Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization

Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization.

Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function.

Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns).

CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.