Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Effect of Dialysate and Plasma Sodium on Mortality in a Global Historical Hemodialysis Cohort.

SIGNIFICANCE STATEMENT: This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance hemodialysis patients. Using a large multinational cohort of 68,196 patients, we found that lower dialysate sodium concentrations (≤138 mmol/L) were independently associated with higher mortality compared with higher dialysate sodium concentrations (>138 mmol/L). The risk of death was lower among patients exposed to higher dialysate sodium concentrations, regardless of plasma sodium levels. These results challenge the prevailing assumption that lower dialysate sodium concentrations improve outcomes in hemodialysis patients. The study confirms that until robust evidence from randomized trials that are underway is available, nephrologists should remain cautious in reconsideration of dialysate sodium prescribing practices to optimize cardiovascular outcomes and reduce mortality in this population. BACKGROUND: Excess mortality in hemodialysis (HD) patients is largely due to cardiovascular disease and is associated with abnormal fluid status and plasma sodium concentrations. Ultrafiltration facilitates the removal of fluid and sodium, whereas diffusive exchange of sodium plays a pivotal role in sodium removal and tonicity adjustment. Lower dialysate sodium may increase sodium removal at the expense of hypotonicity, reduced blood volume refilling, and intradialytic hypotension risk. Higher dialysate sodium preserves blood volume and hemodynamic stability but reduces sodium removal. In this retrospective cohort, we aimed to assess whether prescribing a dialysate sodium ≤138 mmol/L has an effect on survival outcomes compared with dialysate sodium >138 mmol/L after adjusting for plasma sodium concentration. METHODS: The study population included incident HD patients from 875 Fresenius Medical Care Nephrocare clinics in 25 countries between 2010 and 2019. Baseline dialysate sodium (≤138 or >138 mmol/L) and plasma sodium (<135, 135-142, >142 mmol/L) concentrations defined exposure status. We used multivariable Cox regression model stratified by country to model the association between time-varying dialysate and plasma sodium exposure and all-cause mortality, adjusted for demographic and treatment variables, including bioimpedance measures of fluid status. RESULTS: In 2,123,957 patient-months from 68,196 incident HD patients with on average three HD sessions per week dialysate sodium of 138 mmol/L was prescribed in 63.2%, 139 mmol/L in 15.8%, 140 mmol/L in 20.7%, and other concentrations in 0.4% of patients. Most clinical centers (78.6%) used a standardized concentration. During a median follow-up of 40 months, one third of patients ( n =21,644) died. Dialysate sodium ≤138 mmol/L was associated with higher mortality (multivariate hazard ratio for the total population (1.57, 95% confidence interval, 1.25 to 1.98), adjusted for plasma sodium concentrations and other confounding variables. Subgroup analysis did not show any evidence of effect modification by plasma sodium concentrations or other patient-specific variables. CONCLUSIONS: These observational findings stress the need for randomized evidence to reliably define optimal standard dialysate sodium prescribing practices.

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

BACKGROUND: Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30 days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. RESULTS: Of 12 814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. CONCLUSIONS: Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.

Partial replacement of d-glucose with d-allose ameliorates peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid in rats.

BACKGROUND: Peritoneal dialysis (PD) is a crucial dialysis method for treating end-stage kidney disease. However, its use is restricted due to high glucose-induced peritoneal injury and hyperglycaemia, particularly in patients with diabetes mellitus. In this study, we investigated whether partially replacing d-glucose with the rare sugar d-allose could ameliorate peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid (PDF). METHODS: Rat peritoneal mesothelial cells (RPMCs) were exposed to a medium containing d-glucose or d-glucose partially replaced with different concentrations of d-allose. Cell viability, oxidative stress and cytokine production were evaluated. Sprague-Dawley (SD) rats were administrated saline, a PDF containing 4% d-glucose (PDF-G4.0%) or a PDF containing 3.6% d-glucose and 0.4% d-allose (PDF-G3.6%/A0.4%) once a day for 4 weeks. Peritoneal injury and PD efficiency were assessed using immuno-histological staining and peritoneal equilibration test, respectively. Blood glucose levels were measured over 120 min following a single injection of saline or PDFs to 24-h fasted SD rats. RESULTS: In RPMCs, the partial replacement of d-glucose with d-allose increased cell viability and decreased oxidative stress and cytokine production compared to d-glucose alone. Despite the PDF-G3.6%/A0.4% having a lower d-glucose concentration compared to PDF-G4.0%, there were no significant changes in osmolality. When administered to SD rats, the PDF-G3.6%/A0.4% suppressed the elevation of peritoneal thickness and blood d-glucose levels induced by PDF-G4.0%, without impacting PD efficiency. CONCLUSIONS: Partial replacement of d-glucose with d-allose ameliorated peritoneal injury and hyperglycaemia induced by high concentration of d-glucose in PDF, indicating that d-allose could be a potential treatment option in PD.

