The effect of a single dose of BNT162b2 vaccine on the incidence of severe COVID-19 infection in patients on chronic hemodialysis: a single-centre study.

INTRODUCTION: In this single-centre retrospective observational study, the 8-week safety and the efficiency of a single dose of BNT162b2 vaccine was studied in 83 HD patients. METHODS: All clinically stable adult ESRD patients on chronic HD for at least 4 weeks were screened for participation in the study. Exclusion criteria for enrollment in the study included a medical history of COVID-19 infection within the last 12 weeks or delivery of both vaccine doses less than 8 weeks apart from each other. The same patients during the 8-week period that preceded the vaccination served as controls of themselves. The vaccine was administered intramuscularly in the deltoid muscle, on a dialysis day, at least 30 min either pre- or post-dialysis. The primary end-point of the study was severe COVID-19 infection, and/or death due to COVID-19 pneumonitis. Furthermore, all vaccinated patients were scrutinized for any local or systemic reactions within the first 7 days post-vaccination. RESULTS: Amongst 113 adult HD patients in our Unit, in total 83 patients had the first 30 µg dose of the BNT162b2 vaccine and were considered eligible to be included in the study. The 8-week survival rate was 91% for the controls and 100% for the vaccine group. No life-threatening allergic reaction or other side-effect was observed post-vaccination. CONCLUSION: The BNT162b2 vaccine can be safely used in HD patients and seems to offer significant protection against the infection even after the first vaccine dose.

A call to optimize haemodialysis vascular access care in healthcare disrupted by COVID-19 pandemic.

The COVID-19 pandemic has resulted in major disruption to the delivery of both routine and urgent healthcare needs in many institutions across the globe. Vascular access (VA) for haemodalysis (HD) is considered the patient's lifeline and its maintenance is essential for the continuation of a life saving treatment. Prior to the COVID-19 pandemic, the provision of VA for dialysis was already constrained. Throughout the pandemic, inevitably, many patients with chronic kidney disease (CKD) have not received timely intervention for VA care. This could have a detrimental impact on dialysis patient outcomes in the near future and needs to be addressed urgently. Many societies have issued prioritisation to allow rationing based on clinical risk, mainly according to estimated urgency and need for treatment. The recommendations recently proposed by the European and American Vascular Societies in the COVID-19 pandemic era regarding the triage of various vascular operations into urgent, emergent and elective are debatable. VA creation and interventions maintain the lifeline of complex HD patients, and the indication for surgery and other interventions warrants patient-specific clinical judgement and pathways. Keeping the use of central venous catheters at a minimum, with the goal of creating the right access, in the right patient, at the right time, and for the right reasons, is mandatory. These strategies may require local modifications. Risk assessments may need specific "renal pathways" to be developed rather than applying standard surgical risk stratification. In conclusion, in order to recover from the second wave of COVID-19 and prepare for further phases, the provision of the best dialysis access, including peritoneal dialysis, will require working closely with the multidisciplinary team involved in the assessment, creation, cannulation, surveillance, maintenance, and salvage of definitive access.

Coronary artery disease in dialysis patients: evidence synthesis, controversies and proposed management strategies.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among patients with end-stage renal disease (ESRD). Clustering of traditional atherosclerotic and non-traditional risk factors drive the excess rates of coronary and non-coronary CVD in this population. The incidence, severity and mortality of coronary artery disease (CAD) as well as the number of complications of its therapy is higher in dialysis patients than in non-chronic kidney disease patients. Given the lack of randomized clinical trial evidence in this population, current practice is informed by observational data with a significant potential for bias. Furthermore, guidelines lack any recommendation for these patients or extrapolate them from trials performed in non-dialysis patients. Patients with ESRD are more likely to be asymptomatic, posing a challenge to the correct identification of CAD, which is essential for appropriate risk stratification and management. This may lead to "therapeutic nihilism", which has been associated with worse outcomes. Here, the ERA-EDTA EUDIAL Working Group reviews the diagnostic work-up and therapy of chronic coronary syndromes, unstable angina/non-ST elevation and ST-elevation myocardial infarction in dialysis patients, outlining unclear issues and controversies, discussing recent evidence, and proposing management strategies. Indications of antiplatelet and anticoagulant therapies, percutaneous coronary intervention and coronary artery bypass grafting are discussed. The issue of the interaction between dialysis session and myocardial damage is also addressed.

