The Removal of Uremic Solutes by Peritoneal Dialysis.

ABSTRACT: Peritoneal dialysis (PD) is now commonly prescribed to achieve target clearances for urea or creatinine. The International Society for Peritoneal Dialysis has proposed however that such targets should no longer be imposed. The Society's new guidelines suggest rather that the PD prescription should be adjusted to achieve well-being in individual patients. The relaxation of treatment targets could allow increased use of PD. Measurement of solute levels in patients receiving dialysis individualized to relieve uremic symptoms could also help us identify the solutes responsible for those symptoms and then devise new means to limit their accumulation. This possibility has prompted us to review the extent to which different uremic solutes are removed by PD.

Peritoneal Dialysis Prescription and Adequacy in Clinical Practice: Core Curriculum 2023.

As the global prevalence of peritoneal dialysis (PD) continues to grow, practitioners must be equipped with prescribing strategies that focus on the needs and preferences of patients. PD is an effective form of kidney replacement therapy that offers numerous benefits to patients, including more flexibility in schedules compared with in-center hemodialysis (HD). Additional benefits of PD include salt and water removal without significant changes in patient hemodynamics. This continuous yet gentle removal of solutes and fluid is associated with better-preserved residual kidney function. Unfortunately, sometimes these advantages are overlooked at the expense of an emphasis on achieving small solute clearance targets. A more patient-centered approach emphasizes the importance of individualized treatment, particularly when considering incremental PD and other prescriptions that align with lifestyle preferences. In shifting the focus from small solute clearance targets to patient needs and clinical goals, PD remains an attractive, patient-centered form of kidney replacement therapy.

Anxiety and psychosocial impact during coronavirus disease 2019 in home dialysis patients.

The severe acute respiratory syndrome coronavirus (SARS-Cov-2) resulting in the coronavirus disease 2019 (COVID-19) is documented to have a negative psychosocial impact on patients. Home dialysis patients may be at risk of additional isolating factors affecting their mental health. The aim of this study is to describe levels of anxiety and quality of life during the COVID-19 pandemic among home dialysis patients. This is a single-centre survey of home dialysis patients in Toronto, Ontario. Surveys were sent to 98 home haemodialysis and 43 peritoneal dialysis patients. Validated instruments (Haemodialysis and Peritoneal Dialysis Treatment Satisfaction Questionnaire, Generalized Anxiety Disorder 7 Item [GAD7] Scale, Patient Health Questionnaire [PHQ-9], Illness Intrusiveness Ratings Scale, Family APGAR Questionnaire and The Self Perceived Burden Scale) assessing well-being were used. Forty of the 141 patients surveyed, participated in September 2020. The mean age was 53.1 ± 12.1 years, with 60% male, and 85% home haemodialysis, 80% of patients rated their satisfaction with dialysis at 8/10 or greater, 82% of respondents reported either "not at all" or "for several days" indicating frequency of anxiety and depressive symptoms, 79% said their illness minimally or moderately impacted their life, 76% of respondents were almost always satisfied with interactions with family members, 91% were never or sometimes worried about caregiver burden. Among our respondents, there was no indication of a negative psychosocial impact from the pandemic, despite the increased social isolation. Our data further supports the use of home dialysis as the optimal form of dialysis.

The use of virtual physician mentoring to enhance home dialysis knowledge and uptake.

Home dialysis therapies are flexible kidney replacement strategies with documented clinical benefits. While the incidence of end-stage kidney disease continues to increase globally, the use of home dialysis remains low in most developed countries. Multiple barriers to providing home dialysis have been noted in the published literature. Among known challenges, gaps in clinician knowledge are potentially addressable with a focused education strategy. Recent national surveys in the United States and Australia have highlighted the need for enhanced home dialysis knowledge especially among nephrologists who have recently completed training. Traditional in-person continuing professional educational programmes have had modest success in promoting home dialysis and are limited by scale and the present global COVID-19 pandemic. We hypothesize that the use of a 'Hub and Spoke' model of virtual home dialysis mentorship for nephrologists based on project ECHO would support home dialysis growth. We review the home dialysis literature, known educational gaps and plausible educational interventions to address current limitations in physician education.

Predictors of Care Gaps in Home Dialysis: The Home Dialysis Virtual Ward Study.

