Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study

The aim of this study was to determine whether cardiac autonomic neuropathy (CAN) is an independent risk factor for kidney function decline in type 1 diabetes mellitus over a 15 year follow-up period.

Eighty seven participants with type 1 diabetes and eGFR >30 ml/min per 1.73 m² underwent cardiovascular autonomic reflex testing at baseline. Renal data were retrieved at 4 year intervals over 15 years. Stratification of participants into Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease progression prognostic risk was done by using eGFR and urinary albumin/creatinine ratio (UACR). Longitudinal changes in eGFR and UACR were analysed using linear mixed-effects models with adjustment for potential confounders to determine whether CAN is an independent predictor of eGFR and UACR change over 15 years.

At baseline, higher KDIGO risk category was associated with increased severity of CAN (r=0.38, p<0.001) and increase in UACR (p<0.001) compared with the lower risk group. Participants with established CAN at baseline exhibited greater mean (SD) eGFR decline of 14.8 (21.6) ml/min per 1.73 m², compared with 3.1 (7.3) and 3.3 (7.4) ml/min per 1.73 m² in the early stage and those without CAN (p=0.004). Mean (SD) increases in UACR were 0.4 (0.9), 11.3 (30.4) and 4 (8.9) mg/mmol for no CAN, early CAN and established CAN (p=0.03), respectively. After adjusting for potential confounders, baseline CAN was independently associated with both accelerated eGFR decline (p=0.018) and greater increases in UACR (p=0.002) over time.

CAN is an independent predictor of both accelerated eGFR decline and increased albuminuria in type 1 diabetes. The study also explored the relationship between CAN and KDIGO prognostic risk in diabetic kidney disease, demonstrating that increased severity of CAN is associated with higher KDIGO prognostic risk.