Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases

Background: The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. CAN is recognized as a prognostic marker for adverse kidney outcomes in diabetic kidney disease (DKD). However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. This study elucidated the prevalence of CAN and its clinicopathologic characteristics in patients with nondiabetic CKD.

Methods: This cross-sectional analysis evaluated 165 nondiabetic CKD patients who underwent kidney biopsy from 2020 to 2023. HRV was quantified using the coefficient of variation of the RR interval (CVRR). CAN was diagnosed based on the CVRR and defined using the CVRR reference value-derived by defining the age and sex-dependent lower normal limits as the 2.5 percentile point of the distribution of the CVRR values in healthy individuals.

Results: The median patient age was 47.0 (34.0-57.0) years, and 50.9% were male. The median estimated glomerular filtration rate was 65.0 (42.0-85.0) mL/min/1.73m², and the CVRR was 3.5 (2.4-4.7)% and 16 patients (9.7%) were diagnosed with CAN. CAN was frequently associated with kidney dysfunction, dyslipidemia, and advanced interstitial fibrosis/tubular atrophy (IF/TA). Multivariable analysis revealed that IF/TA was associated with CVRR, independent of established risk factors for CAN (P = 0.045).

Conclusions: The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA.