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Considering the growing relevance of fibroblast growth factor-23 (FGF23) and increased cardiovascular mortality in dialysis population, an analysis was performed to assess the influence of dialysis modality (peritoneal dialysis and hemodialysis) on level of FGF23. A cross-sectional study was performed in 80 continuous ambulatory peritoneal dialysis (CAPD) and 65 hemodialysis (HD) patients without residual renal function. Levels of calcium, phosphate, parathyroid hormone and FGF23 were measured, and their correlations were analyzed. Data on demographics, dialysis modality and FGF23 level were also analyzed. A significant correlation was found between FGF23 and serum calcium, serum phosphate and dialysis vintage in dialysis patients. Level of FGF23 was significantly higher in hemodialysis patients than that in peritoneal dialysis population. Multivariable regression revealed that, compared to CAPD, hemodialysis was found to be a predictor for higher FGF23 level, which was independent of serum calcium and phosphate level (P

The discovery of induced pluripotent stem (iPS) cells has broadened the promises of regenerative medicine through the generation of syngeneic replacement cells or tissues via the differentiation of patient-specific iPS cells. To apply iPS cell-mediated therapy to patients with genetic disorders, however, genome-editing technologies with high efficiency and specificity are needed. Recently, several targeted genome-editing strategies mediated by zinc finger nuclease and transcription activator-like effector nuclease have been applied to human and mouse iPS cells. Furthermore, spontaneous homologous recombination can restore genotype to wild type in mouse iPS cells heterozygous for genetic mutations. Through genome editing, the clinical application of patient-specific genetic mutation-free iPS cells to genetic disorders can finally be realized.

Human urotensin II (hUII) is a newly discovered substance that can dilate small blood vessels to decrease the blood pressure (BP). Our previous studies showed that some volume-overloaded patients on peritoneal dialysis can maintain normal BP (congestive heart failure excluded), suggesting that these patients have volume resistance capacity. This study is to investigate whether hUII plays an important role in this subgroup of patients on peritoneal dialysis. In this study, 105 patients on continuous ambulatory peritoneal dialysis were enrolled. Volume load was evaluated by the overhydration (OH) value obtained by bioimpedance analysis. OH2.0 kg was defined as normal volume (NV), and OH ≥ 2.0 kg as high volume (HV). Systolic blood pressure (SBP)130 mmHg was defined as normotension (NT) and ≥130 mmHg as hypertension (HT). The patients were thus divided into four subgroups: (1) normotension with normal volume (NT-NV), (2) normotension with high volume (NT-HV), (3) normal volume with hypertension (HT-NV), and (4) high volume with hypertension (HT-HV). hUII was measured using radioimmunoassay method. hUII was significantly higher in normal SBP group than that in high SBP group (p0.05). hUII was higher in the NT-HV group compared with that in the HT-HV group (p0.05). Our study suggests that hUII may be involved in the pathogenesis of the volume resistance HT in peritoneal dialysis patients.

Background: Removal and control of excess fluid with dialysis is considered critical for protection against cardiovascular sequelae. Antihypertensive agents including beta-blockers may influence hemodynamics, which may limit fluid removal during hemodialysis (HD). Methods: Fifty chronic HD patients underwent bioimpedance measurement before and after a midweek dialysis session. Data on volume status, blood pressure, antihypertensive medications, and bioimpedance were analyzed. Results: Patients in the high-volume status group used a significantly higher percentage of beta-blockers than patients in the low-volume status group (54.2 vs. 19.2%, respectively, p = 0.01). Multivariable regression revealed that the use of beta-blockers was independently positively associated with fluid overload (p < 0.05). Intradialytic muscle cramping occurred more often in the beta-blocker group than the control group (44.4 vs. 12.5%, respectively, p = 0.02). Conclusions: Our results suggest that the use of beta-blockers was associated with fluid overload in HD patients, and patients being treated with them experienced more intradialytic muscle cramping during dialysis.

Background: Left ventricular hypertrophy (LVH) is an important, independent negative predictor of cardiovascular morbidity and mortality in the general population and in dialysis patients. Previous studies suggest a sex dimorphism in the prevalence of LVH; however, this issue has never been approached in dialysis patients. Methods: This study enrolled 237 prevalent dialysis patients: 49 on hemodialysis (HD) and 188 on peritoneal dialysis (PD) from a single center. LVH was defined by echocardiography measurements, which were normalized to body surface area (BSA) and height2.7, respectively. Results: The mean ages in HD and PD patients were 60 ± 14 and 60 ± 13 years, with a median dialysis vintage of 43 and 20 months, respectively. Although there was no significant difference in age, diabetes, proportion of uncontrolled hypertension, antihypertensive medication and blood pressure between male and female patients within each dialysis modality, the prevalence of LVH (whether indexed to BSA or height2.7) was consistently higher in females than in males. When these patients were divided into LVH or non-LVH groups, a significant difference in sex distribution was observed between the two groups (62.0% vs. 41.0% when the BSA-indexed standard was used, p < 0.01; 62.8% vs. 37.1% when the height2.7-indexed standard was used, p < 0.001). In logistic regression analysis, female sex was identified as a risk factor of LVH (odds ratio, OR = 2.48, 95% confidence interval, CI = 1.33–4.59; when BSA-indexed LVH was treated as dependent variable, and OR = 4.05, 95% CI = 1.96–8.38, when height2.7-indexed LVH was treated as dependent variable) even after adjustment for age, diabetes, blood pressure and antihypertensive medication. Conclusion: This study showed that the prevalence of LVH determined by echocardiography was significantly higher in female dialysis patients than in male dialysis patients. Compared with males, female patients had a 2.5- to 4-fold higher risk to develop LVH even after adjustment for other potential confounding factors, which may indicate that elderly females in the uremic scenario are more prone to develop LVH than elderly males.