Frontiers in hemodialysis: Innovations and technological advances.

As increasing demand for hemodialysis (HD) treatment incurs significant financial burden to healthcare systems and ecological burden as well, novel therapeutic approaches as well as innovations and technological advances are being sought that could lead to the development of purification devices such as dialyzers with improved characteristics and wearable technology. Novel knowledge such as the development of more accurate kinetic models, the development of novel HD membranes with the use of nanotechnology, novel manufacturing processes, and the latest technology in the science of materials have enabled novel solutions already marketed or on the verge of becoming commercially available. This collaborative article reviews the latest advances in HD as they were presented by the authors in a recent symposium titled "Frontiers in Haemodialysis," held on 12th December 2019 at the Royal Society of Medicine in London.

Sudden cardiac death in dialysis patients: different causes and management strategies.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.

Recent advances in treatment of haemodialysis.

Haemodialysis remains the most widely used treatment for patients with end-stage renal disease. Despite the progress that has occurred in the treatment of end-stage renal disease over the last six decades, there has been a failure to translate this into the desired clinical benefits, with morbidity and mortality rates among patients on haemodialysis remaining unacceptably high. Recently, however, there have been expectations that the significant advances that took place over the last few years may result in improved outcomes. New medications for the treatment of anaemia and secondary hyperparathyroidism, as well as novel trends in the areas of iron therapy, diabetes management and physical exercise are among the most important advances which, taken together, are changing the standards of care for patients on haemodialysis. The latest advances, of relevance not only to specialists in Renal Medicine but also to general practitioners caring for these patients, are reviewed in this collaborative paper.

Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.

Calcium balance in hemodialysis: More uncertainty than certainty.

There is controversy about the choice of dialysate calcium concentration (DCa), with strong arguments both in favor of and against the use of a low or high DCa, as they can both be potentially harmful. Evidence suggests that calcium mass balance is positive with a DCa 3.5 mEq/L, negative or neutral with the use of DCa 2.5 mEq/L, whereas both positive and negative balances have been observed with the use of DCa 3.0 mEq/L. Overall, the use of DCa >2.5 mEq/L is usually associated with an increase in serum calcium level and a decrease in serum PTH level and use of lower vitamin D analogue dose, with the opposite effects usually observed with the use of lower DCa. Most of the available evidence is from small-sized and crossover studies; hence, evidence should be regarded with caution and applied in a patient-specific manner. As there are a lot of significant unanswered questions regarding calcium balance and the optimal DCa in hemodialysis patients, further high-quality research is needed to clarify many still unclear aspects of calcium homeostasis and balance in these patients. In conclusion, with the existing evidence the choice of DCa needs to be individualized and contextualized in the setting of each patient's calcium balance needs and homeostatic response, taking also into account oral calcium intake (dietary and medicinal), any other relevant therapy administered, such as vitamin D analogues, the type of renal mineral bone disorder, and associated cardiovascular comorbidity.

Exit-Site Relocation: A Novel, Straightforward Technique for Exit-Site Infections.

Background:Exit-site infection (ESI) and tunnel infection (TI) of the peritoneal dialysis (PD) catheter are significant causes of catheter or even method loss as well as patient morbidity. Among the methods that have been in use thus far, the removal and replacement of the catheter often needs to be followed by switching temporarily to hemodialysis, whereas catheter splicing or unroofing of the tunnel tract and shaving/removal of the superficial catheter cuff have not gained universal acceptance thus far.Methods:We treat chronic ESI with exit-site relocation under local anesthetic with removal of the external cuff. For the purposes of this study, we conducted a retrospective cohort analysis of all exit-site relocations performed using that technique over a 5-year period.Results:Twenty-seven patients (16 male, mean age 58 years, range 23 - 81 years) with chronic ESI underwent exit-site relocation under local anesthetic as a day-case procedure. Follow-up was 47.5 ± 22.4 months (range 10.8 - 79.4 months). No dialysate leaks occurred following the procedure. Peritoneal dialysis was resumed immediately. The procedure resulted in long-term resolution of the infection in 20 of the 27 patients (74%). In 7 patients (26%), the catheter had to be removed eventually, either because of ESI recurrence (5 patients) or TI (2 patients), which in 2 cases was subsequently complicated by PD peritonitis, and the patients were switched to hemodialysis.Conclusion:The technique described herein is a safe, straightforward, and effective method for the treatment of chronic ESI while the patient remains on PD and avoids switching to hemodialysis.

