Use of ultrapure dialysate in reduction of chronic inflammation during hemodialysis

Chronic inflammation contributes to the pathogenesis of several complications of hemodialysis therapy. It is thought that backfiltration of bacteria-derived contaminations during dialysis may induce a chronic inflammatory state. High-sensitivity C-reactive protein (hs-CRP) is one of the tools which can take a hold on such a chronic inflammatory condition. We examined the effect of ultrapure dialysate which contributes to chronic inflammation with hs-CRP and tried to reduce endotoxin (ET) levels at the end of the dialysate from 70 EU/l to <1.0 EU/l (ultrapure dialysate). Other dialysis conditions, except ET level, were fixed. We investigated the hs-CRP of 23 patients receiving regular dialysis before the use of ultrapure dialysate and 1 year after use of it prospectively. The data showed a significant decrease in the median value of the hs-CRP from 0.16 to 0.07 mg/dl (p < 0.05). The value of serum beta(2)-microglobulin decreased from 33.2 to 28.4 mg/dl (p < 0.01) and the hemoglobin level increased from 10.0 to 11.0 g/dl (p < 0.05). These results indicate that even a dialysate containing 70 EU/l of ET level may induce a chronic inflammatory state. hs-CRP is a very useful marker of chronic inflammation and the use of ultrapure dialysate is necessary to improve a chronic inflammatory state. The targeted ET level at the end of the dialysate should be set at < or = 1.0 EU/l.     

Review: Clinical usefulness of ultrapure dialysate--recent evidence and perspectives

It has generally been accepted that biological contamination of dialysate deteriorates the biocompatibility of dialysis therapy and accelerates dialysis-related complications such as dialysis-related amyloidosis (DRA) and malnutrition-inflammation-atherosclerosis (MIA) syndrome. During the past decade several studies have clarified that very slight amounts of contamination can lead to inflammatory response, and we could not confirm biological dialysate quality only by measuring endotoxin levels despite of measuring viable cell counts or biofilms. To achieve this, the European Renal Association/European Dialysis Transplantation Association and the American National Standardization Institute/Association for the Advancement of Medical Instrumentation published new standards for dialysate, in which very strict control levels were recommended with regard to viable bacterial cell counts. In 2004 JSDT raised the required standard of the levels of endotoxin, and began to develop a standard for bacterial cell counts. In Japan, many chronic kidney disease patients are treated with centralized dialysate supply systems which have weak spots in disinfecting the system. This causes some difficulties in making a standard for viable bacterial cell counts. In the present paper, we summarize evidences of clinical usefulness of ultrapure dialysate and perspectives of the standard for dialysate in Japan.     

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。     

Experimental models for the study of pulmonary fibrosis: current usefulness and future promise

Diffuse interstitial lung diseases form a group of respiratory diseases about which many questions remain to be answered. In recent years there have been major advances in the correct diagnostic classification of each disease, and therefore, the essential foundations have been laid for investigation of their pathophysiology. However, both the triggers and the precise mechanisms that lead to irreversible changes in the lung parenchyma remain to be identified. Idiopathic pulmonary fibrosis is the most common diffuse interstitial lung disease and has the worst prognosis. Current treatments are empirical and the response is random; furthermore, they do not improve survival. Consequently, most basic research has focused on the pathophysiology of the disease and on identifying an effective therapeutic approach. The aim of this review is to describe the experimental studies that have begun to open the way towards an understanding of the complex process of fibrosis.     

Clinical pictures of unknown origin in neurology: past, present and future usefulness of artificial intelligence

Although, in the course of the last 50 years, the achievements in the medical field have been astonishing, at the beginning of the third millennium a number of clinical pictures are still left without a precise nosographic origin. In the past, the delay in scientific communication was the main explanation presented for the lack of understanding of clinical pictures of unknown nosographic origin. The history of medicine provides excellent examples of this dispersion of human capital, even if the history of clinical neurology presents "exceptions" (the pictures that we now call de la Tourette's syndrome and Parkinson's disease) that indicate that major clinical syndromes could be clearly detected and relatively rapidly diffused even in the 19th century. Contrary to the past, the delay in scientific communication no longer seems an obstacle to the sharing of medical knowledge. Nevertheless, the problem of the in-depth comprehension of clinical pictures of unknown nosographic origin still remains dominant, mainly because of the limited spread of ample and flexible online accessible databases of unknown nosographic origin clinical syndromes. The need for interactive electronic archives and other artificial intelligence resources in order to promote progress in clinical knowledge is discussed in this paper.     

