Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

BACKGROUND: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. METHODS: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. RESULTS: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). CONCLUSIONS: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

The effect of implementing a dialysis start unit on modality decision among patients with unplanned start kidney replacement therapy.

INTRODUCTION: Many individuals start dialysis in an acute setting with suboptimal pre-dialysis education. These individuals are often treated with central venous catheter insertion and initiation of in-center hemodialysis and only a minority will transfer to a home-based therapy. The dialysis start unit is a program performing in-center hemodialysis in a separate space while providing support and education on chronic kidney disease and treatment options in the initial weeks of kidney replacement therapy. We aimed to assess the uptake of home dialysis therapies between 2013 and 2021 among patients who started acute inpatient hemodialysis at University Health Network, Toronto and underwent dialysis at the dialysis start unit. METHODS: This is a retrospective observational cohort study based on prospectively collected data. Patients' demographics were obtained from electronic charts. In the dialysis start unit, all patients received dialysis modality education by a nurse educator, dedicated home dialysis nurses, and the allied health care team. FINDINGS: During 2013-2021, 122 patients were dialyzed in the dialysis start unit and included in the study. Among those patients, 68 patients ultimately chose home dialysis (57 peritoneal dialysis and 11 home hemodialysis). Fifty-four patients continued in-center hemodialysis. Patients adopting home dialysis were less likely to have diabetes and hypertension as the etiology of kidney failure and more likely to have glomerulonephritis or vasculitis. DISCUSSION: Dialysis modality education is implementable in advanced chronic kidney disease. Individualized education and care after unplanned start dialysis can potentially enhance home dialysis choice and utilization.

Intraoperative hemodialysis with supra- and infradiaphragmatic catheters for liver transplantation.

PURPOSE: The benefits of intraoperative dialysis during orthotopic liver transplantation remain controversial. In patients with anuric renal failure and portopulmonary hypertension, maintaining venous return during caval clamping and unclamping along with minimizing fluid overload is critical to avoiding right ventricular strain and failure. CLINICAL FEATURES: We present the case of a 54-yr-old female who underwent orthotopic liver transplantation for alcohol-related liver disease with acute decompensation including severe hepatorenal syndrome (anuric requiring dialysis), probable hepatopulmonary syndrome, moderate pulmonary hypertension (right ventricular systolic pressure, 44 mm Hg), hepatic encephalopathy (grade 2), and esophageal varices. Prior to incision, pulmonary arterial pressures were 48/28 (mean, 35) mm Hg with a central venous pressure of 30 mm Hg, cardiac output of 7.4 L·min-1, and pulmonary vascular resistance of 98 dynes·sec·cm-5. In the context of right ventricular strain and volume overload observed on transthoracic echocardiography, we inserted an additional dialysis catheter into the right femoral vein. We initiated dialysis using the two catheters as a circuit (femoral line to the dialysis machine; blood was reinjected via the subclavian line) acting as a limited venovenous bypass, allowing right ventricular offloading and hemodialysis throughout the case. We removed 4.5 L via hemodialysis during the surgery, while avoiding acidosis, hyperkalemia, and sodium shifts. The patient tolerated reperfusion adequately despite pre-existing right ventricular dilation and dysfunction. CONCLUSION: We report on the use two hemodialysis catheters in a patient undergoing orthotopic liver transplantation as a circuit for simultaneous anuric hepatorenal syndrome and moderate pulmonary hypertension with right ventricular dilation and dysfunction. We believe this technique was instrumental in the patient's successful transplant.

RéSUMé: OBJECTIF: Les avantages de la dialyse peropératoire pendant une transplantation hépatique orthotopique demeurent controversés. Chez la patientèle atteinte d'insuffisance rénale anurique et d'hypertension portopulmonaire, il est essentiel de maintenir le retour veineux pendant le clampage et le déclampage de la veine cave ainsi que de minimiser la surcharge hydrique, afin d'éviter la déformation et l'insuffisance ventriculaires droites. CARACTéRISTIQUES CLINIQUES : Nous présentons le cas d'une femme de 54 ans qui a bénéficié d'une transplantation hépatique orthotopique pour une maladie hépatique liée à l'alcool avec une décompensation aiguë comprenant un syndrome hépatorénal sévère (anurie nécessitant une dialyse), un syndrome hépatopulmonaire probable, une hypertension pulmonaire modérée (pression systolique ventriculaire droite, 44 mm Hg), une encéphalopathie hépatique (grade 2) et des varices œsophagiennes. Avant l'incision, les pressions artérielles pulmonaires étaient de 48/28 (moyenne, 35) mm Hg avec une pression veineuse centrale de 30 mm Hg, un débit cardiaque de 7,4 L·min−1 et une résistance vasculaire pulmonaire de 98 dynes·sec·cm−5. Dans le contexte de la déformation ventriculaire et de la surcharge volémique droites observées à l'échocardiographie transthoracique, nous avons inséré un cathéter de dialyse supplémentaire dans la veine fémorale droite. Nous avons amorcé la dialyse en créant un circuit avec les deux cathéters (ligne fémorale en direction de l'appareil de dialyse; sang réinjecté via la ligne sous-clavière) agissant comme un pontage veino-veineux limité, permettant la décharge du ventricule droit et l'hémodialyse tout au long du cas. Nous avons retiré 4,5 L par hémodialyse pendant la chirurgie, tout en évitant l'acidose, l'hyperkaliémie et les changements en sodium plasmatique. La patiente a toléré la reperfusion de manière adéquate malgré la dilatation et le dysfonctionnement préexistants du ventricule droit. CONCLUSION: Nous rapportons l'utilisation de deux cathéters d'hémodialyse pour créer un circuit chez une patiente bénéficiant d'une transplantation hépatique orthotopique pour le traitement d'un syndrome hépatorénal anurique simultané à une hypertension pulmonaire modérée avec dilatation et dysfonctionnement du ventricule droit. Nous pensons que cette technique a joué un rôle déterminant dans la réussite de la greffe chez la patiente.