Background: Arterial stiffness is a major risk factor for cardiovascular and all-cause mortality in patients with end-stage renal disease. It has been reported that female and elderly diabetes mellitus (DM) patients treated with peritoneal dialysis (PD) had a higher risk of death. However, the underlying mechanism remains unknown. The present study tried to investigate whether older female DM patients have increased arterial stiffness. Methods: One hundred and eighty-one continuous ambulatory PD patients in a single center were enrolled. On enrollment, demographic data were collected. Carotid-femoral pulse wave velocities (PWV) were checked at the same time. Results: As expected, age had a significant impact on PWV both in DM and non-DM patients. There was no significant difference in PWV between male and female patients under the age of 50. No significant difference in PWV was found between male and female non-DM patients over the age of 50. However, the comparison of PWV reached statistical significance between male and female DM patients over the age of 50 (12.44 ± 1.83 m/s vs. 13.56 ± 1.86 m/s, p < 0.05). Conclusions: Our study showed that female DM patients over the age of 50 had the highest PWV as compared to other patient groups. Increased arterial stiffness might have contributed to the worst outcome of this population on PD treatment.

The relationship between overweight or obesity and mortality in peritoneal dialysis (PD) patients remains controversial. Both pulse-wave velocity (PWV) and endothelial dysfunction are related to an increased risk of cardiovascular disease. However, the association between PWV, endothelial dysfunction, and visceral adipose tissue in PD patients is not well-understood.One hundred and sixteen PD patients were enrolled in this cross-sectional study. The overall fat ratio and visceral-fat level of PD patients were measured by multiple-frequency bioelectrical impedance analysis (BIA). Carotid-femoral pulse-wave velocity (C-F PWV) was measured as an indicator of aortic stiffness. Endothelial function was evaluated by brachial-artery flow-mediated dilation (FMD). The association between these monitored parameters was assessed by statistical analyses.Bivariate correlation analysis showed that C-F PWV was positively correlated with visceral-fat level (r = 0.343, P.001), whereas FMD was negatively correlated with visceral-fat level (r = -0.354, P.01). Multiple regression analysis indicated that age, diabetic status, visceral-fat level, and duration of dialysis were determinants of PWV (adjusted R(2) = 0.316, P.001), whereas visceral-fat level and glucose load were the determinants of FMD (adjusted R(2) = 0.130, P.01).Visceral-fat level was an independent predictor of PWV and FMD in PD patients, and could be considered one of the risk factors for cardiovascular disease in PD patients.

BackgroundVolume overload is thought to be the most important cause of hypertension in peritoneal dialysis (PD) patients. However, there is also evidence that normalization of volume overload is not always accompanied by a drop in blood pressure (BP). In the present study, we hypothesized that dysregulation of peripheral resistance due to endothelial dysfunction would constitute an important determinant of BP response in overhydrated PD patients.MethodsWe performed an observational, prospective cohort study including all prevalent PD patients at the Peking University Third Hospital between 1 June 2006 and 30 November 2006. After baseline measurements, including echocardiography and bioelectrical impedance analysis, patients fulfilling inclusion criteria were reevaluated after 2 months of follow-up. All patients that exhibited significant changes in BP and extracellular water (ECW) between 2 visits were asked to undergo a second ultrasound. These patients were then divided into group A (parallel change between BP and ECW; n = 12) and group B (paradoxical change between BP and ECW; n = 10).ResultsThe cohort included 22 patients (13 males) with a mean age of 59 ± 13 years, on dialysis for 23.3 ± 32.6 months. There were no baseline differences between groups A and B. However, while patients in group A significantly increased their cardiac output, total peripheral resistance remained stable. In group B, cardiac output did not change significantly but total peripheral resistance decreased significantly.ConclusionIn PD patients, a significant increase in fluid volume is not necessarily linked to a significant increase in BP. Rather, the change in total peripheral resistance was found to be the most important determinant of the extent to which increased fluid volume affected BP.

Li-Tao Cheng1, Li-Jun Tang1,2, Hui-Min Chen1,3, Wen Tang1, Tao Wang11Division of Nephrology, Peking University Third Hospital, Beijing, China; 2Division of Nephrology, Qilu Hospital of Shandong University, Ji’nan, China; 3Division of Cardiology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, ChinaBackground: Hypoalbuminemia is a risk factor for cardiovascular events and mortality in dialysis patients, but the underlying mechanism remains unclear. Meanwhile, increased pulse wave velocity (PWV), the marker of arterial stiffness, has been proved to be an independent predictor of cardiovascular disease. The relationship between serum albumin and PWV in continuous ambulatory peritoneal dialysis patients (CAPD) was studied.Methods: Sixty-two CAPD patients were studied. The average age was 63 ± 12 years and dialysis duration was 23 ± 22 months. Serum albumin, C-reactive protein (CRP), and carotid-femoral PWV were measured.Results: Among these patients, 43.5% were men. The mean serum albumin concentration was 37 ± 4 g/L and PWV was 11.9 ± 2.3 m/s. PWV positively correlated with age (r = 0.35, P < 0.01), diabetes (yes = 1, no = 0; r = 0.292, P < 0.05), systolic blood pressure (SBP; r = 0.493, P < 0.001) and CRP (r = 0.295, P < 0.05), but negatively correlated with serum albumin (r = −0.357, P < 0.01). In multiple regression analysis, SBP (β = 0.615, P < 0.001), age (β = 0.414, P < 0.01), albumin (β = −0.315, P < 0.05) and total cholesterol (β = 0.275, P < 0.05) were independent determinants of PWV. In a non-inflamed subgroup (CRP < 3 mg/L, n = 30), albumin still negatively correlated with PWV (r = −0.66, P < 0.001).Conclusion: Serum albumin inversely correlated with increased PWV in CAPD patients, suggesting that increased arterial stiffness might be the link between hypoalbuminemia and increased cardiovascular mortality in dialysis patients.Keywords: hypoalbuminemia, cardiovascular events, pulse wave velocity, arterial stiffness, peritoneal dialysis

Background. Hypertension is common in patients with chronic kidney disease (CKD), and isolated systolic hypertension (ISH) accounts for most patients with inadequate blood pressure (BP) control. However, it remains unclear whether the prevalence of ISH would increase with the advancement of CKD. Methods. CKD patients of stages 3, 4 and 5 were recruited (n = 324). Based on office systolic BP (SBP) and diastolic BP (DBP), they were classified into any of the four hypertensive subtypes: normotension (SBP/DBP

