Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials.

RATIONALE & OBJECTIVE: The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. STUDY DESIGN: Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. SETTING & STUDY POPULATIONS: Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. SELECTION CRITERIA FOR STUDIES: Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. DATA EXTRACTION: 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. ANALYTIC APPROACH: Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. RESULTS: 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, -40.84 [95% CI, -48.09 to-33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (-0.50 [95% CI, -1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (-0.14% [95% CI, -0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. LIMITATIONS: Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. CONCLUSIONS: Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.

The role of icodextrin in peritoneal dialysis: protocol for a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have found several advantages of icodextrin compared with glucose in the application of peritoneal dialysis (PD), such as an improvement of peritoneal ultrafiltration during the long dwell and a reduction in episodes of uncontrolled fluid overload. However, the effect of icodextrin on patient-relevant outcomes remains unclear. This review aims to evaluate the benefits and harms of icodextrin in comparison with conventional glucose PD solution in patients with end-stage kidney disease receiving PD. METHODS: Randomized controlled trials of icodextrin comparing with conventional glucose solution in patients with end-stage kidney disease who received PD will be deemed eligible. We will conduct systematic searches in MEDLINE, EMBASE, CENTRAL, Ichushi-Web, Chinese and Japanese databases, and in clinical trials registries (ClinicalTrials.gov, International Clinical Trials Registry Platform Search Portal (ICTRP), EU Clinical Trials Register, Japan Registries Network (JPRN), China's Clinical Trial Registry (ChiCTR)). Furthermore, we will check conference proceedings and search references from relevant studies manually. Relevant pharmaceutical companies, authors, and experts will be contacted in an effort to identify further studies. We will not apply any limitations regarding language, publication status, and publication date when searching for eligible studies. The selection of studies, data extraction, and risk of bias assessment will be carried out by two independent reviewers. Data synthesis will be performed using RevMan 5 software with either a fixed effects model or random-effects model, depending on the presence of heterogeneity. For the assessment of statistical heterogeneity, I2 will be calculated. Sources of clinical heterogeneity will be evaluated through subgroup analyses. If there are ten or more studies included in the meta-analysis, we will investigate the publication bias using funnel plots and Egger's test. The quality of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. DISCUSSION: We assume that our systematic review will be more comprehensive compared to those published previously due to contacting the relevant pharmaceutical companies and a systematic search of published and unpublished non-English studies from China, Taiwan, and Japan. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096951.

Transition Between Different Renal Replacement Modalities: Gaps in Knowledge and Care-The Integrated Research Initiative.

Patients with end-stage kidney disease (ESKD) have different options to replace the function of their failing kidneys. The "integrated care" model considers treatment pathways rather than individual renal replacement therapy (RRT) techniques. In such a paradigm, the optimal strategy to plan and enact transitions between the different modalities is very relevant, but so far, only limited data on transitions have been published. Perspectives of patients, caregivers, and health professionals on the process of transitioning are even less well documented. Available literature suggests that poor coordination causes significant morbidity and mortality.This review briefly provides the background, development, and scope of the INTErnational Group Research Assessing Transition Effects in Dialysis (INTEGRATED) initiative. We summarize the literature on the transition between different RRT modalities. Further, we present an international research plan to quantify the epidemiology and to assess the qualitative aspects of transition between different modalities.

Remote Patient Management for Home Dialysis Patients.

Remote patient management (RPM) offers renal health care providers and patients with end-stage kidney disease opportunities to embrace home dialysis therapies with greater confidence and the potential to obtain better clinical outcomes. Barriers and evidence required to increase adoption of RPM by the nephrology community need to be clearly defined. Ten health care providers from specialties including nephrology, cardiology, pediatrics, epidemiology, nursing, and health informatics with experience in home dialysis and the use of RPM systems gathered in Vienna, Austria to discuss opportunities for, barriers to, and system requirements of RPM as it applies to the home dialysis patient. Although improved outcomes and cost-effectiveness of RPM have been demonstrated in patients with diabetes mellitus and heart disease, only observational data on RPM have been gathered in patients on dialysis. The current review focused on RPM systems currently in use, on how RPM should be integrated into future care, and on the evidence needed for optimized implementation to improve clinical and economic outcomes. Randomized controlled trials and/or large observational studies could inform the most effective and economical use of RPM in home dialysis. These studies are needed to establish the value of existing and/or future RPM models among patients, policy makers, and health care providers.

Contrasting Perceptions of Home Dialysis Therapies Among In-Center and Home Dialysis Staff.

Home dialysis offers many advantages over in-center dialysis, but peritoneal dialysis and home hemodialysis are infrequently used. To better understand why, a survey of dialysis healthcare professionals (N = 273) in the United States was conducted to assess their knowledge, perceptions, and beliefs about home dialysis modalities. Most survey respondents demonstrated a lack of knowledge about home dialysis and perceived many barriers to home therapy, which may affect patient modality choice; however, 90% of respondents stated they would choose home dialysis for themselves if they required dialysis. Additional staff education may help reduce misperceptions, address knowledge gaps, and subsequently, increase use of home modalities.