Integrated home dialysis model: facilitating home-to-home transition.

Peritoneal dialysis (PD) and home hemodialysis (HHD) are the two home dialysis modalities offered to patients. They promote patient autonomy, enhance independence, and are generally associated with better quality of life compared to facility hemodialysis. PD offers some advantages (enhanced flexibility, ability to travel, preservation of residual kidney function, and vascular access sites) but few patients remain on PD indefinitely due to peritonitis and other complications. By contrast, HHD incurs longer and more intensive training combined with increased upfront health costs compared to PD, but is easier to sustain in the long term. As a result, the integrated home dialysis model was proposed to combine the advantages of both home-based dialysis modalities. In this paradigm, patients are encouraged to initiate dialysis on PD and transfer to HHD after PD termination. Available evidence demonstrates the feasibility and safety of this approach and some observational studies have shown that patients who undergo the PD-to-HHD transition have clinical outcomes comparable to patients who initiate dialysis directly on HHD. Nevertheless, the prevalence of PD-to-HHD transfers remains low, reflecting the multiple barriers that prevent the full uptake of home-to-home transitions, notably a lack of awareness about the model, home-care "burnout," clinical inertia after a transfer to facility HD, suboptimal integration of PD and HHD centers, and insufficient funding for home dialysis programs. In this review, we will examine the conceptual advantages and disadvantages of integrated home dialysis, present the evidence that underlies it, identify challenges that prevent its success and finally, propose solutions to increase its adoption.

Vascular Access Considerations in Home Hemodialysis.

There is a global interest in expanding home dialysis utilization among patients with ESKD. Home hemodialysis (HHD) is an appealing KRT option for this population because of its multiple clinical and quality of life benefits. Central to successful HHD is the establishment and maintenance of a functioning vascular access that serves as a patient's lifeline while on therapy. While the selection of a vascular access type is influenced by individual patient circumstances, the arteriovenous fistula is generally the preferred access method. Training patients to use their dialysis access requires attention to safety, risk management, and monitoring for complications to minimize adverse events and technique failure. Policies incorporating systematic frameworks for quality improvement and assurance, in conjunction with the measurement of metrics relating to vascular access, are tools that should be used by HHD programs to enhance the value of care delivered. In this perspective, we aim to describe what is currently known about the various vascular access options in HHD and to elucidate what needs to be taken into consideration in the selection and care of this access.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

INTRODUCTION: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. METHODS: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). RESULTS: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. CONCLUSIONS: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Patient Survival With Extended Home Hemodialysis Compared to In-Center Conventional Hemodialysis.

Introduction: More frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up. Methods: We matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters. Results: The mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement. Conclusion: These results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.

Integrated Care: A Person-Centered and Population Health Strategy for the COVID-19 Pandemic Recovery and Beyond.

The COVID-19 pandemic has mandated a re-imagination of how healthcare is administered and delivered, with a view towards focusing on person-centred care and advancing population health while increasing capacity, access and equity in the healthcare system. These goals can be achieved through healthcare integration. In 2019, the University Health Network (UHN), a consortium of four quaternary care hospitals in Ontario, Canada, established the first stage of a pilot program to increase healthcare integration at the institutional level and vertically with other primary, secondary and tertiary institutions in the Ontario healthcare system. Implementation of the program was accelerated during the COVID-19 pandemic and demonstrated how healthcare integration improves person-centred care and population health; therefore serving as the foundation for a health system response for the COVID-19 pandemic recovery and beyond.

BNT162b2 versus mRNA-1273 Third Dose COVID-19 Vaccine in Patients with CKD and Maintenance Dialysis Patients.

BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations. METHODS: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants ( n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1). RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63). CONCLUSIONS: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 .

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.

Andreas Pierratos Tribute: Personal Reflections.

Since the passing of Andreas Pierratos on November 15, 2022, we have had many occasions to reflect on what our relationship with a friend and colleague has meant. We have done this in solitude, with colleagues while at work and more recently, in a tribute organized at Humber River Hospital on March 26, 2023. We also had the opportunity to expand, in the February 2023 issue of the Nephrology News & Issues, on his many contributions to nephrology and to the betterment of patients' lives. For this collaboration, we thought we would share our personal reflections of this unique individual, with the hope that this effort would provide a deeper appreciation of his unique humanity.

Systems Innovations to Increase Home Dialysis Utilization.

Globally, there is an interest to increase home dialysis utilization. The most recent United States Renal Data System (USRDS) data report that 13.3% of incident dialysis patients in the United States are started on home dialysis, while most patients continue to initiate KRT with in-center hemodialysis. To effect meaningful change, a multifaceted innovative approach will be needed to substantially increase the use of home dialysis. Patient and provider education is the first step to enhance home dialysis knowledge awareness. Ideally, one should maximize the number of patients with CKD stage 5 transitioning to home therapies. If this is not possible, infrastructures including transitional dialysis units and community dialysis houses may help patients increase self-care efficacy and eventually transition care to home. From a policy perspective, adopting a home dialysis preference mandate and providing financial support to recuperate increased costs for patients and providers have led to higher uptake in home dialysis. Finally, respite care and planned home-to-home transitions can reduce the incidence of transitioning to in-center hemodialysis. We speculate that an ecosystem of complementary system innovations is needed to cause a sufficient change in patient and provider behavior, which will ultimately modify overall home dialysis utilization.