Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

The alpha-1 antitrypsin (AAT) protein has an important role in the anti-inflammatory and apoptotic response. AAT inhibits not only serine proteases but also cysteine and aspartic proteases. Apoptosis results from the sequential activation of cysteine proteases of the caspase family. This study aimed to evaluate the effect of AAT on formaldehyde-induced apoptosis of human peritoneal mesothelial cells (HPMCs).

HPMCs were cultured and treated with formaldehyde (250 µM) to induce apoptosis. In the AAT group, the cultured HPMCs were pretreated with AAT (2 mg/mL) for 1 h before formaldehyde treatment. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays to determine cell viability, and flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays to detect apoptosis. The MTT assays were used to find optimal concentrations of formaldehyde and AAT. We measured caspase-3 activity and used Western blotting to estimate Bcl-2 and Bad expression.

Flow cytometry and TUNEL assays revealed that formaldehyde exposure significantly increased apoptosis compared with the control treatment, but pretreatment with AAT significantly inhibited this effect. Compared with the control, caspase-3 activity was significantly increased and the ratio of Bcl-2 to Bad expression significantly decreased following treatment with formaldehyde. However, caspase-3 activity was significantly lower and the Bcl-2 to Bad expression ratio higher in the AAT group than in the formaldehyde-only group.

AAT inhibits formaldehyde-induced apoptosis of HPMCs via a caspase-mediated pathway. These data support a potential use for AAT as a therapeutic agent for the inhibition of peritoneal cell apoptosis during peritoneal dialysis.

Peritoneal dialysis (PD)-associated peritonitis carries significant morbidity, mortality, and is a leading cause of PD technique failure. This study aimed to assess the scope and variability of PD-associated peritonitis reported in randomized trials and observational studies.

Cochrane Controlled Register of Trials, MEDLINE, and Embase were searched from 2007 to June 2018 for randomized trials and observational studies in adult and pediatric patients on PD that reported PD-associated peritonitis as a primary outcome or as a part of composite primary outcome. We assessed the peritonitis definitions used, characteristics of peritonitis, and outcome reporting and analysis.

Seventy-seven studies were included, three were randomized trials. Thirty-eight (49%) of the included studies were registry-based observational studies. Twenty-nine percent (n = 22) of the studies did not specify how PD-associated peritonitis was defined. Among those providing a definition of peritonitis, three components were reported: effluent cell count (n = 42, 54%), clinical features consistent with peritonitis (e.g. abdominal pain and/or cloudy dialysis effluent) (n = 35, 45%), and positive effluent culture (n = 19, 25%). Of those components, 1 was required to make the diagnosis in 6 studies (8%), 2 out of 2 were required in 22 studies (29%), 2 out of 3 in 11 studies (14%), and 3 out of 3 in 4 studies (5%). Peritonitis characteristics and outcomes reported across studies included culture-negative peritonitis (n = 47, 61%), refractory peritonitis (n = 42, 55%), repeat peritonitis (n = 9, 12%), relapsing peritonitis (n = 5, 7%), concomitant exit site (n = 16, 21%), and tunnel infections (n = 8, 10%). Peritonitis-related hospitalization was reported in 38% of the studies (n = 29), and peritonitis-related mortality was variably defined and reported in 55% of the studies (n = 42). Peritonitis rate was most frequently reported as episodes per patient year (n = 40, 52%).

Large variability exists in the definitions, methods of reporting, and analysis of PD-associated peritonitis across trials and observational studies. Standardizing definitions for reporting of peritonitis and associated outcomes will better enable assessment of the comparative effect of interventions on peritonitis. This will facilitate continuous quality improvement measures through reliable benchmarking of this patient-important outcome across centers and countries.

Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients.

This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved.

In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65–1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75–1.16).

In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.

There is substantial variation in peritonitis rates across peritoneal dialysis (PD) units globally. This may, in part, be related to the wide variability in the content and delivery of training for PD nurse trainers and patients.

The aim of this study was to test the feasibility of implementing the Targeted Education ApproaCH to improve Peritoneal Dialysis Outcomes (TEACH-PD) curriculum in real clinical practice settings.

This study used mixed methods including questionnaires and semi-structured interviews (pretraining and post-training) with nurse trainers and patients to test the acceptability and usability of the PD training modules implemented in two PD units over 6 months. Quantitative data from the questionnaires were analysed descriptively. Interviews were analysed using thematic analysis.

