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Background: Patients with chronic kidney disease have a higher risk of severe disease and mortality from COVID-19 than the general population. Objective: To compare hospitalization and mortality rates during the pandemic among chronic hemodialysis (HD) patients and the general population in Lima (Peru). Methods: This retrospective cohort included an assessment of the database of chronic HD patients of the health service providers of the social health insurance benefit networks of Lima and Callao between 2019 and 2021. Hospitalization and mortality rates were obtained for every 1,000 individuals, and variations in the percentages of COVID-19 cases and deaths were calculated. These rates were compared with those of the general population data and standardized by age and sex. Results: An average of 3,937 chronic HD patients were evaluated each month. Of these, 4.8% had COVID-19 and 64.97% were mild cases. The hospitalization rates per 1,000 patients were 19.5, 29.28, and 36.7 in 2019, 2020, and 2021, respectively. The mortality rates per 1,000 patients were 5.9, 9.74, and 11.49 in 2019, 2020, and 2021, respectively. When compared to the standardized general population, the peaks of both rates coincided with the plateaus of the waves during the pandemic. The hospitalization rate for COVID-19 was 12 times higher in HD patients than in the general population, and the mortality rate for COVID-19 was twice as high. Conclusion: HD patients had higher hospitalization and standardized mortality rates than the general population. Peaks in hospitalizations and mortality coincided with the plateaus of the first and second waves of the pandemic. Resumo Histórico: Pacientes com DRC apresentam maior risco de doença grave e mortalidade por COVID-19 do que a população geral. Objetivo: Comparar taxas de hospitalização e mortalidade durante a pandemia entre pacientes em hemodiálise crônica (HD) e a população geral em Lima (Peru). Métodos: Esta coorte retrospectiva incluiu avaliação do banco de dados de pacientes em HD crônica dos prestadores de serviços de saúde das redes de benefícios do seguro social de saúde de Lima e Callao, entre 2019–2021. Obteve-se taxas de hospitalização e mortalidade para cada 1.000 indivíduos, e foram calculadas variações nas porcentagens de casos de COVID-19 e óbitos. Estas taxas foram comparadas com os dados da população geral e padronizadas por idade e sexo. Resultados: Uma média de 3.937 pacientes em HD crônica foram avaliados mensalmente. Destes, 4,8% tinham COVID-19, 64,97% eram casos leves. As taxas de hospitalização por 1.000 pacientes foram 19,5; 29,28; e 36,7 em 2019, 2020, e 2021, respectivamente. As taxas de mortalidade por 1.000 pacientes foram 5,9; 9,74 e 11,49 em 2019, 2020, e 2021, respectivamente. Quando comparados à população geral padronizada, os picos das taxas coincidiram com os platôs das ondas da pandemia. A taxa de hospitalização para COVID-19 foi 12 vezes maior em pacientes em HD do que na população geral e a taxa de mortalidade por COVID-19 foi duas vezes maior. Conclusão: Pacientes em HD apresentaram taxas de hospitalização e mortalidade padronizada mais elevadas do que a população geral. Os picos das hospitalizações e mortalidade coincidiram com os platôs da primeira e segunda ondas da pandemia.

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4months (interquartile ranges [IQR], 0.8-3.8), 10.8months (IQR, 4.5-16.9), and 17.5months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Background Restless legs syndrome (RLS) is characterized by an urge to move the extremities, accompanied by paraesthesiae, in the evening and at night. Uraemic RLS, a type of secondary RLS, occurs commonly in chronic kidney disease and end-stage renal disease. Progression of uraemic RLS over time is unclear. Therefore we investigated the prevalence, progression over time, risk factors and impact on survival of uraemic RLS in a cohort of dialysis patients. Methods We reviewed at the 7-year follow-up a cohort of haemodialysis (HD) patients we had previously investigated for RLS, through interviews, validated questionnaires and analysis of demographic and clinical data. Results At the 7-year follow-up, RLS was present in 16% of patients, with a persistence rate of 33%. A correlation was obtained between RLS and older age, diabetes, low albumin and low body mass index. RLS was associated with reduced overall survival (median survival of 3.3 versus 3.7 years), particularly with the continuous form of RLS (1.61 years). There was a higher incidence of myocardial infarction and peripheral vascular disease, although not reaching statistical significance. RLS patients had absolute higher scores in all quality of life domains. A large majority of study patients (96%) reported being symptom-free within a few days or weeks following kidney transplantation. Conclusions The development of RLS, especially the continuous form, in patients undergoing HD has important consequences associated with decreased survival. Our results indicated an association between uraemic RLS and ageing, diabetes and malnutrition. Considerable efforts should be focused on the treatment of RLS, since it significantly and persistently impacts the quality of life of HD patients. Kidney transplantation could represent an effective treatment option for that RLS impacts on dialysis patients' quality of life, thus confirming the secondary nature of RLS in most HD patients.

