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Blood Purification 2015Many pieces of evidence of online hemodiafiltration (HDF) have been reported, and the clinical advantage of postdilution online HDF with sufficient substitution is now... (Review)
Review
Many pieces of evidence of online hemodiafiltration (HDF) have been reported, and the clinical advantage of postdilution online HDF with sufficient substitution is now established. After the approval of online HDF in 2012, the number of online HDF patients has been dramatically increasing in Japan and reached 10% of the total dialysis population at the end of 2013. One of the marked characteristics of Japanese online HDF is a widespread use of predilution treatment and, in 2013, 90.8% of online HDFs were carried out with the predilution mode. The main reason for the wide use of predilution online HDF results from the low blood flow rate in Japan, by which it is difficult to substitute a sufficient volume during the limited treatment time. Other reasons to choose the predilution mode include the reduction of albumin loss and the suppression of membrane fouling during treatment. Contrary to postdilution treatment, adequate clinical evidence has not been reported for predilution online HDF to provide a better outcome of the patients. A further clinical trial is expected to elucidate the clinical advantages over conventional hemodialysis for predilution online HDF.
Topics: Aged; Dialysis Solutions; Female; Hemodiafiltration; Humans; Japan; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged
PubMed: 26344508
DOI: 10.1159/000437405 -
Kidney International Aug 2010The recently published KDIGO (Kidney Disease: Improvement of Global Outcomes) guideline (GL) for dialysate calcium suggests a narrow range of dialysate inlet calcium... (Review)
Review
The recently published KDIGO (Kidney Disease: Improvement of Global Outcomes) guideline (GL) for dialysate calcium suggests a narrow range of dialysate inlet calcium concentrations (C(di)Ca(++)) of 2.50-3.00 mEq/l. The work group's primary arguments supporting the GL were (1) there is a negligible flux of body Ca(++) during dialysis and (2) C(di)Ca(++) of 2.50 mEq/l will generally result in neutral Ca(++) mass balance (Ca(MB)). We believe we have shown that both of these arguments are incorrect. Kinetic modeling and analysis of dialyzer Ca(++) transport during dialysis (J(d)Ca(++)) demonstrates that more than 500 mg of Ca can be transferred during a single dialysis and that on average 76% of this Ca flux is from the miscible calcium pool rather than plasma pool. Kinetic modeling of intestinal calcium absorption (Ca(Abs)) shows a strong dependence of Ca(Abs) on the dose of vitamin D analogs and weaker dependence on the level of Ca intake (Ca(INT)). We used the Ca(Abs) model to calculate Ca(Abs) as a function of total Ca(INT) and prescribed doses of vitamin D analogs in 320 hemodialysis patients. We then calculated total dialyzer calcium removal (TJ(d)Ca(++)) and the C(di)Ca(++) that would be required to achieve TJ(d)Ca(++)=Ca(Abs), that is, Ca(MB)=0 over the whole dialysis cycle (that is, covering both the intra- and the inter-dialytic period). The results indicate that 70% of patients on Ca-based binders and 20-50% of patients on non-Ca-based binders would require C(di)Ca(++) <2.50 mEq/l to prevent long-term Ca accumulation.
Topics: Calcium; Dialysis Solutions; Humans; Incidence; Practice Guidelines as Topic; Renal Dialysis; Vitamin D
PubMed: 20520595
DOI: 10.1038/ki.2010.157 -
Scientific Reports Apr 2023In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide...
In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.
Topics: Humans; Icodextrin; Hydrolysis; Kinetics; Glucans; Peritoneal Dialysis; Dialysis Solutions; Peritoneum; Glucose; alpha-Amylases; Ultrafiltration
PubMed: 37085652
DOI: 10.1038/s41598-023-33480-w -
Clinical Journal of the American... Aug 2015Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A...
Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and Drug Administration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and Drug Administration of anticipated shortages. This notification requirement has allowed the Food and Drug Administration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and Drug Administration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and Drug Administration, and communication with all stakeholders is essential.
