低钙透析液对腹膜透析患者钙磷代谢的影响

目的横断面研究腹膜透析患者使用低钙透析液的安全性及其影响因素。方法选择西安交通大学医学院第一附属医院肾脏内科腹膜透析超过6个月的患者共39例，其中男24例，女15例，年龄56．49±19．31岁，其中使用常规（ca 1．75mmol／L）透析液8例，低钙（ca 1．25mmol／L）透析液31例，比较两组血清钙、磷、甲状旁腺激素、血压以及使用碳酸钙的情况。结果两组血钙无明显差异；常规透析液组血磷和钙磷乘积高于低钙组，两组iPTH无明显差异。低钙组服用碳酸钙剂量明显高于常规透析液组。低钙组服用碳酸钙与未服用碳酸钙血钙无明显差异，服用碳酸钙组血磷控制较为理想、钙磷乘积更接近正常，未服用碳酸钙组血PTH明显升高。结论腹膜透析患者使用低钙透析液有利于控制血磷和血压，有效预防钙磷乘积升高。提高对碳酸钙的依从性是预防使用低钙透析液后引起继发性甲状旁腺功能亢进的关键。     

枸橼酸碳酸氢盐透析液对血液透析患者高血压的影响

目的:比较枸橼酸碳酸氢盐透析液与普通碳酸氢盐透析液治疗维持性血液透析患者透析中血压的影响。方法:20例患者随机分为两组,各10例,分别使用枸橼酸碳酸氢盐透析液和普通碳酸氢盐透析液进行透析,第一组患者使用普通碳酸氢盐透析液治疗4周后切换为枸橼酸碳酸氢盐透析液治疗4周。第二组患者直接切换为枸橼酸碳酸氢盐透析液治疗4周后再次切换成普通碳酸氢盐透析液治疗4周。记录透析前后及透析过程中的实验室数据进行统计分析。结果:(1)使用枸橼酸碳酸氢盐透析液的患者透析过程中患者的平均收缩压明显低于普通碳酸氢盐透析液透析时(P0.01),平均动脉压(MAP)较普通碳酸氢盐透析液透析时降低(P0.05);枸橼酸碳酸氢盐透析液透析时患者透析中高血压的发生率为3.3%,明显低于使用普通碳酸氢盐透析液透析时(20%,P0.01)。(2)使用不同透析液透析时患者透析前血清总钙离子与离子钙水平无统计学差异,枸橼酸碳酸氢盐透析液透析时患者透析后血清总钙离子和离子钙水平明显著低于普通碳酸氢盐透析液透析时(P0.01)。普通碳酸氢盐透析液透析时患者透后血清总钙离子及离子钙水平较透前显著升高(P0.01),使用枸橼酸碳酸氢盐透析时患者仅出现透后血清离子钙水平下降(P0.01),而透析前、后血清总钙离子水平无明显改变。(3)不同透析液透析前、后BUN均无统计学差异。虽然枸橼酸碳酸氢盐透析液透析时患者尿素清除指数(Kt/V)要略高于普通碳酸氢盐透析液透析时,但两者之间无统计学差异。两组患者均未出现严重的低血压、低钙血症及抽搐等不良反应。结论:应用枸橼酸碳酸氢盐透析液治疗的患者透析中血压的控制明显优于普通碳酸氢盐透析液。其血压控制佳、高血压发生率低,无严重低血压、抽搐以及碱中毒等不良反应。透析后离子钙浓度减低,但并未发生明显低钙血症。证实了其在临床应用的有效性和安全性。     

High‐calcium dialysate: A factor associated with inflammation,malnutrition and mortality in non‐diabetic maintenance haemodialysis patients

Aim: Chronic inflammation, which is common in dialysis patients, often causes malnutrition and even protein‐energy wasting. However, the association of high‐calcium dialysate with malnutrition and/or inflammation in non‐diabetic maintenance haemodialysis patients remains unclear. This study investigated the possible adverse effects of high‐calcium dialysate and mortality in this population. Methods: A total of 717 non‐diabetic haemodialysis patients participated in this 2 year prospective study. The subjects were categorized into three subgroups based on whether dialysate calcium concentrations were high (3.5 mEq/L), standard (3.0 mEq/L) or low (2.5 mEq/L). Demographic, haematological, nutritional and inflammatory markers, biochemical and dialysis‐related data were obtained for cross‐sectional analysis. Causes of death and mortality rates were also analyzed for each subgroup. Results: Patients with high‐calcium dialysate (n = 82) had a higher incidence of malnutrition and inflammation (61.0% vs 44.1% and 43.9%, respectively) than those with standard‐ and low‐calcium dialysate (n = 528 and 107). Backward stepwise multiple regression analysis revealed that high‐calcium dialysate was negatively correlated with nutritional index, serum albumin levels, but positively associated with the inflammatory marker of serum ferritin levels. At the end of the 2 year follow up, 45 patients had died. Cox multivariate analysis demonstrated that high‐calcium dialysate was a significant associated factor (relative risk 2.765; 95% confidence interval 1.429–5.352) for 2 year all‐cause mortality in these patients. Conclusion: The analytical results indicate that high‐calcium dialysate is associated with malnutrition and inflammation as well as 2 year mortality in non‐diabetic maintenance haemodialysis patients and the findings suggest that this population, even those with optimal mineral balance, should avoid high‐calcium dialysate.     