High Osmol Gap Hyponatremia Caused by Icodextrin: A Case Series Report.

Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.

Glucose-induced pseudohypoxia and advanced glycosylation end products explain peritoneal damage in long-term peritoneal dialysis.

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.

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes.

INTRODUCTION: Peritoneal dialysis (PD) is a life maintaining treatment in patients with end-stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described. MATERIALS AND METHODS: Mesothelial (MeT-5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin-based, amino acid-based, and glucose-based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed. RESULTS: Cell proliferation and cell-mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected. CONCLUSIONS: In 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

Effect of low-calcium and standard-calcium dialysate on serum calcium, phosphorus and full-segment parathyroid hormone in patients on peritoneal dialysis: A retrospective observational study.

OBJECTIVE: To investigate the effects of low-calcium and standard-calcium dialysate in patients with chronic kidney disease on peritoneal dialysis, and find out which dialysate has less vascular calcification effect. METHODS: A total of 141 patients who had undergone peritoneal dialysis (PD) for 2 years in the PD centre from January 2012 to December 2017 were included and divided into two groups according to the calcium concentration of the PD fluid used. There were 79 cases in the low-calcium group, with a dialysate calcium concentration of 1.25 mmol/L and 62 cases in the standard-calcium group, with a dialysate calcium concentration of 1.75 mmol/L. The demographic characteristics and clinical information before initiation of PD were collected and compared between the two groups. Information on the serum calcium, phosphorus and PTH, systolic and diastolic blood pressures and the use of antihypertensive and phosphate-lowering drugs in the second year of dialysis was also collected and compared between the two groups. Vascular calcification was assessed in patients on PD treatment. RESULTS: The mean serum calcium concentrations before initiation of PD in the low- and standard-calcium groups were 1.94 ± 0.27 and 1.89 ± 0.28 mmol/L, respectively. The serum calcium concentrations after PD were 2.30 ± 0.21 and 2.41 ± 0.23 mmol/L, respectively. After PD, the serum calcium concentration in both groups was significantly increased (p < 0.05). The serum calcium concentration in the low-calcium group after PD treatment was lower than that in the standard-calcium group, and the difference was statistically significant (p < 0.05). Compared with the standard-calcium group, patients in the low-calcium group had significantly higher parathyroid hormone concentrations (p < 0.05). More types of phosphate-lowering drugs were used (59.49%) in the low-calcium group than that in the standard-calcium group (35.48%; p < 0.05). The number of antihypertensive drug usage were also higher in the low-calcium group, and the difference was statistically significant (p < 0.05). As for the vascular calcification effect, the two groups have shown no statistical difference in abdominal aortic calcification rate, carotid arteriosclerosis rate and aortic arch calcification rate (p < 0.05). CONCLUSION: We found that low-calcium PD fluid may increase the PTH level and the proportion of CKD patients using antihypertensive drug and phosphorus-lowering drug, but the vascular calcification effect of the low and standard calcium PD fluid needs further exploration. This paper provides new evidence for the choice of dialysate for PD, low-calcium dialysate has no outstanding advantages for long term dialysis.

[Intervention of modified Shenling Baizhu San on peritoneal fibrosis induced by peritoneal dialysate with different sugar concentration in rats].

