Peritoneal Dialysis Solutions Research Articles

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).

Rapid point-of-care test for diagnosis of peritonitis in peritoneal dialysis patients.

Periplex® is a rapid point-of-care test based on the detection of interleukin-6 (IL-6) or matrix metalloproteinase-8 (MMP-8) to diagnose peritonitis in peritoneal dialysis (PD) patients. This single-centre study was conducted in Singapore General Hospital from 2019 to 2022. The study recruited PD patients suspected of having peritonitis. Periplex was performed at the presentation and recovery of peritonitis. Primary outcomes were sensitivity and specificity of Periplex at presentation. The positive and negative predictive values of tests were also performed. A total of 120 patients were included in the study. The mean age was 60.9 ± 14.9 years, 53% were male, 79% were Chinese and 47.5% had diabetes mellitus. Periplex was positive in all patients with peritonitis (n = 114); sensitivity of 100%; 95% confidence interval (CI): 100-100%. Periplex was falsely positive in three patients with non-infective eosinophilic peritonitis, resulting in a low specificity of 50%; 95% CI: 41.1-59.0%. Periplex had a positive predictive value of 97.4% and a negative predictive value of 100%. During recovery from peritonitis, Periplex had high specificity (93.6%) and negative predictive value (98.7%) to indicate the resolution of infection. MMP-8 was more sensitive than IL-6 in detecting peritonitis. Periplex was positive in all patients with peritonitis regardless of the types of PD solutions used. Periplex had high sensitivity, and positive and negative predictive values in the diagnosis of peritonitis can be considered as a screening tool for peritonitis. Given its high specificity and negative predictive value, it may also be used to document the resolution of peritonitis.

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10mg once daily and then placebo or vice versa. Each treatment period will last 8weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Intercellular communication in peritoneal dialysis.

Long-term peritoneal dialysis (PD) causes structural and functional alterations of the peritoneal membrane. Peritoneal deterioration and fibrosis are multicellular and multimolecular processes. Under stimulation by deleterious factors such as non-biocompatibility of PD solution, various cells in the abdominal cavity show differing characteristics, such as the secretion of different cytokines, varying protein expression levels, and transdifferentiation into other cells. In this review, we discuss the role of various cells in the abdominal cavity and their interactions in the pathogenesis of PD. An in-depth understanding of intercellular communication and inter-organ communication in PD will lead to a better understanding of the pathogenesis of this disease, enabling the development of novel therapeutic targets.

Why should we use a low sodium dialysis solution for peritoneal dialysis?

Overhydration is highly prevalent in patients on peritoneal dialysis (PD), with inappropriately high sodium load supposedly playing a central role in the pathophysiology of the conditions. Recent studies have revealed the novel role of the interstitium as a buffer system for sodium ions, and it has been reported that patients on dialysis, including PD, present increased levels of sodium in the interstitium, such as in subcutaneous tissue and muscle. Hence, therapy for correction of overhydration should target the excess extracellular volume and the excess sodium storage in the interstitium. The ultrafiltrate obtained using the currently available PD solutions is hypo- to isonatric as compared to serum, which is disadvantageous for prompt and efficient sodium removal from the body in patients with overhydration. In contrast, use of low sodium PD solutions is characterised by iso- to hypernatric ultrafiltrate, which may beneficial for reducing sodium storage in the interstitium. Trials of low sodium PD solutions have reported possible clinical merits, for example, decreased blood pressure, reduced dryness of mouth and decreased body water content as assessed using bioimpedance methods. Given these observations and the high prevalence of overhydration in current PD populations, it makes medical sense that low sodium solutions be positioned as the new standard solution in the future. However, for medical safety, that is, to avoid hyponatremia and excessive decreases in blood pressure, further studies are needed to establish the appropriate compositions and applications of low sodium solutions.

Sterility of antibiotic-admixed peritoneal dialysis solution over time.