Endocrine-disrupting chemicals in CAPD dialysate and effluent

Environmental contamination by endocrine-disrupting chemicals (EDC) has been a major focus of recent research and policy discussions. EDC-suspected man-made chemicals used as raw materials or plasticizers have been shown to elute from plastic products. To examine whether the dialysate for continuous ambulatory peritoneal dialysis (CAPD) is contaminated with EDC, we determined bisphenol A (BPA), nonylphenol (NP), di-(2-ethylhexyl)phthalate (DEHP) and di-n-butyl phthalate (DBP) in the pre-used dialysate and in the peritoneal effluent from renal failure patients by gas chromatography/mass spectrometry. Concentrations of BPA, NP, DEHP and DBP were 0.02-0.23 ppb (microg/l), 0.09-0.22, 1.1-3.7, and <0.1-2.1 ppb, respectively, in the pre-used dialysate, and <0.01-0.07, <0.1-0.45, 0.35-1.23, and 0.42-1.76 ppb, respectively, in the effluent, from which the maximal daily contamination of BPA and NP by CAPD was estimated at the microgram level and that of phthalate esters at the 10-microg level. These concentrations are far less than the toxic dosage reported so far, so that CAPD is unlikely to contaminate patients seriously.     

透析液钙离子浓度的选择

钙磷代谢紊乱及骨病是慢性肾功能不全特别是透析病人的重要并发症之一。有证据表明，高磷血症、增高的钙磷乘积和甲状旁腺功能亢进可以导致血管钙化和发生心血管事件的危险性增加，与透析病人增加的患病率及死亡率相关。因此，维持合适的钙磷代谢平衡及甲状旁腺激素水平已成为人们关注的热点。     

Rapid count of microbial cells in dialysate

An apparatus for the non-culture method (NCM) of microbial cell count was formerly developed and named a bioplorer. The bioplorer NCM is based on the double staining of cells with 4', 6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI) and the automatic analysis of their fluorescent microscopic images. Viable cells can be stained with DAPI, while dead cells can be stained with DAPI and PI. In this study, the bioplorer NCM has been applied to the dialysate. The viable and dead cells in dialysate could be counted within 20 min. The detection limit expressed by log(10)[cells/100 mL] was 2.0. When cell-spiked dialysate samples containing prescribed number of Bacillus subtilis cells were assayed, the numbers of cells determined by the bioplorer NCM (N(VIA)(NCM)) and a conventional culture method (CM) on R2A medium (N(VIA)(R2A-CM)) were similar in the range of 2.6-4.6 within the 95% confidence interval (NCM-CM equivalent range). When test solutions sampled from a practical facility in a hospital were assayed, N(VIA)(NCM) was greater than, but comparable to, N(VIA)(R2A-CM). The endotoxin (ET) in the test samples were assayed as well using a test kit for limulus amoebocyte lysate assay. The results of microbial cells and ET concentration indicated that the dialysate supplying line was clean and well maintained. The bioplorer NCM can determine if the microbial contamination of dialysate supplying facilities is greater than 2.6 (398 cells/100 mL).     

