Supplementation of Antioxidants in Chronic Kidney Disease: Clinical Necessity or Wishful Thinking? A Bench to Bedside Translational Research.

Chronic Kidney Disease (CKD) patients are at increased risk for atherosclerosis, cardiovascular disease (CVD) and progression to end stage kidney disease (ESKD). This heavy CVD risk cannot be solely at-tributed to traditional Framingham risk factors. Oxidative stress (OS), defined as the disruption of balance between prooxidants and antioxidants in favor of the former, has emerged as a novel risk factor for CVD and CKD progression. Specifically, lipid peroxidation has been identified as a trigger for endothelial dys-function, the first step towards atherogenesis and protein oxidation has been associated with CKD progres-sion. The oxidation of proteins and lipids starts early in CKD, increases gradually with disease progression and is further exacerbated in ESKD, due to dialysis related factors. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease and progression of CKD, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from ex-perimental and clinical studies that test antioxidants for their possible beneficial effects against CVD and CKD progression such as vitamins E and C, statins, omega-3 fatty acids, trace elements, polyphenols and N-acetylcysteine.

The association of home blood pressure with all-cause mortality in hemodialysis patients: A prospective observational study.

INTRODUCTION: Prior observational studies conducted in the hemodialysis population have suggested a reverse association between dialysis-unit blood pressure (BP) and mortality. The present study aimed to investigate the prognostic association of home versus dialysis-unit BP with all-cause mortality in hemodialysis patients. METHODS: At baseline, 146 patients receiving maintenance hemodialysis underwent assessment of their BP with the following methods: (i) 2-week averaged routine predialysis and postdialysis BP measurements; (ii) home BP monitoring for 1 week that included duplicate morning and evening BP measurements with the use of validated devices. RESULTS: Over a median follow-up period of 38 months (interquartile range [IQR]: 22-54), 44 patients (31.1%) died. In Kaplan-Meier curves, predialysis and postdialysis systolic BP (SBP) was not associated with all-cause mortality, while home SBP appeared to be of prognostic significance (log rank p = 0.029). After stratifying patients into quartiles, all-cause mortality was lowest when home SBP was ranging from 128.1 to 136.8 mmHg (quartile 2). In univariate Cox regression analysis, using quartile 2 as a referent category, the risk of all-cause mortality was 3.32-fold higher in quartile 1, 1.53-fold higher in quartile 3 and 3.25-fold higher in quartile 4. The risk-association remained unchanged after adjustment for several confounding factors (adjusted hazard ratio: 4.79, 1.79, 3.63 for quartiles 1, 3, and 4 of home systolic BP, respectively). CONCLUSION: Our findings suggest that among hemodialysis patients, 1-week averaged home SBP is independently associated with all-cause mortality. In sharp contrast, SBP recorded either before or after dialysis over 2 weeks is not prognostically informative.

Anakinra for Refractory Pseudogout in Patients with End-stage Renal Disease on Haemodialysis.

Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1ß appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1ß receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.

Dialysis Patients Respond Adequately to Influenza Vaccination Irrespective of Dialysis Modality and Chronic Inflammation.

(1) Background: Chronic inflammation and suboptimal immune responses to vaccinations are considered to be aspects of immune dysregulation in patients that are undergoing dialysis. The present study aimed to evaluate immune responses in hemodialysis (HD) and online hemodiafiltration (OL-HDF) patients to a seasonal inactivated quadrivalent influenza vaccine (IQIV). (2) Methods: We enrolled 172 chronic dialysis patients (87 on HD and 85 on OL-HDF) and 18 control subjects without chronic kidney disease in a prospective, cross-sectional cohort study. Participants were vaccinated with a seasonal IQIV, and antibody titers using the hemagglutination inhibition (HI) assay were determined before vaccination (month 0) and 1, 3, and 6 months thereafter. Demographics and inflammatory markers (CRP, IL-6, IL-1ß) were recorded at month 0. The primary endpoints were the rates of seroresponse (SR), defined as a four-fold increase in the HI titer, and seroprotection (SP), defined as HI titer ≥ 1/40 throughout the study period. Statistical analyses were conducted in R (version 3.6.3) statistical software. The differences between groups were analyzed using chi-square and t-test analyses for dichotomous and continuous variables, respectively. To identify independent determinants of SR and SP, generalized linear models were built with response or protection per virus strain as the dependent variable and group, age, sex, time (month 0, 1, 3, 6), diabetes, IL-6, dialysis vintage, HD access, and HDF volume as independent explanatory variables. (3) Results: SR and SP rates were similar between control subjects, and dialysis patients were not affected by dialysis modality. SP rates were high (> 70%) at the beginning of the study and practically reached 100% after vaccination in all study groups. These results applied to all four virus strains that were included in the IQIV. IL-6 levels significantly differed between study groups, with HD patients displaying the highest values, but this did not affect SP rates. (4) Conclusions: Dialysis patients respond to influenza immunization adequately and similarly to the general population. Thus, annual vaccination policies should be encouraged in dialysis units. OL-HDF reduces chronic inflammation; however, this has no impact on SR rates.

Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy.

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Gender-Related Differences in the Levels of Ambulatory BP and Intensity of Antihypertensive Treatment in Patients Undergoing Peritoneal Dialysis.

Prior studies have shown that among patients with chronic kidney disease not yet on dialysis, the faster progression of kidney injury in men than in women is, at least partly, explained by sex differences in ambulatory blood pressure (BP) control. The present study aimed to investigate potential differences in the levels of ambulatory BP and intensity of antihypertensive treatment between men and women with end-stage kidney disease undergoing long-term peritoneal dialysis (PD). In a case-control design, 48 male PD patients were matched for age and heart failure status with 48 female patients in a 1:1 ratio. Ambulatory BP monitoring was performed with an oscillometric device, the Mobil-O-Graph (IEM, Stolberg, Germany). The BP-lowering medications actually taken by the patients were prospectively recorded. No gender-related differences were observed in 24 h systolic BP (129.0 ± 17.9 vs. 128.5 ± 17.6 mmHg, p = 0.890). In contrast, 24 h diastolic BP was higher in men than in women (81.5 ± 12.1 vs. 76.8 ± 10.3 mmHg, p = 0.042). As compared with women, men were being treated with a higher average number of antihypertensive medications daily (2.4 ± 1.1 vs. 1.9 ± 1.1, p = 0.019) and were more commonly receiving calcium-channel-blockers (70.8% vs. 43.8%, p = 0.007) and ß-blockers (85.4% vs. 66.7%, p = 0.031). In conclusion, the present study shows that among PD patients, the levels of ambulatory BP and intensity of antihypertensive treatment are higher in men than in women. Longitudinal studies are needed to explore whether these gender-related differences in the severity of hypertension are associated with worse cardiovascular outcomes for male patients undergoing PD.

Association of Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio with Calcification and Cardiovascular Markers in Chronic Kidney Disease.

We aimed to investigate the association between Red Blood Cell Distribution Width (RDW) and Neutrophil-to-Lymphocyte Ratio (NLR), simple, rapidly assessed markers from the complete blood count with vascular calcification (VC)/stiffness and cardiovascular disease (CVD) in chronic kidney disease (CKD). Dephosphorylated, uncarboxylated matrix Gla-protein (dp-ucMGP), and central/peripheral hemodynamics' parameters were measured in 158 CKD patients, including Hemodialysis and Peritoneal Dialysis. Spearman's rho analysis showed that RDW correlated with C-reactive protein (CRP) (r = 0.29, p < 0.001), dp-ucMGP (r = 0.43, p = < 0.0001), central diastolic blood pressure (DBP) (r = -0.19, p = 0.02), and albuminuria (r = -0.17, p = 0.03). NLR correlated with the duration of CVD (r = 0.32, p < 0.001), CRP (r = 0.27, p = 0.01), dp-ucMGP (r = 0.43, p < 0.0001), central DBP (r = -0.32, p < 0.0001) and eGFR (r = -0.25, p = 0.04). In multiple regression models, circulating dp-ucMGP was an independent predictor of RDW (ß = 0.001, p = 0.001) and NLR (ß = 0.002, p = 0.002). In CKD patients, RDW and NLR are associated with traditional and novel markers of VC and CVD.

Sleep quality in caregivers of patients with end-stage renal disease.

