73 m²). After adjustment for age, diabetes duration, HbA1c, blood pressure and other confounders, baseline CAN remained an independent predictor of both accelerated eGFR decline and increasing albuminuria. Furthermore, individuals with CAN had a 3.5-fold higher risk of reaching a composite renal endpoint over the 15-year follow-up.
Conclusions: Cardiac autonomic neuropathy is an independent predictor of long-term renal function decline and diabetic kidney disease progression in individuals with type 1 diabetes. These findings suggest that CAN assessment may improve risk stratification and help identify patients who could benefit from earlier renoprotective interventions.
Comments: Cardiac autonomic neuropathy is traditionally regarded as a cardiovascular complication associated with increased mortality, while diabetic kidney disease has generally been considered a separate microvascular complication. This study provides compelling longitudinal evidence that these complications are closely linked and that CAN is not merely associated with but independently predicts future renal deterioration over 15 years. A major strength of the study is the exceptionally long follow-up combined with standardized CART-based assessment of autonomic function and repeated evaluation of renal outcomes. The findings also support the concept that autonomic dysfunction may contribute directly to renal injury through altered renal haemodynamics, sympathetic overactivity and neurohormonal activation. Although the study is limited by its relatively modest sample size, the lack of repeated autonomic assessments during follow-up and the use of fixed and not age-related normative reference values for CARTs, it highlights the potential clinical value of CAN screening beyond cardiovascular risk prediction. Incorporating autonomic testing into routine assessment of individuals with type 1 diabetes may improve identification of patients at high risk for progressive diabetic kidney disease and facilitate earlier preventive interventions.
Zoltan Kender
Reference. Soe KK, Robinson E, Oleolo M, Goonoo M, Sloan G, Heller S, Tesfaye S, Marques JLB, Sourbron S, Selvarajah D. Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study. Diabetologia. 2026 Jul 29. doi: 10.1007/s00125-026-06818-y. Epub ahead of print. PMID: 42525138.