Comparison of usefulness of echocardiographic Doppler variables to left ventricular end-diastolic pressure in predicting future heart failure events

We sought to determine whether the echocardiographic Doppler parameters of left ventricular diastolic dysfunction predict future heart failure (HF) events and, if so, which parameters best predict HF. We also examined whether the predictive ability of echocardiographic Doppler parameters was related to their prediction of left ventricular end-diastolic pressure (LVEDP). We studied patients who underwent cardiac catheterization and echocardiography performed within a 30-day period. The end point was HF, defined as new-onset or recurrent HF diagnosed by a physician and requiring the initiation or modification of treatment of HF. We identified 289 patients (mean age 63.5 +/- 12.6 years) with a mean follow-up of 10.9 +/- 10.2 months. A total of 24 HF events occurred. LVEDP was a significant predictor of HF univariately and independently in multiple regression models after adjustment for ejection fraction. In Cox models adjusted for age, gender, LVEDP, and ejection fraction, only the left atrial volume index and early mitral inflow to early diastolic tissue velocity (E/e') ratio remained predictive of HF. A multiple regression model, including all echocardiographic variables, showed a persistent, although attenuated, relation of early to late mitral inflow velocity (E/A) ratio and E/e' with LVEDP (p = 0.06 and p = 0.002, respectively). The addition of E/e' or the left atrial volume indexed to body surface area, but not E/A, to the clinical history and left ventricular ejection fraction provided incremental prognostic information. A LVEDP of > or =20 mm Hg, E/e' ratio of > or =15, and left atrial volume index of > or =23 ml/m(2) identified those with a higher risk of HF. In conclusion, invasively determined LVEDP is an independent predictor of future HF events. E/e' and the left atrial volume indexed to body surface area are the best independent predictors of future HF and provide prognostic information incremental to the clinical history and left ventricular ejection fraction.     

超纯透析对维持性血液透析患者氧化应激和血清C-反应蛋白水平的影响

目的 探讨超纯透析对维持性血液透析患者氧化应激及炎症状态的影响.方法 对26例符合条件的透析患者采用重复测量自身对照的方法,测定普通透析、超纯透析6个月及超纯透析12个月时的透前血中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白蛋白(ALB)、C-反应蛋白的水平.结果 超纯透析12月时MPO、MDA较普通透析时下降(P均＜0.05),ALB上升(P＜0.05),C-反应蛋白降低(P＜0.05).超纯透析6个月、12个月MPO、MDA较普通透析逐渐下降(P均＜0.05);超纯透析6个月、12个月ALB较普通透析时逐渐上升(P＜0.05).结论 超纯透析可以明显改善血液透析患者的全身状况,其机制之一可能是通过降低透析液内的内毒素来改善透析患者体内的氧化应激水平、炎症状态来实现的.     

A comparison of stool fluid and stool dialysate obtained in vivo

Stool fluid has been obtained for analysis by homogenization and high speed centrifugation of fresh stool.This fluid, from two healthy individuals with soft stools has been compared with stool dialysate obtained in vivo by retrieval of swallowed dialysis bags from their stools. Stool fluid was more acid, with a higher osmolality, an increased concentration of organic anions, sugar and ammonia, and a lower bicarbonate concentration than dialysate in vivo. It is suggested that in the individuals studied, dialysate in vivo may not be in equilibrium with the stool fluid surrounding it, and may not represent a true dialysate of faecal water.     

Phosphate enrichment of dialysate for use in standard and extended haemodialysis

Background/Aims: Intensive haemodialysis (HD) sometimes causes hypophosphataemia, but phosphate-containing dialysate is not readily available. We examined the effectiveness of extemporaneously producing a phosphate-rich dialysate for use in HD. Methods: Incremental volumes of Fleet? were added to acid concentrate and predicted to deliver dialysate phosphate concentrations of 0.19-1.1 mmol/l, following mixture with ultrapure water and base concentrate by the HD machine. Results: The achieved concentrations were close to predicted values (p = 0.77) and remained stable throughout an 8-hour 'treatment' time (p = 0.99). The dialysate phosphate concentration had a linear relationship with the Fleet? volume added, defined by the regression equation y = 172.79 x - 1.47 (R(2) = 0.99, r = 0.99, p = 0.003). The dialysate pH, calcium, magnesium and bicarbonate concentrations did not change over the study period (p = 0.28-0.99). Microscopic analysis under polarised light showed no evidence of crystal formation. Conclusion: The study validates a simple, reliable and cost-effective protocol for phosphate supplementation in conventional and extended HD.     

Microbiologic purity of dialysate: rationale and technical aspects

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.