Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D
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AIMS: Circulating endothelial progenitor cells (EPCs) play a pivotal role in vasculogenesis and promote angiogenesis by secreting growth factors. Recent studies have suggested that erythropoietin (EPO) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. The aim of this study was to investigate whether two erythropoiesis-stimulating agents (ESAs) modulate vascular-related factors and EPC mobilization in patients with chronic kidney disease stage G5 and dialysis (CKD G5 and 5D). MATERIALS AND METHODS: We conducted a 12-week prospective study in 63 patients; 21 patients received recombinant human erythropoietin (rhEPO) (EPO group, 4,565.5 ± 1,994.4 IU/week), 21 patients received darbepoetin (DA) (DA group, 40.1 ± 13.8 µg/week), and 21 patients received no ESAs (no-ESA group). Vascular mediators, including EPCs, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), high-sensitivity C-reactive protein, and asymmetric dimethyl arginine, were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45lowCD34+CD133+ cells. We also performed a subanalysis of dialysis (5D) patients (n = 32) in the three groups. RESULTS: In the EPO group, EPC count increased significantly from 0 to 12 weeks in a dose-dependent manner (r = 0.62, p = 0.005), and the increase was more conspicuous in the subgroup of dialysis 5D patients. In the DA group, the EPC number did not change at 12 weeks. Neither rhEPO nor DA affected the serum levels of the aforementioned biomarkers other than EPC. ;Conclusion: We speculate that the pleiotropic effects of rhEPO and DA beyond their hematopoietic effects may differ between CKD G5 and 5D patients.
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Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders. METHODS: Sixty-eight HD patients who were maintained on calcium carbonate (n=33) or sevelamer hydrochloride (n=35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23. RESULTS: Sixty-three patients chewed either HS219 (n=35) or placebo (n=28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels. CONCLUSIONS: The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT01039428, 24 December, 2009.

Blood flow analysis of the head and lower limbs by the laser Doppler blood flowmeter during LDL apheresis.

The presence of peripheral arterial disease substantially increases the risk for both morbidity and mortality among end-stage renal disease patients. Low-density lipoprotein (LDL) apheresis has been also applied for the treatment of peripheral arterial disease to reduce LDL levels, resulting in the improvement of the blood flow to the ischemic limbs. In this study, we investigated the continuous changes of the tissue blood flows in the lower limbs and head during LDL-apheresis treatment by a non-invasive method (the non-invasive continuous monitoring method (NICOMM) system). In this study, the tissue blood flow in both the head and lower limbs showed a significantly enhancement from before to after treatment. The tissue blood flow in the lower limbs showed a significantly larger improvement than that in the head. The short-term effects of LDL apheresis were confirmed by using the NICOMM system; thus, this system will be useful for the determination of the appropriate schedule of LDL apheresis for long-term effectiveness.

Prediction method for decreases in blood pressure during hemocatharsis therapy by arteriolar blood flow measurement.

In clinical practice, the prediction of changes in blood pressure during hemocatharsis therapy depends on invasive monitoring, the physician's experience, or blood pressure measurement when patients ask for it. It is extremely difficult to predict blood pressure variation in patients under general anesthesia or with disturbance of consciousness. Therefore, the prediction of blood pressure variation during hemocatharsis therapy is an important issue. To address this issue, we invented a new noninvasive continuous blood flow monitor using arteriolar blood flow measurement by laser Doppler flowmetry. Then we examined and determined some extremely important phenomena, including the relationship between rapid blood pressure change and arteriolar blood flow, and failures of the cerebral blood flow autoregulatory mechanism, through measurements in clinical practice of hemodialysis, specific hemocatharsis therapy, and drug monitoring. The results suggest that blood pressure variation during hemocatharsis therapy is highly predictable by arteriolar blood flow measurement. Therefore, this new method for arteriolar blood flow measurement might be widely useful for patients under anesthesia, anesthesia monitoring in neonatal infants and animals (no conversation ability), as well as for hemocatharsis therapy.

Analysis of hemodynamics during blood purification therapy using a newly developed noninvasive continuous monitoring method.