The aim of this study was to evaluate the self-reported quality of sleep among caregivers of patients who are receiving hemodialysis (HD) and peritoneal dialysis (PD). In 64 caregivers of patients of the University General Hospital of Evros in Northeastern Greece, who were receiving HD and PD, the following instruments were administered: Pitsburgh Sleep Quality Index (PSQI), Zung Depression Rating Scale (ZDRS), Self-Anxiety Scale (SAS), Well - Being Index (WHO- 5). The mean PSQI value of caregivers was 5.27 ±3.40 and 39% of them had poor sleep quality. "Poor sleepers" had significantly lower levels of quality of life (p=0.02), elevated levels of anxiety (p=0.006) and higher scores in the depression scale (p=0.009) compared to "good sleepers". In the regression analysis depression was found to have the greatest contribution to the variability of 'sleep quality' (standardized beta = 0.62, p<0.001) and quality of sleep seemed to improve as years of dialysis that the patient underwent increased (standardized beta = -0.28, p=0.007). Physicians should screen caregivers' sleep quality, especially during the first stages of the illness.

Microbiome, Immunosenescence, and Chronic Kidney Disease.

The gut microbiome is known as an important predictive tool for perceiving characteristic shifts in disease states. Multiple renal diseases and pathologies seem to be associated with gut dysbiosis which directly affects host homeostasis. The gastrointestinal-kidney dialogue confers interesting information about the pathogenesis of multiple kidney diseases. Moreover, aging is followed by specific shifts in the human microbiome, and gradual elimination of physiological functions predisposes the microbiome to inflammaging, sarcopenia, and disease. Aging is characterized by a microbiota with an abundance of disease-associated pathobionts. Multiple factors such as the immune system, environment, medication, diet, and genetic endowment are involved in determining the age of the microbiome in health and disease. Our present review promotes recently acquired knowledge and is expected to inspire researchers to advance studies and investigations on the involved pathways of the gut microbiota and kidney axis.

The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease.

We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan-Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17-5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07-7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20-13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.

Unraveling the Interconnection Patterns Across Lung Microbiome, Respiratory Diseases, and COVID-19.

Albeit the lungs were thought to be sterile, recent scientific data reported a microbial microbiota in the lungs of healthy individuals. Apparently, new developments in technological approachesincluding genome sequencing methodologies contributed in the identification of the microbiota and shed light on the role of the gut and lung microbiomes in the development of respiratory diseases. Moreover, knowledge of the human microbiome in health may act as a tool for evaluating characteristic shifts in the case of disease. This review paper discusses the development of respiratory disease linked to the intestinal dysbiosis which influences the lung immunity and microbiome. The gastrointestinal-lung dialogue provides interesting aspects in the pathogenesis of the respiratory diseases. Lastly, we were further interested on the role of this interconnection in the progression and physiopathology of newly emergedCOVID-19.

Focus on the Gut-Kidney Axis in Health and Disease.

The recent new developments in technology with culture-independent techniques including genome sequencing methodologies shed light on the identification of microbiota bacterial species and their role in health and disease. Microbiome is actually reported as an important predictive tool for evaluating characteristic shifts in case of disease. Our present review states the development of different renal diseases and pathologies linked to the intestinal dysbiosis, which impacts on host homeostasis. The gastrointestinal-kidney dialogue provides intriguing features in the pathogenesis of several renal diseases. Without any doubt, investigation of this interconnection consists one of the most cutting-edge areas of research with potential implications on our health.

Use of a temporary shunt to preserve the patency of a hemodialysis graft while performing ipsilateral axillo-femoral bypass.

Increased blood flow in the subclavian artery feeding a vascular access for hemodialysis can rarely induce steal phenomena in the vertebral and internal mammary artery leading to potentially life-threatening conditions. On the contrary, transient interruption of blood flow in the subclavian artery feeding a dialysis arteriovenous fistula can theoretically induce access thrombosis. Here, we describe a technical maneuver preserving continuous ipsilateral upper arm access flow when constructing a unilateral axillo-femoral polytetrafluoroethylene bypass operation for critical limb ischemia in a hemodialysis patient.

Endovascular Repair of an Inadvertent Right Vertebral Artery Rupture during Dialysis Catheter Insertion.