Topics: Cooperative Behavior; Dialysis Solutions; Drug Industry; Health Services Accessibility; Humans; Interdisciplinary Communication; International Cooperation; Peritoneal Dialysis; Strategic Stockpile; Time Factors; United States; United States Food and Drug Administration
PubMed: 25896999
DOI: 10.2215/CJN.12061214 -
American Journal of Kidney Diseases :... Jun 2020The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell... (Meta-Analysis)
Meta-Analysis
RATIONALE & OBJECTIVE
The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies.
SETTING & STUDY POPULATIONS
Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition.
SELECTION CRITERIA FOR STUDIES
Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports.
DATA EXTRACTION
2 independent reviewers selected studies and extracted data using a prespecified extraction instrument.
ANALYTIC APPROACH
Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs.
RESULTS
19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, -40.84 [95% CI, -48.09 to-33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (-0.50 [95% CI, -1.19 to 0.18] mmol/L; low certainty) and hemoglobin A levels (-0.14% [95% CI, -0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive.
LIMITATIONS
Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data.
CONCLUSIONS
Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.
Topics: Dialysis Solutions; Glucose; Humans; Icodextrin; Kidney Failure, Chronic; Peritoneal Dialysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32033860
DOI: 10.1053/j.ajkd.2019.10.004 -
Oxidative Medicine and Cellular... 2017Peritoneal dialysis (PD) patients manifest excessive oxidative stress (OS) compared to the general population and predialysis chronic kidney disease patients, mainly due... (Review)
Review
Peritoneal dialysis (PD) patients manifest excessive oxidative stress (OS) compared to the general population and predialysis chronic kidney disease patients, mainly due to the composition of the PD solution (high-glucose content, low pH, elevated osmolality, increased lactate concentration and glucose degradation products). However, PD could be considered a more biocompatible form of dialysis compared to hemodialysis (HD), since several studies showed that the latter results in an excess accumulation of oxidative products and loss of antioxidants. OS in PD is tightly linked with chronic inflammation, atherogenesis, peritoneal fibrosis, and loss of residual renal function. Although exogenous supplementation of antioxidants, such as vitamins E and C, N-acetylcysteine, and carotenoids, in some cases showed potential beneficial effects in PD patients, relevant recommendations have not been yet adopted in everyday clinical practice.
Topics: Antioxidants; Atherosclerosis; Dialysis Solutions; Fibrosis; Glucose; Humans; Inflammation; Oxidative Stress; Peritoneal Dialysis; Peritoneum; Renal Insufficiency, Chronic
PubMed: 29750088
DOI: 10.1155/2017/3494867 -
Peritoneal Dialysis International :... Jan 2024Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is... (Review)
Review
Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is the most important functional change, and peritoneal fibrosis is the major morphological alteration. Both are caused by the continuous exposure to dialysis solutions that are different from plasma water with regard to the buffer substance and the extremely high-glucose concentrations. Glucose has been incriminated as the major cause of long-term peritoneal membrane changes, but the precise mechanism has not been identified. We argue that glucose causes the membrane alterations by peritoneal pseudohypoxia and by the formation of advanced glycosylation end products (AGEs). After a summary of UF kinetics including the role of glucose transporters (GLUT), and a discussion on morphologic alterations, relationships between function and morphology and a survey of the pathogenesis of UF failure (UFF), it will be argued that impaired UF is partly caused by a reduction in small pore fluid transport as a consequence of AGE-related vasculopathy and - more importantly - in diminished free water transport due to pseudohypoxia, caused by increased peritoneal cellular expression of GLUT-1. The metabolism of intracellular glucose will be reviewed. This occurs in the glycolysis and in the polyol/sorbitol pathway, the latter is activated in case of a large supply. In both pathways the ratio between the reduced and oxidised form of nicotinamide dinucleotide (NADH/NAD ratio) will increase, especially because normal compensatory mechanisms may be impaired, and activate expression of hypoxia-inducible factor-1 (HIF-1). The latter gene activates various profibrotic factors and GLUT-1. Besides replacement of glucose as an osmotic agent, medical treatment/prevention is currently limited to tamoxifen and possibly Renin/angiotensis/aldosteron (RAA) inhibitors.