Should a fistula first policy be revisited in elderly haemodialysis patients?

Life-sustaining haemodialysis requires a durable vascular access (VA) to the circulatory system. The ideal permanent VA must provide longevity for use with minimal complication rate and supply sufficient blood flow to deliver the prescribed dialysis dosage. Arteriovenous fistulas (AVFs) have been endorsed by many professional societies as the VA of choice. However, the high prevalence of comorbidities, particularly diabetes mellitus, peripheral vascular disease and arterial hypertension in elderly people, usually make VA creation more difficult in the elderly. Many of these patients may have an insufficient vasculature for AVF maturation. Furthermore, many AVFs created prior to the initiation of haemodialysis may never be used due to the competing risk of death before dialysis is required. As such, an arteriovenous graft and, in some cases, a central venous catheter, become a valid alternative form of VA. Consequently, there are multiple decision points that require careful reflection before an AVF is placed in the elderly. The traditional metrics of access patency, failure and infection are now being seen in a broader context that includes procedure burden, quality of life, patient preferences, morbidity, mortality and cost. This article of the European Dialysis (EUDIAL) Working Group of ERA-EDTA critically reviews the current evidence on VA in elderly haemodialysis patients and concludes that a pragmatic patient-centred approach is mandatory, thus considering the possibility that the AVF first approach should not be an absolute.

Sleep apnea syndrome, inflammation and oxidative stress in hemodialysis patients.

INTRODUCTION: Sleep apnea syndrome (SAS) is an established cardiovascular risk factor in the general population related to inflammation and oxidative stress and is very common among hemodialysis patients. Cardiovascular disease and its complications is the main cause of death among hemodialysis patients. The aim of the present study was to investigate the role of SAS in the promotion of inflammation and oxidative stress and thus in the augmentation of cardiovascular risk in hemodialysis patients. METHODS: Thirty-seven hemodialysis patients underwent an overnight full polysomnography study. The following morning blood samples were obtained and TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density lipoprotein) were measured. FINDINGS: We investigated the correlation of patients' markers of inflammation and oxidative stress with their sleep parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory disturbance index; DI, desaturation index, mean and minimum SpO2 and percentage of sleep time with SpO2 < 90%). TNF-α correlated positively with BMI (r = 0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r = 0.336, P = 0.042) and percentage of sleep time with SpO2 < 90% (r = 0.415, P = 0.012) and negatively with mean SpO2 (r = -0.364, P = 0.027). Myeloperoxidase correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02) and percentage of sleep time with SpO2 < 90% (r = 0.388, P = 0.019). Finally, oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P = 0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO2 <90% (r = 0.389, P = 0.019). CONCLUSIONS: These results indicate that, in hemodialysis patients, the severity of SAS and nocturnal hypoxia correlated positively with markers of inflammation and oxidative stress.

Genome-wide scan identifies a copy number variable region at 3p21.1 that influences the TLR9 expression levels in IgA nephropathy patients.

Immunoglobulin A nephropathy (IgAN) is a complex multifactorial disease characterized by genetic factors that influence the pathogenesis of the disease. In this context, an intriguing role could be ascribed to copy number variants (CNVs). We performed the whole-genome screening of CNVs in familial IgAN patients, their healthy relatives and healthy subjects (HSs). In the initial screening, we included 217 individuals consisting of 51 biopsy-proven familial IgAN cases and 166 healthy relatives. We identified 148 IgAN-specific aberrations, specifically 105 loss and 43 gain, using a new statistical approach that allowed us to identify aberrations that were concordant across multiple samples. Several CNVs overlapped with regions evidenced by previous genome-wide genetic studies. We focused our attention on a CNV located in chromosome 3, which contains the TLR9 gene and found that IgAN patients characterized by deteriorated renal function carried low copy number of this CNV. Moreover, the TLR9 gene expression was low and significantly correlated with the loss aberration. Conversely, IgAN patients with normal renal function had no aberration and the TLR9 mRNA was expressed at the same level as in HSs. We confirmed our data in another cohort of Greek subjects. In conclusion, here we performed the first genome-wide CNV study in IgAN identifying structural variants that could help the genetic dissection of this complex disease, and pointed out a loss aberration in the chromosome 3, which is responsible for the downregulation of TLR9 expression that, in turn, could contribute to the deterioration of the renal function in IgAN patients.

