Blood pressure variability is an independent risk factor for mortality and cardiovascular events in hemodialysis patients. Dialysate sodium concentration may not only have effects on blood pressure but also on blood pressure variability. We investigated whether dialysate sodium concentration lowering could decrease home blood pressure variability in hemodialysis patients. Forty‐three hemodialysis patients at their dry weight assessed by bioimpedance methods with pre‐dialysis serum sodium >136 mmol/L were recruited. Firstly, patients underwent a 1‐month standard dialysis with dialysate sodium concentration of 138 mmol/L, and then the dialysate sodium concentration was decreased to 136 mmol/L for 8 weeks. Home blood pressure was assessed on waking up and at bedtime for 1 week. Coefficient of variation was used to define home blood pressure variability. After the intervention, whole‐day systolic blood pressure variability decreased from 5.7 ± 2.6% to 4.3 ± 1.7% and evening systolic blood pressure variability decreased from 7.9 ± 4.1% to 6.2 ± 3.1%. Morning systolic blood pressure variability had a reduction from 7.8 ± 2.4% to 5.9 ± 3.3% but did not achieve statistical significance (P = 0.077). Whole‐day, morning and evening systolic blood pressure were decreased significantly. Less changes were observed in diastolic blood pressure parameters. Interdialytic weight gain mildly but significantly decreased. Volume parameters, dietary sodium intake and incidence of adverse events were similar throughout the study period. Lowering dialysate sodium concentration could improve home blood pressure variability among hemodialysis patients who had achieved their dry weight.

angiotensin-converting enzyme 2 (ace2), an important component of the renin-angiotensin system, protects against renal tubulointerstitial fibrosis, but its level of involvement in the mechanism of diabetic nephropathy (dn) currently remains unclear. Herein, the effects of ace2 in dn and the associated mechanisms were investigated using serum and renal biopsy specimens from patients with dn and control participants, and human renal proximal tubular epithelial cells (HrPTepics). The present study determined that the circulating concentration of ace2 was high, but renal ace2 expression was markedly lower, and there was abundant expression of arkadia, an e3 ubiquitin ligase, in patients with dn. In vitro, ace2 attenuated high-glucose-induced tubular epithelial to mesenchymal cell transition (eMT), which was demonstrated by increased expression of α-SMa and loss of e-cadherin expression, as demonstrated by western blot analysis and reverse transcription-quantitative Pcr. adenovirus-mediated ace2 overexpression was also revealed to significantly inhibit Arkadia expression and alleviated high-glucose-induced eMT, while ace2 inhibition had the opposite effects. Furthermore, western blot analysis demonstrated that ace2-alleviated eMT was associated with downregulated arkadia and increased SMad family member 7 (Smad7) protein, followed by TGF-β/Smad pathway inhibition in HrPTepics. in conclusion, ace2 is protective in dn, which may be due to the inhibition of arkadia-mediated Smad7 degradation, whereby TGF-β/Smad-mediated eMT is ameliorated in high-glucose-stimulated HrPTepics.

Blood pressure variability is an independent predictor of adverse clinical events in hemodialysis patients. Volume overload is one of the most important factors affecting blood pressure homeostasis. In the present study, we explored the effects of dry weight reduction on home blood pressure variability in volume overload hemodialysis patients. Hemodialysis patients with volume overload had their dry weight gradually decreased under the guidance of bioimpedance methods, which was represented by calf‐bioimpedance ratio (Calf‐BR). Home blood pressure was measured on waking up and at bedtime for 1 week at baseline and at the end of the two‐month study. Coefficient of variation was used to define home blood pressure variability. Thirty‐eight hemodialysis patients had their dry weight significantly decreased from 60.7 ± 11.3 to 59.6 ± 10.7 kg (P = 0.003) accompanied with a significant reduction in calf‐BR (0.828 ± 0.023 vs. 0.786 ± 0.020, P<0.001). The systolic and diastolic blood pressure decreased significantly. Moreover, the whole‐day, morning, and evening systolic blood pressure variability gradually and significantly decreased by the end of the study (5.6 ± 2.1% versus 4.0 ± 1.7%, P<0.001; 7.7 ± 3.5% vs. 6.3 ± 2.7%, P = 0.005; 7.5 ± 2.8% vs. 5.9 ± 2.3%, P = 0.002, respectively). Diastolic blood pressure variability parameters were unchanged. The interdialytic weight gain and the incidence of adverse events were similar throughout the study period. Gradual dry weight reduction by bioimpedance methods improved home blood pressure variability in hemodialysis patients with chronic fluid overload.