We developed Mixed Matrix Membrane Adsorbers (MMMAs) formed by cellulose acetate and various sorbent particles (activated carbon, zeolites ZSM-5 and clinoptilolite) for the removal of urea, creatinine and uric acid from aqueous solutions, to be used in the regeneration of spent dialysate water from Hemodialysis (HD). This process would allow reducing the disproportionate amount of water consumed and permits the development of closed-loop HD devices, such as wearable artificial kidneys. The strategy of MMMAs is to combine the high permeability of porous membranes with the toxin-capturing ability of embedded particles. The water permeability of the MMMAs ranges between 600 and 1500 L/(h m2 bar). The adsorption of urea, the limiting toxin, can be improved of about nine times with respect to the pure cellulose acetate membrane. Flow experiments demonstrate the feasibility of the process in a real HD therapy session.

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p=0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p=0.552; iliac: 52.0% and 59.5%, respectively, p=0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363–0.985; p=0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system. Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

The ADMET profile of drugs is strongly affected by human serum albumin (HSA), due to its leading role as carrier of poorly soluble compounds in plasma; a critical assessment of the binding capacity of HSA and the evaluation of binding competition between drugs are therefore pivotal for a reliable pharmacokinetic and pharmacodynamic characterization. In clinical practice, a potential source of impairment in the binding properties of HSA is the use of octanoate and N-acetyltryptophan as stabilizers during the production of pharmaceutical-grade HSA for infusion (i-HSA), which is currently administered in the treatment of a growing range of pathological conditions. The peculiar sensitivity of circular dichroism (CD) spectroscopy towards the stereochemical features of high-affinity binding events is herein exploited to achieve a site-specific assessment of the effect of stabilizers on the binding properties of i-HSA. The binding affinity and capacity of fatty-acid-free HSA towards site-selective induced circular dichroism (ICD) markers for the three high-affinity binding sites of HSA was compared to that of i-HSA submitted to ultrafiltration and dialysis to remove both stabilizers. Results showed a considerable impairment of the binding capacity of i-HSA at site II and a relatively lower influence on the binding properties of site I. Ultrafiltration proved to be ineffective in depleting octanoate, while the proposed dialysis protocol, which involves a pH-induced reversible unfolding of the protein, resulted in a total clearance of both stabilizers, confirmed by the full restoration of the binding properties of HSA at all binding sites. The outcomes of this study proved that CD spectroscopy is a suitable technique to evaluate the binding properties of i-HSA, ensuring an assessment of the availability of the binding sites and the possibility of monitoring the clearance of stabilizers. Eventually, the proposed method for their depletion might constitute a connection bridge between albumin in vitro studies and its clinical applications.

Purpose The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. Methods We reviewed the results of the studies carried out in the last few years examining the effects of standard pharmacologic treatment, hemodialysis, kidney transplantation, renal nerve ablation and carotid baroreceptor stimulation on parasympathetic and sympathetic control of the cardiovascular system in patients with renal failure. Results Drugs acting on the renin–angiotensin system as well as central sympatholytic agents have been documented to improve autonomic cardiovascular control. This has also been shown for hemodialysis, although with more heterogeneous results related to the type of dialytic procedure adopted. Kidney transplantation, in contrast, particularly when performed together with the surgical removal of the native diseased kidneys, has been shown to cause profound sympathoinhibitory effects. Finally, a small amount of promising data are available on the potential favorable autonomic effects (particularly the sympathetic ones) of renal nerve ablation and carotid baroreceptor stimulation in chronic kidney disease. Conclusions Further studies are needed to clarify several aspects of the autonomic responses to therapeutic interventions in chronic renal disease. These include (1) the potential to normalize sympathetic activity in uremic patients by the various therapeutic approaches and (2) the definition of the degree of sympathetic deactivation to be achieved during treatment.

