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

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

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

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

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

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

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

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

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

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

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

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

The effects of vitamin E-coated membrane dialyzer compared to simvastatin in patients on chronic hemodialysis.

BACKGROUND: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes. METHODS: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3, and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo) A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL), and plasma oxidized low-density lipoproteins (oxLDL) levels were determined. RESULTS: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1 at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in a significant decrease in CRP, which correlated with decreases in both total (r = 0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1, oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1 (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly from the corresponding VEM effects. CONCLUSIONS: The 6-month use of VEM resulted in more direct and immediate anti-inflammatory effects compared with those caused by the 6-month treatment with simvastatin. Simvastatin caused a more intense decrease in the markers of inflammation, which was in part correlated with its lipid-lowering effects.

Effects of vitamin E-coated membrane dialyser on markers of oxidative stress and inflammation in patients on chronic haemodialysis.

BACKGROUND: In the present prospective, controlled, observational cohort study, we investigated the effects of the use of a vitamin E-coated membrane dialyser (VEM) on markers of chronic inflammation, oxidative stress and endothelial cell apoptosis in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD), as long as evidence of their effects on these pathogenetic routes are inconclusive as yet, despite their use for the last several years. METHODS: Thirty-five stable ESRD patients underwent HD with the use of VEM for 6 months. Another 25 age- and sex-matched ESRD patients, being dialysed with conventional dialysers, served as controls. In both patient groups, beyond complete haematology and biochemistry work-up, serum CRP, apolipoproteins A1 and B, lipoprotein (a) (Lp(a)), hsIL-6, MCP-1, sICAM-1, sVCAM-1, sE-selectin, sFas and sFasL as well as plasma oxLDL, TBARS and TAS levels were determined at baseline and at 6 months of the study. RESULTS: In the VEM group at 6 months, a significant reduction in CRP (P = 0.004), IL-6 (P = 0.004) and sICAM-1 (P = 0.04) levels was observed compared with baseline, along with a remarkable change in all markers of oxidative stress, i.e. increase in TAS (P = 0.005) and decrease in TBARS (P = 0.04) and oxLDL (P < 0.001). No significant changes were noted in the other parameters studied in the VEM group or in any parameter studied in the controls. Between the groups, significant differences were found in the change of CRP (P = 0.001), sICAM-1 (P = 0.03) and oxLDL (P = 0.04) compared with baseline. CONCLUSIONS: HD with the use of VEM resulted in a significant reduction in inflammation and oxidative stress markers. Larger prospective randomized studies will need to confirm the findings of the present observational study.

Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis.

AIM: We investigated the effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in hyperlipidemic endstage renal disease patients on chronic hemodialysis (HD). METHODS: In 25 hyperlipidemic HD patients who received 10 mg of simvastatin for 6 months and another 25 controls, the extended lipid profile and serum hsIL-6, MCP-1, sICAM-1, sVCAM-1, and sE-selectin, plasma oxLDL, and serum sFas and sFasL levels were determined at baseline, 3 months and 6 months. In 18 patients of the simvastatin group, the expression of CD14, CD16, CD62L and CD64 on monocyfes was determined with flow cytometry. RESULT: Simvastatin treatment resulted in significant reductions in serum lipid levels at 3 months and beyond, compared to at baseline. Moreover, at 6 months, simvastatin caused a significant reduction in CRP (p < 0.001), which correlated to the decrease in total and LDL cholesterol levels, as well as a significant reduction in IL-6 (p=0.001), sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), oxLDL (p=0.001), sFas (p=0.02) and CD14 expression (p < 0.001), compared to baseline values. No significant changes in the controls were noticed during the study. CONCLUSION: In conclusion, in hyperlipidemic HD patients, simvastatin treatment resulted in a significant reduction in markers of endothelial dysfunction, inflammation, oxidative stress, endothelial cell apoptosis and peripheral blood monocyte stimulation. The reduction in CRP appears to be related to the lipid-lowering effects of simvastatin.

Validity of plasma fibrinogen, D-dimer, and the von Willebrand factor as markers of cardiovascular morbidity in patients on chronic hemodialysis.