Impact of inflammation on anti-oxidative effects of vitamin E-coated membrane dialyzer in patients on chronic hemodialysis.

Hemodialysis (HD) with the use of vitamin E-coated membrane (VEM) dialyzers is shown to exert anti-inflammatory and antioxidative effects in patients with end-stage renal disease on HD. However, the association of baseline inflammatory status with the antioxidative effects of VEM has not been investigated thus far. Thirty-five stable end-stage renal disease patients treated with VEM for 6 months were enrolled in the present prospective, observational cohort study. For the previous 3 months minimum, 17 (48%) patients were dialyzed with a cellulose, eight (23%) patients with a hemophane, and 10 (29%) patients with a polysulfone 1.2 to 1.5 m(2) hollow fiber dialyzer. The effects of treatment on oxidized low-density lipoprotein (oxLDL) were stratified according to half percentiles of baseline serum logC-reactive protein and interleukin-6, and the association between treatment goal, arbitrarily defined as a minimum 30% decrease in baseline oxLDL, was assessed with the use of logistic regression analysis. The higher C-reactive protein and interleukin-6 half percentiles were independently and additively associated with a higher odds ratio for achieving treatment goal. Adjustment for baseline oxLDL, age, sex, HD duration, smoking, and body mass index did not attenuate the odds ratios, whereas the history of diabetes, as primary renal disease, significantly decreased the odds ratio for achieving treatment goal. Increased baseline C-reactive protein and interleukin-6 are independent, additive factors associated with the effect of VEM on oxLDL in HD patients.

Diagnostic accuracy of arterial line blood gas measurements as an estimate of arteriovenous fistula recirculation.

AIM: We studied the diagnostic accuracy of blood gas determination as a novel method for the estimation of arteriovenous fistula (AVF) recirculation (RC). METHODS: In 25 patients on chronic haemodialysis, with failure of a previously well functioning native AVF (mean two-needle urea-based RC: 41 ± 10%), arterial line (AL) as well as a peripheral vein (PV) blood samples drawn by the end of a 4 h haemodialysis session, before and after the surgical repair of their AVF. RESULTS: Compared to PV samples, patients with RC had significantly higher AL blood pCO2 and pO2 values (P < 0.001) and lower AL blood pH and K(+) values (P < 0.001), findings that were reversed after the surgical restoration of adequate AVF function. On regression analysis, urea RC values were correlated positively with AL pCO2 values (r = 0.683, P < 0.001) and negatively with AL pH values (r = 0.896, P < 0.001). AL pCO2 > 40 mmHg was shown to have the best sensitivity and AL pH < 7.25 the best specificity. RC index, that is, the AL pCO2 /pH ratio, was found to have superior test characteristics compared to pH and pCO2 (sensitivity 95% and specificity 88% for values >5.5) making it a powerful diagnostic as well as screening tool. CONCLUSION: We propose the regular AL blood gas measurement as a novel method of AVF function surveillance and RC diagnosis. AL blood pH < 7.25, pCO2 > 40 mmHg and RC index > 5.5, escorted by rather high pO2 and low K(+) by the end of dialysis session, but probably earlier as well, signify an important RC (>20%) and warrant further investigation of AVF patency.

Vascular access malfunction: towards a more genecentric view.

A well-functioning vascular access is the cornerstone for an optimal hemodialysis treatment and an issue of major importance for the outcome of patients on chronic hemodialysis. Over the last few years reports supporting the aspect that mechanisms involved in vascular access malfunction are genetically controlled have been published. Triggered by two cases reported herein, we present a comprehensive review of the literature on an evolving field of particular significance to patients on hemodialysis.