OBJECTIVE: To investigate the effect of modified Shenling Baizhu San on the pathological changes and extracellular matrix (ECM) in rats with peritoneal fibrosis induced by peritoneal dialysate fluid (PDF) with different sugar concentration and its mechanism. METHODS: Seventy male Sprague-Dawley (SD) rats were randomly divided into control group, different sugar content PDF model groups and corresponding traditional Chinese medicine intervention groups, with 10 rats in each group. Peritoneal fibrosis model was reproduced by intraperitoneal injection of 100 mL×kg-1×d-1 PDF containing 1.5%, 2.5% and 4.25% sugar once a day for 8 weeks. The rats in the control group were given the same amount of normal saline. The rats in the traditional Chinese medicine intervention groups were treated with gavage of 10 mL/kg of modified Shenling Baizhu San (containing 2.014 g crude drug per liter) immediately after modeling. The PDF model groups and the control group were given the same amount of normal saline by gavage. After 8 weeks, the peritoneal ultrafiltration volume of rats in each group was measured. The peritoneal tissues were collected and stained with hematoxylin-eosin (HE), and the structural changes and thickness of the parietal peritoneum were observed under a light microscope. After Masson staining, the deposition of collagen fibers was observed under a light microscope. Western blotting was used to detect the protein expressions of E-cadherin, α-smooth muscle actin (α-SMA) and Vimentin, the main components of ECM in parietal peritoneum. The positive expressions of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1) were detected by immunohistochemical staining. RESULTS: Compared with the control group, PDF with different sugar contents could induce peritoneal fibrosis in rats, and the degree of fibrosis was gradually aggravated with the increase of sugar content, which was manifested as peritoneal thickening, increased collagen fiber deposition, decreased peritoneal ultrafiltration volume, down-regulated expressions of E-cadherin and MMP-9 in peritoneal tissue, and up-regulated expressions of α-SMA, Vimentin, TIMP-1 and TGF-ß1, and the pathological changes and ECM accumulation in peritoneal tissues were more serious in 4.25% PDF model group. After the intervention of modified Shenling Baizhu San, compared with the corresponding PDF model groups, the peritoneal fibrosis of rats was improved to varying degrees, and the effect of the 4.25% PDF+traditional Chinese medicine intervention group was more significant, the parietal peritoneum was significantly thinner (µm: 101.86±16.01 vs. 140.65±10.13, P < 0.05), collagen fiber deposition was significantly reduced, peritoneal ultrafiltration volume was significantly increased (mL: -0.01±3.45 vs. -3.53±1.84, P < 0.05), the expressions of E-cadherin and MMP-9 in peritoneal tissues were significantly up-regulated [E-cadherin protein (E-cadherin/ß-actin): 0.84±0.08 vs. 0.28±0.05, MMP-9 (A value): 0.60±0.15 vs. 0.37±0.01, both P < 0.05], and the expressions of α-SMA, Vimentin, TIMP-1 and TGF-ß1 were significantly down-regulated [α-SMA protein (α-SMA/ß-actin): 0.36±0.08 vs. 1.05±0.09, Vimentin protein (Vimentin/ß-actin): 0.53±0.07 vs. 1.19±0.04, TIMP-1 (A value): 0.49±0.06 vs. 0.87±0.02, TGF-ß1 (A value): 0.67±0.04 vs. 0.89±0.10, all P < 0.05]. CONCLUSIONS: The degree of peritoneal fibrosis gradually increased with the increase of PDF sugar content in rats. Modified Shenling Baizhu San can improve peritoneal fibrosis induced by PDF with different sugar contents in rats, and the mechanism is related to the changes in the expression of fibrosis markers and ECM accumulation.

High glucose dialysate-induced peritoneal fibrosis: Pathophysiology, underlying mechanisms and potential therapeutic strategies.