BACKGROUND: Home dialysis patients may be at an increased risk of adverse events after transitional states. The home dialysis virtual ward (HDVW) trial was conducted in Canadian dialysis centers and aimed to evaluate potential care gaps and patient satisfaction during the HDVW. METHODS: The HDVW was a multicenter single-arm trial including peritoneal dialysis and home hemodialysis patients after 4 different events (hospital discharge, medical procedure, antibiotics, completion of training). Telephone-led interviews using a standardized assessment tool were performed over a 2-week period to assess a patient's care and adjust treatment as required. Upon completion, patients were surveyed to evaluate their perceived impact on domains of care using a rating scale; 1 not satisfied to 10 completely satisfied. RESULTS: The HDVW trial included 193 patients with a median number of potential care gaps/interventions of 1 (0-2) per patient. Patients admitted to the HDVW after hospital discharge were at a higher risk of potential gaps in care (OR 2.16, 95% CI 1.29-3.62), while longer dialysis vintage was -associated with a lower number of gaps/interventions (OR 0.97 per year, 95% CI 0.95-0.98). A total of 105/193 (54%) patients completed satisfaction surveys. Patients were highly satisfied with the HDVW (median rating scale score 8, IQR 2) and felt it had a positive impact (rating scale score ≥7) on their overall health, understanding of treatment and access to a nephrologist. CONCLUSION: The HDVW was effective at identifying several potential care gaps, and patients were satisfied across several domains of care. This intervention may be valuable in supporting home dialysis patients during care transitions.

Ethical issues in dialysis therapy.

Treatment for end-stage kidney disease is a major economic challenge and a public health concern worldwide. Renal-replacement therapy poses several practical and ethical dilemmas of global relevance for patients, clinicians, and policy makers. These include how to: promote patients' best interests; increase access to dialysis while maintaining procedural and distributive justice; minimise the influence of financial incentives and competing interests; ensure quality of care in service delivery and access to non-dialytic supportive care when needed; minimise the financial burden on patients and health-care system; and protect the interests of vulnerable groups during crisis situations. These issues have received comparatively little attention, and there is scant ethical analysis and guidance available to decision makers. In this Health Policy, we provide an overview of the major ethical issues related to dialysis provision worldwide, identify priorities for further investigation and management, and present preliminary recommendations to guide practice and policy.

Should we look beyond Kt/V urea in assessing dialysis adequacy?

Since the advent of maintenance dialysis therapy, our interpretation of what adequate dialysis really is has broadened and become more controversial. This is not only due to our changing and aging dialysis population but also to our evolving knowledge base. As nephrologists, we strive to achieve both quality and (often) quantity of life for our patients and we feel reassured when we have a quantifiable marker to show for our efforts. However, we suggest that adequate dialysis reaches far beyond the realms of attaining a particular biochemical result. Dialysis adequacy should encompass a more comprehensive assessment of patient well-being. This metric could comprise quality of life and patient-specified goals, sufficient small solute and middle molecule clearance, optimal blood pressure control, and effective bone-mineral balance, all in the context of minimizing mortality and morbidity, and a livable dialysis regimen for the patient.

Incremental peritoneal dialysis: New ideas about an old approach.

Coping with the transition from end-stage kidney disease to dialysis can be challenging for patients and their care partners. Introducing incident dialysis patients to incremental forms of dialysis is associated with better quality of life and reduced cost. Incremental hemodialysis (HD) has generated significant interest over the last decade with treatments that focus on clinical criteria rather than prespecified Kt/Vurea targets. Incremental peritoneal dialysis (PD) has traditionally focused on the sum of residual renal and peritoneal clearances to achieve a specific Kt/Vurea value. Gradual increases in the PD dose were prescribed as the residual kidney function declined. Adopting a new approach to incremental PD similar to what has been done for incremental HD would obviate the need for Kt/Vurea and focus exclusively on clinical criteria. New incremental PD may be considered less disruptive to incident dialysis patients, and may be more likely to be accepted as treatment. It will also reduce our obsession with small solute kinetics and enhance encounters with patients by focusing instead on the holisitc clinical assessment.

Visions in a Crystal Ball: The Future of Peritoneal Dialysis.

BACKGROUND: Peritoneal dialysis (PD) is one of the corner stones of renal replacement therapy and should be strongly considered if preemptive kidney transplantation is not available. SUMMARY: There are several initiatives that may help the growth in the use of PD around the world. First, PD is an underused and valuable option in patients with heart failure and the chronic cardiorenal syndrome, especially in those with frequent hospitalizations despite optimal medical therapy. To identify these patients, an interdisciplinary approach of nephrologists and cardiologists is needed. These patients and other CKD patients with significant residual kidney function may do well with a regimen employing fewer than the usual number of bag exchanges, referred to as "incremental" dialysis. Second, acute kidney injury (AKI) is a worldwide burden with high morbidity and mortality, especially in low income countries. To reach the goal of zero preventable deaths caused by AKI by 2025 endorsed by the International Society of Nephrology, PD is the therapy of choice for treatment in this setting. Third, although dextrose has served well as the osmotic agent in PD solutions, there has been a continuous search for alternative agents. Hyperbranched polyglycerol might be such an osmole. Finally, to obviate the need for production and delivery of bags of PD solution, the development of home-generated dialysate is of interest. Key Message: The future of PD lies not only in accruing experience from the past decades, but also in staying open to other uses.