Ten PD trainers and 14 incident PD patients were included. Mean training duration to complete the modules were 10.9 h (range 6–17) and 24.9 h (range 15–35), for PD trainers and patients, respectively. None of the PD patients experienced PD-related complications at 30 days follow-up. Three (21%) patients were transferred to haemodialysis due to non-PD–related complications. Ten trainers and 14 PD patients participated in the interviews. Four themes were identified including use of adult learning principles (trainers), comprehension of online modules (trainers), time to complete the modules (trainers) and patient usability of the manuals (patient).

This TEACH-PD study has demonstrated feasibility of implementation in a real clinical setting. The outcomes of this study have informed refinement of the TEACH-PD modules prior to rigorous evaluation of its efficacy and cost-effectiveness in a large-scale study.

Exit-site infection (ESI) is a common complication in peritoneal dialysis (PD) patients. Clearly understanding the risk factors may be useful for the prevention of ESI. This study was to explore the prevalence and risk factors of ESI in incident PD patients.

We evaluated ESI in incident PD patients who had catheter insertion in our center between 1 January 2009 and 31 December 2013, with follow-up for 1 year. We collected data on demographics, clinical features, and nursing care methods of the exit site (ES).

We recruited 1133 incident PD patients (687 male (60.6%); mean age 47.0 ± 15.1 years), and 245 (21.6%) had diabetes. Median follow-up was 12.0 months. One hundred and thirty-one patients had 139 episodes of ESI with a rate of 92.8 patient-months per episode (0.13 episodes per year). Coagulase-negative staphylococcus was the main pathogen, accounting for 33.8% of the ESIs. Gram-positive rods, Staphylococcus aureus, Pseudomonas, fungi, and other organisms accounted for 23.0%, 15.8%, 1.4%, 1.4%, and 2.9%, respectively. No bacterial growth was found in 15.1%. There were no differences in demographic and laboratory data (age, gender, primary kidney disease, hemoglobin, white blood cell, serum albumin, blood urea nitrogen, serum creatinine, and C-reactive protein) between the ESI and non-ESI groups. Poor competency of ES care, poor catheter immobilization, history of catheter-pulling injury, and mechanical stress on the ES were significantly associated with increased risk of ESI.

The prevalence of ESI was 0.13 episodes per year. Poor competency of ES care, catheter mobilization, history of catheter-pulling injury, and mechanical stress by waist belt or the protective bag of PD on ES were risk factors for ESI.

For the treatment of peritoneal dialysis-associated peritonitis (PDAP), ceftazidime is routinely admixed with peritoneal dialysis (PD) solutions before its intraperitoneal administration. One of the major degradation products of ceftazidime is pyridine, a potentially toxic compound. Depending on the type of PD solution, ceftazidime is exposed to an environment with acidic or basic pH, and depending on the type of dosing and individual unit practices related to preparation and storage, ceftazidime can be at body temperature for 4–10 h, resulting in potentially varying rates of degradation to pyridine by-product. No study has investigated whether the amount of generated pyridine exceeds the maximum daily exposure limit of 2 mg when ceftazidime-PD admixtures are kept at body temperature. Therefore, the current study aimed to determine the levels of pyridine generated in PD-ceftazidime admixtures kept at 37°C for various time points.

Ceftazidime was admixed with 2 L Dianeal (1.5%, 2.5% and 4.25% dextrose) and 2 L Physioneal (1.36%, 2.27% and 3.86% glucose) PD solutions to obtain a concentration of 125 mg/L (continuous dosing model) or 500 mg/L (intermittent dosing model). A total of 36 PD admixtures (3 bags for each type of PD solution and 3 bags for each type of dosing) were prepared and stored at 37°C for 10 h. An aliquot was withdrawn at time 0 (baseline) and after 2, 6, 8 and 10 h of storage. The withdrawn samples were then analysed to determine the concentrations of ceftazidime and pyridine using high-performance liquid chromatography.

With the intermittent dosing model (500 mg/L), ceftazidime was found to be stable for only 2 and 6 h when admixed with 3.86% and 2.27% glucose Physioneal PD solutions, respectively. While ceftazidime (500 mg/L) retained more than 90% of its initial concentration in the three types of Dianeal and 1.36% dextrose Physioneal solutions for 10 and 8 h, respectively, the generated amount of pyridine ranged between approximately 290% and 371% more than the daily recommended limit. With the continuous dosing model (125 mg/L), ceftazidime was found to be stable for 6 h in all three types of Physioneal PD solutions, but the total amount of generated pyridine with four daily exchanges (6 h each) was estimated to be 170–360% over the daily recommended limit. Ceftazidime (125 mg/L) was chemically stable when admixed with three types of Dianeal PD solutions and stored at 37°C for 10 h, and the levels of pyridine were estimated to be less than the maximum recommended daily limit.