Objective In dialysis patients, volume overhydration is common and is related to increased risk of cardiovascular morbidity and mortality. However, it remains unclear whether volume overload imposes those detrimental effects through endothelial dysfunction. Methods In this cross-sectional study, 81 stable patients on continuous ambulatory peritoneal dialysis in a single center were recruited. Volume status was evaluated by extracellular water, assessed by bioimpedance analysis, and normalized to individual height (nECW). Endothelial function was estimated by endothelial-dependent flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. Results There were 37 male and 44 female patients (mean age 61 ± 12 years, dialysis vintage 20 ± 23 months). FMD in female patients was significantly higher than that in male patients (9.17% ± 6.23% vs 6.31% ± 5.01%, p < 0.05). FMD was negatively correlated with weight ( r = -0.308, p < 0.01), body mass index ( r = -0.242, p < 0.05), systolic blood pressure ( r = -0.228, p < 0.05), ECW ( r = -0.404, p < 0.001), and nECW ( r = -0.418, p < 0.001). No correlation was found between FMD and other variables. In multiple stepwise regression analysis, calcium x phosphate product (² = 0.422, p < 0.001), nECW (² = -0.343, p < 0.01), and dialysis vintage (² = -0.237, p < 0.05) were independent determinants of FMD (adjusted R2 = 0.327 for this model). Conclusion There was independent correlation between index of volume status and FMD, and higher nECW was related to worse endothelial function. The results of this study may help us understand the underlying mechanism of volume overhydration leading to increased cardiovascular morbidity and mortality in dialysis patients.

Left ventricular hypertrophy (LVH) is common in dialysis patients, and an independent predictor of mortality. While recent studies have shown no differences in mortality between the two most common dialysis modalities, hemodialysis (HD) and peritoneal dialysis (PD), their impact on LVH is controversial. We thus performed cardiac ultrasound studies in prevalent dialysis patients receiving either HD or PD and compared LVH.We included 48 HD and 62 PD patients receiving treatment for at least three months in our dialysis center. All patients underwent echocardiographic examination and blood pressure measurements immediately following therapy. Volume status was assessed by bioelectrical impedance analysis.There was no baseline difference in demographics or comorbidities between HD and PD patients. As expected, extracellular water (ECW) in post-HD patients was significantly lower than that in pre-HD and PD patients, while cardiac output (CO) and systolic blood pressure (SBP) were higher in pre-HD than that in post-HD or PD patients. There was no significant difference in CO or SBP between post-HD and PD patients. Left ventricular mass index (LVMI) was markedly higher in HD patients as compared to PD patients. Thus, the prevalence of LVH according to the Framingham criteria was 68.8% in HD patients and 45.2% in PD patients. Subgroup analysis showed similar results in the patients who had been on single-modality dialysis for at least two years and in the anuric patients. Finally, in a linear regression model (r(2) = 0.364, p0.001), SBP, treatment modality (to be in HD), and ECW were all independent predictors of LVMI.In a cross-sectional analysis of prevalent Chinese patients, we found a higher LVMI and a higher prevalence of LVH in HD than in PD patients. As LVMI was associated with high blood pressure and volume overload, we suggest that in these patients, PD may preserve more physiological hemodynamics even during long-term therapy.

Background/Aim: Volume overload is believed to play a pivotal role in the pathogenesis of hypertension in dialysis patients. Although the extracellular water (ECW) content in hypertensive dialysis patients was significantly higher than in normotensive dialysis patients on the whole, there was considerable overlap in ECW between the two groups. Little is known about the hemodynamic characteristics in subgroups of patients with normotension but a high volume (HV) status or with hypertension but a normal volume (NV) status. We investigate the overlap in ECW between controlled and uncontrolled hypertension in dialysis patients. Methods: Fifty-two patients (mean age 62 years, 26 males and 26 females) on peritoneal dialysis were enrolled into this study. The ECW was assessed by bioimpedance analysis and normalized by individual height in meters (NECW). The mean value of NECW in both sexes was arbitrarily set to define NV status (lower than mean value) or HV status (higher than mean value). All patients were thus divided into four subgroups: controlled hypertension with NV (CHT-NV), controlled hypertension with HV (CHT-HV), uncontrolled hypertension with NV (UHT-NV) and uncontrolled hypertension with HV (UHT-HV). The stroke volume, cardiac output and total peripheral resistance were echocardiographically measured and their respective indices were calculated. Results: There were 12 (23%), 8 (15%), 14 (27%) and 18 (35%) patients in the CHT-NV, CHT-HV, UHT-NV and UHT-HV subgroups, respectively. The four subgroups were matched for sex, diabetes and age. The NECW in the CHT-HV group was higher than that in CHT-NV and UHT-NV groups (p < 0.01), but was comparable with that in the UHT-HV group. The stroke volume and cardiac output indices in the CHT-HV group were not significantly different from those in the CHT-NV and UHT-NV groups. The total peripheral resistance index in the CHT-HV group was lower than that in UHT-NV and CHT-NV groups (p < 0.05), but was comparable to that in the UHT-HV group. There was no difference in heart rate among the four groups. Conclusions: The overlap in ECW between controlled hypertension and uncontrolled hypertension in dialysis patients was related to a significant difference in total peripheral resistance index, but not to significant differences in stroke volume and cardiac output indices. The CHT-HV patients were characterized by lower total peripheral resistance indices.