Human peritoneal mesothelial cells isolated from spent dialysate fluid maintain contaminating macrophages via production of macrophage colony stimulating factor

BACKGROUND: Human peritoneal mesothelial cells (HPMC) are useful for the analysis of peritoneal reactions to various insults and to peritoneal dialysate. HPMC can be readily obtained from spent dialysis fluid, but leucocyte contamination is a major problem when using these cells for in vitro experiments. Therefore, we examined the persistence of leucocyte contamination in HPMC cultures obtained from spent dialysate. METHODS: Cells were obtained from spent patient dialysate bags by centrifugation and analysed for specific cell phenotypes by flow cytometry at the initial collection and during sequential passages in cell culture. Cell proliferation was assessed by either bromodeoxyuridine incorporation or a dehydrogenase assay. Cytokine secretion was analysed by enzyme-linked immunosorbent assay. RESULTS: Spent dialysate bags contained two major cell populations: CD45+ leucocytes and cytokeratin-8/18+ cells. Initially, most collected cells were CD45+, but their numbers decreased rapidly during the first week of culture. However, a persistent contamination of CD45+ leucocytes, approximately 20% of cells, was evident during the next three passages. This persistent CD45+ contamination was identified as CD68+ macrophages and contained bromodeoxyuridine + proliferating cells. These macrophages could be removed by fluorescence-activated cell sorting using anti-CD45 antibody, resulting in highly purified HPMC which expressed cytokeratin-8/18 and calretinin. Supernatant obtained from these purified HPMC contained macrophage colony stimulating factor and induced proliferation of bone marrow-derived macrophages. CONCLUSION: Spent dialysate contains macrophages which persist in culture and are associated with HPMC secretion of macrophage colony stimulating factor and macrophage proliferation. Therefore, contaminating macrophages should be specifically removed from HPMC preparations before performing in vitro studies.     

Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis

Background. In 2006, there were 16 796 toxic exposures attributedto valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT)reported to the US Toxic Exposure Surveillance System. Of these,30% (5046) were treated in a health care facility with 12 casesresulting in death. These drugs are highly protein bound andpoorly dialyzable; however, it has been suggested that albumin-supplementeddialysate may enhance dialytic clearance. We investigated whetherthe addition of albumin to dialysate affects dialytic clearanceof VPA, CBZ and PHT. Methods. VPA, CBZ and PHT were added to a bovine blood-basedin vitro continuous hemodialysis circuit, which included a polysulfoneor an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculatedfrom spent dialysate and pre-dialyzer plasma concentrations.VPA, CBZ and PHT clearances with control (albumin-free) dialysatewere compared to clearances achieved with 2.5% or 5% human albumin-containingdialysate. The influences of blood flow (180 and 270 mL/min)and dialysate flow (1, 2 and 4 L/h) on dialysis clearance werealso assessed. Results. The addition of 2.5% albumin to dialysate significantlyenhanced dialytic clearance of VPA and CBZ, but not PHT. Useof 5% albumin dialysate further increased VPA and CBZ clearance.Overall, drug clearance was related directly to dialysate flowbut independent of blood flow. Conclusion. Continuous hemodialysis with albumin-supplementeddialysate significantly enhanced VPA and CBZ, but not PHT, clearancecompared to control dialysate. Continuous hemodialysis withalbumin-supplemented dialysate may be a promising therapy toenhance dialytic clearance of selected highly protein-bounddrugs.     

