Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

BACKGROUND: The exact pathophysiological mechanisms of SGLT-2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT-2 inhibitors have potential anti-proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT-2 inhibitor drugs limit the generalizability of pre-clinical studies. METHODS: This is a narrative review discussing the potential anti-cancer effects of SGLT-2 inhibitors, an oral glucose-lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre-clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT-2 inhibitors in cancer treatment. RESULTS: Type II diabetes is linked to various comorbidities and malignancies, but some glucose-slowering medications may have a preventive role in cancer. The use of SGLT-2 inhibitors was associated with bladder cancer based on mice studies. However, meta-analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT-2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti-cancer effects of doxorubicin. Combining SGLT-2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT-2 inhibitors in various types of cancer. CONCLUSION: More large-scale pre-clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT-2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre-clinical and clinical data regarding the potential anti-cancer effects of SGLT-2 inhibitors including the hypothetical pathophysiological mechanisms.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR) or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose cotransporter-2 inhibitors to tolvaptan, induced an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predates current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKA) or direct anticoagulants (DOAC). Moreover, it remains unclear which is more effective and safer between them, because estimated creatinine clearance < 25-30 ml/min was an exclusion criterion of the randomized control trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint because they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC vs. OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in hemodialysis patients with AF and undergoing LAAC compared to patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient, to consider individual risks and benefits of each treatment option is underlined.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Updated Strategies in Non-Culprit Stenosis Management of Multivessel Coronary Disease-A Contemporary Review.

The prevalence of multivessel coronary artery disease (CAD) in acute coronary syndrome (ACS) patients underscores the need for optimal revascularization strategies. The ongoing debate surrounding percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), hybrid interventions, or medical-only management adds complexity to decision-making, particularly in specific angiographic scenarios. The article critically reviews existing literature, providing evidence-based perspectives on non-culprit lesion revascularization in ACS. Emphasis is placed on nuances such as the selection of revascularization methods, optimal timing for interventions, and the importance of achieving completeness in revascularization. The debate between culprit-only revascularization and complete revascularization is explored in detail, focusing on ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including patients with cardiogenic shock. Myocardial revascularization guidelines and recent clinical trials support complete revascularization strategies, either during the index primary PCI or within a short timeframe following the culprit lesion PCI (in both STEMI and NSTEMI). The article also addresses the complexities of decision-making in NSTEMI patients with multivessel CAD, advocating for immediate multivessel PCI unless complex coronary lesions require a staged revascularization approach. Finally, the article provided contemporary data on chronic total occlusion revascularization in ACS patients, highlighting the prognostic impact. In conclusion, the article addresses the evolving challenges of managing multivessel CAD in ACS patients, enhancing thoughtful integration into the clinical practice of recent data. We provided evidence-based, individualized approaches to optimize short- and long-term outcomes. The ongoing refinement of clinical and interventional strategies for non-culprit lesion management remains dynamic, necessitating careful consideration of patient characteristics, coronary stenosis complexity, and clinical context.

The conundrum of the complex relationship between acute kidney injury and cardiac arrhythmias.

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine levels, reduced urine output or both. Death may occur in 16-49% of patients admitted to an intensive care unit with severe AKI. Complex arrhythmias are a potentially serious complication in AKI patients with pre-existing or AKI-induced heart damage and myocardial dysfunction, with fluid overload, especially electrolyte and acid-base disorders, representing the pathogenetic mechanisms of arrhythmogenesis. Cardiac arrhythmias, in turn, increase the risk of poor renal outcomes, including AKI. Arrhythmic risk in AKI patients receiving kidney replacement treatment may be reduced by modifying dialysis/replacement fluid composition. The most common arrhythmia observed in AKI patients is atrial fibrillation. Severe hyperkalaemia, sometimes combined with hypocalcaemia, causes severe bradyarrhythmias in this clinical setting. Although the likelihood of life-threatening ventricular arrhythmias is reportedly low, the combination of cardiac ischaemia and specific electrolyte or acid-base abnormalities may increase this risk, particularly in AKI patients who require kidney replacement treatment. The purpose of this review is to summarize the available epidemiological, pathophysiological and prognostic evidence aiming to clarify the complex relationships between AKI and cardiac arrhythmias.