Intraperitoneal antibiotics may be required daily for up to three weeks to treat peritoneal dialysis (PD)-related peritonitis. In some jurisdictions, antibiotic-admixed PD solutions are required to be used within 24 h due to concerns regarding microbial contamination and growth. This requires patients to attend the PD unit daily or alternatively for staff to perform home delivery with associated transport, staffing and cost implications. The aim of this study was to determine if significant microbial growth occurs in PD solutions following their injection with antibiotic or sterile water. Twelve PD solution bags were admixed with cefazolin sodium 1 g, diluted in 10 mL sterile water, while a further 12 PD solution bags were admixed with 10 mL sterile water using aseptic technique (AT) under supervision. All bags were stored at room temperature. Three bags from each experimental group were sampled for microbiologic culture at 0-, 24-, 48- and 72-h intervals. One sterile water admixed bag sampled at 24 h yielded a Corynebacterium spp. after microbiologic culture. A repeat specimen from the same bag at day nine returned a negative culture result. All other sterile water and cefazolin admixed bags returned negative culture results at all time points. Antibiotic-admixed PD solutions prepared using AT and stored at room temperature remained sterile for up to 72 h. This suggests that patients can be safely issued with a supply of antibiotic-admixed PD bags for up to three days at a time.

Pantoea agglomerans: A rare infectious outbreak affecting maintenance hemodialysis patients in a tertiary care hospital.

Pantoea agglomerans is an environmental pathogen known to cause infection in immunocompromised individuals, particularly after thorn injuries. However, previous data showed few cases of human disease caused by contaminated medical products such as parenteral nutrition, anesthetic agents, blood, and peritoneal dialysis solutions. Infection in hemodialysis patients is rare. In this study, we presented a detailed account of several hemodialysis patients infected with this contagious pathogen and compared them with noninfected dialysis patients. We retrospectively reviewed the hospital records of 105 hemodialysis patients. Seventeen of 105 patients were diagnosed with P. agglomerans infection. We carefully analyzed their entire in-hospital course. Among infected patients, 52.9% were male with a median age of 49 (IQR: 32-66) years. Compared to the noninfected patients, age below 50 years, prior kidney transplantation, prior immunosuppression and antibiotics use, and dialysis via a tunneled vascular catheter were the significant epidemiological features. Despite negative microbiological investigations, we suspect the possible infectious spread via infected central venous catheter was the likely infectious source. Most importantly, all patients responded well to intravenous antibiotics. Only two patients required the removal of the tunneled catheter. Their mortality rate was 0%. P. agglomerans infection, although considered rare, is becoming increasingly prevalent among dialysis patients. Its occurrence must be appraised as an infectious outbreak rather than mere contamination. Prompt treatment, source identification, and early implementation of preventive strategies should always be the goal to curtail this infection at an early stage.

A review of research progress on mechanisms of peritoneal fibrosis related to peritoneal dialysis.

Peritoneal dialysis (PD) is an effective alternative treatment for patients with end-stage renal disease (ESRD) and is increasingly being adopted and promoted worldwide. However, as the duration of peritoneal dialysis extends, it can expose problems with dialysis inadequacy and ultrafiltration failure. The exact mechanism and aetiology of ultrafiltration failure have been of great concern, with triggers such as biological incompatibility of peritoneal dialysis solutions, uraemia toxins, and recurrent intraperitoneal inflammation initiating multiple pathways that regulate the release of various cytokines, promote the transcription of fibrosis-related genes, and deposit extracellular matrix. As a result, peritoneal fibrosis occurs. Exploring the pathogenic factors and molecular mechanisms can help us prevent peritoneal fibrosis and prolong the duration of Peritoneal dialysis.

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions.

To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.

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

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. 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 ≥30days 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. Of 12814 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)]. 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.

Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study

BackgroundCategorization of the capacity of ultrafiltration during a peritoneal equilibration test (PET) is a usual step during the monitoring of peritoneal transport characteristics of Peritoneal Dialysis (PD) patients. Quantifying the peritoneal residual volume (Vr) after the dwell preceding the PET (Vrpre) and at the end of the test (Vrpost) could help to improve the accuracy of the estimation of this variable. MethodFollowing a prospective design, we calculated Vrpre and Vrpost in 116 patients, incident or prevalent on DP, who underwent one or two (n = 27) PET with 3,86/4,25% glucose-based PD solutions and complete drainage at 60 min. We evaluated the consistency of Vr by comparing Vrpre and Vrpost, as also these two parameters in repeated tests. We scrutinized potential associations between demographic and clinical factors, on one side, and the amount of Vr on the other, as also the impact of correcting ultrafiltration during PET for Vr on the categorization of the capacity of ultrafiltration. ResultsAs a mean, Vrpost was larger than Vrpre. Consequently, correction of ultrafiltration for Vr resulted in significantly higher values than those obtained according to the standard procedure (494 vs. 449 mL, p < 0,0005). We disclosed marked inconsistencies for different estimations of Vr in the same patients (Vrpre vs Vrpost and repeated PET studies). Moreover, no demographic or clinical variable was able to predict the amount of Vr. We observed a significant deviation (>200 mL) between both methods of estimation of the capacity of utrafiltration in only 12,9% of the patients. However, 21,1% of the patients categorized as cases of ultrafiltration failure according to the standard procedure did not maintain this condition after correction for Vr. ConclusionsCorrection for Vr of the capacity of ultrafiltration during a PET carries, as a mean, a minor impact on the categorization of this parameter. However, the results of the test can be significantly affected in 12,9% of the cases. We have been unable to detect demographic or clinical predictors of Vr, which suggests a random component for the mechanics of single peritoneal exchanges. We suggest that Vr should be estimated at the time of categorizing the capacity of ultrafiltration, whenever inconsistencies during serial PET studies are detected.

#4950 CARNITINE ACETYLTRANSFERASE (CRAT) MODULATES MESOTHELIAL CELL RESPONSE TO FIBROTIC STRESS

Abstract Background and Aims It has been shown that long-term exposure to the high glucose load of peritoneal dialysis (PD) fluids can induce peritoneal fibrosis causing loss of peritoneal ultrafiltration capacity. TGF-beta is a master regulator factor in the onset of peritoneal fibrosis and recent findings suggest that production of it is dependent on a hyper-glycolytic state caused by glucose-based PD solutions. Currently, a different class of bio-compatible PD solutions are under development; they are based on two synergistic strategies: reducing the amount of glucose, and using osmotic-metabolic agents that may provide metabolic benefits able to mitigate local and systemic glucose over-exposure [1, 2]. One such is L-carnitine [1]. The aim of the present study is to explore the role of L-carnitine and carnitine acetyltransferase (CrAT, a key enzyme in L-carnitine metabolism) on the modulation of TGF-beta pro-fibrotic effects. Method CrAT proved overexpressed in the human mesothelial cell line Met5A. Plasmid-coding CrAT ORF (Origene RG21296) was transfected by Lipofectamine 3000 and subsequently cells underwent antibiotic selection. Single clones were isolated, and CrAT expression was measured at the gene and protein level by real-time PCR and WB respectively. Metabolomic analyses were performed on WT and CrAT overexpressing mesothelial cells. WT and CrAT-overexpressing mesothelial cells were also treated with and without TGF-beta in the presence of physiological and supra-physiological L-carnitine concentrations (50 μM and 2 mM, respectively). The expression of fibrosis and inflammatory markers was analyzed. Results Gene and protein expression analyses confirmed CrAT overexpression in several clones and the two with the highest expression rate were used in subsequent analyses. WT and CrAT-overexpressing mesothelial cells displayed a different metabolic profile, as gleaned by unsupervised hierarchical clustering analysis of the top 50 significant metabolites employing ANOVA and partial least square-discriminant analysis (Figure 1). Most interestingly, they showed a different behavior in response to TGF-beta (Figure 2). In detail: treatment with TGF-beta significantly increased the expression of fibrotic markers alpha-smooth muscle actin (alpha-SMA) and vimentin (VIM) as well as that of pro-inflammatory markers interleukine-6 (IL-6) and interleukine-1β (IL-1β) at a physiological L-carnitine concentration (50 μM). Treatment with supra-physiological L-carnitine levels (2 mM) significantly reduced the up-regulation of the markers analyzed. Similarly, TGF-b was unable to modulate the expression of alpha-SMA, VIM, IL-6 and IL-1β in CrAT-overexpressing cells. Conclusion Studying CrAT-overexpressing mesothelial cells may prove to be a useful tool in elucidating how L-carnitine metabolism manages to keep in check the development of fibrosis and inflammation during PD. The use of L-carnitine as an osmo-metabolic agent in PD solutions could significantly slow down the progression of fibrosis in PD therapy.

