Search

Background: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload., Methods: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging., Results: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake., Conclusions: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status., Clinical Trial Registry Name and Registration Number: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998., (Copyright © 2020 by the American Society of Nephrology.)

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, -14.9 ± 6.3%/h vs -9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, -11.8 ± 3.4%/h vs -5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

Hypercalcemia and hyperparathyroidism in patients receiving maintenance hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal concentration remains controversial. Here, we conducted a systematic review and a meta-analysis of seven randomized controlled trials examining a total of 622 patients to investigate the optimal concentration for MHD for 6 months or longer. The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52 mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38), respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three studies showed that a low concentration was preferred for lowering arterial calcifications or atherosclerosis in different arteries, but one study showed that coronary arterial calcifications increased with a low concentration. Two studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed that a dialysate with a low Ca concentration lowered the serum Ca levels in patients receiving long-term MHD, but further studies are needed to determine the optimal Ca concentration in terms of CVD and MBD.

Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

Fresenius Medical Care's NaturaLyte dialysate has been associated with increased risk of sudden cardiac death by causing metabolic alkalosis from its acetate content based on retrospective data using pre-dialysis bicarbonate levels only. The study objective was to measure inter/intra-dialytic changes in serum bicarbonate and degree of alkalosis conferred by varying concentrations of NaturaLyte bicarbonate dialysate. Thirty-nine hemodialysis patients were divided into four groups based on prescribed bicarbonate dialysate concentrations; Group 1 (N = 9): 30-32 mEq/L, Group 2 (N = 5): 33-34 mEq/L, Group 3 (N = 10): 35-36 mEq/L, Group 4 (N = 15): 37-40 mEq/L. Serial (pre-dialysis, immediate post-dialysis, 2 h post-dialysis, and 68 h post-dialysis) bicarbonate levels were measured. Mean pre-dialysis serum bicarbonate levels (representing 44 h post-dialysis levels) in all four groups were not statistically different. Pre-dialysis and 68 h post-dialysis bicarbonate levels in each group were also not significantly different. However, immediate post-dialysis and 2 h post-dialysis bicarbonate levels were significantly increased in all four groups proportional to dialysate dose. There was statistically significant inter-group bicarbonate level difference (P < 0.05) except between the first and second (P = 0.43) and second and third (P = 0.07) groups in the immediate post-dialysis period. Similar results were obtained for the 2 h post-dialysis period. High bicarbonate dialysate causes large and rapid fluctuations in serum bicarbonate levels during the intra/inter-dialytic period, which returns to baseline within 44 to 68 h after dialysis. This refutes the necessity to correct pre-dialysis acidosis with high bicarbonate dialysate since rapid equilibration is likely to occur and unnecessarily exposes patients to large shifts in their acid base balance., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Dialysate composition is a critical aspect of the hemodialysis prescription. Despite this, trial data are almost entirely lacking to help guide the optimal dialysate composition. Often, the concentrations of key components are chosen intuitively, and dialysate composition may be determined by default based on dialysate manufacturer specifications or hemodialysis facility practices. In this review, we examine the current epidemiological evidence guiding selection of dialysate bicarbonate, calcium, magnesium, and potassium, and identify unresolved issues for which pragmatic clinical trials are needed., (© 2017 Wiley Periodicals, Inc.)

In advanced renal disease, the kidney is unable to maintain phosphate balance due to decreased urinary excretion as well as the imbalance of the bone metabolic axis. It is well established that hyperphosphatemia is associated with increased cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, there are no randomized controlled trials that demonstrate a clear benefit on hard outcomes in lowering serum phosphate levels to recommended targets in the CKD or dialysis population. In addition, while calcium-based phosphate binders have traditionally been the standard of care in the treatment of hyperphosphatemia, data regarding the increased risk of vascular mineralization continues to emerge. Clinicians continue to search for new phosphate-lowering therapies as well as investigate novel nutritional perspectives. The Kidney Disease: Improving Global Outcomes is currently revising the guidelines on phosphate goals in CKD. This review will outline the history of phosphate targets and phosphate binders, and explore innovative phosphate-lowering therapies. Based on current data, clinicians moving forward should continue to treat end-stage renal disease patients with hyperphosphatemia based on individual risk factors for vascular mineralization., (© 2017 Wiley Periodicals, Inc.)

Small solute clearance achieved during a single hemodialysis session has been traditionally evaluated by urea clearance, normalized for total body water (Kt/Vurea) for more than 30 years. By consensus, the target sessional KtVurea for thrice weekly treatments has been increased from 0.9 to 1.2 over the years. Although this is supported by observational studies, there is a fundamental lack of prospective studies to support this threshold target. In clinical practice achieving sessional Kt/Vurea targets are most closely followed in the US. Yet there appears to be a paradox in that by following Kt/Vurea targets in the US hemodialysis patient survival is better for men and the obese, the opposite of what is seen in the general population. Delivery of a lower dose of hemodialysis to women and smaller men can be explained by underestimation of total body water. The advent of bioimpedance techniques which can measure both body water and body composition will potentially allow a rescaling and re-evaluation of the importance of small solute clearances (Kt/Vurea) in the hemodialysis patient population., (© 2017 Wiley Periodicals, Inc.)

Oligo-anuric individuals receiving hemodialysis (HD) are dependent on the dialysis machine to regulate sodium and water balance. Interest in adjusting the dialysate sodium concentration to promote tolerance of the HD procedure dates back to the early years of dialysis therapy. Evolution of dialysis equipment technologies and clinical characteristics of the dialysis population have prompted clinicians to increase the dialysate sodium concentration over time. Higher dialysate sodium concentrations generally promote hemodynamic stabilization and reduce intradialytic symptoms but often do so at the expense of stimulating thirst and promoting volume expansion. The opposite may be true for lower dialysate sodium concentrations. Observational data suggest that the association between dialysate sodium and outcomes may differ by serum sodium levels, supporting the trend toward individualization of the dialysate sodium prescription. However, lack of randomized controlled clinical trial data, along with operational safety concerns related to individualized dialysate sodium prescriptions, have prevented expert consensus regarding the optimal approach to the dialysate sodium prescription., (© 2017 Wiley Periodicals, Inc.)