Background In patients with end stage renal disease and atrial fibrillation (AF), undergoing chronic dialysis, direct oral agents are contraindicated and warfarin does not fully prevent embolic events while increasing the bleeding risk. The high hemorrhagic risk represents the main problem in this population. Aim of the study was to estimate the safety and efficacy for thromboembolic prevention of left atrial appendage (LAA) occlusion in a cohort of dialysis patients with AF and high hemorrhagic risk. Methods Ninety-two dialysis patients with AF who underwent LAA occlusion were recruited. For comparative purposes, two cohorts of dialysis patients with AF, one taking warfarin (oral anticoagulant therapy, OAT cohort, n = 114) and the other not taking any OAT (no-therapy cohort, n = 148) were included in the study. Primary endpoints were (1) incidence of peri-procedural complications, (2) incidence of 2-year thromboembolic and hemorrhagic events, (3) mortality at 2 years. In order to evaluate the effect of the LAA occlusion on the endpoints with respect to the OAT and No-therapy cohorts, a multivariable Cox regression model was applied adjusted for possible confounding factors. Results The device was successfully implanted in 100% of cases. Two major peri-procedural complications were reported. No thromboembolic events occurred at 2-year follow-up. The adjusted multivariable Cox regression model showed no difference in bleeding risk in the OAT compared to the LAA occlusion cohort in the first 3 months of follow-up [HR 1.65 (95% CI 0.43–6.33)], when most of patients were taking two antiplatelet drugs. In the following 21 months the bleeding incidence became higher in OAT patients [HR 6.48 (95% CI 1.32–31.72)]. Overall mortality was greater in both the OAT [HR 2.76 (95% CI 1.31–5.86)] and No-Therapy [HR 3.09 (95% CI 1.59–5.98)] cohorts compared to LAA occlusion patients. Conclusions The study could open the way to a non-pharmacological option for thromboembolic protection in dialysis patients with AF and high bleeding risk.

International audience; In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.

Humic acids (HA) from compost of domestic-waste origin were characterized by IR and UV-Vis spectra and by elemental analysis. The molecular structure was investigated by treatment with the monocarboxylic acid HCOOH and CH3COOH, dialysis experiments and size-exclusion chromatography (SEC). In contrast to former reports, HCOOH and CH3COOH caused the simple precipitation of HA. SEC experiments gave chromatograms with a broad peak, with an elution volume at the maximum height of the peak very close to that of the globular protein bovine serum albumin, a value slightly above the fractional range of the gel used for SEC tests. The chromatogram profile was found to be independent on HA concentration. The eluted fractions exhibited sharper peaks than the pristine HA sample. It can be concluded that the HA extracted from compost do not consist of relatively small molecules held together by weak intermolecular interactions (as reported in the literature), but rather have a canonical macromolecular structure. The simple approach employed here is proposed as a reference procedure for testing the chemical structure of humic acids of any origin.

Background/Aims: The coronavirus disease 2019 (CO­VID-19) pandemic is the major current health emergency worldwide, adding a significant burden also to the community of nephrologists for the management of their patients. Here, we analyzed the impact of COVID-19 infection in renal patients to assess the time to viral clearance, together with the production and persistence of IgG and IgM antibody response, in consideration of the altered immune capacity of this fragile population. Methods: Viral clearance and antibody kinetics were investigated in 49 renal patients recovered from COVID-19 infection: 7 of them with chronic decompensated renal failure, 31 under dialysis treatment, and 11 kidney transplant recipients. Results: The time span between the diagnosis of infection and recovery based on laboratory testing (2 negative nasopharyngeal swabs in consecutive days) was 31.7 ± 13.3 days. Three new positive cases were detected from 8 to 13 days following recovery. At the first serological determination after swab negativization, all the patients developed IgG and IgM antibodies. The semiquantitative analysis showed a progressive increase in IgG and a slow reduction in IgM. Discussion/Conclusion: In subjects with decompensated chronic kidney disease, under dialysis and in transplant recipients, viral clearance is lengthened compared to the general population. However, in spite of their common status of immunodepression, all of them were able to produce specific antibodies. These data might provide useful insights for monitoring and planning health-care activities in the weak category of patients with compromised renal function recovered from COVID-19.