低钙透析联合个体化碳酸钙及骨化三醇在维持性血液透析患者中的应用

目的探讨低钙透析液联合个体化碳酸钙及骨化三醇在维持性血液透析患者中的应用价值。方法选择进行血液透析治疗3个月以上的慢性肾功能衰竭患者50例,所有患者均选用Ca^2＋为1．25mmol／L的透析液进行透析;根据钙磷乘积水平将患者分为正常组和升高组,并根据全段甲状旁腺激素（iPTH）水平分为4组：A组（〈100pg／ml）、B组（100～300pg／ml）、C组（300～1000pg／ml）、D组（〉1000pg／ml）;根据钙磷乘积和iPTH分组予个体化碳酸钙及骨化三醇治疗;监测所有患者治疗前和治疗后第4、8、12、16、24周时的iPTH、血钙、血磷、钙磷乘积及碱性磷酸酶（ALP）水平。结果（1）治疗后第12、16、24周时的总体血钙水平均较治疗前明显增高（均P〈0．01）;治疗后第8、12、16、24周时的总体血磷、iPTH水平和钙磷乘积均较治疗前明显降低（均P〈0．01）;治疗前、后的总体ALP水平的差异均无统计学意义（均P〉0．05）。（2）A组与B组治疗前、后iPTH水平的差异均无统计学意义（均P〉0．05）,其余各组间iPTH水平的差异均有统计学意义（均P〈0.05或0.01）,A、B、C组与D组间ALP水平的差异均有统计学意义（均P〈0．01）;钙磷乘积正常组和升高组治疗前后血磷和钙磷乘积水平的差异均有统计学意义（均P〈0．01）。（3）随着治疗时间的延长,高钙血症的发生率有增加的趋势,但整体差异均无统计学意义（均P〉0．05）。结论低钙透析联合个体化碳酸钙及骨化三醇可有效降低维持性血液透析患者iPTH、血磷及钙磷乘积水平,但仅对于iPTH〉300Pg／ml及钙磷乘积升高者有效。     

维持性血液透析患者血清和透析液对脂肪细胞凋亡的影响

目的观察维持性血液透析（HD）患者血清及其与常规透析液（CD）或高纯透析液（HPD）联合干预对脂肪细胞凋亡的影响。方法采集20例HD患者（CD和HPD治疗各10例）血样并分离血清,ELISA法检测血清肿瘤坏死因子α（TNF-α）水平。分别以HD患者血清（HDPS组）、HD患者血清联合CD（HDPS＋CD组）和HD患者血清联合HPD（HDPS＋HPD组）对经体外诱导分化成熟的3T3-L1脂肪细胞进行干预,48 h后收集细胞。Hoechst 33258染色荧光显微镜观察细胞形态学改变;Annexin-V-FITC/PI双标记流式细胞术检测细胞凋亡。PCR检测CD和HPD中细菌DNA片段表达。结果 ELISA法检测结果显示,与HPD治疗HD患者比较,CD治疗HD患者血清TNF-α水平显著升高（P〈0.05）。在HDPS组和HDPS＋CD组,荧光显微镜观察可见呈典型凋亡形态学改变的细胞增多,两组细胞凋亡率均显著高于HDPS＋HPD组（P〈0.05）。PCR检测显示,CD和HPD中细菌DNA表达分别为902.79±60.57和454.87±32.22,两者差异有统计学意义（P〈0.05）。结论 HDPS可诱导3T3-L1脂肪细胞凋亡,可能与患者血清TNF-α水平升高有关。与HD患者血清联合CD干预比较,联合HPD干预诱导的脂肪细胞凋亡率较低且HPD中细菌DNA表达较少。     

Relationship between interdialytic weight gain and acid-base status in hemodialysis by bicarbonate

The aim of this study was to determine the relationship between interdialytic weight gain and acid-base balance pre- and posthemodialysis in uremic patients undergoing hemodialysis with a high bicarbonate dialysate (39 mmol/L). To this end we studied 8 stable uremic patients on regular hemodialysis thrice weekly who had stable hematocrit values for at least 3 months, similar clinical characteristics including dry weight but widely varying interdialytic weight gain. Arterial line blood samples were collected anaerobically in heparinized syringes pre- and posthemodialysis in 4 consecutive hemodialysis sessions for the determination of pH, Paco2, and HCO3. Prehemodialysis values (mean +/- SD) were pH = 7.34 +/- 0.03, Paco2 = 36.43 +/- 1.4, and Hco3 = 20.1 +/- 1.55. Posthemodialysis values were pH= 7.47 +/- 0.02, Paco2 = 38.72 +/- 2.0, and HCO3 = 27.73 +/- 1.72. In other words, patients were moderately acidemic prior to and moderately alkalemic after the hemodialysis session. Of note, a significant negative correlation was revealed between the interdialytic weight gain and the values of prehemodialysis blood pH (r = -0.721, p < 0.001) and HCO3 (r = -0.836, p < 0.001) and posthemodialysis pH (r = -0.533, p < 0.001), Paco2 (r = -0.623, p < 0.001) and HCO3 (r = -0.815, p < 0.001), suggesting an important role of the interdialytic weight gain on acid-base equilibrium of uremic patients undergoing hemodialysis. Thus, patients with high interdialytic weight gains may require higher bicarbonate concentrations to achieve normal acid-base status whereas patients with low interdialyic weight gains may require lower bicarbonate concentrations to prevent alkalemia at the end of dialysis.     

