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Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient’s quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3–6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score. Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Background and Aim: The study aimed to prospectively evaluate the effects of lowering the dialysate calcium concentration (DCa) to 1.25 mmol/l on Chinese patients undergoing maintenance hemodialysis (MHD), which are largely unknown to date. Methods: A singer-center, prospective, randomized trial was conducted for 2 years. The DCa in one group was decreased from 1.5 to 1.25 mmol/l but there was no change in the other group. The clinical outcomes, biochemical parameters, medicine treatments and markers of vascular change were compared among the 2 groups at different time intervals. Results: At baseline, the groups were similar with respect to serum levels of calcium, phosphorus, intact parathyroid hormone and fibroblast growth factor-23 as well as carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cf-PWV). It was found that the serum phosphorus concentration in the lower DCa group had decreased markedly at 2-year follow-up (0-month: 7.13 ± 1.56 mg/dl; 24-month: 5.92 ± 1.73 mg/dl; p = 0.005). Serum calcium (p = 0.018), cIMT (p = 0.029) and cf-PWV (p = 0.024) in DCa 1.25 group were significantly lower than those in 1.5 group at the 24-month visit. Kaplan-Meier curve revealed that patients in DCa 1.25 group had a better rate of survival. In the multivariate Cox regression analysis, cIMT (HR 1.010; 95% CI 1.002-1.217; p = 0.015) and cf-PWV (HR 1.265; 95% CI 1.022-1.567; p = 0.031) were potential risk factors for mortality in those patients. Importantly, we showed that the average change in these 2 risk variables were both associated with the average change in levels of serum calcium and phosphorus. Conclusion: Our results indicate that lowering DCa to 1.25 mmol/l may be suitable for the MHD patients in our unit.

Background: The role of aldosterone has been less investigated compared to the renin-angiotensin-aldosterone system in renovascular hypertension. The purpose of the present study was to compare the effects of a selective aldosterone receptor blocker, eplerenone (EP), and an angiotensin II receptor type 1 antagonist (AT1RA), losartan (LO) on cardiac and renal damage produced by two-kidney, one-clip (2K-1C) renovascular hypertension in rats. Method: Wistar rats (n = 48) were placed on one of six groups. Group 1 received sham operation. From group 2 to 6, all rats were made as 2K-1C renovascular hypertension. Group 2 received vehicle. Group 3 orally received 100 mg/kg/day of EP from the initiation of the study. Group 4 received 100 mg/kg/day of LO, from the initiation of the study. Groups 5 and 6 received EP and LO from the 4th week after the clipping respectively. Systolic blood pressure (SBP) and urinary protein excretion (UPE) were measured before and every 2 weeks. The remnant kidney was obtained for histopathological analysis and for measurement of endothelial cell nitric oxide synthase (ecNOS) gene expression (GE). Results: SBP increased in the placebo group (132.1 ± 2.4 vs. 115.0 ± 0.6 mm Hg in sham group at week 10, p = 0.019). Treatment with LO or EP from the beginning of the study decreased SBP significantly as measured in the sham group at week 10. The placebo group developed significant UPE (21.7 ± 1.9 mg/day) compared with the sham group (13.4 ± 0.8 mg/day, p < 0.05). Treatment with both LO (12.5 ± 1.5 mg/day, p < 0.01 vs. placebo) and EP (14.8 ± 1.0 mg/ day, p < 0.05 vs. placebo) significantly decreased UPE. On the other hand, the late start of treatment with EP failed to decrease the increased UPE. UPEs were not significantly different between the LO- and EP-treated groups throughout the study. There was no significant pathological change in heart and kidney in all groups. In heart, ecNOS GE was significantly increased in the EP-treated (from the beginning of the study) rats compared with placebo group (0.47 ± 0.01 vs. 0.43 ± 0.01, p < 0.05). LO did not have an effect on ecNOS GE in heart. In aorta, ecNOS GE was significantly increased in the two EP-treated groups compared with the placebo group (0.22 ± 0.01, 0.22 ± 0.02 vs. 0.15 ± 0.01, p < 0.05, respectively). LO also did not have an effect on ecNOS GE in aorta. In kidney, ecNOS GE was significantly increased in the LO group (from the beginning of the study) and two EP-treated groups compared with placebo. Conclusion: This study demonstrated that EP treatment significantly reduced SBP and UPE compared with placebo in both development and established 2K-1C renovascular hypertension. EP was as effective as LO in lowering the blood pressure of this renin-dependent animal model.

Background: Cell-to-cell interaction is thought to be an important feature of a variety of biological processes. As far as the proinflammatory process is concerned, the interaction between mesangial cells and monocytes/macrophages induces the expression of monocyte chemoattractant protein-1 (MCP-1), and this may play a role in glomerulonephritis. In this study, we investigated whether the cell-to-cell interaction between immune cells and renal fibroblasts induces MCP-1 gene expression, which may be involved in interstitial inflammation in the kidney. Methods: Human renal fibroblast cell lines, tNKF (from a normal kidney) and tFKIF (from a kidney with fibrosis), and peripheral blood mononuclear cells (PBMC) were used to assess the effect of cell-to-cell contact on the expression of MCP-1 mRNA in the fibroblasts. The expression of the MCP-1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor-α (TNF-α) and the culture supernatant from PBMC. RT-PCR was used to detect MCP-1 mRNA expression. Neutralizing antibodies to intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) were used to block the cell-to-cell contact between the fibroblasts and PBMC. Results: TNF-α and the culture supernatant from PBMC increased MCP-1 gene expression in tNKF cells. Contact culture with PBMC also significantly increased MCP-1 gene expression in tNKF cells. Although the basal level of MCP-1 mRNA was higher in tFKIF than tNKF cells, tFKIF cells did not respond significantly to any stimulation in this study. Following pretreatment with anti-ICAM-1 antibody, MCP-1 gene expression in tNKF cells was significantly suppressed in contact culture with PBMC. Anti-VCAM-1 antibody treatment had no effects. Conclusion: It is suggested that the interaction between renal fibroblasts and PBMC was mediated through direct contact and by secreted humoral factors. ICAM-1 on renal fibroblasts may be involved in the direct cell-to-cell interaction inducing MCP-1 gene expression, which seems to be involved in renal interstitial inflammation.