Renal disease is the common denominator of a number of underlying disease conditions, whose prevalence has been dramatically increasing over the last two decades. Two aspects are particularly relevant to the subject of this review: (I) most cases are gathered under the umbrella of chronic kidney disease since they require—predictably for several lustrums—continuous clinical monitoring and treatment to slow down disease progression and prevent complications; (II) cardiovascular disease is a terrible burden in this population of patients, in that it claims many lives yearly, while only a scant minority reach the renal disease end stage. Why indeed a review on DNA methylation and renal disease? As we hope to convince you, the present evidence supports the role of the existence of various derangements of the epigenetic control of gene expression in renal disease, which hold the potential to improve our ability, in the future, to more effectively act toward disease progression, predict outcomes and offer novel therapeutic approaches.

In the present work, dialysis was used to recover vanillin while being produced by partial photocatalytic oxidation of ferulic acid in an aqueous solution at ambient temperature. The relatively high value of the permeate flux through a dense polyether-block amide membrane allowed continuously extracting vanillin from the reacting solution, thus avoiding its successive oxidation. The rate of vanillin formation was improved, compared to other reactor configurations, because intermediate compounds permeated from the reacting solution and did not hinder the reaction, while ferulic acid permeated in the opposite direction to partially replenish the reactor with the substrate. The photocatalytic membrane reactor obtained by the effective coupling of dialysis with the photocatalytic reaction improved the production yield. For instance, with the utilized experimental set up, the total amount of vanillin produced after 5 h in the membrane reactor was more than one-third higher than in the photocatalytic reactor without dialysis. The results obtained with a mathematical model agree with the experimentally observed behavior. The model allowed estimating vanillin diffusivity in the membrane and showed that concentration polarization might limit the process.

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.

Aims: To estimate the safety and the efficacy of the off label left atrial appendage (LAA) occlusion in chronic dialysis patients with atrial fibrillation (AF). In this preliminary paper, we report the design of the study and the data on peri-procedural complications. Methods: This is a prospective cohort study. Primary endpoints are i) incidence of peri-procedural complications, ii) cumulative incidence of two-year thromboembolic events iii) cumulative incidence of two-year bleedings iiii) mortality at two years. Adverse events and death within 30 days of the procedure were recorded. Results: Fifty patients who underwent LAA occlusion between May 2014 and September 2017 were recruited. Both the mean age of the sample study and the dialysis duration were high [71.8 (9.6) years and 59.4 (78.2) months, respectively]. Most patients (84%) were hypertensive and 62% suffered a previous major bleeding. About half of them presented cardiovascular diseases. CHA2DS2VASCs and HASBLED scores were 4.0 (1.5) and 4.4 (0.9), respectively. Most patients (88%) showed atrial dilatation and 44% left ventricular hypertrophy; 32% had left ventricular ejection fraction

Rationale: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. Methods: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. ­Results: Fifteen subjects had baseline measurements, of which 7 had an AHI p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. Conclusions: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect.

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease–mineral and bone disorder (CKD–MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.

Previous studies have investigated constructs that facilitate adaptation to chronic disease and improve quality of life and constructs that lead to psychopathological complications. The purpose of this research is to investigate the impact of coping and emotional regulation on the quality of life of patients on dialysis. Three questionnaires were administered to 78 patients on dialysis: Coping Orientations to Problems Experienced, Short Form (36), and Cognitive Emotion Regulation Questionnaire. Regressions analyses indicated that age, Rumination, Positive Refocusing, Avoidance Strategies, Approach to the Problem, and Transcendent Orientation predicted Physical Health. With regard to Mental Health, the predictors were gender, Self-Blame, Acceptance, Rumination, Positive Reappraisal, Catastrophizing, Avoidance Strategies, and Transcendent Orientation. This study confirms the relationship between emotional regulation, coping, and quality of life. The results highlight the need for total care of the patients, including an assessment of both physical state and psychological functioning in order to promote total well-being.