腹膜透析液添加尿激酶对尿毒症并发脑梗死患者保护作用及机制

目的探讨腹膜透析液添加尿激酶对尿毒症并发脑梗死患者血清超氧化物歧化酶（SOD）、丙二醛（MDA）及血浆内皮素（ET）、一氧化氮（NO）的影响。方法将60例尿毒症并发脑梗死患者随机分为腹膜透析液添加尿激酶治疗组（30例）和常规治疗组（30例）,同时选择同期年龄在40岁以上的正常人30例为健康对照组（无肝肾脑等疾病）,两治疗组基础干预相同,尿激酶治疗组在常规治疗基础上在腹膜透析液添加尿激酶,治疗8周后观察两组患者SOD、MDA、ET、NO及临床症状的变化。用比色法测定血清MDA和SOD水平,用放射免疫法测定血浆ET的变化,NO采用硝酸还原法测定。结果①治疗前与健康对照组比较,尿激酶治疗组和常规治疗组血清SOD活性降低（P〈0．05）,NO降低（P〈0．05）,MDA含量升高（P〈0．05）,血浆内ET水平升高（P〈0．01）。②治疗8周后,常规治疗组和尿激酶治疗组可降低血浆ET水平和升高NO;与常规治疗组比较,尿激酶治疗组在降低ET和升高NO方面疗效更为显著（P〈0．01）。③常规治疗组未见SOD、MDA的变化,尿激酶治疗组能够回升SOD活性,降低MDA含量,与健康对照组及常规治疗组有明显差别（P〈0．05,P〈0．05）。结论腹膜透析液添加尿激酶可降低氧化应激反应,降低血浆ET和升高NO水平,对尿毒症并发脑梗死患者有治疗作用。     

Calcium balance and serum ionized calcium fluctuations in on-line haemodiafiltration in relation to ultrafiltration rate and dialysate calcium concentration

The use of high ultrafiltration rates in haemodiafiltration(HDF) has been suggested for improving the clearance of smalland large molecules. This strategy has become economically applicablewith the development of safe techniques for on-line productionof sterile infusate from dialysate, which enables us to infuselarge substitution fluid volumes without further increasingthe cost of the sessions. The effect of increasing the ultrafiltrationrate in HDF on electrolyte balance has not yet been evaluated.The aim of this study was to evaluate the effects of variationsof the ultrafiltration rate on calcium kinetics in HDF usingthree different dialysate calcium concentrations. Since theincrease in ultrafiltration rate augments the convective calciumloss, variations of intrasession calcium balance could resultfrom modifications of the ultrafiltration rate. In the present study we found no significant variations in calciumbalance and serum ionized calcium (iCa) levels during on-lineHDF treatment when increasing the mean ultrafiltration ratefrom 60 to 100 ml/min in the presence of an adequate and correspondingincrease in the infusion rate (from 2.5 to 5 l/h). During thebalance studies, pretreatment serum iCa was on the average 1.32mmol/l and weight loss 3.2 kg. Mean calcium loss during treatmentwas 2.8 and 3.3 mmol at infusion rates of 2.5 and 5 l/h with1.63 mmol/l of calcium in both the dialysate and infusate; calciumloss rose to 5.9 and 11.2mmol at infusion rates of 2.5 l/h andto 5.7 and 14.2 mmol at infusion rates of 5 l/h when the dialysateand infusate calcium was reduced respectively to 1.5 and 1.25mmol/l. Serum iCa significantly increased at the end of thesession with the higher dialysate concentration, while it decreasedto 1.28 mmol/l and 1.20 mmol/l with the lower two concentrations.Linear regression ana lysis showed no variation in serum iCaduring treatment when the iCa concentration in the dialysatewas equal to pretreatment serum iCa. A neutral calcium balancewould be expected using 1.75 mmol/l of calcium in the dialysate. In conclusion, increasing the ultrafiltration rate from 60 to100 ml/min did not significantly affect calcium kinetics inon-line HDF. The main factors affecting calcium mass transferand serum iCa fluctuation during treatment were the dialysatecalcium concentration and the iCa gradient between dialysateand pretreatment serum levels.