#3853 THE EFFECT OF PERITONEAL CAVITY FLUSHING ON ACID BASE BALANCE OF PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Flushing peritoneal cavity with dialysis fluid with short time dwells it is a necessity in some cases for peritoneal dialysis patients. Such cases are overhydration with pulmonary congestion or peritonitis before the initiation of antibiotic treatment as an effort to reduce pain. The aim of this study was to investigate the effect of frequent exchanges with peritoneal dialysis (PD) fluid with bicarbonate as a buffer on acid base balance of peritoneal dialysis patients. Method This is a single center cohort study of 18 stable PD patients (m=10.f=8). Their median age was 57 (47, 71) years, their median PD duration was 33 (16, 89) months and they all fulfill the criteria for achieving adequacy targets [median Kt/V 2.17 (1.99, 3.3)] with good nutrition markers [ median albumin levels 3.9 (3.6, 4) gr/dl]. A sample of arterial blood gas (ABG) was taken from the patients before the procedure and after full drainage of the peritoneal cavity . The procedure included 4 times flushing of 1000 ml of dialysis fluid remaining for15 minutes In the peritoneal cavity each time . At the end of the procedure a new blood sample for ABG was taken. We used PD solution with bicarbonate as a buffer (34 mmol/Lt). We estimated the alterations of pH, of bicarbonate (HCO3-), of pCO2, of Base Excess(ΒΕ), of ionized calcium (iCa++) and lactate (Lac) Results Using the non parametric related samples Wilcoxon signed method we found a statistically significant increase in arterial HCO3- concentration between the values before and after the procedure [HCO3-before:25.4 (22, 28), HCO3after:26.5 (24, 29) mEq/lt-P = .023]. Likewise there was a statistically significant increase in BE with median values before the procedure 1 (-1.2,2.9) and after the flushing 2 (-0.6,3,8), P = .018. Even though there was a statistically significant increase in the bases expression of the acid base balance of the patients there wasn't any statistically significant alterations in pH levels- i.e. Alkalemia (pHbefore=7.41,pHafter=7.42 – P = .35) or pCO2 levels i.e. Compensatory Respiratory Acidosis (pCO2προ=40, pCO2μετα=40 – P = .179) nor to the levels of ionized calcium Conclusion Flushing of peritoneal cavity using peritoneal dialysis solution with bicarbonate as a buffer is safe and in this study was not correlated with the development of metabolic alkalosis