The usual manifestation of brachial artery aneurysms is the incidental finding of a swelling of the arm, combined with paresthesia or pain in some cases. The etiology is often traumatic or secondary to drug abuse. Pathophysiology of brachial artery dilation in these cases is not completely clear. We herein describe a case of a 61-year-old male presenting with a giant, painful, pulsatile mass on his left arm. He was submitted to a cadaveric kidney transplant in 2005. He had a functioning arteriovenous fistula (AVF) on his right arm, and a spontaneously thrombosed radiocephalic AVF on his left arm. The aneurysm was surgically resected, sparing the median nerve that was totally entrapped and an inverted segment of the basilic vein interposed. At the follow-up, the patient did not present neurological or ischemic disturbs, and the vein graft maintained its patency.

Simple Summary This study aimed to improve the moment of dialysis because the emotional management of a person during treatment can help to reduce stress, anxiety and depression. This process positively affects the acceptance and progress of treatment and improves the self-management of the disease, a very important achievement in chronic kidney disease. Serotonin and oxytocin are important neuromodulators of different human behaviours, such as affectivity and socialization, and are involved in the control of stress, anxiety and social cooperation. The relationship between humans and domestic animals provides psychophysical well-being and can facilitate interpersonal bonds by favouring mechanisms involved in social relations. Dogs due to their ethological characteristics, allow the establishment of an active relationship through play, communication and interaction. Animal-assisted activities (AAAs) are structured interventions aimed at improving the psychophysical conditions of people in stressful conditions. Our study was aimed at determining the circulating levels of serotonin and oxytocin in patients who participated in an AAAs program with a dog during dialysis treatment. Our study aimed to measure the levels of serotonin and oxytocin in patients affected by end-stage renal disease (ESRD), undergoing dialysis and participating in a program of animal-assisted activities (AAAs) with a dog. Ten patients with comparable levels of ESRD were enrolled. A blood sample was taken before the start of the study in order to establish basal levels. Eleven meetings were held once a week for 3 months during the last hour of dialysis, and blood samples were collected before and after AAAs. Two more meetings, one month apart from each other, were held two months later without the dog but with the same veterinarian zootherapist. Blood was drawn at the beginning and at the end of each meeting. The samples were then processed for the measurement of serotonin and oxytocin, and data obtained were analysed using analysis of variance with mixed effect models. The results show an increasing level of both serotonin and oxytocin between subsequent meetings with the dog and an increasing trend of inter-intervention levels. Overall, the results suggest that AAAs lead to modifications of serotonin and oxytocin levels, which are also accompanied by behavioural changes of patients.

Given the rising prevalence of end-stage renal disease and subsequent progressive increase of patients starting renal replacement therapy, a great attention is given by scientific community to the assessment of life perception and Quality of Life (QoL) in dialysis patients. A broad literature review was conducted on PubMed and PsyInfo databases for articles published between January 2000 and July 2016 in order to understand the biological and psychosocial variables potentially affecting the QoL of the patients under artificial substitution of kidney function.Five domains related to the concepts of physical functions, mood, sleep, spirituality, and social support have been identified.The findings in this review suggest that the variables related to physical activity and depression seem to have a direct impact on QoL and Health-Related Quality of Life (HRQoL). Others, such as anxiety, awareness, empowerment, the presence of sleep disorders, satisfaction, support from the staff, social support, spirituality and religion have a clear correlation with the QoL dimensions.These results suggest the primary importance of the assessment biological and psychosocial variables by specific tools and the inclusion of effective interventions targeted to patients and their caregivers.

Background: Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype–phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown. Methods: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype. Results: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17–0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08–0.20]. This difference was significant (P = 0.048). Conclusions: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients’ relatives to be investigated and promptly treated.

