Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1. Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point) Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point) Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point) Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B) Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point) Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and ‘lymphatic’ reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point) Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point)

BackgroundSeveral studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients.MethodsIn this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups.ResultsOur study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate.ConclusionIn an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.

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It is not clear whether the association of increased peritoneal protein clearance (PPCl) with worse survival on peritoneal dialysis (PD) is a consequence of either local or systemic inflammation or indicative of generalized endothelial dysfunction associated with comorbidity. To investigate this we determined the relationship of PPCl to comorbidity, membrane area (equivalent to low molecular weight peritoneal solute transport rate), local and systemic inflammation and hypoalbuminaemia, and for each of these with patient survival. 257 incident patients from three GLOBAL Fluid Study centers were included in this analysis. Clinical profiles were collected at baseline along with a peritoneal equilibration test, 24-h dialysate protein and paired plasma and dialysate cytokine measurements. Although peritoneal protein clearance was associated with increased age and severe comorbidity on univariate analysis, only dialysate IL-6, peritoneal solute transport rate, plasma albumin and cardiac comorbidities (ischaemic heart disease and left ventricular dysfunction) were independent explanatory variables on multivariate analysis. While peritoneal protein clearance and daily peritoneal protein loss were associated with survival in univariate analysis, on multivariate analysis only plasma IL-6, age, residual kidney function, comorbidity, and plasma albumin were independent predictors. Peritoneal protein clearance is primarily a function of peritoneal membrane area and local membrane inflammation. The association with comorbidity and survival is predominantly explained by its inverse relationship to hypoalbuminaemia, especially in diabetics.

Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (-1.76 L 95% CI: -2.70, -0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported.

Objective: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. Methods: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. Results: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients’ MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). Conclusion: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.

IL-6 is a vital inflammatory factor in the peritoneal cavity of patients undergoing peritoneal dialysis (PD). The present study examined the effect of IL-6 trans-signaling on structural alterations of the peritoneal membrane. We investigated whether the epithelial-to-mesenchymal transition (EMT) process of human peritoneal mesothelial cells (HPMCs) and the production of proangiogenic factors were controlled by IL-6 trans-signaling. Its role in the peritoneal alterations was detected in a mouse model. The morphology of HPMCs and levels of cytokines in PD effluent were also explored. Stimulation of HPMCs with the IL-6 and soluble IL-6 receptor complex (IL-6/S) promoted the EMT process of HPMCs depending on the STAT3 pathway. In a coculture system of HPMCs and human umbilical vein endothelial cells, IL-6/S mediated the production of VEGF and angiopoietins so as to downregulate the expression of endothelial junction molecules and finally affect vascular permeability. Daily intraperitoneal injection of high glucose-based dialysis fluid induced peritoneal fibrosis, angiogenesis, and macrophage infiltration in a mouse model, accompanied by phosphorylation of STAT3. Blockade of IL-6 trans-signaling prevented these peritoneum alterations. The fibroblast-like appearance of HPMCs ex vivo was upregulated in patients undergoing prevalent PD accompanied by increasing levels of IL-6, VEGF, and angiopoietin-2 in the PD effluent. Taken together, these findings identified a critical link between IL-6 trans-signaling and structural alterations of the peritoneal membrane, and it might be a potential target for the treatment of patients undergoing PD who have developed peritoneal alterations.

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