Background: While a high blood pressure (BP) in patients receiving maintenance ambulatory peritoneal dialysis (CAPD) is associated with congestive heart failure and an increased mortality, the relevance of diurnal variations in BP is unknown. Methods:In a prospective study, we enrolled 76 prevalent patients receiving stable CAPD (age 60.4 ± 13.8 years; 37 males). BP was measured over 24 h using an automated device. We also performed routine clinical and biochemical measurements, as well as the Karnofsky index to evaluate physical activity. Volume status was assessed using bioimpedance analysis. Results: 69 patients (with an average time on dialysis of 24.4 ± 22.5 months) completed the study. Of these, 16 patients experienced a drop in BP >10% at night (dippers), while 53 patients did not (non-dippers). Comparing these two groups, dippers had significantly lower extracellular water (ECW) (13.8 ± 2.1 vs. 15.9 ± 3.3 l; p < 0.05), normalized extracellular water (nECW) (0.22 ± 0.05 vs. 0.26 ± 0.04 l/m; p < 0.05), and serum albumin (38.2 ± 2.9 vs. 35.9 ± 3.7 g/l; p < 0.05). Age, Karnofsky index, vintage, residual renal Kt/V and peritoneal Kt/V, total Kt/V, dose of antihypertensive drugs, mean systolic and diastolic BP did not significantly differ between these groups. Correlation analysis showed the coefficient of variation (CV) of BP positively correlated with E/T (r2 = 0.292; p < 0.05), diabetic (r2 = 0.267; p < 0.05), male (r2 = 0.257; p < 0.05), nECW (r2 = 0.278; p < 0.05) and ECW (r2 = 0.249; p < 0.05) negatively correlated with albumin (r2 = –0.280; p < 0.05). Furthermore, in a multivariate linear regression model, E/T, albumin and sex were independently associated with CV for BP. Conclusions: We show that reduced BP variation is common in CAPD patients and associated with volume overload and hypoalbuminemia. Furthermore, the relationship between nutritional, inflammatory status and dipping needs further studies.

Background/Aims: The optimal dose of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Trial tests the hypothesis that higher dose continuous veno-venous hemodiafiltration (CVVHDF) at an effluent rate of 40 ml/kg/h will increase survival compared to CVVHDF at 25 ml/kg/h of effluent dose. Results: This trial is currently randomizing critically ill patients in 35 intensive care units in Australia and New Zealand with a planned sample size of 1,500 patients. This trial will be the largest trial ever conducted on acute blood purification in critically ill patients. Conclusion: A trial of this magnitude and with demanding technical requirements poses design difficulties and challenges in the logistics, conduct, data collection, data analysis and monitoring. Our report will assist in the development of future trials of blood purification in intensive care. This study was registered with ClinicalTrials.gov (NCT00221013).

Chronic kidney disease (CKD) has emerged as a serious public health problem worldwide. How a CKD program should be organized, though, is still unknown. Therefore, we conducted a study to investigate the burden of CKD in a large university hospital and explore the possible approaches to care CKD appropriately in China.This is a retrospective cohort study of all new cases of CKD in a large hospital determined by a persistently increased serum creatinine (SCr) level (1.47 mg/dL,130 umol/L for more than three months) measured in the hospital laboratory. An abbreviate MDRD equation was used to estimate GFR from initial SCr values.There was a large CKD population in the hospital. In all, 1,006 cases had definite chronic kidney disease. Excepting the nephrology department, CKD patients were distributed in 18 disciplines and departments, with the focus on outpatient department and emergency department. In total, 1,257 cases were suspicious of CKD, who had only one or two tests of serum creatinine without detailed follow-up data. Furthermore, when SCr level is higher than 442 umol/L, there were 129 cases with only one test result.CKD is a great burden in the hospital. Multidiscipline cooperation based on outpatient, emergency department, and good follow-up system establishments are necessary for appropriate CKD care. Future work is needed to explore how to organize a good CKD management program to advance the care of patients with CKD.

Although cases of anti-erythropoietin (anti-EPO) antibody-induced pure red cell aplasia (PRCA) have been reported since 1998, the role of anti-EPO antibodies in the development of PRCA is controversial, with many conflicting opinions. Here, we present a patient who had serial serum anti-EPO antibody levels measured both before and after the development of PRCA to observe the relationship between serial changes in anti-EPO antibody and hemoglobin levels. Enzyme-linked immunosorbent assays were used for the detection of anti-EPO antibodies. The patient's serum anti-EPO antibody levels showed a characteristic change over time: negative before the development of PRCA, strongly positive when PRCA was diagnosed, decreasing after receiving prednisone, and eventually became negative. More importantly, an inversely close association between changes in serum anti-EPO antibody and hemoglobin levels was shown. The characteristic changes in this case indicate that anti-EPO antibody might have a role in the development of PRCA, and monitoring the titer of anti-EPO antibody may be of great value in the diagnosis and treatment of PRCA.

Background: Fluid overload is not uncommon in patients on continuous ambulatory peritoneal dialysis (CAPD). Previous studies suggested that residual renal function (RRF) played an important role in maintaining fluid balance. However, good fluid status should be a balance between fluid intake and removal. Therefore, in the present study, we investigated the effect of RRF on patients’ fluid status after focusing on the balance between fluid intake and removal in CAPD patients. Methods: In this cross-sectional study, 195 stable CAPD patients in a single center were included. Patients were divided into three groups according to their urine output: anuric group with urine ≤100 ml/day, oliguric group with urine ≤400 ml/day and UO >400 ml group with urine >400 ml/day. Fluid status was evaluated by bioimpedance analysis and mean arterial pressure (MAP). The sodium removal and plasma sodium concentration were also measured. All the patients were educated to try to achieve good volume control by focusing on salt and fluid intake and their removals. Results: There were 51, 31 and 113 patients in anuric, oliguric and UO >400 ml group, respectively. Anuric patients were older and had been on CAPD longer than that of the oliguric and UO >400 ml patients (p < 0.05). The urine output in the three groups were 9.28 ± 22.68, 236.13 ± 75.43 and 1,013.34 ± 541.54 ml/day, respectively (p < 0.001). Bioimpedance analysis showed that the differences of extracellular water, intracellular water and total body water were not statistically significant among the three groups. However, there was significant difference in MAP among the three groups (MAP in anuric, oliguric and UO >400 ml groups were 93.27 ± 13.35, 96.63 ± 9.94 and 102.36 ± 13.70 mm Hg, p < 0.01), and UO >400 ml group had higher MAP than anuric and oliguric groups (p < 0.05). The total sodium removal (renal + peritoneal) in anuric, oliguric and UO >400 ml groups were 96.44 ± 60.18, 98.95 ± 73.82 and 134.64 ± 72.44 mmol/day, respectively (p < 0.01). The UO >400 ml group also had higher plasma sodium concentration than anuric and oliguric groups (plasma sodium in the three groups were 137.49 ± 3.43, 137.82 ± 2.63 and 139.15 ± 3.30 mmol/l, respectively; p < 0.01). Conclusions: This study showed that extracellular water among anuric, oliguric and UO >400 ml groups was not significantly different, which suggested that RRF may be not so important as expected in maintaining good volume status. The higher blood pressure in patients with higher RRF and higher sodium and fluid removal in the present study suggested restricting salt and fluid intake might be more important for better blood pressure control in CAPD patients.