Carbon-based dots (CDs) and their functionalized (nano)composites have recently attracted attention due to their seemingly easy preparation and numerous potential applications, ranging from those in the biomedical field (i.e., imaging and drug delivery) to those in (opto)electronics (i.e., solar cells and LEDs). This protocol details step-by-step procedures for synthesis, purification, functionalization and characterization of nitrogen-doped carbon nanodots (NCNDs), which we have been preparing for the past few years. First, we describe the bottom-up synthesis of NCNDs, starting with the use of molecular precursors (arginine (Arg) and ethylenediamine (EDA)) and making use of microwave-assisted hydrothermal heating. We also provide guidelines for the purification of these materials, through either dialysis or low-pressure size-exclusion chromatography (SEC). Second, we outline post-functionalization procedures for the surface modification of NCNDs, such as alkylation and amidation reactions. Third, we provide instructions for the preparation of NCNDs with different properties, such as color emission, electrochemistry and chirality. Given the fast evolution of preparations and applications of CDs, issues that might arise from artifacts, errors and impurities should be avoided. In this context, the present protocol aims to provide details and guidelines for the synthesis of high-quality nanomaterials with high reproducibility, for various applications. Furthermore, specific needs might require the CDs to be prepared by different synthetic procedures and/or from different molecular precursors, but such CDs can still benefit from the purification and characterization procedures outlined in this protocol. The sample preparation takes various time frames, ranging from 4 to 18 d, depending on the adopted synthesis and purification steps. This protocol describes the synthesis, purification, functionalization and characterization of nitrogen-doped carbon nanodots (NCNDs). In addition, examples of how to tailor the color emission, electrochemistry and chirality of NCNDs are provided.

The gut microbiota is considered to be a novel important factor to take into account in the pathogenesis of chronic kidney disease and uremia. Much attention has been paid to specific uremic retention solutes of microbial origin, such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide. However, other novel less well studied compounds, such as hydrogen sulfide and related sulfur metabolites (sulfane sulfur, lanthionine, etc.), should be included in a more comprehensive appraisal of this topic, in light of the potential therapeutic opportunities for the future.

Chemotherapy and extracorporeal treatment reduce serum free light chains (FLCs) allowing the recovery of acute kidney injury (AKI) caused by myeloma cast nephropathy (MCN). We report the first case of recovery from AKI in a patient with MCN who underwent the removal of FLCs using the PEPA filter, with an undisclosed cut-off, combined with chemotherapy for multiple myeloma (MM).

The aim of this study was to investigate the epidemiology of kidney replacement treatment (KRT) in Italy with a focus on gender and residence. As a population-based study using administrative databases from the Campania region of Italy between 2015 and 2018, the study outcomes included diagnoses of haemodialysis, peritoneal dialysis, kidney transplant, and mortality. A total of 11,713 residents in Campania were on KRT from 2015 to 2018. The annual prevalence ranged between 1000 and 1015 patients per million population (pmp) for haemodialysis, between 115 and 133 pmp for peritoneal dialysis, and between 2081 and 2245 pmp for kidney transplant. The annual incidence ranged between 160 and 185 pmp for de novo haemodialysis and between 59 and 191 pmp for kidney transplant. Annual mortality ranged between 12.8% and 14.2% in haemodialysis, between 5.2% and 13.8% in peritoneal dialysis, and between 2.4% and 3.3% in kidney transplant. In Cox regression targeting mortality, significant HRs were found for age (95%CI = 1.05/1.05), kidney transplant (compared to haemodialysis: 0.37/0.47), residence in suburban areas (1.03/1.24), and de novo dialysis incidence in years 2015&ndash, 2018 (1.01/1.17). The annual rate of kidney transplant was 2.6%. In regression targeting kidney transplant rate, significant HRs were found for female gender (0.67/0.92), age (0.93/0.94), residence in suburban areas (0.65/0.98), and de novo incidence of dialysis in 2015&ndash, 2018 (0.49/0.71). The existence of socioeconomic inequities in KRT is suggested by the evidence that gender and suburban residence predicted mortality and/or access to kidney transplant.