Until the outcomes of this in vitro study are confirmed by appropriate in vivo studies, continuous dosing of ceftzadime–Dianeal admixtures for the treatment of PDAP may be preferred over continuous dosing of ceftazidime–Physioneal admixtures, and intermittent dosing of ceftazidime–Physioneal and ceftazidime–Dianeal admixtures, as ceftazidime remains stable and the generated levels of pyridine are below the maximum recommended daily exposure.

Intraperitoneal (IP) cefazolin and ceftazidime during the short-dwell (≤ 2 h) automated exchange has been shown to provide adequate dialysate and plasma concentrations for up to 24 h in peritoneal dialysis (PD) patients without peritonitis. This study aimed to evaluate plasma and dialysate concentration of this novel IP cefazolin and ceftazidime regimen during the first 24 h in PD patients with peritonitis.

Cefazolin and ceftazidime (2500 mg each) were added to in to a 5-L bag containing 2.5% of dextrose PD fluid which was placed on the warmer of PD cycling machine. Patients underwent five exchanges of 2-L PD fluid over 10 h by the PD cycling machine without last fill or additional dwell. Plasma samples and dialysate samples were collected over 24 h. Cefazolin and ceftazidime concentrations in plasma and dialysate were determined by high-performance liquid chromatography.

Seven PD patients with peritonitis participated in this study. Plasma cefazolin and ceftazidime levels increased substantially within the first few hours, peaked around 6–10 h, and sustained well above the target plasma concentrations (10 mg L⁻¹ for cefazolin and 16 mg L⁻¹ for ceftazidime) until 24 h. Dialysate cefazolin and ceftazidime levels were sustained above the target peritoneal concentrations (2 mg L⁻¹ for cefazolin and 8 mg L⁻¹ for ceftazidime) throughout the PD session except in some samples which the antibiotics levels were unusually low, probably from beta-lactamase activity.

IP cefazolin and ceftazidime during the short-dwell automated exchange could provide adequate dialysate and plasma concentrations in peritonitis patients. This novel regimen is a promising regimen for peritonitis in PD patients.

Peritoneal dialysis (PD) is a more cost-effective therapy to treat kidney failure than in-center hemodialysis, but successful therapy requires a functioning PD catheter that causes minimal complications. In 2015, the North American Chapter of the International Society for Peritoneal Dialysis established the North American PD Catheter Registry to improve practices and patient outcomes following PD catheter insertion.

The objective of this study is to propose a methodology for defining insertion-related complications that lead to significant adverse events and report the risk of these complications among patients undergoing laparoscopic PD catheter insertion.

Patients undergoing laparoscopic PD catheter insertion were enrolled at 14 participating centers in Canada and the United States and followed using a Web-based registry. Insertion-related complications were defined as flow restriction, exit-site leak, or abdominal pain at any point during follow-up. We also included infections or bleeding within 30 days of insertion, and any immediate postoperative complications. Adverse events were categorized as PD never starting or termination of PD therapy, delay in the start of PD therapy or interruption of PD therapy, an emergency department visit or hospitalization, or need for invasive procedures. Cause-specific cumulative incidence functions were used to estimate risk.

Five hundred patients underwent laparoscopic PD catheter insertion between 10 November 2015 and 24 July 2018. The cumulative risk of insertion-related complications 6 months from the date of insertion that led to an adverse event was 24%. The risk of flow restriction, exit-site leak, and pain at 6 months was 10.2%, 5.7%, and 5.3%, respectively. PD was never started or terminated in 6.4% of patients due to an insertion-related complication. Leaks and flow restrictions were most likely to delay or interrupt PD therapy. Flow restrictions were the primary cause of invasive procedures. Fifty percent of the complications occurred before the start of PD therapy.

Insertion-related complications leading to significant adverse events following laparoscopic placement of PD catheters are common. Many complications occur before the start of PD. Insertion-related complications are an important area of focus for future research and quality improvement efforts.

End-stage renal disease has been imposing a heavy economic burden on public health; however, few studies have been performed on the cost-effectiveness of dialysis modalities. We aim to estimate the cost-effectiveness of different dialysis modalities in China.

Cost-effectiveness analyses were performed using Markov models based on published data of hemodialysis (HD) and peritoneal dialysis (PD) modalities in China. Sensitivity analyses were conducted to identify key variables influencing the results.

