Hemodialysis is associated with higher serum FGF23 level when compared with peritoneal dialysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.05). CONCLUSIONS: These findings demonstrate that FGF23 levels are significantly higher in hemodialysis patients than that in peritoneal dialysis patients. We demonstrate an important association between dialysis modality (HD vs CAPD) and higher FGF23, independent of classical determinants (serum calcium and phosphate level).

High-throughput salting-out assisted liquid-liquid extraction with acetonitrile for the determination of anandamide in plasma of hemodialysis patients with liquid chromatography tandem mass spectrometry.

Anandamide (AEA) is an endocannabinoid present in human plasma that is associated with several physiological functions and disease states. However, low AEA plasma levels pose challenges in terms of analytical characterization. Classical liquid-based lipid extraction and solid-phase extraction require complicated procedures and the drying down of relatively large volumes of solvents, making them unsuitable for high-throughput analysis. Here a high-throughput salting-out assisted liquid-liquid extraction (SALLE) method with acetonitrile and mass spectrometry compatible salts for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of AEA in human plasma has been developed and validated. The seamless interface of SALLE and LC-MS eliminated the drying-down step, only 100 µL of plasma is required and minimal volumes of organic solvent are used. Good reproducibility, accuracy and precision were demonstrated during the method validation. The method is linear up to 10 ng/mL with a lower limit of quantitation of 0.1 ng/mL for AEA, the accuracy for AEA was from 93.3 to 96.7% and the precision was <8.57%. This new methodology was successfully applied to analysis of clinical samples from maintenance hemodialysis patients.

[Influence on AM fungi infection rate and medicine quality of Pinellia ternata in condition of three soil impact factors].

OBJECTIVE: To explore the influence on AM fungi infection rate and medicine quality of Pinellia ternate in the condition of three soil impact factors. METHOD: Set the orthogonal test of three factors and levels. Determinate the AM fungi infection rate in early stage of mature & stage of mature of P. ternata, and the water content, water soluble extract, butanedioic acid content and alkaloid content of P. ternata tuber that be harvested also had be determinated. RESULT AND CONCLUSION: With the P levels to 30 mg x kg(-1) and 90 mg x kg(-1), AM fungi infection was the best when mixed inoculated of EM. Microbial agent inoculated played a decisive role in P. ternata growth and physiological activity, secondary influenced factor was P concentration, and the water stress was the minimal impact. Mixed inoculated of AM fungi and EM treatment with the low P levels (30, 90 mg x kg(-1)) proved better effect on enhancing the water extract content, anedioic acid and alkaloid content, while decreasing the water contents of P. ternata tuber.

Effects of beta-blocker use on volume status in hemodialysis 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.

Genome editing in induced pluripotent stem cells.

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.

Roles of human urotensin II in volume resistance hypertension in peritoneal dialysis patients.

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. OH < 2.0 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 (p < 0.05). hUII was higher in the NT-HV group compared with that in the HT-HV group (p < 0.05). Our study suggests that hUII may be involved in the pathogenesis of the volume resistance HT in peritoneal dialysis patients.

Role of arachidonoylethanolamine in blood pressure regulation in volume-resistant patients on peritoneal dialysis.

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<130 mmHg was defined as controlled hypertension (CHT) and ≥130 mmHg as uncontrolled hypertension (UHT). The patients were divided into four subgroups: (1) controlled hypertension with normal volume (CHT-NV), (2) controlled hypertension with high volume (CHT-HV), (3) uncontrolled hypertension with normal volume (UHT-NV), and (4) uncontrolled hypertension with high volume (UHT-HV). AEA was measured by ultra performance liquid chromatography-tandem mass spectrometry. AEA was significantly higher in the HV group as compared with the NV group (P<0.05). In addition, AEA was also significantly higher in the CHT-HV group as compared with the UHT-NV group (P<0.05). These results may suggest a compensatory function of AEA and TRPV1 pathway to lower blood pressure during volume expansion in CAPD patients.

Cure of ADPKD by selection for spontaneous genetic repair events in Pkd1-mutated iPS cells.

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.

[Arbuscular mycorrhiza of cultivated and wild Pinellia ternata].