#4983 THE UNEXPECTABLE BALANCE OF PROINFLAMMATORY CELLS IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Chronic kidney disease (CKD) is a complex and heterogeneous disease and is increasingly becoming a global public health concern. It is is characterized by a persistent inflammation state which appear to be caused by cytokines, grown factors and hormones. Peritoneal dialysis (PD) accounts for 9% of all kidney replacement therapy (KRT) and over time, some changes are expected to occur in the peritoneal membrane mainly due to exposure to PD solutions, infectious processes and non-infectious complications. This inflammatory process is poorly understood and needs further clarification, but Th17 cells and Th1 cells seem to be involved. Therefore, we aimed to quantify the frequency of peripheral immune cells and the concentration of IL-17A in peripheral blood (PB) and peritoneal effluent (PE) and compare to a healthy control group. Method In a cross-sectional study of 26 PD patients and 10 healthy, age and sex-matched controls we evaluated PB and PE frequencies of T lymphocytes, T CD4, T CD8 and Th1 cells by flow cytometry as well as IL-17 concentrations using enzyme-linked immunosorbent assay. Comparisons were performed between PD patients and controls and between the different groups of PD patients according to PD modality, number of exchanges, dialysate tonicity, extraneal use, infusion and daily total volumes, type of peritoneal transport and volume indexes. Statistical analyses were performed using the SPSS statistics version 26. Results Table 1 summarizes the main characteristics of PD patients and controls. Overall, in comparison with the control group, the frequency of Th1 cells in PB of PD patients was significantly lower (P = 0.001). On the other hand, frequency of Th1 cells substantially expanded in the PE, as compared to the PB (P = 0.001). PD patients also presented lower Th17 cells frequencies (P = 0.061) and those prescribed Extraneal had the lowest frequencies of Th17 (P = 0.030). IL-17A concentration was significantly higher in PE vs PB of PD patients (P = 0.012). Finally, the frequency of total lymphocytes in high PD transporters was significantly higher in comparison with high-average transporters (P = 0.021). Conclusion In our cohort, PE presented high concentrations of proinflammatory cells and cytokines. Th1 cells rather than Th17 cells were increased, pointing to a predominant cytolytic activity but IL-17 was also increased. Treatment with Extraneal associated with a lower frequency of these cells, somehow counterbalancing the inflammatory millieu associated with high glucose concentrations.

Grafting of Crown Ether and Cryptand Macrocycles on Large Pore Stellate Mesoporous Silica for Sodium Cation Extraction.

Regulation of the sodium cations level in the case of renal failure diseases is a very challenging task for clinicians, and new pollutant extractors based on nanomaterials are emerging as potential treatments. In this work, we report different strategies for the chemical functionalization of biocompatible large pore mesoporous silica, denoted stellate mesoporous silica (STMS), with chelating ligands able to selectively capture sodium. We address efficient methods to covalently graft highly chelating macrocycles onto STMS NPs such as crown ethers (CE) and cryptands (C221) through complementary carbodiimidation reactions. Regarding sodium capture in water, C221 cryptand-grafted STMS showed better capture efficiency than CE-STMS due to higher sodium atom chelation in the cryptand cage (Na+ coverage of 15.5% vs. 3.7%). The sodium selectivity was hence tested with C221 cryptand-grafted STMS in a multi-element aqueous solution (metallic cations with the same concentration) and in a solution mimicking peritoneal dialysis solution. Results obtained indicate that C221 cryptand-grafted STMS are relevant nanomaterials to extract sodium cations in such media and allow us to regulate their levels.

Exploration of patients' preference for modalities of care among peritoneal dialysis patients in Singapore: a single-center experience.

Peritoneal dialysis (PD) is home-based dialysis therapy and therefore a suitable modality for kidney failure patients, particularly, during the COVID-19 pandemic. The present study examined patients' preferences for different PD-related services. This was a cross-sectional survey study. Anonymized data from PD patients followed up at a single center in Singapore were collected using an online platform. The study focused on telehealth services, home visits, and monitoring of quality-of-life (QoL). A total of 78 PD patients responded to the survey. The majority of participants were Chinese (76%), married (73%), and between 45 and 65years old (45%). The in-person visit was preferred over teleconsultation for consultation with nephrologists (68% versus 32%), counseling for kidney disease and dialysis by renal coordinators (59%), whereas the telehealth service was favored over in-person visit for dietary counseling (60%) and medication counseling (64%). Most participants (81%) preferred medication delivery over self-collection, and the acceptable turnaround time was 1 week. Sixty percent would like to have a regular home visit, but 23% refused such visits. The preferred frequency of home visits was one-to-three visits within the first 6 months (74%) and then 6 monthly for subsequent visits (40%). The majority of participants (87%) agreed with QoL monitoring, and the preferred frequency of monitoring varied between 6 monthly (45%) and yearly (40%). Participants also indicated three key areas in research to improve QoL, such as the development of artificial kidneys, portable PD devices, and simplification of PD procedure. Participants also would like to see improvement in two main areas of PD services, such as delivery service for PD solutions and social (instrumental, informational, and emotional) support. Most PD patients preferred in-person visits with nephrologists or renal coordinators; however, they favored telehealth services with dieticians and pharmacists. PD patients also welcomed home visit service and QoL monitoring. Future studies should confirm these findings.