Intrauterine life to adulthood: a potential risk factor for chronic kidney disease.

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.

Shared decision making in patients with kidney failure.

'Elderly' is most commonly defined as an individual aged 65 years or older. However, this definition fails to account for the differences in genetics, lifestyle and overall health that contribute to significant heterogeneity among the elderly beyond chronological age. As the world population continues to age, the prevalence of chronic diseases, including chronic kidney disease (CKD), is increasing and CKD frequently progresses to kidney failure. Moreover, frailty represents a multidimensional clinical entity highly prevalent in this population, which needs to be adequately assessed to inform and support medical decisions. Selecting the optimal treatment pathway for the elderly and frail kidney failure population, be it hemodialysis, peritoneal dialysis, or conservative kidney management is complex, because of the presence of comorbidities associated with low survival rates and impaired quality of life. Management of these patients should involve a multidisciplinary approach including doctors from various specialties, nurses, psychologists, dieticians, and physiotherapists. Studies are mostly retrospective and observational, lacking adjustment for confounders or address selection and indication biases, making it difficult to use these data to guide treatment decisions. Throughout this review we discuss the difficulty of making a one-size-fits-all recommendation for the clinical needs of older patients with kidney failure. We advocate that a research agenda for optimization of the critical issues we present in this review be implemented. We recommend prospective studies that address these issues, and systematic reviews incorporating the complementary evidence of both observational and interventional studies. Furthermore, we strongly support a shared decision making process matching evidence with patient preferences to ensure that individualized choices are made regarding dialysis vs. conservative kidney management, dialysis modality, and optimal vascular access.

Preparing European Nephrology for the next pandemic: lessons from the ERACODA collaboration.

Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of a similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss the challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators and researchers.

Kidney transplantation: a possible solution to obstructive sleep apnea in patients with end-stage kidney disease.

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently reported among patients with chronic kidney disease resulting in considerable morbidity and mortality. OSA may cause repetitive stimulation of the sympathetic nervous system and elevations in pulmonary artery pressure leading to an elevated risk of cardiac and vascular complications in patients with chronic kidney disease. Furthermore, OSA is associated with progressive worsening of kidney injury and loss of renal function. METHODS: In this systematic review and meta-analysis, we evaluated the effect of renal transplantation on the progression of OSA in patients with end-stage kidney disease. RESULTS: The meta-analysis included eight studies with a total of 401 patients. Findings showed that kidney transplantation does not lead to a statistically significant effect on the apnea-hypopnea index (MD 2.6 events/hr, 95% CI -3.2 to 8.3, p = 0.21), total sleep time (MD 14.7 min/night, 95% CI -8.4 to 37.8, p = 0.76), sleep efficiency (MD 2.5%, 95% CI -1.4 to 6.3, p = 0.57), slow wave sleep (MD 0.4% of total sleep time, 95% CI -7.5 to 8.4, p = 0.05), and rapid eye movement sleep (MD 0.6% of total sleep time, 95% CI -2.2 to 3.3, p = 0.98). There was no statistically significant effect of kidney transplantation on OSA in patients with chronic renal disease.

Fatty kidney: A possible future for chronic kidney disease research.

BACKGROUND: Metabolic syndrome is a growing twenty-first century pandemic associated with multiple clinical comorbidities ranging from cardiovascular diseases, non-alcoholic fatty liver disease and polycystic ovary syndrome to kidney dysfunction. A novel area of research investigates the concept of fatty kidney in the pathogenesis of chronic kidney disease, especially in patients with diabetes mellitus or metabolic syndrome. AIM: To review the most updated literature on fatty kidney and provide future research, diagnostic and therapeutic perspectives on a disease increasingly affecting the contemporary world. MATERIALS AND METHOD: We performed an extensive literature search through three databases including Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) and PubMed/Medline Web of Science in November 2021 by using the following terms and their combinations: 'fatty kidney', 'ectopic fat', 'chronic kidney disease', 'cardiovascular event', 'cardio-metabolic risk', 'albuminuria' and 'metabolic syndrome'. Each study has been individually assessed by the authors. RESULTS: Oxidative stress and inflammation, Klotho deficiency, endoplasmic reticulum stress, mitochondrial dysfunction and disruption of cellular energy balance appear to be the main pathophysiological mechanisms leading to tissue damage following fat accumulation. Despite the lack of large-scale comprehensive studies in this novel field of research, current clinical trials demonstrate fatty kidney as an independent risk factor for the development of chronic kidney disease and cardiovascular events. CONCLUSION: The requirement for future studies investigating the pathophysiology, clinical outcomes and therapeutics of fatty kidney is clear.