Central venous (CV) catheterization is not only an invaluable diagnostic modality but also an essential therapeutic tool for the treating physician, enabling rapid and reliable intravenous administration of drugs and fluids, providing venous access to patients undergoing long-term continuous or repeated intravenous treatment such as chemotherapy, or it can be used for hemodialysis in patients suffering from acute or chronic renal disease. On the other hand, CV catheterization can lead to a wide range of life-threatening complications for the patient especially if left untreated or become late-diagnosed. In particular, arterial injuries are among the most feared complications that require early clinical suspicion for prompt diagnosis and management. We report the case of a 79-year-old female dialysis patient who suffered from a vertebral artery (VA) injury complicated by a herald bleeding on the third postintervention day after an internal jugular vein dialysis catheter replacement. The patient initially presented neurological signs of a stroke and urgently treated endovascularly after immediate diagnosis of VA rupture was made. Imaging techniques are evidence-based tools that help minimize these mechanical complications, including inadvertent arterial puncture and therefore should be practiced and taught in training programs to avoid the potentially devastating consequences of CV catheterization.

Comparison of standard forearm prosthetic loop grafts to composite semiloop forearm grafts ("semi-grafts") in hemodialysis patients: A prospective study.

INTRODUCTION: To prospectively assess the performance of composite semiloop antebrachial grafts ("semi-grafts," SGs) in hemodialysis patients. METHODS: Eighty-five patients who received 67 loop antebrachial grafts (LG-group) and 25 antebrachial semigrafts (SG-group) were enrolled. SGs were defined as those originating from the brachial artery and anastomosed with the proximal mature mid-antebrachial cephalic vein. Cephalic vein length should be at least 10 cm in length and of ≥5 mm in diameter for inclusion in the SG-group. LG-group included all possible outflow vein options of minimum diameter 3 mm. Kaplan-Meier statistics was used for comparison of groups. FINDINGS: Main indication for a SG was a failing radiocephalic fistula with extensive distal cephalic vein stenosis not amenable to correction or failed after endovascular repair or requiring long interposition grafting. The mean follow-up period was 20.16 ± 22.6 and 29.6 ± 36.7 months for the LG- and SG-group, respectively (P = 0.14). Forty-two patients died during the follow-up. Primary patency (up to first intervention or failure) at 6 and 12 months for LG- vs. SG-group was 93.9% vs. 83.7% and 47% vs. 55.8% (P = 0.08). Secondary patency (up to abandonment) was 58.2% vs. 61.1% and 36% vs. 45.8% at 12 and 24 months (P = 0.18). Mortality at 48 months was 22.4% (LG-group) and 24% (SG-group) (P = 0.9). DISCUSSION: There was a trend toward better primary and secondary patency rates for the SGs especially in the long-term. This is a valuable option in selected patients that access surgeons and nephrologists should be aware of.

Comparison of multiple fluid status assessment methods in patients on chronic hemodialysis.

PURPOSE: Control of hydration status is an important constituent of adequate and efficient hemodialysis (HD) treatment. Nevertheless, there are no precise clinical indices for early recognition of small changes in fluid status of patients undergoing chronic hemodialysis therapy. This study aimed to evaluate and compare the widely used and reliable method of indexed inferior vena cava diameter (IVCDi) with established and more recently available techniques (bioelectrical impedance analysis [BIA], continuous blood volume monitoring [Crit-line], and the B-line score [BLS] with lung ultrasonography) for estimating the hydration status of patients on HD. METHODS: Fifty-three patients undergoing chronic HD thrice weekly were included in the study. Evaluation of hydration status methods (IVCDi, BLS, BIA, and Crit-line) was performed thrice weekly before and after HD. Receiver operating characteristic curve analysis was performed to evaluate the discriminative power of (methods) the BLS, BIA, and Crit-line for predicting over- and underhydration of patients, as determined by the reference method, IVCDi. RESULTS: BLS showed the most promising results in predicting overhydration, as determined by IVCDi, compared with BIA and Crit-line and presented a sensitivity of 77% and specificity of 74%. The accuracy of the BLS was higher than that of BIA (0.81 vs. 0.71, p = 0.032) and Crit-line (0.61, p = 0.001). BLS also showed more promising results in predicting underhydration, as determined by IVCDi, than BIA and Crit-line and presented a sensitivity of 78% and a specificity of 73%. The accuracy of the BLS was higher than that of BIA (0.83 vs. 0.76, p = 0.035) and Crit-line (0.50, p < 0.001). CONCLUSIONS: The BLS is a useful and easily performed technique that has recently become available for accurate evaluation of dry weight and fluid status in patients with end-stage renal disease undergoing chronic HD. This method might help recognize asymptomatic lung congestion in these patients.