Topics: Humans; Peritoneal Dialysis; Glucose; Glycosylation; Peritoneum; Dialysis Solutions; Water; Ultrafiltration
PubMed: 37723976
DOI: 10.1177/08968608231196033 -
Journal of Nephrology Apr 2021Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to... (Review)
Review
Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available (icodextrin and amino acids) and preclinical studies on alternative solutions under development (taurine, polyglycerol, carnitine and xylitol). In addition to the expected benefit of a glucose-sparing approach, we describe an 'osmo-metabolic' approach in formulating novel PD solutions, in which there is the possibility of exploiting the pharmaco-metabolic properties of some of the osmolytes to attenuate the systemic side effects due to glucose. This approach has the potential to ameliorate pre-existing co-morbidities, including insulin resistance and type-2 diabetes, which have a high prevalence in the dialysis population, including in PD patients.
Topics: Dialysis Solutions; Glucose; Humans; Icodextrin; Peritoneal Dialysis; Peritoneum
PubMed: 32767274
DOI: 10.1007/s40620-020-00804-2 -
BMC Nephrology Jun 2021Chronic kidney disease is highly prevalent across the globe with more than 2 million people worldwide requiring renal replacement therapy. Interdialytic weight gain is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic kidney disease is highly prevalent across the globe with more than 2 million people worldwide requiring renal replacement therapy. Interdialytic weight gain is the change in body weight between two sessions of haemodialysis. Higher interdialytic weight gain has been associated with an increase in mortality and adverse cardiovascular outcomes. It has long been questioned whether using a lower dialysate sodium concentration during dialysis would reduce the interdialytic weight gain and hence prevent these adverse outcomes.
METHODS
This study was a single blinded cross-over study of patients undergoing twice weekly haemodialysis at the Aga Khan University Hospital, Nairobi and Parklands Kidney Centre. It was conducted over a twelve-week period and patients were divided into two groups: dialysate sodium concentration of 137 meq/l and 140 meq/l. These groups switched over after a six-week period without a washout period. Univariate analysis was conducted using Fisher's exact test for categorical data and Mann Whitney test for continuous data.
RESULTS
Forty-one patients were included in the analysis. The mean age was 61.37 years, and 73% were males. The mean duration for dialysis was 2.53 years. The interdialytic weight gain was not significantly different between the two groups (2.14 for the 137 meq/l group and 2.35 for the 140 meq/l group, p = 0.970). Mean blood pressures were as follows: pre-dialysis: DNa 137 meq/l: systolic 152.14 ± 19.99, diastolic 78.99 ± 12.20, DNa 140 meq/l: systolic 156.95 ± 26.45, diastolic 79.75 ± 11.25 (p = 0.379, 0.629 respectively). Post-dialysis: DNa 137 meq/l: systolic 147.29 ± 22.22, diastolic 77.85 ± 12.82 DNa 140 meq/l: systolic 151.48 ± 25.65, diastolic 79.66 ± 15.78 (p = 0.569, 0.621 respectively).
CONCLUSION
There was no significant difference in the interdialytic weight gain as well as pre dialysis and post dialysis systolic and diastolic blood pressures between the two groups. Therefore, using a lower dialysate sodium concentration does not appear useful in altering the interdialytic weight gain or blood pressure although further studies are warranted with a larger sample size, taking into account residual renal function and longer duration for impact on blood pressures.
Topics: Blood Pressure; Cross-Over Studies; Dialysis Solutions; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Single-Blind Method; Sodium; Weight Gain
PubMed: 34139998
DOI: 10.1186/s12882-021-02401-2 -
Clinical Journal of the American... Aug 2022Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired... (Review)
Review
Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGF, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.
Topics: Dialysis Solutions; Glucose; Humans; Hypoxia; Inflammation; NAD; Peritoneal Dialysis; Peritoneum; Vascular Endothelial Growth Factor A
PubMed: 35168992
DOI: 10.2215/CJN.15371121