Advancement in blood purification therapy extends not only to consoles and dialyzers, but also to patient management during blood purification therapy. However, no monitor has been devised for hemodynamics during blood purification therapy that is carried out continuously and non-invasively. By studying the laser Doppler flowmeter (LDF), we have developed a probe that can continuously measure changes in blood flow in tissues of the head and lower extremities during blood purification therapy. By applying the improved LDF, we have developed a non-invasive continuous monitoring method (NICOMM). Hemodynamics in various types of blood purification therapies were also studied by simultaneously measuring with an automatic oscillometric sphygmomanometer.

Development of a new method for monitoring blood purification: the blood flow analysis of the head and foot by laser Doppler blood flowmeter during hemodialysis.

The management of blood pressure in hemodialysis patients greatly affects not only their quality of life, but also the duration of dialysis (dialysis life). Approximately 25% of dialysis patients suffer from continuous low blood pressure; however, the relationship between blood pressure and blood flow during dialysis has not been established. We hypothesized that with complete extracorporeal circulation, blood purification methods might affect blood flow, resulting in a change in blood pressure. The purpose of this study was to develop a noninvasive continuous monitoring method (NICOMM) as a microcirculation monitor by devising a laser-Doppler flowmeter (LDF) system with a wavelength of 780 nm. The aim was to use this system to simultaneously measure blood flow rate in both the head and the foot during dialysis and to determine the effectiveness of NICOMM by measuring blood flow and arterial distensibility. When exhibiting a significant decline in blood pressure at 240 min after the initiation of hemodialysis, a drop in blood flow in parallel with the blood pressure fall was recorded by the LDF. However, no changes were observed, in the readings by a continuous hematocrit monitor (Crit-Line monitor, CLM). Furthermore, a significant correlation was registered between mean arterial blood pressure and blood flow rate in the earlobe tissue from 180 min after the initiation of hemodialysis to the completion of hemodialysis (p < 0.001, r = 0.78). Comparisons were made by measuring vascular dehydration using the CLM. NICOMM showed more stable readings than the CLM in monitoring blood flow in response to changes in blood pressure.

Effect of combined treatment of oral sorbent with protein-restricted diet on change of reciprocal creatinine slope in patients with CRF.

BACKGROUND: Low-protein diet (LPD) is one therapy and AST-120, an oral carbon adsorbent, is the other therapy to reduce blood levels of indoxyl sulfate in patients with chronic renal failure (CRF). Based on the different mechanisms of reducing indoxyl sulfate levels, the addition of AST-120 to an LPD was investigated. METHODS: Seven hundred twenty-two patients with chronic glomerulonephritis (CGN) and 162 patients with diabetic nephropathy (DN) were stratified by protein intake: less than 0.50 g/kg/d (0.50-g/kg/d group), 0.51 to 0.65 g/kg/d (0.65-g/kg/d group), and 0.66 to 0.80 g/kg/d (0.80-g/kg/d group). To analyze the effect of combined AST-120 therapy (6 g/d) in patients on LPD therapy, the slope of the reciprocal of serum creatinine (1/Cr slope), which represents progression of CRF, was applied. RESULTS: (1) In patients with CGN, the addition of AST-120 with an LPD was as follows: the 1/Cr slope in the 0.50-g/kg/d (n = 152), 0.65-g/kg/d (n = 318), and 0.80-g/kg/d (n = 252) groups changed significantly from -430 x 10(-5) to -83 x 10(-5), -333 x 10(-5) to -102 x 10(-5), and -431 x 10(-5) to -116 x 10(-5) dL/mg/wk. (2) In patients with DN, the addition of AST-120 with an LPD was as follows: the 1/Cr slope in the 0.65-g/kg/d (n = 74) and 0.80-g/kg/d (n = 68) groups changed significantly from -602 x 10(-5) to -125 x 10(-5) and -646 x 10(-5) to -185 x 10(-5) dL/mg/wk. CONCLUSION: It is suggested that the addition of AST-120 to a mild LPD provides the comparable effect with a strict LPD in the point of suppressing the progress of CRF.