Comparison of Disinfection Procedures on the Catheter Adapter-Transfer Set Junction.

Peritonitis is a significant complication of peritoneal dialysis (PD), contributing to mortality and technique failure. Suboptimal disinfection and/or a loose connection at the catheter adapter-transfer set junction are forms of touch contamination that can compromise the integrity of the sterile fluid path and lead to peritonitis. Proper use of the right disinfectants for connections at the PD catheter adapter-transfer set interface can help eliminate bacteria at surface interfaces, secure connections, and prevent bacteria from entering into the sterile fluid pathway. Three studies were conducted to assess the antibacterial effects of various disinfecting agents and procedures, and ensuing security of the catheter adapter-transfer set junction. An open-soak disinfection procedure with 10% povidone iodine improves disinfection and tightness/security of catheter adapter-transfer set connection.

Volume-Based Peritoneal Dialysis Prescription Guide to Achieve Adequacy Targets.

UNLABELLED: ♦ BACKGROUND: The use of automated and continuous ambulatory peritoneal dialysis (APD and CAPD) prescriptions (Rxs) to achieve adequate uremic toxin and fluid removal targets is important for attaining optimal patient outcomes. One approach for predicting such Rxs is the use of kinetic modeling. ♦ METHODS: Demographic data and peritoneal membrane characteristics derived from a peritoneal equilibration test (PET) were available from 1,005 patients in North American centers who participated in a national adequacy initiative in 1999. Twelve patient subgroups were identified according to peritoneal membrane transport type and tertiles of total body water, assumed equal to urea distribution volume (Vurea). Each patient was then modeled using PD Adequest 2.0 to be treated by 12 CAPD and 34 APD Rxs using both glucose and icodextrin solutions to achieve adequacy targets of weekly urea Kt/V of 1.7 and 1 L of daily ultrafiltration (UF). Residual kidney function (RKF) was assumed to be 0, 2, 4, and 6 mL/min. Feasible peritoneal dialysis (PD) Rxs were identified where: 1) the 95% confidence limit achieved the goal of meeting the targets for urea Kt/V, daily UF, and both in 85%, 75%, and 70% of patients, respectively; 2) average PD solution dextrose concentration was < 2.5%; and 3) the number of daytime exchanges was minimized. ♦ RESULTS: Feasible PD Rxs were similar when RKF was ≥ 2 mL/min, allowing condensed recommendations based on RKF ≥ 2 mL/min or < 2 mL/min. Individuals with lower or slower membrane transport required relatively greater 24-h solution volumes to achieve adequacy targets when RKF fell below 2 mL/min. With increasing Vurea, there was disproportionately greater dependence on RKF to achieve targets. While multiple Rxs achieving urea Kt/V and daily UF goals were identified for all membrane transport types, use of icodextrin in the long dwell reduced the need for a midday exchange in APD, glucose exposure, required fill and 24-h dwell volumes, irrespective of RKF and Vurea. While these benefits were most notable in high and high-average transporters, similar results were also seen in low and low-average transporters. ♦ CONCLUSIONS: Kinetic modeling identified multiple APD and CAPD Rxs that achieved adequate uremic solute and fluid removal for patients, irrespective of RKF and Vurea. Use of icodextrin rather than glucose in the long dwell reduced the complexity of the PD regimen, total glucose exposure, and 24-h total treatment solution volumes. Irrespective of modeling, adequacy of any PD prescription should be based upon individual clinical evaluation both for volume and solute removal.

Avoidable iatrogenic hypoglycemia in patients on peritoneal dialysis: the risks of nonspecific glucose monitoring devices and drug-device interaction.

BACKGROUND AND OBJECTIVES: Health care professionals (HCPs) depend upon "point-of-care" (POC) glucometers to provide appropriate treatment in emergency and hospital environments. Most devices located in these settings use nonspecific test strip methodology (NSTSM), which is unable to distinguish glucose from nonglucose sugars, including maltose. This flaw can result in erroneous administration of insulin and harm to patients. Icodextrin is a colloidal osmotic agent used in peritoneal dialysis (PD) solutions to augment ultrafiltration and waste removal. The main metabolite of icodextrin is maltose. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Three representative case reports of inappropriate medical action related to in-hospital use of NSTSM monitoring in PD patients using icodextrin are provided to emphasize importance of this interaction and HCP awareness. RESULTS: PD patients using icodextrin before hospitalization exhibited marked discrepancy between blood glucose (BG) measurements obtained from POC-NSTSM glucometers and those obtained by glucose-specific methods in clinical chemistry laboratories leading to inappropriate administration of insulin by HCPs and symptomatic hypoglycemia in all patients. None of the patients received icodextrin during hospitalization. CONCLUSIONS: Non-nephrology HCPs are unaware that POC glucometers are nonglucose specific and do not possess comprehensive knowledge of drug metabolism, particularly for uncommonly seen agents. The case reports highlight the absolute need for use of glucose-specific assays in BG determinations for patients using icodextrin within 2 weeks of hospitalization. To avoid future devastating consequences including severe hypoglycemia, coma, or death related to the drug-device interaction described, hospital protocols should require that all PD patients' BGs are measured in central chemistry laboratories.