OBJECTIVE: To study the arbuscular mycorrhiza and arbuscular mycorrhizal fungi associated with cultivated and wild Pinellia ternata in Guizhou province. METHOD: Wild and cultivated P. ternata roots were observed through staining and microscopic examination, the arbuscular mycorrhizal fungi spores were isolated through wet thieving according to Gerdemann & Nicolson (1963), the spores were identified following the description of Schenck & Pérez (1988), and some previous publications. RESULT: The typical arbuscular mycorrhiza (AM) structure was showed according to a research of wild and cultivated P. ternata. In the survey of AM fungi species in the rhizosphere of wild and cultivated P. ternata, 3 genera and 21 species were found, 3 genera and 7 species were identified. 5 species of them belong to Glomus, 1 species belongs to Scutellospora, 1 species belongs to Gigaspora, including Glomus mosseae, G. intraradices, G. melanosporum, G. deserticola, G. aggregatum, Scutellospora castanea, Gigaspora albida, and one of them was a new record, i.e., Scutellospora castanea which was the dominant species in Bijie. CONCLUSION: The diversity of AM fungi between wild and cultivated Pinellia ternata was showed on this survey, the fungi associated with wild ones are different form the cultivated ones, such as Gigaspora albida only occurs in cultivated ones, Glomus melanosporum only occurs in wild ones, while Glomus mosseae and Glomus intraradices occur in both wild and cultivated ones, and there were specialization species in Bijie, all these can provide new though for solving degradation problem of cultivated Pinellia ternata.

[Study on influence of arbuscular mycorrhizal fungi Pinellia ternata yield and chemical composition].

OBJECTIVE: To study the influence of arbuscular mycorrhizal fungi to Pinellia ternata leaf index, propagation coefficient, tuber yield and chemical composition. METHOD: The Pinellia ternata leaf length, width, plant height and leafstalk diameter were measured during growing time till P. ternata loded. The leaf index was calculated and the tuber yield were measured after harvest. The contents of guanosine was determined by HPLC method, and the alkaloid contents were determined by spectrophotometric method. RESULT AND CONCLUSION: Inoculated AM fungi could increase P. ternata propagation coefficient and the yield of tuber. Inoculated AM fungi could increase P. ternata leaf index, made leaf tends to be more like bamboo leaf type. Inoculated AM fungi could delayed P. ternata lodging time; G. mosseae + G. intraradices treatment (early inolulation time) proved better influence on increasing fresh weight and dry weight of P. ternata tuber and the propagation coefficient. Inoculated AM fungi could increase guanosine and alkaloid contents of Pinellia ternata tuber, and the contents of guanosine and alkaloid in inoculated treatments were higher than those in cultivated P. ternata from Hezhang; G. mosseae + G. intraradices treatment (later inolulation time) proved good effect on increasing the contents of guanosine and alkaloid.

Refractory ascites due to portal hypertension in autosomal dominant polycystic kidney disease (ADPKD) patients successfully treated with peritoneal dialysis.

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.

Residual renal function and arterial stiffness mediated the blood pressure change during interdialytic weight gain in hemodialysis 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.

Correlation between pulse wave velocity and fluid distribution in hemodialysis patients.

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.

Effect of nutrition on arterial stiffness in peritoneal dialysis patients.

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.

Serum uric acid and endothelial dysfunction in continuous ambulatory peritoneal dialysis patients.

UNLABELLED: 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 mumol/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 (beta = -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.

Sex difference in the prevalence of left ventricular hypertrophy in dialysis patients.

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 height(2.7), 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 height(2.7)) 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 height(2.7)-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 height(2.7)-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.

Increased arterial stiffness in elderly female diabetic peritoneal dialysis patients.

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.

Relationship between serum albumin and pulse wave velocity in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: 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 carotidfemoral 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 (beta = 0.615, P < 0.001), age (beta = 0.414, P < 0.01), albumin (beta = -0.315, P < 0.05) and total cholesterol (beta = 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.

Peripheral resistance modulates the response to volume overload in peritoneal dialysis patients.

BACKGROUND: Volume 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. METHODS: We 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). RESULTS: The 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. CONCLUSION: In 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.