Background: Regional citrate anticoagulation (RCA) during hemodialysis interferes with calcium homeostasis. Optimal ionized calcium (iCa) target range during RCA and consequent calcium balance are unknown., Methods: In a randomized controlled trial (ACTRN12613001029785) 30 chronic hemodialysis patients were assigned to normal (1.1-1.2 mmol/) or low (0.95-1.05 mmol/l) iCa target range during a single hemodialysis with RCA. The primary outcome was calcium mass balance during the procedure, using a partial spent dialysate collection method; magnesium mass balance was also measured. Intact parathormone (iPTH), total calcium (tCa) and magnesium were measured before and after procedures., Results: Mean iCa during procedures was significantly different in the two groups (1.12±0.06 in normal and 1.06±0.07 mmol/l in low iCa group, p <0.001), resulting in different tCa (2.18±0.22 vs. 1.95±0.17, p = 0.003) after the procedure. Mean delivered calcium during the procedure was 58.3±4.8 mmol in the normal and 51.5±8.2 mmol in the low iCa group (p = 0.010), which resulted in a significantly higher mean positive calcium mass balance of 14.6±8.3 mmol (584±333 mg) per procedure in normal as compared to 7.2±8.5 mmol (290±341 mg) in low iCa group (p = 0.024). Linear mixed effects model showed a significant interaction effect of time and iCa target range group on iPTH, i.e. a significant increase in iPTH in the low as compared to normal iCa target group (p = 0.008). Magnesium mass balance was mildly negative and comparable in both groups., Conclusions: Low iCa target range resulted in a significantly less positive calcium mass balance, but in a significant increase in iPTH. To achieve a more neutral calcium balance, we recommend allowing a mild hypocalcemia during hemodialysis with RCA, especially when it is used for prolonged periods., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of the current prospective study was to evaluate the effects of low sodium dialysate on oxidative stress parameters, blood pressure (BP) and endothelial dysfunction in maintenance hemodialysis (HD) patients., Methods: After baseline measurements were taken, the dialysate sodium concentration was reduced from 140 to 137 mEq/L. Oxidative stress parameters and flow-mediated dilatation (FMD %) were measured before and after 6 months of HD with low sodium dialysate. Interdialytic weight gain (IDWG) and pre- and post-dialysis BP were monitored during the study., Results: A total of 52 patients were enrolled and 41 patients completed the study. There was a significant reduction in systolic blood pressure at the end of the study [130.00 (90.00-190.00) vs. 120.00 (90.00-150.00), p < 0.001]. Similarly, there were significant improvements in IDWG [2670.00 (1670.00-4300.00) vs. 1986.00 (1099.00-3998.00), p < 0.001] and FMD % [7.26 (4.55-8.56) vs. 9.56 (6.55-12.05), p < 0.001]. Serum MDA levels (p < 0.001) were significantly decreased; serum SOD (p < 0.001) and GPx (p < 0.001) activities were significantly increased after low sodium HD compared to standard sodium HD., Conclusion: Our data seem to suggest a potential role of 137 mEq/L sodium dialysate for improving hemodynamic status, endothelial function and reducing oxidative stress than 140 mEq/L sodium dialysate in maintenance HD patients.

Background: Peritoneal dialysis (PD) is used as an alternative to hemodialysis in end-stage renal disease (ESRD). Icodextrin has been used as a hyperosmotic agent in PD. The aim of the study was to assess two different point-of-care testing (POCT) glucose strips, affected and not affected by icodextrin, with serum glucose concentrations of the patients using and not using icodextrin., Methods: Fifty-two chronic ambulatory peritoneal dialysis (CAPD) patients using icodextrin (Extraneal®) and 20 CAPD patients using another hyperosmotic fluid (Dianeal®) were included in the study. Duplicate capillary and serum glucose concentrations were measured with two different POCT glucose strips and central laboratory hexokinase method. Assay principles of glucose strips were based on glucose dehydrogenase-pyrroloquinoline quinone (GDH-PQQ) and a mutant variant of GDH (Mut Q-GDH). The results of both strips were compared with those of hexokinase method., Results: Regression equations between POCT and hexokinase methods in icodextrin group were y = 2.55x + 1.12 mmol/l and y = 1.057x + 0.16 mmol/l for the GDH-PQQ and Mut Q-GDH methods, respectively. The mean difference between the results of hexokinase and those of GDH-PQQ and Mut Q-GDH in icodextrin group was 3.41 ± 1.56 and 0.72 ± 0.64 mmol/l, respectively. However, the mean differences were found much lower in the control group; 0.64 mmol/l for GDH-PQQ and 0.52 mmol/l for Mut Q-GDH., Conclusion: Compared to GDH-PQQ, glucose strips of Mut Q-GDH correlated better with hexokinase method in PD patients using icodextrin., (© 2015 Wiley Periodicals, Inc.)

Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa., (© 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Aims: To evaluate the capability of an electrolytes-enriched solution to prevent metabolic disorders during continuous veno-venous hemodiafiltration (CVVHDF)., Methods: Serum biochemistry and clinical tolerance were compared during CVVHDF treatments with an electrolyte-enriched (Phoxilium) or standard solutions in 10 acute renal failure patients., Results: As compared to standard fluids, serum potassium and phosphate levels were maintained in the normal range with Phoxilium without any supplementation but total serum calcium levels were significantly lower. Bicarbonatemia was slightly higher (24-26 vs. 21.5-24.5 mmol/l, p < 0.05) with conventional solutions and was associated with a significant increased level of pH (>7.44). Despite the absence of glucose in the Phoxilium solution, blood glucose levels and glucose supplementation were similar between treatments. Clinical tolerance and efficiency of CVVHDF sessions were comparable., Conclusion: Phoxilium effectively prevented hypophosphatemia and hypokalemia during CVVHDF. It was, however, associated with a slight metabolic acidosis and hypocalcemia compared with conventional solutions., (© 2016 S. Karger AG, Basel.)