Peritoneal dialysis is an efficient renal replacement therapy for patients with end-stage kidney disease. However, continuous exposure of the peritoneal membrane to dialysate frequently leads to peritoneal fibrosis, which alters the function of the peritoneal membrane and results in withdrawal from peritoneal dialysis in patients. Among others, high glucose dialysate is considered as a predisposing factor for peritoneal fibrosis in patients on peritoneal dialysis. Glucose-induced inflammation, metabolism disturbance, activation of the renin-angiotensin-aldosterone system, angiogenesis and noninflammation-induced reactive oxygen species are implicated in the pathogenesis of high glucose dialysate-induced peritoneal fibrosis. Specifically, high glucose causes chronic inflammation and recurrent peritonitis, which could cause migration and polarization of inflammatory cells, as well as release of cytokines and fibrosis. High glucose also interferes with lipid metabolism and glycolysis by activating the sterol-regulatory element-binding protein-2/cleavage-activating protein pathway and increasing hypoxia inducible factor-1α expression, leading to angiogenesis and peritoneal fibrosis. Activation of the renin-angiotensin-aldosterone system and Ras-mitogen activated protein kinase signaling pathway is another contributing factor in high glucose dialysate-induced fibrosis. Ultimately, activation of the transforming growth factor-ß1/Smad pathway is involved in mesothelial-mesenchymal transition or epithelial-mesenchymal transition, which leads to the development of fibrosis. Although possible intervention strategies for peritoneal dialysate-induced fibrosis by targeting the transforming growth factor-ß1/Smad pathway have occasionally been proposed, lack of laboratory evidence renders clinical decision-making difficult. We therefore aim to revisit the upstream pathways of transforming growth factor-beta1/Smad and propose potential therapeutic targets for high glucose-induced peritoneal fibrosis.

Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.

Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.

Risk factors for early dialysate leakage around the exit site after catheter placement in pediatric peritoneal dialysis: a single-center experience.

BACKGROUND: Dialysate leakage, a major complication in peritoneal dialysis (PD), causes difficulty in continuing PD. However, literature evaluating risk factors for leakage in detail and the appropriate break-in period to avoid leakage in pediatric patients is scarce. METHODS: We conducted a retrospective study on children aged < 20 years who underwent Tenckhoff catheter placement between April 1, 2002, and December 31, 2021, at our institution. We compared clinical factors between patients with and without leakage within 30 days of catheter insertion. RESULTS: Dialysate leakage occurred in 8 of 102 (7.8%) PD catheters placed in 78 patients. All leaks occurred in children with a break-in period of < 14 days. Leaks were significantly more frequent in patients with low body weight at the catheter insertion, single-cuffed catheter insertion, a break-in period ≤ 7 days, and a long PD treatment time per day. Only one patient who had leakage with a break-in period > 7 days was neonate. PD was suspended in four of the eight patients with leakage and continued in the others. Two of the latter had secondary peritonitis, one of whom required catheter removal, and leakage improved in the remaining patients. Three infants had serious complications from bridge hemodialysis. CONCLUSIONS: A break-in period of > 7 days and if possible 14 days is recommended to avoid leakage in pediatric patients. Whereas infants with low body weight are at high risk of leakage, their difficulty in inserting double-cuffed catheter, hemodialysis complications, and possible leakage even under long break-in period make prevention of leakage challenging.

Water quality and adverse health effects on the hemodialysis patients: An overview.

Hemodialysis is considered a treatment of choice for patients with renal failure worldwide, allowing the replacement of some kidney functions by diffusion and ultrafiltration processes. Over 4 million people require some form of renal replacement therapy, with hemodialysis being the most common. During the procedure, contaminants in the water and the resulting dialysate may pass into the patient's blood and lead to toxicity. Thus, the quality of the associated dialysis solutions is a critical issue. Accordingly, the discussion of the importance of a dialysis water delivery system controlled by current standards and recommendations, with efficient monitoring methods, disinfection systems, and chemical and microbiological analysis, is crucial for improving the health outcomes of these patients. The importance of treatment, monitoring, and regulation is emphasized by presenting several case studies concerning the contamination of hemodialysis water and the adverse effects on the respective patients.

Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis.

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

Peritoneal dialysis related eosinophilic peritonitis: a case report and review of the literature.