The Clinical Frailty Scale as a triage tool for ICU admission of dialysis patients with COVID-19: an ERACODA analysis.

BACKGROUND: Several guidelines recommend using the Clinical Frailty Scale (CFS) for triage of critically ill coronavirus disease 2019 (COVID-19) patients. This study evaluates the impact of CFS on intensive care unit (ICU) admission rate and hospital and ICU mortality rates in hospitalized dialysis patients with COVID-19. METHODS: We analysed data of dialysis patients diagnosed with COVID-19 from the European Renal Association COVID-19 Database. The primary outcome was ICU admission rate and secondary outcomes were hospital and ICU mortality until 3 months after COVID-19 diagnosis. Cox regression analyses were performed to assess associations between CFS and outcomes. RESULTS: A total of 1501 dialysis patients were hospitalized due to COVID-19, of whom 219 (15%) were admitted to an ICU. The ICU admission rate was lowest (5%) in patients >75 years of age with a CFS of 7-9 and highest (27%) in patients 65-75 years of age with a CFS of 5. A CFS of 7-9 was associated with a lower ICU admission rate than a CFS of 1-3 [relative risk 0.49 (95% confidence interval 0.27-0.87)]. Overall, mortality at 3 months was 34% in hospitalized patients, 65% in ICU-admitted patients and highest in patients >75 years of age with a CFS of 7-9 (69%). Only 9% of patients with a CFS ≥6 survived after ICU admission. After adjustment for age and sex, each CFS category ≥4 was associated with higher hospital and ICU mortality compared with a CFS of 1-3. CONCLUSIONS: Frail dialysis patients with COVID-19 were less frequently admitted to the ICU. Large differences in mortality rates between fit and frail patients suggest that the CFS may be a useful complementary triage tool for ICU admission in dialysis patients with COVID-19.

Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

The Usefulness of Assessing Heart Rate Variability in Patients with Acute Myocardial Infarction (HeaRt-V-AMI).

BACKGROUND: Heart rate variability (HRV) could have independent and critical prognostic values in patients admitted for ST segment elevation myocardial infarction (STEMI). There are limited data in the literature regarding HRV assessment in STEMI setting. Thus, we aim to investigate the potential correlations between HRV and adverse outcomes in a contemporary cohort of patients presenting with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: We will perform a prospective, observational cohort study in a single healthcare center. Adult patients aged ≥18 years presenting with STEMI in sinus rhythm will be enrolled for primary PCI within 12 h from symptoms onset. Time domain, frequency domain, and nonlinear HRV parameters will be measured using a medically approved wrist-wearable device for 5 min segments during myocardial revascularization by primary PCI. Additional HRV measurements will be performed one and six months from the index event. The primary composite outcome will include all-cause mortality and major adverse cardiovascular events (during the hospital stay, one month, and one year following admission). Several secondary outcomes will be analyzed: individual components of the primary composite outcome, target lesion revascularization, hospitalizations for heart failure, ventricular arrhythmias, left ventricular ejection fraction, and left ventricular diastolic function. CONCLUSIONS: Our study will enlighten the reliability and usefulness of HRV evaluation as a prognostic marker in contemporary patients with STEMI. The potential validation of HRV as a risk marker for adverse outcomes following STEMI will ensure a background for including HRV parameters in future risk scores and guidelines.

A randomized multicenter trial on a lung ultrasound-guided treatment strategy in patients on chronic hemodialysis with high cardiovascular risk.

Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Accurate and early detection of sleepiness, fatigue and stress levels in drivers through Heart Rate Variability parameters: a systematic review.