Training patients for automated peritoneal dialysis: A survey of practices in six successful centers in the United States.

In the United States, the majority of patients on peritoneal dialysis (PD) use a cycler or automated peritoneal dialysis (APD). The aim of this study was the identification of common features in nurse-led APD training programs that were likely to contribute to successful home dialysis. This study collected data on nurse-led APD training programs in six high-performing PD centers. A 13-point survey, which focused on training tools, topics covered methods used, and level of support at home, was administered during group face-to-face interviews with the PD training nurses. Data were reviewed for trends between centers. Training programs in all six centers focused on essential information and skill sets to begin home dialysis using APD, with simple instructions and a hands-on approach. Every center initially trained patients on continuous ambulatory PD before APD. The clinics provided ongoing education, reinforcement, and retraining of concepts and skills through discussion, quizzes, and topic-specific monthly training sessions. All clinics provided 24-hour support for patients. Adopting the best practices identified in this study has the potential to improve APD training.

Health-related quality of life and hemoglobin levels in chronic kidney disease patients.

BACKGROUND: The relationship between quality of life (QofL) and anemia has been the subject of recent debates; it has been suggested that the QofL changes associated with the treatment of anemia of chronic kidney disease (CKD) or ESRD patients should not be used in making decisions to treat anemia in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examines the relationship between Kidney Disease Quality of Life (KDQofL) questionnaire domains and hemoglobin (Hgb) levels in 1200 patients with stage 3, 4, and 5 CKD followed in seven centers. QofL measures were compared in a stepwise fashion for hemoglobin levels of <11, 11 to <12, 12 to <13, and > or =13. ANOVA was used to examine the relationship between QofL scores and Hgb level, age, CKD stage, and albumin level; a history of diabetes, congestive heart failure, or myocardial infarction; use of erythropoetic-stimulating agents (ESA); and the interaction of hemoglobin level and ESA. RESULTS: The results demonstrate that with increasing Hgb levels there is a statistically significant increase in all four physical domains, the energy/vitality domain, and the physical composite score of the SF-36, and the general health score on the kidney disease component of the questionnaire. The most dramatic improvements in these various domains occurred between the <11 and the 11 to 12 group. CONCLUSIONS: Higher Hgb levels are associated with improved QofL domains of the KDQofL questionnaire. These findings have implications for the care of CKD patients in terms of the initiation of and the Hgb target of ESA therapy.

A prospective evaluation of renal replacement therapy modality eligibility.

BACKGROUND: Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts. METHODS: We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices. RESULTS: Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant. CONCLUSIONS: Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.

Perceived knowledge among patients cared for by nephrologists about chronic kidney disease and end-stage renal disease therapies.

The need to educate patients in order to enable them to participate in making appropriate choices for all therapeutic options in end stage renal disease would seem obvious yet there are many barriers to providing such information. We measured 'perceived knowledge' of the therapeutic options for end stage renal disease in a cohort of patients with chronic kidney disease in established treatment programs. A self administered questionnaire was given to 676 patients with stage 3-5 chronic kidney disease as part of the CRIOS study designed to identify trends in practice patterns and outcomes over a 4 year period. The median patient age was 66, about three-fourths were Caucasian and almost half were diabetic. When patients were asked to rate their level of knowledge, about one-third reported limited or no understanding of their chronic kidney disease and no awareness regarding their treatment options. A significant and substantial number of patients indicated they had no familiarity with transplant, hemodialysis, and continuous ambulatory or automated peritoneal dialysis. Perceived knowledge improved with the progression of kidney disease and frequency of nephrology visits; however, only about half of patients with 4 or more nephrology appointments in the prior year reported knowing of hemodialysis, continuous ambulatory peritoneal dialysis or transplant. Age, gender and disease had no impact on levels of patient knowledge, but African-Americans reported having significantly less understanding than Asians or Caucasians. These findings suggest that the lack of perception concerning the treatment options chronic kidney and end stage renal disease reflects, in part, problems with the education of patients by nephrologists and not a lack of referral of these patients to nephrologists for care. The discrepancy of perceived knowledge between African-Americans and other races needs special attention.