I pazienti con malattia renale allo stadio terminale (ESRD) sono caratterizzati da una mortalità molto elevata ed in particolare, è stato dimostrato, che il rischio di mortalità tende ad aumentare nei pazienti sedentari. Gli effetti positivi dell’attività fisica riscontrati nella popolazione generale possono essere molto rilevanti per i pazienti con ESRD. Oltre ad una potenziale riduzione del rischio cardiovascolare, l’esercizio fisico può incrementare la funzionalità fisica migliorando di conseguenza la qualità di vita. Diversi studi riguardanti l’esercizio fisico in emodialisi suggeriscono che l’incremento dell’attività fisica di questi pazienti migliora le prestazioni fisiologiche ed i risultati clinici. Infatti, mentre un’attività fisica di resistenza determina un aumento della massa muscolare e della forza, un’attività fisica aerobica è associata ad un maggior consumo di ossigeno, ad una riduzione della depressione e quindi, ad un miglioramento delle funzioni cognitive. Purtroppo, nonostante i potenziali benefici che un programma di esercizio personalizzato apporterebbe ai pazienti in dialisi, tra i trattamenti di routine della maggior parte delle Unità Operative di Nefrologia e Dialisi non rientrano né una valutazione accurata di performance fisica del paziente né una consulenza specifica che possa indirizzare il paziente sedentario verso un percorso allenante specifico. Patients with end-stage renal disease (ESRD) are characterized by very high mortality and in particular, it has been demonstrated that the risk of mortality tends to increase in sedentary patients. The positive effects of physical activity in the general population may be very significant for patients with ESRD. In addition to a potential reduction in cardiovascular risk, exercise can increase physical functionality, thus improving the quality of life. Several studies on exercise in hemodialysis suggest that increased physical activity of these patients improves physiological performance and clinical outcomes. In fact, while physical activity of resistance results in increased muscle mass and strength, physical aerobic activity is associated with increased oxygen consumption, reduced depression, and hence improved cognitive function. Unfortunately, despite the potential benefits of a personalized exercise program to dialysis patients, routine treatments of most Nephrology and Dialysis Operations Units do not include a thorough assessment of the patient's physical performance or specific advice that could direct the sedentary patient to a specific training course.

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish (Danio rerio), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects.

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and/or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

In the present chapter it is shown how photocatalytic membrane reactors utilizing membrane processes, which are not pressure driven, can exploit various mechanisms to obtain a substantial improvement of the process. The fundamentals of this particular type of membrane reactors are reviewed including the effects of the most important parameters and the methods and rules of coupling photocatalysis and membrane separation. The survey of the studies on photocatalytic membrane reactors (PMRs) utilizing pervaporation, dialysis, membrane contactors and membrane distillation offers the opportunity of discussing the advantages with respect to PMRs adopting pressure driven membrane processes. Indeed, the strengths of the investigated processes are the high retention of the photocatalytic powders with minor fouling problems, the simpler and cheaper apparatuses and the possibility of selectively removing or recovering the products. Finally, the reasons, which currently limit the application of these membrane reactors, are illustrated together with the very interesting future perspectives.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review describes our current understanding of the bi-directional relationship between OSA and CKD. RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia may lead to worsening of kidney function. One potential mechanism is activation of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP therapy. In ESRD, fluid overload plays an important role in the pathogenesis of OSA and fluid removal by ultrafiltration leads to marked improvements in sleep apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney function. In patients with ESRD, fluid overload plays an important role in the pathogenesis of OSA.

An internet survey was set up to assess the geriatric competence and perceived needs of 337 members of the Italian society of nephrology (SIN). The survey assessed how well aware nephrologists are of the typical geriatric conditions and needs of their elderly chronic kidney disease (CKD) patients. SIN associates were also questioned about their current use of comprehensive geriatric assessment, prescription of potentially nephrotoxic drugs, and screening for osteoporosis. The main finding is that CKD and dialysis are almost unanimously perceived as typically geriatric conditions, but knowledge and use of geriatric tools are scanty. While use of potentially inappropriate drugs is rare, almost half of the patients are not screened for osteoporosis. The significant clinical gaps observed could greatly impair the management of older CKD patients, and call for an urgent educational intervention.