Background: A seasonal variation in blood pressure (BP) has been observed in hemodialysis and renal transplant patients. However, this phenomenon in continuous ambulatory peritoneal dialysis (CAPD) patients, whose hemodynamics are different from hemodialysis patients, has not been reported before. In addition, the contribution of extracellular water (ECW) in the seasonal variation in BP is not clear. Methods: All stable CAPD patients (n = 122) dialyzed in a single center from January 1, 2003 to December 12, 2004 were studied. Systolic blood pressure (SBP), diastolic blood pressure (DBP), weight and ECW (by bioimpedance analysis) were measured in every patient. Climatic data were obtained from the Beijing Weather Bureau. These data were pooled together and grouped according to the calendar month. Results: In general, an apparent seasonal variation in BP was observed in CAPD patients. BP began to decrease from spring and reached the lowest level in summer, then increased from autumn and reached its peak in winter. The seasonal variation in BP in male patients was similar to that in female patients, but in comparison to non-diabetic patients there was no apparent seasonal variation in the BP of diabetic patients. SBP and DBP negatively correlated with the average atmospheric temperature (r = –0.768, p < 0.001 and r = –0.764, p < 0.001, respectively). BP also negatively correlated with rainfall and humidity, but this correlation disappeared when temperature was controlled in partial correlation analysis. Weight and ECW fluctuated throughout the year but showed no seasonal variation. Conclusion: On the whole there was an apparent seasonal variation in blood pressure in CAPD patients. As opposed to non-diabetic patients, there was no apparent seasonal variation in BP in diabetic patients. The seasonal variation in BP was influenced more by temperature than rainfall and humidity, and the change in ECW was not seasonal, suggesting that other mechanisms such as total peripheral resistance might play a more important role in this phenomenon.

Background: It is not uncommon that diabetic peritoneal dialysis (PD) patients are volume overloaded and this may have contributed to the inferior outcome of diabetic patients. In the present cohort study, we compared the difference between diabetics and nondiabetics during the first year of PD after implementing strict volume control. Methods: Seventeen diabetic and 40 nondiabetic incident PD patients were followed for 1 year. Fluid status was evaluated by bioimpedance analysis and blood pressure. Nutritional status was evaluated by subjective global nutritional assessment. Results: At the initiation, compared with the nondiabetics, diabetics had a significantly higher extracelluar volume, systolic blood pressure and lower serum albumin. One year later, there were no statistical differences in these parameters between the two groups. The prevalence of malnutrition decreased in all patients, although malnutrition remained slightly higher in diabetic patients. Conclusions: Our study suggests that diabetics can do as well as nondiabetics on PD. Appropriate diabetic care, especially strict volume control, may be critical for the success of diabetic patients on PD treatment.

The modulus of elasticity between the perovskite and rock salt blocks (the unit cell of YBa 2 Cu 3 O 7− δ is composed of them) in Y-system superconductors (YBa 2 Cu 3 O 7− δ , δ =0.07–0.62) have been calculated. A clear correlation among the superconducting transition temperature and the modulus of elasticity between the perovskite and rock salt blocks in the Y-system superconductors is established. Also, the correlation between the static mechanical properties and the superconducting transition temperature was discussed. We suggest that the perovskite and rock salt blocks are somewhat independent structural units in physical properties, and the interaction between the two blocks is important in determining the superconducting properties.

YBCO thin films grown on SrTiO 3 , yttria-stabilized zirconia (YSZ), and YSZ with a CeO 2 buffer layer, by pulsed laser deposition, were studied by high resolution X-ray diffraction, including rocking curves, and Φ-scans. It is shown that the distortion of the thin films is different in the different substrates. The lattice mismatch between them can partially explain this. The larger mismatch corresponds to the larger distortion of the films, which can be determined by the full width at half maximum (FWHM) in the rocking curve and Φ-scan curve. As the mismatch between the film and substrate increases, the FWHM of both rocking curve and Φ-scan curve increases simultaneously. But, the YBCO on the YSZ with CeO 2 buffer layer does not obey this regulation. The careful calculation of the cohesive energy of the thin films and substrates, especially considering the effect of the interaction of the YBCO and substrates, indicates there is a close relationship between the cohesive energy and the distortion of the films. Using this to explain the distortion is better than using mismatch.

The discovery of induced pluripotent stem (iPS) cells has broadened the promises of regenerative medicine through the generation of syngeneic replacement cells or tissues via the differentiation of patient-specific iPS cells. To apply iPS cell-mediated therapy to patients with genetic disorders, however, genome-editing technologies with high efficiency and specificity are needed. Recently, several targeted genome-editing strategies mediated by zinc finger nuclease and transcription activator-like effector nuclease have been applied to human and mouse iPS cells. Furthermore, spontaneous homologous recombination can restore genotype to wild type in mouse iPS cells heterozygous for genetic mutations. Through genome editing, the clinical application of patient-specific genetic mutation-free iPS cells to genetic disorders can finally be realized.