Background: Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections predict mortality in HD patients, and HD acutely improves the central pressure waveform. Potassium (K) plays a crucial role in cardiac electrophysiology, and patients with end-stage kidney disease depend on HD for neutral K balance. We aimed to study the impact of dialysate K concentrations on central arterial pressure waveform., Methods: Thirty-three chronic HD patients were studied before and after a HD session, and the prescribed dialysate K concentration was recorded. In a subset of 23 patients without arrhythmias, pulse wave analysis was performed on radial arteries. Nine patients had dialysate K set to 1 mmol/L (group 1), and 14 patients had K set to 2 or 3 mmol/L (group 2). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness., Results: HD reduced the AIx in group 1 only (p = 0.0005). Likewise, central systolic pressure was reduced in group 1 only (p = 0.006). The relative reduction of AIx post-HD was significantly higher in group 1 compared with group 2 (p < 0.0001). The association between low dialysate K and AIx reduction remained statistically significant after adjustment for variables including the change in central and peripheral systolic pressure and mean arterial pressure., Conclusion: Low dialysate K is strongly and independently associated with the acute improvement of AIx.

Introduction: The correction of metabolic acidosis caused by renal failure is achieved by adding bicarbonate during dialysis. In order to avoid the precipitation of calcium carbonate and magnesium carbonate that takes place in the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid, usually acetate, which is not free of side effects. Thus, citrate appears as an advantageous alternative to acetate, despite the fact that its acute effects are not accurately known., Objective: To assess the acute effect of a dialysis fluid containing citrate instead of acetate on acid-base balance and calcium-phosphorus metabolism parameters., Material and Methods: A prospective crossover study was conducted with twenty-four patients (15 male subjects and 9 female subjects). All patients underwent dialysis with AK-200-Ultra-S monitor with SoftPac® dialysis fluid, made with 3 mmol/L of acetate and SelectBag Citrate®, with 1 mmol/L of citrate and free of acetate. The following were measured before and after dialysis: venous blood gas monitoring, calcium (Ca), ionic calcium (Cai), phosphorus (P) and parathyroid hormone (PTH)., Results: Differences (p<0.05) were found when using the citrate bath (C) compared to acetate (A) in the postdialysis values of: pH, C: 7.43 (0.04) vs. A: 7.47 (0.05); bicarbonate, C: 24.7 (2.7) vs. A: 27.3 (2.1) mmol/L; base excess (BEecf), C: 0.4 (3.1) vs. A: 3.7 (2.4) mmol/L; corrected calcium (Cac), C: 9.8 (0.8) vs. A: 10.1 (0.7) mg/dL; and Cai, C: 1.16 (0.05) vs. A: 1.27 (0.06) mmol/L. No differences were found in either of the parameters measured before dialysis., Conclusion: Dialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease., (Copyright © 2015. Published by Elsevier España, S.L.U.)

Background: Diabetes-related foot problems are bound to increase. However, medical therapies for wound care are limited; therefore, the need for development of new treatment modalities to improve wound healing in diabetic patients is essential and constitutes an emerging field of investigation., Methods: Animals were randomly divided into 8 groups (I-VIII) (32 rats/group), all were streptozotocin (STZ)-induced diabetics except groups III and VIII were non-diabetic controls. The study comprised two experiments; the first included 3 groups. Group I injected with mononuclear cells (MNCs) derived from human umbilical cord blood (HUCB), group II a diabetic control group (PBS i.v). The second experiment included 5 groups, groups IV, V, and VI received topical HUCB-haemodialysate (HD), calves' blood HD, and solcoseryl, respectively. Group VII was the diabetic control group (topical saline). Standard circular wounds were created on the back of rats. A sample of each type of HD was analyzed using the high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) system. Wound area measurement and photography were carried out every 4 days. Plasma glucose, catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and platelets count were assessed. Wound samples were excised for hydroxyproline (HP) and histopathological study., Results: Treatment with HUCB MNCs or HUCB-HD resulted in wound contraction, increased CAT, NO, platelets count, body weights, and HP content, and decreased MDA and glucose., Conclusion: Systemic administration of HUCB MNCs and topical application of the newly prepared HUCB-HD or calves' blood HD significantly accelerated the rate of diabetic wound healing and would open the possibility of their future use in regenerative medicine.

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)

The effect of sterilization was quantitatively evaluated for modern super high-flux dialyzers in terms of solute transport performances for autoclave sterilization (AC), gamma ray sterilization (G-ray), combination of these two and no sterilization (NS) as reference. A commercial polysulfone dialyzer (Kawasumi Laboratory Co., Tokyo, Japan) was chosen for investigation with six different sterilization processes, i.e., sterilization with AC one time and two times, that with G-ray using either no additives or an additive, that with AC one time followed by G-ray using no additive and that with NS. In vitro dialysis and ultrafiltration experiments were performed with aqueous test solution as pseudo blood, varying Q(B) , Q(D) , and Q(F) . Creatinine (MW113), vitamin B(12) (MW1355), and α-chymotrypsin (MW25000) were chosen as test solutes for dialysis experiments. Clearances (C(L) ) calculated from dialysis experiments and the sieving coefficient for albumin (MW66000) from ultrafiltration experiments were compared among six models. A dialyzer with NS showed much lower clearances for all three solutes than those with sterile. Therefore, the sterilization increases the solute transfer performances. Although no significant changes in clearances for creatinine and vitamin B(12) were found among five sterile models, much higher clearances for α-chymotrypsin were found in AC sterile models. Then, the effect of sterilization may become greater with the increase of molecular weight of solutes. According to the results of the sieving coefficient for albumin, AC may have enlarged the pore size of the membrane that could increase clearances for large solutes without changing those for relatively small solutes. The sterilization increases the solute clearance even in so-called super high-flux dialyzers and the effect of sterilization may be greater in larger solutes., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)

Background: Biocompatible peritoneal dialysis fluids (PDF) are buffered with lactate and/or bicarbonate. We hypothesized that the reduced toxicity of the biocompatible solutions might unmask specific effects of the buffer type on mesothelial cell functions., Methods: Human peritoneal mesothelial cells (HPMC) were incubated with bicarbonate (B-)PDF or lactate-buffered (L-)PDF followed by messenger RNA (mRNA) and protein analysis. Gene silencing was achieved using small interfering RNA (siRNA), functional studies using Transwell culture systems, and monolayer wound-healing assays., Results: Incubation with B-PDF increased HPMC migration in the Transwell and monolayer wound-healing assay to 245 ± 99 and 137 ± 11% compared with L-PDF. Gene silencing showed this effect to be entirely dependent on the expression of aquaporin-1 (AQP-1) and independent of AQP-3. Exposure of HPMC to B-PDF increased AQP-1 mRNA and protein abundance to 209  ± 80 and 197  ±  60% of medium control; the effect was pH dependent. L-PDF reduced AQP-1 mRNA. Addition of bicarbonate to L-PDF increased AQP-1 abundance by threefold; mRNA half-life remained unchanged. Immunocytochemistry confirmed opposite changes of AQP-1 cell-membrane abundance with B-PDF and L-PDF., Conclusions: Peritoneal mesothelial AQP-1 abundance and migration capacity is regulated by pH and buffer agents used in PD solutions. In vivo studies are required to delineate the impact with respect to long-term peritoneal membrane integrity and function.