Maria Cappuccilli,1 Gabriele Donati,1 Giorgia Comai,1 Olga Baraldi,1 Diletta Conte,1 Irene Capelli,1 Valeria Aiello,1 Andrea Pession,2 Gaetano La Manna1 1Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis, and Renal Transplant Unit, 2Molecular Laboratory of Pediatrics, Hematology–Oncology Unit, St Orsola Hospital, University of Bologna, Bologna, Italy Background: The aim of this study was the application of complementarity-determining region-3 spectratyping analysis to determine T-cell-repertoire complexity and to detect T-cell-clone expansion, as a measure of immune response in nonfunctioning kidney transplants (group hemodialysis-transplant [HD-Tx]), nontransplanted dialysis patients (group hemodialysis [HD]), and normal subjects as controls (group C).Patients and methods: Analysis of T-cell receptor (TCR) diversity by spectratyping was applied to peripheral blood samples collected from 21 subjects: eight in group HD-Tx, seven in group HD, and six in group C.Results: Considering the extent of the skew in TCR variable region repertoires as a measure of clonal T cells, we found that the number of altered spectra showed a progressive increase from normal subjects to dialysis patients and to nonfunctioning kidney transplants, respectively. Healthy subjects had the lowest number of altered spectra, and patients with nonfunctioning kidney transplants the highest. Differences were significant for group HD-Tx vs group C (P=0.017) and group HD vs group C (P=0.015), but not between nonfunctioning kidney-transplant recipients and dialysis patients (group HD-Tx vs group HD).Conclusion: Although dialysis appears to be a weaker trigger for clonal expansion of T cells, our data suggest that the utilization of complementarity-determining region-3 spectratyping analysis of the TCR repertoire might be useful to monitor specific immunoactivation in patients before and after kidney transplantation. Keywords: dialysis, nonfunctioning kidney transplant, T-cell repertoire, TCR spectratyping&nbsp

Hemodialysis, peritoneal dialysis and conservative care are nowadays the main treatment options to help persons suffering from advanced kidney diseases. The Authors intend to deal with ethical issues concerning decision-making process about these treatments. Data confirmed that among patients who have the choice between two medically accepted and available options that are believed to have a chance of promoting the patient's welfare some patients prefer a treatment option; the other option is the treatment of choice for the others. In decision-making process, a prominent role must be given to patient's values and his/her judgment about the impact of the treatment options on his/her quality of life, in personal assessment of benefits and burdens. Thus, share decision-making is the recommended model for decision-making in this context; the physician has the important role to guide this process, ascertaining the patient's preferences and personal values.

Objectives Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites’ dialyzability is lacking. Methods We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds’ plasma concentrations at three different time points during dialysis. Results Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds’ clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. Discussion While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance +/- SD: baseline, 328 +/- 96 m; 6 months, 367 +/- 113 m) but not in the control group (baseline, 321 +/- 107 m; 6 months, 324 +/- 116 m; P

Summary Background The use of bilateral internal thoracic artery (BITA) grafting has been proposed for dialysis patients with multivessel coronary artery disease, primarily because of hypothetical long-term survival benefits. Aims To investigate the outcome of BITA grafting in dialysis patients. Methods This was a retrospective analysis of the use of BITA grafting in 105 consecutive patients with end-stage renal failure on chronic dialysis in three European centres with extensive experience in BITA. Baseline patient characteristics, operative data, early postoperative complications and late survival were reviewed. Outcomes of patients from one of the three centres who underwent either BITA (n = 40) or single internal thoracic artery (SITA) grafting (n = 19) were also analysed; a one-to-one propensity score (PS)-matched analysis was performed. Results There were 19 (18.1%) hospital deaths. Despite differences in preoperative patient characteristics and surgical features, in each centre, hospital mortality was greater than the 75th percentile of expected operative risk (EuroSCORE II). Diseased ascending aorta and extracardiac arteriopathy were found to be predictors of hospital death (odds ratio 9.7; P = 0.006) and complicated hospital course (odds ratio 2.54; P = 0.035), respectively. The 7-year non-parametric estimates of freedom from all-cause death and cardiac or cerebrovascular death were 59% (95% confidence interval: 52.3–65.7%) and 75.6% (95% confidence interval: 71.2–80%), respectively. There were no significant differences in early and late outcomes between BITA and SITA PS-matched groups. Conclusions BITA grafting remains a risky operation for chronic dialysis patients, even when performed routinely. No long-term survival benefits for the use of BITA versus SITA were proven.