Over a 10-year time horizon, the base-case cost-effectiveness analysis indicated that PD-first absolutely dominated the HD-first option by gaining 0.13 more quality-adjusted life years (QALYs) and costing RMB ¥81,081 less. When using reported mortality of HD and PD from the United States, the PD-first option still dominated HD-first with higher QALYs and lower costs. Sensitivity analyses revealed that the results were more sensitive to the direct cost of HD, utility of HD, utility of PD, direct cost of PD, PD mortality, and HD mortality, while less sensitive to the indirect costs and transition probabilities. The HD utility needed to be at least 0.148 higher than PD utility for HD to be cost-effective. PD was about 72% likely to be considered cost-effective compared with HD, regardless of the willingness-to-pay for QALYs.

PD appears to be more cost-effective than HD in China, and the major influential factors on the cost-effectiveness are the direct costs of HD, utility of HD, utility of PD, direct costs of PD, PD mortality, and HD mortality.

Fear of catastrophic events and uncertainty about safety at home are barriers to choosing peritoneal dialysis (PD). Remote monitoring may address these concerns and is increasingly being used in patients on automated peritoneal dialysis (APD). This study aims to describe clinicians’ perspectives and experiences of remote monitoring in caring for patients on PD.

We conducted semi-structured interviews with nephrologists and dialysis nurses across nine dialysis units in New Zealand who had experience using remote monitoring with patients on APD. Interviews were transcribed and analysed using thematic analysis.

Thirteen registered nurses and 12 nephrologists or nephrologists-in-training (total N = 25) participated. Four themes were identified: promoting and maintaining PD (providing reassurance to patients through continual surveillance, supporting confidence at home and sustaining PD as the patient-preferred treatment); enabling data-driven decisions (using comprehensive clinical data in providing timely and accessible care, and identifying and supporting patient adherence); establishing boundaries for use (negotiating privacy and independence, clarifying clinician and patient responsibilities and strengthening nursing innovation and capability); and enhancing patient-focused care (developing empathy for patients, enabling self-management and reducing time and financial burden in accessing care).

Remote monitoring is valued by clinicians in promoting and maintaining patients on PD and enabling data-driven decisions. Remote monitoring enhances patient-focused care, but clinicians also emphasise the need to protect patient privacy and establish boundaries for use. Remote monitoring that supports the clinicians’ role and adheres to principles of data security maintains patient privacy may enhance care and outcomes for patients on PD.

Icodextrin is a high molecular weight, starch-derived glucose polymer that is used as an osmotic agent in peritoneal dialysis (PD) to promote ultrafiltration. There has been wide variation in its use across Australia and the rest of the world, but it is unclear whether these differences are due to patient- or centre-related factors.

Using the Australia and New Zealand Dialysis and Transplant Registry, all adult patients (>18 years) who started PD in Australia between 1 January 2007 and 31 December 2014 were included. The primary outcome was icodextrin use at PD commencement. Hierarchical logistic regression clustered around the treatment centre was applied to determine the patient- and centre-related characteristics associated with icodextrin use. The impact of centre-level practice pattern variability on icodextrin uptake was estimated using the intra-cluster correlation coefficient (ICC).

Of 5948 patients starting on PD in 58 centres during the study period, 2002 (33.7%) received icodextrin from the outset. Overall uptake of icodextrin increased from 29% in 2010 to 42.5% in 2014. Patient-level characteristics associated with an increased likelihood of commencing PD with icodextrin included male sex (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.35–1.77; p < 0.001), prior haemodialysis or kidney transplantation (OR 1.26, 95% CI 1.09–1.47), obesity (OR 1.66, 95% CI 1.41–1.96), diabetes mellitus (OR 2.32, 95% CI 2.03–2.64) and residing in a postcode with the highest decile of socio-economic status (OR 1.43, 95% CI 1.11–1.85). The centre-level characteristic associated with an increased likelihood of commencing PD with icodextrin was routine assessment of a peritoneal equilibration test (OR 1.45, 95% CI 1.27–1.66). Centres with fewer patients on automated peritoneal dialysis (APD) were less likely to start on icodextrin (APD proportion <57%; OR 0.45, 95% CI 0.20–0.99). Centre factors accounted for 25% of the variation in icodextrin use solution among incident PD patients (ICC 0.25).

Icodextrin use in incident Australian PD patients is increasing variable and associated with both patient and centre characteristics. Centre-related factors explained 25% of variability in icodextrin use.