20-70% of peritoneal dialysis patients have some signs of malnutrition. Anorexia, protein and amino acid losses in dialysate, advanced age of elderly patients, inflammation and cardiac failure are among the main causes. Modern dialysis solutions aim to reduce these causes, but none of them is without side effects: glucose is relatively safe and brings additional energy but induces anorexia and lipid abnormalities, amino acids compensate dialysate losses but may increase uremia and acidosis, icodextrin helps control hyperhydration and chronic heart failure and minimizes glucose side effects, but may sometimes cause inflammation, and poly chamber bags allow the replacement of lactate by bicarbonate and are more biocompatible, decrease GDP, induce less inflammation and have a better effect on nutritional status. However, it appears that the management of nutrition with the different solutions available nowadays necessitates various combinations of solutions adapted to different patient profiles and there is not actually a single universal solution to minimize malnutrition in peritoneal dialysis patients., (Copyright © 2012 S. Karger AG, Basel.)

Proper volume management continues to be a major challenge in patients requiring renal replacement therapy. In patients performing peritoneal dialysis the introduction of icodextrin represented a major advance in this effort. Recent studies have demonstrated a potential role for the use of novel dialysis strategies employing icodextrin to further enhance ultrafiltration and to improve cardiac indices in patients with ultrafiltration failure. These alternative strategies include the use of icodextrin in non-traditional patient populations (low transporters), the simultaneous use of glucose-based and icodextrin solutions in combination, and the use of icodextrin twice daily rather than for just a single dwell. This paper will briefly review the current status of these alternative dialysis strategies with icodextrin. In addition, the potential role for icodextrin to decrease postoperative adhesions will be discussed as well., (Copyright © 2012 S. Karger AG, Basel.)

Peritoneal dialysis (PD) is the treatment modality of choice in pediatric CKD5D patients awaiting renal transplantation. Facing many decades of renal replacement therapy long term preservation of peritoneal membrane function is of particular importance in this patient group. Whereas conventional PD fluids induce severe morphological and functional alterations of the peritoneal membrane within a few years, reduction of glucose degradation product content by multichamber systems, replacement of glucose by icodextrin and amino acids, and of lactate by bicarbonate at a neutral to physiological pH are expected to preserve peritoneal membrane integrity. Based on numerous in vitro, experimental and clinical studies, the European Pediatric Dialysis Working Group recommended the use of low glucose degradation product solutions whenever possible. Icodextrin is considered a useful option, in particular in children with sodium and water overload, even though infants may absorb higher amounts of icodextrin and achieve less ultrafiltration. The concept of amino acid-based PD fluids is intriguing, but pediatric benefits are insufficiently described and cannot replace tube feeding in malnourished children. Bicarbonate-based PD fluids better control metabolic acidosis and have been recommended in children with acute kidney injury and impaired lactate metabolism. This review discusses the scientific evidence and potential advantages of PD solutions with an improved biocompatibility profile, with a particular focus on pediatric studies., (Copyright © 2012 S. Karger AG, Basel.)

For many years, lactate has been used successfully as a buffer in peritoneal dialysis solutions although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution have been evaluated for about 15 years. RCT studies demonstrated a benefit for acid base improvement, while observational reports showed other clinical effects such as a preservation of residual renal function, less inflammatory effect and peritonitis prevention. In addition, there is a consensus that local biocompatibility is improved. Therefore, as bicarbonate is the physiological buffer of the body, it should become the solution of choice in PD patients., (Copyright © 2012 S. Karger AG, Basel.)

Background: The systemic effects of absorbed glucose degradation products (GDPs) contained within the conventional peritoneal dialysis solutions (cPDS) are largely unknown, while they appear to affect also cardiovascular function. The aim of the present study was to evaluate if the new bicarbonate-based less bioincompatible new peritoneal dialysis solutions ameliorate cardiac structural and functional status as well as the peritoneal net ultrafiltration (UF) and residual renal function. Patients and methods. This is a single centre, prospective cohort study of 12 stable continues ambulatory peritoneal dialysis patients (four women, eight men) mean aged 71.3 ± of 6.01 years and mean peritoneal dialysis (PD) duration 31.9 ± 21.33 months, treated with the usual cPDS (Medital Bieffe®, with increased GDPs, low pH and lactate as a buffer system). The patients changed for a 6-month period to the newer biocompatible PD solutions (BicaVera, Fresenius® low GDPs, normal pH, bicarbonate as a buffer) and at the end of this time, they returned to their previous schema of conventional solutions, for another 6 months. During the study period, the left ventricle ejection fraction (EF), left ventricle end systolic and diastolic diameter (LVESD, LVEDD), left ventricle mass index (LVMI), glyoxal serum and peritoneal concentrations, net UF and 24 h urine volume were repeatedly estimated: at the beginning of the study (T0), after 6 months with the biocompatible solutions (T6) and at the end of study (T12), after the 6-month period using again the cPDS. The UF volume and glyoxal concentrations were estimated at end of a 4 h dwell of an exchange with a PD solution of 2.27 % glucose., Results: There was a statistically significant difference between the mean levels of EF, LVESD, LVEDD, LVMI, UF and glyoxal serum and peritoneal concentrations at the beginning (T0) and in the middle of the study (T6) (for serum glyoxal P = 0.005, for peritoneal glyoxal P = 0.0004, for EF P = 0.0004, for LVESD P = 0.023, for LVEDD P = 0.002, for LVMI P = 0.0005 and for UF P = 0.005) as well as between the mean values in the middle (T6) and at the end of the evaluation period (T12) (for serum glyoxal P = 0.043, for peritoneal glyoxal P = 0.006, for EF P = 0.00009, for LVESD P = 0.012, for LVEDD P = 0.00014, for LVMI P = 0.00013 and for UF P = 0.048). On the other hand, no statistically significant difference was revealed between the T0 and T12 mean values of glyoxal (serum and peritoneal), EF, LVESD, LVEDD, LVMI and UF. During the study period, there was no statistically significant difference in daily urine volume and glomerular filtration rate., Conclusions: The use of bicarbonate-based PDS induced a statistically significant improvement of left ventricle structure (LVESD, LVEDD and LVMI) and functional (EF) indicators. These beneficial effects on left ventricle in combination with the improvement of net UF may designate a protective role of the newer bicarbonate peritoneal solutions on cardiovascular function morbidity and mortality risk of PD patients.