Induced pluripotent stem cells (iPSCs) generated by epigenetic reprogramming of personal somatic cells have limited therapeutic capacity for patients suffering from genetic disorders. Here we demonstrate restoration of a genomic mutation heterozygous for Pkd1 (polycystic kidney disease 1) deletion (Pkd1(+/−) to Pkd1(+/R+)) by spontaneous mitotic recombination. Notably, recombination between homologous chromosomes occurred at a frequency of 1~2 per 10, 000 iPSCs. Southern blot hybridization and genomic PCR analyses demonstrated that the genotype of the mutation-restored iPSCs was indistinguishable from that of the wild-type cells. Importantly, the frequency of cyst generation in kidneys of adult chimeric mice containing Pkd1(+/R+) iPSCs was significantly lower than that of adult chimeric mice with parental Pkd1(+/−) iPSCs, and indistinguishable from that of wild-type mice. This repair step could be directly incorporated into iPSC development programmes prior to cell transplantation, offering an invaluable step forward for patients carrying a wide range of genetic disorders., マウスiPS細胞を用いた遺伝性疾患の治療モデル－多発性嚢胞腎(ADPKD)モデルマウスの治療－. 京都大学プレスリリース. 2012-2-10.

In this study we explored the possible role of arachidonoylethanolamine (AEA) in regulating blood pressure in patients on continuous ambulatory peritoneal dialysis (CAPD). One hundred and five patients on CAPD were enrolled. Volume status was evaluated by the overhydration (OH) value obtained by bioimpedance analysis. OH < 2.0 kg was defined as normal volume (NV) and OH ≥ 2.0 kg as high volume (HV). Home mean systolic blood pressure

Refractory ascites is uncommon in autosomal dominant polycystic kidney disease (ADPKD) but it usually makes the patient physically and psychologically handicapped. Two uremic ADPKD patients in our hospital developed refractory ascites after 1 year on hemodialysis. The refractory ascites was due to portal hypertension, which was caused primarily by portal outflow obstruction due to the numerous enlarged cysts in the liver and secondarily by increased portal inflow. We attempted continuous ambulatory peritoneal dialysis (CAPD) to treat the 2 patients and obtained satisfactory results. Not only was the refractory ascites well controlled, but also the portal hypertension disappeared. Based on our experience, we think CAPD could serve as a very effective therapy to treat the refractory ascites of portal hypertension due to polycystic liver in uremic ADPKD patients.

Volume overload is thought to be the main cause of hypertension in dialysis patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis (HD) patients, which was considered as an increase in extracellular water (ECW), on blood pressure (BP) change, was controversial. Our aim was to examine the changes in hemodynamics and arterial stiffness during IDWG in HD patients and attempt to explore the possible mechanism of diverse BP change. Thirty prevalent patients on HD were enrolled. The height, weight, BP, blood chemistry, volume status assessed by bioelectrical impedance analysis, hemodynamic parameters obtained by echocardiography, and pulse wave velocity (PWV) were collected within 1 hour postdialysis and again just before the next dialysis session. Meanwhile, blood samples were drawn to analyze vasoactive hormones, including renin, angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs during the next predialysis were significantly higher than those during the postdialysis. The BP showed no difference between postdialysis and the next predialysis. There was an obvious increase in cardiac output and decrease in total peripheral resistance as a whole during the next predialysis than that during postdialysis. When patients were divided into the BP increase group (BPI group, 13 patients) and BP decrease group (BPD group, 11 patients) according to the change in systolic BP higher than 10 mmHg, both groups displayed a significant increase in weight, ECW, cardiac output, and a decrease in total peripheral resistance. As compared with the BPI group, patients in the BPD group had significantly lower IDWG, shorter time on dialysis treatment, and higher residual renal function. A decrease in catecholamine and endothelin in the next predialysis was obvious in the BPD group. There was a significant decrease in PWV at the next predialysis in the BPD group while the PWV did not change significantly in the BPI group. Our results showed that the diverse BP change during IDWG was significantly affected by residual renal function, PWV, and vasoactive substances.

Background: A poor nutritional state is associated with an increased risk of cardiovascular events in end-stage renal disease. It is unclear whether malnutrition itself can induce cardiovascular disease (CVD). We examined the impact of nutritional status on patients’ arterial stiffness in peritoneal dialysis (PD) patients. Methods: We prospectively enrolled 121 stable PD patients and evaluated them at baseline and 1 year later. According to patients’ Subjective Global Assessment (SGA) changes from baseline to the end, patients were divided into four groups: group 1, SGA from A to B; group 2, SGA remained A, group 3, SGA changed from B to A, and group 4, SGA remained B. Arterial stiffness was assessed by pulse-wave velocity (PWV). Results: At baseline, PWV in well-nourished patients were lower than malnourished patients (p < 0.05). One year later, in group 1, as compared with baseline, PWV increased significantly (p < 0.001) whereas handgrip strength (HGS), daily dietary protein intake and dietary energy intake decreased significantly. In group 3, PWV decreased significantly (p < 0.05) whereas HGS and ALB increased significantly. In groups 1 and 3, lgCRP level remained unchanged. Conclusion: There was a closely longitudinal association between nutritional status and arterial stiffness in PD patients, suggesting a possible impact of nutritional status on arterial function.

To study the dynamic accumulation of flavonoids in Chrysanthemum morifolium in order to chose the optimal harvest time.The flavonoid content was determined in various C. morifolium and in different periods.The accumulation of flavonoid in various Chrysanthemum reached a high level when lingulate flowers were in 50% blossom and tube ones in 30% or lingulate flowers were in 70% blossom and tube ones in 50%. Only few of C. morifolium reached a high level of flavonoid, when 1 both ingulate and tube flowers blossomed fully.

Background: In this study, we focused on whether volume overload plays a role in the development of arterial stiffness. Methods: Seventy-three prevalent hemodialysis patients were enrolled in a cross-sectional study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV), and volume overload was assessed by bioimpedance analysis. Results: Patients were divided into a high PWV group and a low PWV group based on the median of PWV. Age, systolic blood pressure, pulse pressure (PP), extracellular water/total body water ratio (ECW/TBW), diabetic status (all p < 0.01), and history of cardiac events (p < 0.05) were significantly higher in the high PWV group (n = 37) than in the low PWV group. In the correlation analysis, PWV was positively associated with PP, systolic blood pressure, ECW/TBW, age, history of cardiac events, and diabetes (all p < 0.01). Multiple regression analysis showed that PWV was independently related to PP and ECW/TBW (p < 0.01). Conclusion: Volume overload plays an important role in the development of arterial stiffness in hemodialysis patients.

