The association between abnormal heart rate variability and new onset of chronic kidney disease in patients with type 2 diabetes: A ten-year follow-up study

Aims: We investigated the association between cardiovascular autonomic neuropathy (CAN) and the future development of chronic kidney disease (CKD) in patients with type 2 diabetes. Methods: From Jan 2003 to Dec 2004, 1117 patients with type 2 diabetes without CKD (estimated glomerular filtration rate [eGFR]≥60ml/min/1.73m²), aged 25-75 years, were consecutively enrolled. A cardiovascular autonomic function test (AFT) was performed using heart rate variability parameters. The eGFR was measured at least more than once every year, and new onset CKD was defined as eGFR<60ml/min/1.73m² using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: Among the 755 (67.6%) patients who completed the follow-up evaluation for 9.6 years, 272 patients (36.0%) showed a CKD stage ≥3. The patients who developed CKD were older, had a longer duration of diabetes, had hypertension, received more insulin and ACE inhibitor/angiotensin receptor blocker (ARB) treatment, and exhibited lower baseline eGFR, HbA1c, and albuminuria levels. Compared to patients without CKD, more patients with CKD at follow-up had CAN at baseline. In a multivariate analysis, after adjustment for age, sex, diabetes duration, presence of hypertension, mean HbA1c, diabetic complications, use of insulin, ACE inhibitor/ARB, statin, and baseline eGFR, the development of CKD was significantly associated with the presence of CAN (HR 2.62, 95% CI 1.87-3.67, P < 0.001). Conclusions: In this prospective, longitudinal, observational cohort study, we demonstrated that diabetic CAN was an independent prognostic factor for the future development of CKD in type 2 diabetes.