The recently described therapeutic benefits of the hemodialysate actovegin on neuropathic symptoms in diabetic patients with symptomatic polyneuropathy suggest a neuroprotective activity of the drug. To elucidate the possible cellular mechanism of the pharmacological effects of actovegin, we investigated its effects on cultured primary rat neurons in vitro. Primary neurons were cultured for up to 10 days in the presence of increasing doses of actovegin (0.3-1,000 mg/l). Total cell number, dendrite length and the number of excitatory synapses, i.e., the amount of the synaptic V-Glut1 protein, were measured by immunocytochemistry followed by fluorescence microscopy. The apoptotic level in neurons after induction of apoptosis by amyloid peptide Aβ(25-35) was assessed by the level of activated caspase-3. In addition, the capability of the neurons to diminish oxidative stress was assessed by measuring the cellular level of reactive oxygen species ROS in the presence of actovegin. Actovegin treatment yielded an increased maintenance of neuronal cells and total number of synapses and could lower the level of activated caspase-3 in a dose-dependent manner. Dendrite lengths were not significantly affected. In addition, actovegin reduced the cellular level of ROS in cultured neurons. The cellular effects observed suggest neuroprotective and anti-oxidative effects of the drug Actovegin(®), which could at least partially explain its therapeutic benefits.

Background: A rapid decrease of serum potassium concentrations during haemodialysis produces a significant increase in blood pressure parameters at the end of the session, even if effects on intra-dialysis pressure are not seen. Paradoxically, in animal models potassium is a vasodilator and decreases myocardial contractility. The purpose of this trial is to study the precise haemodynamic consequences induced by acute changes in potassium concentration during haemodialysis., Methods: In 24 patients, 288 dialysis sessions, using a randomised single blind crossover design, we compared six dialysate sequences with different potassium profiles. The dialysis sessions were divided into 3 tertiles, casually modulating potassium concentration in the dialysate between the value normally used K and the two cut-off points K+1 and K-1 mmol/l. Haemodynamics were evaluated in a non-invasive manner using a finger beat-to-beat monitor., Results: Comparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p < 0.05, < 0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p < 0.01, < 0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm-5, p < 0.05, < 0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p < 0.01 for comparison K-1 vs. K and K-1 vs. K+1)., Conclusions: A rapid decrease in the concentration of serum potassium during the initial stage of the dialysis-obtained by reducing the concentration of potassium in the dialysate-translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate., Trial Registration Number: NCT01224314.

Background: In Thailand, dialysate endotoxin contamination levels vary from less than 0.001 to 2.0 EU/ml. This difference has prompted an investigation on the production of proinflammatory cytokines and counter-inflammatory mediators of peripheral blood mononuclear cells (PBMCs) after high-flux dialysis., Methods: Patients from four hemodialysis (HD) centers who met the inclusion/exclusion criteria were enrolled into the study. PBMCs were isolated by Ficoll density gradient centrifugation and cultured. Supernatants were tested for interleukin 6 (IL-6), IL-1β and IL-1 receptor antagonist (IL-1Ra) concentration by ELISA., Results: HD centers 1, 2, 3 and 4 had mean dialysate endotoxin contamination levels of 0.001, 0.026, 0.558 and 1.960 EU/ml, respectively. HD center 4 had the highest levels of IL-6 (1,052.3 ± 240.7 pg/10(6) PBMCs), IL-1β (1,297.1 ± 334.6 pg/10(6) PBMCs) and IL-1Ra (2,713.4 ± 1,255.3 pg/10(6) PBMCs). There were no significant differences in cytokine production between HD centers 1 and 2., Conclusion: Our study showed that ultrapure dialysate can minimize the risk of stimulating inflammatory cells. Ultrapure dialysate may prevent or delay endotoxin exposure-related complications., (Copyright © 2011 S. Karger AG, Basel.)