Background: Endothelial dysfunction is an early predictor of cardiovascular events. Hyperuricemia has been shown to be associated with increased cardiovascular mortality. It remains unclear if serum uric acid (UA) is associated with endothelial dysfunction in peritoneal dialysis patients. Methods: In this cross-sectional study, the relationship of UA and endothelial dysfunction was investigated in 189 stable peritoneal dialysis patients. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. Results: UA levels did not differ between 93 male and 96 female patients (416.31 ± 86.93 vs. 395.52 ± 87.47 μmol/l, p > 0.05). Patients were grouped into three tertiles on the basis of their serum UA levels. Systolic blood pressure (p = 0.007), serum phosphate (p = 0.005), high-sensitive C-reactive protein (hs-CRP) (p < 0.001), and FMD (p = 0.016) were all different among UA tertiles. FMD was found to be related with UA (p = 0.002) and hs-CRP (p = 0.006) in a Pearson’s correlation analysis. Multivariate regression analysis showed that only UA was an independent determinant of FMD (β = –0.237, p = 0.036). Conclusion: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

The aim of this study was to validate whether differences in aortic stiffness are responsible for the differences in cardiovascular mortality among hypertension subtypes. Twenty hundred and fifty continuous ambulatory peritoneal dialysis patients were included in the present study. They were classified into four groups: normotensives (n=92) with systolic blood pressure (SBP)

To study on dynamic accumulation of various flavone in Chrysanthemum morifolium, in order to appraise the quality of flavone.The extract was hydrolyzed and the flavonoid components were determined by RP-HPLC.In the samples from Tongxiang, Tezhongboju showed the highest flavonoids content with the total flavone 9.81%, quercetin 4.17 per thousand and apigenin 17.02 per thousand. In the samples from Sheyang, Hongxinju showed the highest content of luteolin with 6.84 per thousand. In the samples from Jiangning, Tezhongboju showed the highest content of total flavone with 7.59%, Yizhongdabaiju showed the highest content of quercetin with 2.78 per thousand, Sheyangxiaobaiju showed the highest content of luteolin with 4.27 per thousand, Sheyanghongxinju showed the highest content of apigenin with 11.20 per thousand. There were differences in the content of flavonoids among the different cultivars, and the same cultivars showed also different when planted in different areas.

In dialysis patients, volume overhydration is common and is related to increased risk of cardiovascular morbidity and mortality. However, it remains unclear whether volume overload imposes those detrimental effects through endothelial dysfunction.In this cross-sectional study, 81 stable patients on continuous ambulatory peritoneal dialysis in a single center were recruited. Volume status was evaluated by extracellular water, assessed by bioimpedance analysis, and normalized to individual height (nECW). Endothelial function was estimated by endothelial-dependent flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter.There were 37 male and 44 female patients (mean age 61 +/- 12 years, dialysis vintage 20 +/- 23 months). FMD in female patients was significantly higher than that in male patients (9.17% +/- 6.23% vs 6.31% +/- 5.01%, p0.05). FMD was negatively correlated with weight (r = -0.308, p0.01), body mass index (r = -0.242, p0.05), systolic blood pressure (r = -0.228, p0.05), ECW (r = -0.404, p0.001), and nECW (r = -0.418, p0.001). No correlation was found between FMD and other variables. In multiple stepwise regression analysis, calcium x phosphate product (beta = 0.422, p0.001), nECW (beta = -0.343, p0.01), and dialysis vintage (beta = -0.237, p0.05) were independent determinants of FMD (adjusted R(2) = 0.327 for this model).There was independent correlation between index of volume status and FMD, and higher nECW was related to worse endothelial function. The results of this study may help us understand the underlying mechanism of volume overhydration leading to increased cardiovascular morbidity and mortality in dialysis patients.

Although the augmentation index (AIx) is widely used to evaluate arterial stiffness in clinics and research, some conflicting data exist in regard to its validity. We therefore performed a series of studies to test the validity of AIx. The first study in 196 peritoneal dialysis patients showed that AIx in diabetics was lower than that in non-diabetic patients (p0.05), which was in contradiction with the previous studies. Further analysis showed that AIx was just weakly correlated with pulse pressure (PP)-a known index of arterial stiffness. We also found that the increase of augmentation pressure (AP) was usually accompanied with increased central PP (C-PP). As AP and C-PP are used as the numerator and denominator in the AIx formula, an increase in the numerator (AP) would not necessarily result in an increase of the quotient (AIx) unless the denominator (C-PP) was stable. We then conducted a second study trying to test the validity of AIx through mathematical ratiocination. The increases in the central second peak (P2) and AP were assumed to represent increased arterial stiffness. Different values of AIx were obtained by varying the central initial systolic peak (P1) and diastolic pressure (DP). Mathematical ratiocination showed that AIx was dependent on multiple factors, F=(DeltaSP-DeltaDP)x(P1-P2)+(DeltaP2-DeltaP1)x(SP-DP), which suggested that a change of AIx would not always be attributable to changes in P2 and AP. This speculation was further proved by clinical data in our third study. In conclusion, through a series of studies and ratiocination, we showed that the augmentation index (AIx or AIx@75bpm) might not be a sensitive surrogate for a change in central pressure waveforms, which is a manifestation of change in large artery function. The limitation of AIx as an index of arterial stiffness is rooted in its formula, which has a clear mathematical flaw.