BACKGROUND: Overt eosinophilic peritonitis (EP) is a relatively uncommon complication of peritoneal dialysis (PD), although not rare. Here we reported a case of EP relieved after changing dialysate.  CASE PRESENTATION: A 28-year old male patient developed cloudy PD effluents within the first month after PD started. Cytological study of PD effluents showed elevated white blood cells and polynuclear cells. Bacteria culture of PD effluents repeated for several times were all negative, and no pathogen was found by metagenomics next generation sequencing (mNGS). Antibiotic therapy for 28-day was ineffective. Based on these and increased eosinophils in peritoneal fluid, he was finally diagnosed as EP. PD dialysate was changed (consists of the same buffer agent and electrolytes, but is packed in bags that do not contain PVC), and the patient's PD effluent became clear. Of note, EP did not relapse 5 months later when the patient started to use the former PD solution again. CONCLUSION: Although PD effluent turbidity almost always represents infectious peritonitis, there are other differential diagnoses including EP. For patients with cloudy fluid accompanied by mild symptoms who do not response to antibiotic therapy, it is reasonable to consider the possibility of this disease. EP tends to heal spontaneously, however, antihistamines or glucocorticoids are required sometimes to avoid catheter obstruction. For patients with no obvious incentives, replacement of dialysate may be useful.

Sodium flux during hemodialysis and hemodiafiltration treatment of acute kidney injury: Effects of dialysate and infusate sodium concentration at 140 and 145 mmol/L.

BACKGROUND: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF). METHODS: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145. RESULTS: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions. CONCLUSIONS: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial.

BACKGROUND: Haemodialysis centres have conventionally provided maintenance haemodialysis using a standard dialysate temperature (eg, 36·5°C) for all patients. Many centres now use cooler dialysate (eg, 36·0°C or lower) for potential cardiovascular benefits. We aimed to assess whether personalised cooler dialysate, implemented as centre-wide policy, reduced the risk of cardiovascular-related death or hospital admission compared with standard temperature dialysate. METHODS: MyTEMP was a pragmatic, two-arm, parallel-group, registry-based, open-label, cluster-randomised, superiority trial done at haemodialysis centres in Ontario, Canada. Eligible centres provided maintenance haemodialysis to at least 15 patients a week, and the medical director of each centre had to confirm that their centre would deliver the assigned intervention. Using covariate-constrained randomisation, we allocated 84 centres (1:1) to use either personalised cooler dialysate (nurses set the dialysate temperature 0·5-0·9°C below each patient's measured pre-dialysis body temperature, with a lowest recommended dialysate temperature of 35·5°C), or standard temperature dialysate (36·5°C for all patients and treatments). Patients and health-care providers were not masked to the group assignment; however, the primary outcome was recorded in provincial databases by medical coders who were unaware of the trial or the centres' group assignment. The primary composite outcome was cardiovascular-related death or hospital admission with myocardial infarction, ischaemic stroke, or congestive heart failure during the 4-year trial period. Analysis was by intention to treat. The study is registered at ClinicalTrials.gov, NCT02628366. FINDINGS: We assessed all of Ontario's 97 centres for inclusion into the study. Nine centres had less than 15 patients and one director requested that four of their seven centres not participate. 84 centres were recruited and on Feb 1, 2017, these centres were randomly assigned to administer personalised cooler dialysate (42 centres) or standard temperature dialysate (42 centres). The intervention period was from April 3, 2017, to March 31, 2021, and during this time the trial centres provided outpatient maintenance haemodialysis to 15 413 patients (about 4·3 million haemodialysis treatments). The mean dialysate temperature was 35·8°C in the cooler dialysate group and 36·4°C in the standard temperature group. The primary outcome occurred in 1711 (21·4%) of 8000 patients in the cooler dialysate group versus 1658 (22·4%) of 7413 patients in the standard temperature group (adjusted hazard ratio 1·00, 96% CI 0·89 to 1·11; p=0·93). The mean drop in intradialytic systolic blood pressure was 26·6 mm Hg in the cooler dialysate group and 27·1 mm Hg in the standard temperature group (mean difference -0·5 mm Hg, 99% CI -1·4 to 0·4; p=0·14). INTERPRETATION: Centre-wide delivery of personalised cooler dialysate did not significantly reduce the risk of major cardiovascular events compared with standard temperature dialysate. The rising popularity of cooler dialysate is called into question by this study, and the risks and benefits of cooler dialysate in some patient populations should be clarified in future trials. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Renal Network, Ontario Strategy for Patient-Oriented Research Support Unit, Dialysis Clinic, Inc., ICES (formerly known as the Institute for Clinical Evaluative Sciences), Lawson Health Research Institute, and Western University.