Thrombogenicity is one of the most important biocompatibility markers of artificial material. Anticoagulation is commonly used to reduce thrombogenicity of the extracorporeal circuit (ECC) during intermittent hemodialysis (IHD). In some situations, systemic anticoagulants are contraindicated. The aim of our study was to compare thrombogenicity parameters during IHD with three different methods without a systemic anticoagulation effect. In a prospective, randomized, and crossover study, we examined 10 stable patients during IHD with (i) regular saline flushes of ECC; (ii) regional citrate anticoagulation (RCA); and (iii) AN69 ST membrane after ECC priming according to the manufacturer's recommendations. Before IHD and after 10, 60, 120, and 240 min, we measured the platelet count and the plasma concentrations of platelet factor 4 (PF4) and thrombin/antithrombin complexes (TAT). All 10 procedures with RCA were successfully completed after 4 h, whereas 6/10 procedures with saline flushes and 5/10 procedures with AN69 ST were finished prematurely because of clotting (P < 0.05). The TAT production was significantly increased during saline flushes and AN69 ST compared with RCA (P < 0.05). Platelet activation demonstrated by rising PF4 was present during all three methods. Markers of coagulation cascade activation were progressively increasing during IHD with RCA, saline flushes, and AN69 ST. The activation was significantly lower during RCA, and according to thrombogenicity, RCA is the most effective among compared anticoagulation methods., (© 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialysis (PD) patients. The possible effects of kidney failure in this model are unknown. The aim was to analyze the effects of chronic kidney failure on peritoneal function and morphology, alone and in combination with PD exposure, in a well-established, long term, peritoneal exposure model in the rat. ♢, Methods: 40 male Wistar rats were randomly assigned into four experimental groups: no nephrectomy, no peritoneal exposure (sham; n = 8); nephrectomy, no peritoneal exposure (Nx; n = 12); no nephrectomy, with peritoneal exposure (PD; n = 8); and nephrectomy, with peritoneal exposure (NxPD; n = 12). The nephrectomy consisted of a one-step 70% nephrectomy. The peritoneal exposure groups were infused once daily for 16 weeks with a 3.86% glucose-based dialysis solution. Development of chronic kidney disease was monitored during the experiment. Peritoneal function and morphological assessment of the peritoneal membrane were performed at the end of the experiment. ♢, Results: During follow-up the nephrectomized groups developed uremia with remarkable renal tubular dilatation and glomerular sclerosis in the renal morphology. Functionally, uremia (Nx) and PD exposure (PD) alone showed faster small solute transport and a decreased ultrafiltration capacity, which were most pronounced in the combination group (NxPD). The presence of uremia resulted in histological alterations but the most severe fibrous depositions and highest vessel counts were present in the PD exposure groups (PD and NxPD). Significant relationships were found between the number of vessels and functional parameters of the peritoneal vascular surface area. ♢, Conclusion: It is possible to induce chronic kidney failure in our existing long-term peritoneal infusion model in the rat. The degree of impairment of kidney function after 16 weeks is comparable to chronic kidney disease stage IV. Uremia per se induces both functional and morphological alterations of the peritoneal membrane. An additive effect of these alterations is present with the addition of chronic kidney failure to the model. The latter makes the present long-term model important in better understanding the pathophysiology of the peritoneal membrane in PD.

Background: Application of icodextrin-based peritoneal dialysis fluid (PDF) provides a potential benefit in patients with diabetes and end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD) because of better ultrafiltration capacity and avoidance of direct glucose exposure. We examined the effect of glucose and icodextrin-based PDF on histological alterations of peritoneal membranes., Methods: Thirty-two male Wistar rats were divided into four groups: control Wistar rats with non-treated (n = 8), streptozotocin (STZ)-induced diabetic rats with 5/6 kidney ablation (n = 8), STZ-induced diabetic rats with 5/6 kidney ablation injected with a standard lactate-buffered 4.25% glucose-based PDF (Dianeal; n = 8) and STZ-induced diabetic rats with 5/6 kidney ablation injected with 7.5% icodextrin-based PDF (Extraneal; n = 8). Intraperitoneal injection was performed once daily with an instillation volume of 20 ml per injection during 8 weeks., Results: Chronic high-glucose-based PDF exposure resulted in increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression, accumulation of advanced glycation end-products (AGEs), and up-regulation of the receptor for AGE (RAGE), which were ameliorated in the icodextrin-based PDF group. The peritoneal damages, such as neoangiogenesis and submesothelial fibrosis, were significantly reduced in icodextrin-based PDF compared to high-glucose-based PDF., Conclusions: Long-term in vivo exposure to high glucose-based PDF promotes the fibrosing process of peritoneal membranes. Icodextrin-based PDF may be helpful in slowing the PDF-induced deterioration of peritoneal function and prolonging the use of peritoneal dialysis in patients with diabetes.

Background: Encapsulating peritoneal sclerosis (EPS) is an uncommon but potentially devastating complication of peritoneal dialysis. We have observed an increased incidence in our centre over the last few years., Methods and Patients: To look at potential risk factors for developing EPS, we reviewed 39 cases diagnosed between 2000 and 2009 and compared these with a control group of 71 patients who had been treated by peritoneal dialysis for a minimum of 4 years. Both groups extensively used icodextrin, >80% of patients., Results: Both groups had been treated by peritoneal dialysis for a similar time: EPS median 54 months (46-87.5), compared to controls 70 (54-79.5). However, more of the EPS group were treated with peritoneal cyclers (75% vs 46%, X(2) = 6.86, P = 0.009) and prescribed more peritoneal dialysate 14.2 l/day +/- 0.7 vs 10.8 +/- 0.5, P < 0.0001. Although both groups were fast transporters, those with EPS had higher D/P creatinine ratios on peritoneal equilibration testing, 0.84 +/- 0.1 vs 0.77 +/- 0.1, P < 0.05, and lower peritoneal test ultrafiltration volumes, 193 +/- 26 ml vs 283 +/- 21 ml, P < 0.05. Discussion. The patients in the EPS group were faster transporters, with lower peritoneal equilibration and 24-h ultrafiltration volumes, and were exposed to greater volumes of peritoneal dialysates compared to peritoneal dialysis vintage controls.

Background: Long-term peritoneal dialysis (PD) with conventional glucose based, lactate-buffered PD fluids may lead to morphological and functional alterations of the peritoneal membrane. It was hypothesized that long-term exposure to a different buffer and a mixture of osmotic agents would cause less peritoneal abnormality., Objectives: To investigate the effects of long-term exposure to a bicarbonate/lactate-buffered dialysis solution with a mixture of osmotic agents: glycerol 1.4%, amino acids 0.5%, and dextrose 1.1% (= 1% glucose) (GLAD) in a rat model with chronic kidney failure., Methods: All rats underwent a peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were randomly divided into 3 groups: GLAD, 3.86% Dianeal (Baxter, Nivelles, Belgium), and buffer (Physioneal without glucose, Baxter). All rats were infused daily for 16 weeks with the appropriate PD fluid. Afterwards, a peritoneal permeability analysis (SPARa) was performed using 3.86% Physioneal in all groups. After the SPARa, the rats were sacrificed to obtain tissue samples for morphometric determinations. Omental tissue was stained with picro Sirius red for assessment of fibrosis and with CD31 for vessel density., Results: GLAD and Dianeal showed faster small solute transport compared to the hypotonic buffer. No differences between the groups were present in ultrafiltration. Dianeal had the lowest value for free water transport and the highest protein clearances. Total triglyceride in plasma was not different between GLAD and the buffer. Vessel density after GLAD exposure (20 V/F) was very similar to the value found for the buffer solution (17 V/F); Dianeal caused a significantly higher value (35 V/F, p < 0.01). Also, the amount of fibrosis was higher in the Dianeal-exposed rats (p < 0.01)., Conclusion: Both hypertonic dialysis solutions increased peritoneal solute transport. GLAD exposure was associated with the best preservation of peritoneal morphology. The results of GLAD were very similar to those of the bicarbonate/lactate-buffered solution without osmotic agents. Studies in humans are needed for further assessment of GLAD.