Background: Malnutrition is a predictor of cardiovascular disease in dialysis patients, but the mechanisms remain unknown. We investigated links between nutritional markers and arterial stiffness in continuous ambulatory peritoneal dialysis patients. Methods: We evaluated the relationship between arterial stiffness evaluated by pulse-wave velocity (PWV) and four estimates of nutritional status (serum albumin, handgrip strength [HGS], subjective global assessment [SGA], and bioelectrical impedance analysis phase angle [PA]) in 124 PD patients. Results: Malnourished patients exhibited a significantly higher PWV than those classified as well-nourished by SGA (p < 0.05). Furthermore, PWV correlated negatively with albumin, HGS and PA (p < 0.001, respectively). PWV was also correlated with age, systolic blood pressure, and C-reactive protein. In multivariate regression analysis, albumin, HGS, SGA and PA were each independently associated with PWV after adjustment. Conclusions: The significant association between each nutritional marker and PWV in PD patients was independent of inflammation and diabetic state, suggesting that malnutrition may contribute to vascular dysfunction.

Although fluid overload contributes to hypertension in CAPD patients, less attention has been paid to the role of excess salt and fluid intake. Therefore, we investigated the role of salt and fluid intake in the development of hypertension in CAPD patients.A total of 165 stable CAPD patients were included into this study. Based on the blood pressure in three consecutive months, they were divided into three groups: persistent hypertensive (PH; n = 33), intercurrent hypertensive (IH; n = 58) and persistent normotensive (PN; n = 74). The IH group was further divided into two phases: normotensive and hypertensive. Fluid status was evaluated by clinical assessment and bioimpedance analysis (BIA).There were no differences in age, gender, and duration of dialysis among groups. Patients were more fluid overloaded in the PH group. Extracellular water (ECW), total body water (TBW), and normalized extracellular water by height (NECW) were higher in the PH group than the PN group (16.77 +/- 3.62 L vs. 14.61 +/- 2.92 L for ECW, p0.01; 32.22 +/- 8.23 L vs. 28.98 +/- 6.00 L for TBW, p0.05; and 10.28 +/- 1.86 L/m vs. 9.08 +/- 1.63 L/m for NECW, p0.01). However, patients in the PH group also had more total fluid removal (TFR) and total sodium removal (TSR) compared with the PN group (1346.82 +/- 431.27 mL/d vs. 1139.28 +/- 412.65 mL/d for TFR, p0.05; and 141.52 +/- 61.57 mmol/d vs. 102.42 +/- 62.51 mmol/d for TSR, p0.01). The same trend was demonstrated when compared values of hypertensive and normotensive phase in IH group; patients had higher ECW, TBW, NECW, TSR, and PNa when they were in hypertensive phase than in the normotensive phase.This study confirmed that fluid overload was closely associated with the development of hypertension in CAPD patients. It also showed that hypertensive patients were in general more fluid overloaded despite a higher fluid and sodium removal as compared with normotensive patients.

Background Dietary salt and fluid restriction is important in controlling fluid balance in patients on continuous ambulatory peritoneal dialysis (CAPD). However, it is often difficult to monitor patients’ dietary total sodium intake (TSI). Usually, total sodium removal (TSR), the sum of urinary sodium removal (USR) and dialysate sodium removal (DSR), is suggested to represent TSI. In the present study, we investigated the reliability of using TSR as a surrogate to TSI in CAPD patients. Methods 40 clinically stable CAPD patients were closely followed for 3 months. Their TSI, USR, DSR, and fluid status were measured twice: at baseline and at the end of this study respectively. Fluid status was evaluated by bioimpedance analysis. Patients with increased sodium intake (group ISI) or decreased sodium intake (group DSI) (both >0.5 g/day or >21.74 mmol/day elemental sodium) were included in this study. Results There were 15 patients in group ISI and 9 patients in group DSI. During the follow-up, although TSI increased in group ISI and decreased in group DSI ( p < 0.05), there were no significant changes in USR, DSR, or TSR in either group. No relationship was found between TSI and TSR. Changes in weight, blood pressure, urine volume, ultra-filtration, and small solute removal (Kt/V and creatinine clearance) were not statistically significant between the two groups. Fluid status deteriorated in group ISI and improved in group DSI ( p < 0.05). Conclusions Our study suggests that changes in total sodium intake do not lead to proportionate changes in total sodium removal in CAPD patients. Therefore, TSR (the sum of USR and DSR) should be used cautiously to monitor TSI in this patient population.

Background: Metabolic acidosis (MA) is common in chronic renal insufficiency (CRI) patients, and its pattern changes as renal function deteriorates. Although the prevalence of acidosis in peritoneal dialysis has been reported to be rather high, the causes of it have not been well studied. The present study was performed to examine the prevalence of metabolic acidosis in our continuous ambulatory peritoneal dialysis (CAPD) patients and its possible causes. Methods: In this cross-sectional study, we analyzed data from patients who received maintenance CAPD in our hospital and had been on dialysis for at least one month. Patients’ demographic features, medications, and intercurrent medical conditions were recorded. Data including blood biochemistry, dialysis adequacy, and nutrition were collected. A serum bicarbonate concentration of less than 23 mmol/l was defined as having acidosis. The normal value of the serum anion gap (AG) was defined as 12 ± 4 mmol/l. Results: A total of 154 patients (76 males and 78 females) with age of 60.04 ± 13.92 years and the time on dialysis of 16.83 ± 21.59 months were included in this study. Sixty-six patients (43%) had a serum bicarbonate of less than 23 mmol/l, among whom 12 patients (8%) were identified as having MA with increased AG, 54 (35%) were identified as having MA with normal AG. Patients who had better residual renal function (RRF) had a significantly lower serum bicarbonate level despite their higher total KT/Vurea as compared to those with lower RRF. In addition, patients with MA and normal AG had the highest RRF and highest total KT/Vurea. All patients with MA and increased AG had significantly lower values of dietary protein intake (DPI) as compared to their values of normalized protein nitrogen appearance (nPNA), and had higher serum urea and phosphate levels as compared with those patients without MA. Conclusion: Our study suggested that CAPD patients with better RRF were more susceptible to metabolic acidosis, which was characterized by normal anion gap and hyperchloremia. Thus, we speculate that renal loss of bicarbonate may to a large extent be responsible for the occurrence of MA in these patients.