Sleepiness, fatigue, and stress in drivers are the leading causes of car crashes. In the late two decades, there is an endeavor to monitor vital signs, stress levels, and fatigue using adapted sensors supported by technological advances. To the best of our knowledge, this systematic review is the first to investigate the role of HRV measurement for sleepiness, fatigue, and stress level monitoring in car drivers. A search was performed in PubMed, Embase, and Cochrane databases using prespecified keywords. Studies were considered for inclusion if they reported original data regarding the association between different HRV measurements and drivers' sleepiness, fatigue, or stress levels. Of the retrieved 749 citations, 19 studies were finally included. The sensibility and specificity of HRV significantly varied across studies, respectively 47.1%-95% and 74.6%-98%. Accuracy was also different, ranging from 56.6% to 95%. Nevertheless, in real-world conditions, confounding factors could affect sympathovagal tone and HRV. Multiple HRV parameters measurement rather than one parameter approach seems to be the optimal strategy for evaluating the vigilance state in drivers that it would be possible to achieve a good performance. As all studies were observational, data should be confirmed in randomized controlled trials. In conclusion, HRV represents a potentially valuable marker for sleepiness, fatigue, and stress monitoring in car drivers. HRV measurements could be implemented in future clinical models and sensors to detect early sleepiness and fatigue and prevent car crashes. More studies with larger populations are needed to support this evidence.

Treating a thrombotic giant dissecting renal artery aneurysm through ex-vivo vascular reconstructive surgery followed by kidney reimplantation.

Renal artery aneurysms, although rare, may give rise to complications both per se (due to the risk of thrombosis and subsequent wall rupture) and by impairment of the renal function (due to extrinsic compression and high blood pressure). We describe a paucisymptomatic young patient with acute thrombosis of a massive dissecting renal artery aneurysm, for which the successful treatment was performed through ex-vivo vascular surgery followed by autotransplantation of the reconstructed kidney. The aneurysm was described through abdominal echography, computed tomography angiography, and transfemoral transcatheter arterial angiography. It originated from an atypical branch emerging at 90 degrees from the left renal artery. After a short branching off, it degenerated into a dissected aneurysmal sac as large as half a kidney (outer diameter of 60 mm), compressing the lower pole of the left kidney and delaying the lower half nephrogram. Ex-vivo surgical exclusion of the aneurysm was successfully performed. The kidney was reimplanted in the left iliac fossa (termino-lateral anastomosis between the renal artery and external left iliac artery, termino-terminal ureteric anastomosis) with excellent postoperative outcomes. For most asymptomatic aneurysms, expectant treatment is a reasonable approach. However, interventional or surgical repair is indicated in certain circumstances depending on the size of the aneurysm and its natural history, rupture risk, and interventional/surgical risks. The renovascular hypertension, dissecting and thrombotic events, its giant size, the young fertile age, and the presence of the flank pain were all indicative of the need for aneurysm exclusion in our case.

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.

COVID-19-related mortality in kidney transplant and haemodialysis patients: a comparative, prospective registry-based study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed haemodialysis (HD) patients and kidney transplant (KT) recipients to an unprecedented life-threatening infectious disease, raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. This study investigated the association of the type of KRT with COVID-19 severity, adjusting for differences in individual characteristics. METHODS: Data on KT recipients and HD patients diagnosed with COVID-19 between 1 February 2020 and 1 December 2020 were retrieved from the European Renal Association COVID-19 Database. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HRs) for 28-day mortality risk in all patients and in the subsets that were tested because of symptoms. RESULTS: A total of 1670 patients (496 functional KT and 1174 HD) were included; 16.9% of KT and 23.9% of HD patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in KT recipients compared with HD patients {HR 0.67 [95% confidence interval (CI) 0.52-0.85]}. In a fully adjusted model, the risk was 78% higher in KT recipients [HR 1.78 (95% CI 1.22-2.61)] compared with HD patients. This association was similar in patients tested because of symptoms [fully adjusted model HR 2.00 (95% CI 1.31-3.06)]. This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, intensive care unit admission and mortality >28 days) and across subgroups. CONCLUSIONS: KT recipients had a greater risk of a more severe course of COVID-19 compared with HD patients, therefore they require specific infection mitigation strategies.