Objective: The anorexia seen in peritoneal dialysis (PD) patients may be due partially to factors of dialysis solutions, such as pH and buffering agent. We tested the effects of different PD solutions in an experimental rat model for appetite., Design: The intraoral intake of a sucrose solution from an implanted intraoral cannula in freely moving male Wistar rats was used to evaluate appetite at 30 minutes and 120 minutes after intraperitoneal (IP) infusion of bicarbonate (25 mmol/L)/lactate (15 mmol/L)-based PD solution (P) and conventional lactate (40 mmol/L)-based PD solution (D) with different concentrations of glucose. We also tested different buffer solutions containing lactate and bicarbonate with different pH but with no glucose., Results: The IP infusion as such and the 30 mL volume did not inhibit appetite; however, appetite was significantly less inhibited by P than by D in the 1.36%, 2.27%, and 3.86% solutions (p < 0.05). Furthermore, intraoral intake was significantly higher in rats receiving IP solution with bicarbonate buffer (pH 7.4) than with lactate buffer (p < 0.05), whereas there was no significant difference in intraoral intake for lactate with pH 5.5, pH 6.6, or pH 7.4., Conclusions: The bicarbonate/lactate solution inhibited appetite less than the lactate solution; this was due partially to the use of bicarbonate. The results show possible benefit on appetite of reducing the lactate concentration in PD solutions.

Background: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency., Methods: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers., Results: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate., Conclusion: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.

Use of one bag of glucose peritoneal dialysis fluid (PDF) results in the development of a dose-related senescent mesothelial cell phenotype not linked to acidic pH or the presence of lactate buffer. This complication derives mostly from oxidative stress induced both by glucose itself and by glucose degradation products (GDPs). New glucose formulations are offered in dual- or three-chambered bags, keeping the glucose at a low pH. The result is a reduced presence but not complete elimination of GDPs. These formulations have the potential to slow injury to the peritoneal membrane. Icodextrin and amino-acid PDFs, used for one exchange daily, have advantages and drawbacks alike. Icodextrin offers excellent ultrafiltration, but on the other hand, mesothelial cells incubated with this osmotic agent show reduced viability and proliferation and DNA damage. These unwanted effects appear to result from a substantial degree of oxidative stress. An amino-acid-based PDF offers a positive nutritional effect; however its ultrafiltration capability is not higher than an equimolar 1.5% glucose solution. Amino-acid solution appears to be more biocompatible than glucose-based fluid. So far glucose PDF offered in a single-compartment bag is not a biocompatible solution for long-term peritoneal dialysis. Icodextrin does not appear to be more biocompatible than glucose. Amino-acid-based solution is less harmful to the mesothelium, but its usefulness is still limited.

Background/aims: The application of electrolyzed water (EW) at the cathode side to manufacture reverse osmosis (RO) water and hemodialysis (HD) solution can actually lead to less oxidative capacity in chemical terms. The present study examined the biological actions of this water on human polymorphonuclear leukocytes (PMNs), and the clinical feasibility of applying this technology to HD treatment., Methods: RO water using EW (e-RO) exhibited less chemiluminescence in luminol-hydrogen peroxide and higher dissolved hydrogen levels (-99.0 ppb) compared with control RO water. The effects of e-RO on PMN viability were tested. HD using e-RO was performed for 12 consecutive sessions in 8 patients for the feasibility test., Results: Basal cellular viability and function to generate superoxide radicals of PMNs were better preserved by e-RO application. In the clinical trial, reductions of blood pressure were noted, but no adverse events were observed. There were no changes in the blood dialysis parameters, although methylguanidine levels were significantly decreased at the end of study., Conclusion: The present study demonstrated the capacity of e-RO to preserve the viability of PMNs, and the clinical feasibility of applying this water for HD treatment. The clinical application of this technology may improve the bio-compatibility of HD treatment., (Copyright 2009 S. Karger AG, Basel.)

Background: Despite the developments in haemodialysis, there are still some difficulties in maintaining the haemodynamic stability. Bioimpedance analysis (BIA) has been proposed for the estimation of dry weight in haemodialysis patients. We aimed to investigate the effects of dialysate sodium and glucose contents on volume distribution in body compartments after haemodialysis by using BIA, a sensitive and reliable method., Methods: Seventeen chronic haemodialysis patients [11 males, 6 females, mean age: 36.9 (18-64) years] were included in the study. Patients were evaluated in three periods. The patients (period 1-P1) underwent haemodialysis with dialysate of 200 mg/dL glucose and 140 mmol/dL sodium for 4.5 h in the middle session of the first week. At the beginning and the end of the session, haematocrit, vital parameters (blood pressure, pulse), ultrafiltrated volume, plasma osmolarity and plasma renin activity were recorded. Also multi-frequency bioelectric impedance analyses (Bodystat Quadscan 4000) were applied to all patients at 5, 50, 100 and 200 kHz, including the impedance index (Z200/Z5). In the second midweek session the same procedure was repeated with same glucose concentration and 135 mmol/dL sodium including dialysate (period 2-P2), and in the third week, it was performed with a dialysate that included 140 mmol/dL sodium and no glucose (period 3-P3)., Results: The change of the ratio of the intracellular volume to total body weight (ICV/TBW) at the beginning and the end of the session was same in all periods. However, there were significant differences in the change (after/before session) ratio for the extracellular volume/total body weight (ECV/TBW) in P2 compared to other periods (P values for P1-P2: <0.001 and P2-P3: 0.007). Likewise, the same was observed in the changes of impedance (P values for P1-P2: 0.08, P1-P3: 0.44 and P2-P3: 0.063). There was a significant increase of hypotensive events in P2 against the other periods (P = 0.001)., Conclusion: Decreasing dialysate sodium concentration results in important haemodynamic changes but the lack of glucose in dialysate does not result in any changes in haemodynamic and inflammatory parameters. The changes in bioimpedance parameters are parallel to haemodynamic changes in the haemodialysis patients.