Renal Tubular Toxicity Associated With Rosuvastatin Therapy.

Preapproval clinical trials examining the safety and efficacy of rosuvastatin demonstrated an increased incidence of proteinuria, hematuria, rhabdomyolysis, and other acute kidney injury of unknown cause at high doses. The latter cases manifested with urine sediment findings and in some cases, renal histology, indicating renal tubular injury in the absence of rhabdomyolysis. Despite these provocative findings, there have been very few reports in the literature regarding non-rhabdomyolysis-mediated acute kidney injury associated with high-dose rosuvastatin since its widespread introduction more than a decade ago, suggesting that it is either a rare entity or systematically underdiagnosed and under-reported. We present a case of renal tubular toxicity attributable to the initiation of rosuvastatin treatment at a dose of 40mg in a patient with no prior evidence of kidney disease. Tubular toxicity should be considered in cases of unexplained kidney injury in the setting of exposure to a potent statin such as rosuvastatin, particularly at high dose. The limited evidence suggests a good kidney prognosis following withdrawal of the agent in these cases.

Dialysis Modality and Readmission Following Hospital Discharge: A Population-Based Cohort Study.

BACKGROUND: Readmissions following hospital discharge among maintenance dialysis patients are common, potentially modifiable, and costly. Compared with patients receiving in-center hemodialysis (HD), patients receiving peritoneal dialysis (PD) have fewer routine dialysis clinic encounters and as a result may be more susceptible to a hospital readmission following discharge. STUDY DESIGN: Population-based retrospective-cohort observational study. SETTINGS & PARTICIPANTS: Patients treated with maintenance dialysis who were discharged following an acute-care hospitalization during January 1, 2003, to December 31, 2013, across 164 acute-care hospitals in Ontario, Canada. For those with multiple hospitalizations, we randomly selected a single hospitalization as the index hospitalization. PREDICTOR: Dialysis modality PD or in-center HD. Propensity scores were used to match each patient on PD therapy to 2 patients on in-center HD therapy to ensure that baseline indicators of health were similar between the 2 groups. OUTCOME: All-cause 30-day readmission following the index hospital discharge. RESULTS: 28,026 dialysis patients were included in the study. 4,013 PD patients were matched to 8,026 in-center HD patients. Among the matched cohort, 30-day readmission rates were 7.1 (95% CI, 6.6-7.6) per 1,000 person-days for patients on PD therapy and 6.0 (95% CI, 5.7-6.3) per 1,000 person-days for patients on in-center HD therapy. The risk for a 30-day readmission among patients on PD therapy was higher compared with those on in-center HD therapy (adjusted HR, 1.19; 95% CI, 1.08-1.31). The primary results were consistent across several key prespecified subgroups. LIMITATIONS: Lack of information for the frequency of nephrology physician encounters following discharge from the hospital in both the PD and in-center HD cohorts. Limited validation of International Classification of Diseases, Tenth Revision codes. CONCLUSIONS: The risk for 30-day readmission is higher for patients on home-based PD compared to in-center HD therapy. Interventions to improve transitions in care between the inpatient and outpatient settings are needed, particularly for patients on PD therapy.

Antibiotic Prophylaxis in Peritoneal Dialysis Patients.

Peritonitis is an important cause of morbidity, mortality, and technique failure in patients on peritoneal dialysis (PD). The most effective approach to peritonitis is prevention, which includes careful patient training and follow-up. Although peritonitis as a result of contiguous spread of bacteria or fungi during invasive procedures, or as a result of seeding of the peritoneum during bacteremia, is uncommon, the likelihood of such spread is often predictable, and the risk can be mitigated with antibiotic prophylaxis. Here, we describe the rationale for, and approach to, antibiotic prophylaxis in PD patients for the prevention of infective episodes.

Peritoneal dialysis: from bench to bedside and bedside to bench.

For patients with end-stage kidney disease unable to receive a kidney transplant, replacement of kidney function with dialysis is necessary to extend life. Peritoneal dialysis (PD) and hemodialysis (HD) are the two major forms of dialysis therapy. HD involves the passage of blood via an extracorporeal circuit whereby removal of small solutes, toxins, and water is achieved across a synthetic, semipermeable dialysis membrane. In contrast, in PD, the dialysis membrane is the highly vascularized internal lining of the peritoneal cavity. Intraperitoneal installation of hypertonic high glucose PD solution creates a transmembrane osmotic and diffusive gradient that facilitates water removal [ultrafiltration (UF)], convection, and diffusion of uremic toxins. Insight into the physiology of solute and water transport across the peritoneal membrane has been enhanced by the proposal of the ''three-pore model'' of peritoneal membrane transport. Transport characteristics and UF capacity of the peritoneal membrane vary among individuals, and deleterious changes in the membrane may ensue over time. The degree to which these changes are a direct consequence of the type and composition of currently available PD solutions, recurrent infectious episodes, genetic differences among individuals, or a combination thereof is the subject of intense study. Adverse consequences resulting from the systemic and local metabolic effects of intraperitoneal glucose exposure, infection of the PD fluid, PD catheter dysfunction, and patient burnout from self-care often limit the long-term success of the therapy. Research aimed at addressing these challenges will examine the use of more biocompatible PD solutions and strategies aimed at attenuating progressive peritoneal membrane injury.