BACKGROUND: Among the non-classic cardiovascular disease risk factors in end-stage renal disease patients on chronic hemodialysis (HD), plasma fibrinogen, D-dimer, and von Willebrand factor (vWf) levels are potential markers of cardiovascular morbidity. We designed this case-control study to investigate their validity and any differences between them. MATERIAL/METHODS: Twenty-five HD patients (18 males, mean age: 63, range: 52-69 years) comprised the group with prevalent cardiovascular disease (CVD) and 50 HD patients (35 males, mean age: 62, range: 40-77 years) with non-evident cardiovascular disease history constituted the second study group. Twenty-five healthy non-smoking volunteers served as controls for comparison with the study groups. RESULTS: Patients with CVD had significantly higher concentrations of plasma fibrinogen, D-dimer, and vWf than patients without incident CVD. All three parameters correlated positively with cardiovascular morbidity, i.e. fibrinogen (r=0.378, P<0.001), logDD (r=0.70, P<0.001), vWf (r=0.214, P<0.001), and logCRP (r=0.704, P<0.001). Among them, D-dimer exhibited the characteristics most coherent with CVD. The age- and sex-adjusted odds ratio (OR) of D-dimer for the presence of CVD was 2.0, which did not change appreciably when adjustments for several pathophysiological clusters of variables were made, except for a marginal reduction in OR following adjustment for markers of inflammation. CONCLUSIONS: Among the coagulation molecules studied, plasma D-dimer levels exhibited the characteristics most coherent with associated CVD and were found to be strongly and independently associated with the prevalence of CVD in HD patients.

The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait.

BACKGROUND: IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22-23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. DESCRIPTION: The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998-2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. CONCLUSION: The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies.

Focal segmental glomerulosclerosis in a patient with large bilateral asymptomatic adrenal myelolipomas.

Adrenal myelolipomas are rare benign tumors, usually discovered by chance in patients with hypertension, obesity or various endocrine disorders. Focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. So far, no association between the two conditions has been described. We report a case of a woman admitted for nephrotic syndrome, in which a coexistence of FSGS and bilateral large adrenal myelolipomas was revealed.

Carotid atherosclerosis is associated with inflammation and endothelial cell adhesion molecules in chronic haemodialysis patients.

BACKGROUND: Recently emerging evidence suggests that endothelial adhesion molecules may participate in atherogenesis. The aim of the present report was to investigate the probable association of circulating ICAM-1, VCAM-1 and E-selectin with atherosclerotic disease in chronic haemodialysis (HD) patients. METHODS: One hundred and twelve HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. In addition, in a follow-up study, the survival of 81 patients after a mean period of 26 months was analysed in relation to ICAM-1 and VCAM-1 levels. RESULTS: IMT and plaque score were significantly higher in HD patients compared with control subjects (P < 0.001 and P < 0.0001, respectively). The above ultrasonographic indices were correlated with age both in controls (P = 0.0001 and P = 0.002, respectively) and HD patients (P = 0.0001 and P = 0.0001, respectively). A significant relationship was observed between IMT and systolic blood pressure (BP) both in controls and in HD patients (P = 0.002 and P = 0.01, respectively). In HD patients, plaque score was also correlated with systolic BP (P = 0.02). In HD patients, IMT and plaque score were correlated significantly with log CRP values (P = 0.01 and P = 0.01, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to plaque score (P = 0.01). IMT was significantly correlated with ICAM-1 and VCAM-1 concentrations (P = 0.0001 and P = 0.003, respectively). Multivariate analysis showed that ICAM-1 concentrations were a strong independent correlate of IMT (P = 0.001). E-selectin concentrations did not show any relation with IMT or plaque score. During the follow-up period, 13 of the 81 patients died. Survival analyses showed that patients with increased ICAM-1 had a shorter survival than patients with normal ICAM-1 values and that serum ICAM-1 levels were a strong predictor of death. CONCLUSIONS: In HD patients, carotid atherosclerosis is associated with inflammation and circulating levels of soluble adhesion molecules ICAM-1 and VCAM-1. The correlations between serum ICAM-1 and IMT and ICAM-1 and survival may indicate that this molecule could be a marker of a process that contributes to the high mortality of HD patients.