Nocturnal haemodialysis is associated with improved vascular smooth muscle cell biology

Abstract

Conventional haemodialysis (CHD) is associated with a reduction in vascular smooth muscle cells (VSMCs) proliferation and an increase in apoptosis. VSMC proliferation, migration, apoptosis and Runx2 expression were assessed under normal conditions (n = 4) and before and after conversion from CHD to NHD (n = 15). Compared to normal, CHD is associated with a reduction in VSMC proliferation [0.49 +/- 0.07 (CHD) versus 1.34 +/- 0.02 RFU, P < 0.01], an augmented caspase-3 activity [0.30 +/- 0.02 (CHD) versus 0.22 +/- 0.02 RFU, P = 0.014] and a 1.4 +/- 0.3 fold increase in Runx2 expression. After conversion to NHD, VSMC proliferation was higher than during CHD [from 0.49 +/- 0.07 (CHD) to 0.68 +/- 0.09 RFU, P = 0.006] and approached that of controls (1.34 +/- 0.02, P > 0.05). Caspase-3 activity was restored to similar values as controls [0.26 +/- 0.02 (NHD) versus 0.22 +/- 0.04 (normal), P > 0.05]. Runx2 expression decreased to similar levels as normal controls. NHD enhanced dialysis dose delivery, lowered blood pressure, plasma parathyroid hormone levels and normalized plasma phosphate (from 1.7 +/- 0.1 to 1.2 +/- 0.1 mmol/L, P < 0.01). The reduction in plasma phosphate correlated with the change in VSMC proliferation (r = -0.71, P = 0.007). We demonstrate that NHD is associated with restoration of abnormal VSMC biology in ESRD. Given the increasing importance of VSMCs in the pathogenesis of atherosclerosis and medial calcification, these data may have important implications for vascular risk in ESRD patients.