Myths in peritoneal dialysis.

PURPOSE OF REVIEW: To clarify misconceptions about the feasibility and risks of peritoneal dialysis that unnecessarily limit peritoneal dialysis uptake or continuation in patients for whom peritoneal dialysis is the preferred dialysis modality. The inappropriate choice of haemodialysis as a result of these misconceptions contributes to low peritoneal dialysis penetrance, increases transfer from peritoneal dialysis to haemodialysis, increases expenditure on haemodialysis and compromises quality of life for these patients. RECENT FINDINGS: Peritoneal dialysis is an excellent renal replacement modality that is simple, cost-effective and provides comparable clinical outcomes to conventional in-centre haemodialysis. Unfortunately, many patients are deemed unsuitable to start or continue peritoneal dialysis because of false or inaccurate beliefs about peritoneal dialysis. Here, we examine some of these 'myths' and critically review the evidence for and against each of them. We review the feasibility and risk of peritoneal dialysis in patients with prior surgery, ostomies, obesity and mesh hernia repairs. We examine the fear of mediastinitis with peritoneal dialysis after coronary artery bypass graft surgery and the belief that the use of hypertonic glucose dialysate causes peritoneal membrane failure. SUMMARY: By clarifying common myths about peritoneal dialysis, we hope to reduce overly cautious practices surrounding this therapy.

Membranous Lupus Nephritis: The Same, But Different.

Membranous lupus nephritis (MLN) has a favorable prognosis compared to proliferative lupus nephritis (PLN) or combined MLN/PLN, although a significant proportion of cases will progress to end-stage kidney disease. There is considerable morbidity associated with thrombotic complications and treatment. Nondirected care includes renin-angiotensin-aldosterone system blockade, cardiovascular risk management, and antimalarial agents. There may be a role for corticosteroid monotherapy in some patients, but this requires further investigation. Clinical trials and observational reports have led to different immunosuppression regimens for MLN, although high-grade evidence favoring a particular agent remains elusive. Established medications used in the treatment of PLN, such as mycophenolate, cyclophosphamide, and azathioprine, may also be efficacious in MLN, or at least steroid sparing. The calcineurin inhibitors appear promising as an alternative treatment in MLN, particularly with emerging experimental data supporting their nonimmunologic antiproteinuric effects. There is also emerging evidence for "multitargeted therapy" in combined MLN/PLN, although the long-term efficacy is still unproved.

We Use Kt/V Urea as a Measure of Adequacy of Peritoneal Dialysis.

In the early days of chronic dialysis therapy, there was recognition that patients on continuous peritoneal dialysis enjoyed improvement in symptoms and signs of kidney failure similar to those receiving hemodialysis, despite slower removal rates of small solutes such as urea and creatinine. It was suggested that removal of toxic middle molecular weight solutes by the peritoneal membrane compensated for this difference. The publication of the National Cooperative Dialysis Study then focused attention on urea clearance as a significant predictor of hospitalization in hemodialysis patients. The peritoneal dialysis community made a mistake in adopting urea kinetics to the peritoneal dialysis process, while ignoring the benefits incumbent in continuous dialysis therapy and middle molecular weight solute removal. Sadly, to this day, despite the publication of many studies that have been unable to find an association between peritoneal small solute kinetics and outcome, Kt/V urea is employed as a marker of adequacy in these patients.

Are Diuretics Underutilized in Dialysis Patients?

While oral diuretics are commonly used in patients with chronic kidney disease for the management of volume and blood pressure, they are often discontinued upon initiation of dialysis. We suggest that diuretics are considerably underutilized in peritoneal dialysis and haemodialysis patients despite numerous potential benefits and few side effects. Moreover, when diuretics are used, optimal doses are not always prescribed. In peritoneal dialysis, the use of diuretics can improve volume status and minimize the need for higher glucose-containing solutions. In patients on haemodialysis, diuretics can help lessen interdialytic weight gain, resulting in decreased ultrafiltration rates and fewer episodes of intradialytic hypotension. This paper will review the mechanism of action of diuretics in patients with renal insufficiency, quantify the risk of side effects and elaborate on the potential advantages of diuretic use in peritoneal dialysis and hemodialysis patients with residual kidney function.