Autophagy in peritoneal fibrosis.

Peritoneal dialysis (PD) is a widely accepted renal replacement therapy for patients with end-stage renal disease (ESRD). Morphological and functional changes occur in the peritoneal membranes (PMs) of patients undergoing long-term PD. Peritoneal fibrosis (PF) is a common PD-related complication that ultimately leads to PM injury and peritoneal ultrafiltration failure. Autophagy is a cellular process of "self-eating" wherein damaged organelles, protein aggregates, and pathogenic microbes are degraded to maintain intracellular environment homeostasis and cell survival. Growing evidence shows that autophagy is involved in fibrosis progression, including renal fibrosis and hepatic fibrosis, in various organs. Multiple risk factors, including high-glucose peritoneal dialysis solution (HGPDS), stimulate the activation of autophagy, which participates in PF progression, in human peritoneal mesothelial cells (HPMCs). Nevertheless, the underlying roles and mechanisms of autophagy in PF progression remain unclear. In this review, we discuss the key roles and potential mechanisms of autophagy in PF to offer novel perspectives on future therapy strategies for PF and their limitations.

Peritoneal dialysis challenges and solutions for continuous quality improvement.

Peritoneal dialysis challenges and solutions for continuous quality improvement.

SGLT-2 inhibitors may increase ultrafiltration in incident peritoneal dialysis patients: a case report

BackgroundAdequate fluid removal to achieve euvolemic status can be difficult in patients with incident peritoneal dialysis (PD). Limited treatments such as increased high dextrose PD solutions and icodextrin are currently available. We reported four incident PD patients whose’ ultrafiltration volume was increased after sodium-glucose cotransporter-2 inhibitors.Case presentation.The four reported cases were diabetic kidney disease stage 5 (cases 1–3) and IgA nephritis (case 4) patients whostartedt PD because of acute pulmonary edema (case 1 and 3), nausea vomiting (case 2), and hyperkalemia (case 4). They had an ultrafiltration volume of 700-1000 ml per day but hpersistentted peripheral pitting edema or pulmonary edema. Their ultrafiltration volincreased after dapagliflozin 5 mg daily, and the fluid overload symptoms ere improved. No hypotension, or hypoglycemia was found, and the urine was not increased during dapagliflozin treatment.ConclusionsSGLT-2 inhibitors may increase ultrafiltration in incident PD patients. More studies are needed to support the safety of SGLT-2 inhibitors in PD patients.

Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-β/Smad signaling pathway.

Peritoneal dialysis (PD) is the mainstay of treatment for renal failure replacement therapy. Although PD has greatly improved the quality of life of end-stage renal disease (ESRD) patients, long-term PD can lead to ultrafiltration failure, which in turn causes peritoneal fibrosis (PF). Silymarin (SM) is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) species that has a variety of pharmacological actions, including antioxidant, anti-inflammatory, antiviral, and anti-fibrotic pharmacological activities. However, the effect of SM on PF and its potential mechanisms have not been clarified. The aim of this study was to investigate the preventive effect of SM on PF in vitro and in vivo as well as elucidate the underlying mechanisms. We established PF mouse models and human pleural mesothelial cell fibrosis in vitro by intraperitoneal injection of high-glucose peritoneal dialysis solution (PDS) or transforming growth factor-β1 (TGF-β1), and evaluated the effect of SM on peritoneal fibrosis in vivo and in vitro. We found that SM alleviated peritoneal dysfunction. Meanwhile, SM inhibited the expression of fibrotic markers (TGF-β1, collagen I, fibronectin) and restored the expression of E-cadherin, BMP-7 in PF mice and TGF-β1-treated Met-5A cells. Furthermore, SM markedly down-regulated the expression of TGF-β1, p-Smad2, and p-Smad3 and up-regulated the expression of smad7. In conclusion, these findings suggested that SM may be an efficient and novel therapy for the prevention of PF through inhibition of TGF-β/Smad signaling.