Background: Ionic dialysance can provide accurate monitoring of dialysis dose during each hemodialysis session. Increasingly, hemodialysis machines incorporate devices that measure ionic dialysance, allowing the dialysis dose to be determined noninvasively in real time and in each session. Because Kt product was proposed as a measure of hemodialysis dose to avoid the reverse J-shaped curve between urea reduction ratio or Kt/V and mortality, we investigated whether ionic dialysance values and Kt measurements are affected by different ionic dialysance monitors (Diascan and online clearance monitoring [OCM]) and dialysis machines., Study Design: Four-period crossover., Setting & Participants: 31 adult long-term hemodialysis patients using 2 different ionic dialysance monitors in 4 dialysis machines: Diascan in Hospal Integra and Gambro AK-200 machines and OCM in Fresenius 4008S and 5008 machines., Predictors: Ionic dialysance monitor and machine used in 4 hemodialysis sessions for each participant., Outcomes: Kt and Kt/V measured by using ionic dialysance and serum urea nitrogen., Results: Mean values for initial and final ionic dialysance were similar for Integra and AK-200 machines, both measured by using Diascan, and for the 4008S and 5008 machines, both measured by using OCM; however, OCM values tended to be greater in the 4008S and 5008 machines. Kt measured in the 4008S and 5008 machines was greater (59.6 +/- 12 and 58.6 +/- 11 L, respectively) than with the Integra and AK-200 machines (53.4 +/- 11 and 53.8 +/- 11 L). Mean urea reduction ratio and Kt/V were 78.0% +/- 8% and 1.89 +/- 0.43 for Diascan monitors and 79.6% +/- 8% and 1.99 +/- 0.44 for OCM monitors, respectively (P < 0.01). Differences between monitors in Kt determination were caused in part by a real difference in dialysis effectiveness (6%) and in part by an intermethod difference (4%). Kt adjusted by Kt/V differences was recalculated, and because of good correlation between Diascan and OCM, we were able to apply a formula (Kt(OCM) = 1.08 Kt(Diascan) - 2; r =0.95) that allowed both Kt quantification methods to be compared., Limitations: Nonblinded nonrandomized small sample., Conclusions: Kt is a valid method for judging dialysis dose in real time by using ionic dialysance measurements. Adjustments to correct intermethod differences may be necessary to ensure generalizability among ionic dialysance monitors.

Introduction: End-stage renal disease causes impairment of all body organs including the heart and the lung. The main problems in the afflicted patients are pulmonary edema due to increased permeability of the capillaries, intravascular and interstitial volume overload, hypertension, and congestive heart failure. These changes cause altered physiologic and mechanical function of the lungs and subsequently increase in airway resistance. We aimed to study the impact of hemodialysis on spirometry parameters., Materials and Methods: In a cross-sectional study performed on 41 patients on maintenance hemodialysis, spirometry was done before and after the dialysis session. The patients were on either acetate or bicarbonate hemodialysis with the same method, dialysis machine, and duration of dialysis. Alterations in spirometry parameters including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and maximal midexpiratory flow rate were determined and their relation with serum electrolytes, serum creatinine, blood urea nitrogen, and hemoglobin were analyzed., Results: Twenty-nine patients undergoing dialysis with bicarbonate dialysate and 21 on dialysis with acetate were compared. Improvement in spirometry parameters was only significant in patients undergoing dialysis with bicarbonate dialysate. All spirometry parameters showed significant increases in the bicarbonate group except for the FEV1/FVC ratio. Furthermore, significant increase in these parameters was only prominent in the men. Postdialysis weight reduction and laboratory indexes had no significant correlation with improvement of spirometry parameters., Conclusions: Dialysis with bicarbonate dialysate causes significant improvement in spirometry parameters in men on maintenance dialysis. This effect might be independent of the effect of removing the volume overload by dialysis.

Background: The majority of citrate protocols for hemodialysis (HD) use calcium (Ca)-free dialysate, a limited number use dialysate with Ca, aiming to simplify the procedure. This randomized clinical study sought to compare the anticoagulant effect of citrate using Ca-free dialysate and dialysate with Ca 1.25 mmol/L., Methods: Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate anticoagulation) were randomly assigned to Ca-free dialysate (25 procedures) or Ca-1.25 dialysate (25 procedures), both with Mg 0.5 mmol/L, Na 138 mmol/L, and bicarbonate 28 mmol/L. Ca-free HD: 15% Na3 citrate 80 ml/hour was infused into the arterial line, and 1 M CaCl2, 14 ml/hour into the venous line. Ca-1.25 group: 15% Na3 citrate 100 ml/hour, 1 M CaCl2 2-4 ml/hour. Polyflux H dialyzers were used. Antithrombotic effect was assessed visually after HD at 3 points: dialyzer, arterial, and venous bubble traps, using a score of 5 (no clotting) to 1 (total clotting)., Results: Ca-free group: arterial bubble trap score 4.7 +/- 0.5, dialyzer 4.5 +/- 0.6, venous bubble trap 4.8 +/- 0.6. Ionized calcium (iCa) at dialyzer inlet 0.34 +/- 0.17, outlet 0.21 +/- 0.06 mmol/L. All HDs were completed successfully. Ca-1.25 group: arterial bubble trap score 4.7 +/- 0.5 (NS), dialyzer 2.6 +/- 1.04 (p<0.01), venous bubble trap 2.4 +/- 0.9 (p<0.01). Volume of clot in venous bubble trap was 1.9 +/- 1.8 mL (range 0.5-6 mL). iCa at dialyzer inlet 0.24 +/- 0.05 mmol/L (p<0.05), outlet 0.63 +/- 0.11 mmol/L (p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to threatening dialyzer clotting, in 6/25 HD procedures (24%), the venous line was changed (p<0.01)., Conclusion: Citrate anticoagulation with Ca-1.25 dialysate resulted in significantly worse anticoagulation of dialyzer and venous bubble trap compared with Ca-free dialysate, despite higher citrate dose.