Background Chronic kidney disease patients are at increased risk of mortality with cardiovascular diseases and infections as the two leading causes of death for end-stage kidney disease treated with hemodialysis (HD). Mortality from bacterial infections in HD patients is estimated to be 100-1000 times higher than in the healthy population. Methods We comprehensively characterized highly pure circulating neutrophils from HD and healthy donors. Results Protein levels and transcriptome of HD patients' neutrophils indicated massive neutrophil degranulation with a dramatic reduction in reactive oxygen species (ROS) production during an oxidative burst and defective oxidative cellular signaling. Moreover, HD neutrophils exhibit severely impaired ability to generate extracellular NET formation (NETosis) in NADPH oxidase-dependent or independent pathways, reflecting their loss of capacity to kill extracellular bacteria. Ectopic hydrogen peroxidase (H2O2) or recombinant human SOD-1 (rSOD-1) partly restores and improves the extent of HD dysfunctional neutrophil NET formation. Conclusions Our report is one of the first singular examples of severe and chronic impairment of NET formation leading to substantial clinical susceptibility to bacteremia that most likely results from the metabolic and environmental milieu typical to HD patients and not by common human genetic deficiencies. In this manner, aberrant gene expression and differential exocytosis of distinct granule populations could reflect the chronic defect in neutrophil functionality and their diminished ability to induce NETosis. Therefore, our findings suggest that targeting NETosis in HD patients may reduce infections, minimize their severity, and decrease the mortality rate from infections in this patient population.

David Tovbin1*, Jony Sheynin4a,4b, Andrea Smeraglio5, Lone Avnon3 and Shimon Storch2 Author Affiliations 1Nephrology, Emek Medical Center 2Bnai-Zion Medical Center (BZMC), Technion, Israel Institute of Technology, Israel 3Pulmonary, Soroka University Medical Center (SMUC), Israel 4aDepartment of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Houston, TX, USA (current affiliation) 4bDepartment of Biomedical Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel 5Department of Internal Medicine, Portland Veterans, Administration Hospital, USA Received: June 27, 2019 | Published: July 10, 2019 Corresponding author: David Tovbin, Department of Nephrology, Emek Medical Center Afula, Israel 18101 Technion, Israel Institute of Technology, Haifa, Israel DOI: 10.26717/BJSTR.2019.19.003315 Also View In:

Mini Review Extremes of serum potassium levels in the general population, cardiac patients and hemodialysis (HD) patients may be critical. Thus, dialysate potassium concentration needs to be individualized to the patients by a standardized approach of the nephrologists.

Background Administration of intravenous iron is an essential treatment of anemia in hemodialysis patients, but it may lead to oxidative stress and increased morbidity and mortality. There is evidence that neutrophil gelatinase-associated lipocalin (NGAL) is protective against oxidative stress and thus the aim of the present study was to investigate the relationship between plasma NGAL and advanced oxidative protein products (AOPP) in hemodialysis patients treated with intravenous iron. Methods In a prospective study, 47 hemodialysis patients (mean age 63 years, SD = 13.6; 40% women) were enrolled from two separate hospitals. Oxidative stress was induced by an intravenous administration of 100 mg iron saccharate 0.5 h after the start of dialysis. Blood samples were drawn at the beginning of the dialysis, 0.5 h after iron administration and at the end of dialysis. NGAL levels were measured from the first blood sample, AOPP levels were measured from all blood samples. Results Our results showed that higher NGAL and AOPP levels at the beginning of the dialysis, prior to iron administration, significantly predicted higher levels of AOPP toward the end of dialysis, (β = 0.355, SE = 0.054, P = 0.035; β = 0.297, SE = 0.159, P = 0.043, respectively). Conclusions Our results suggest that higher level of NGAL is a risk factor for oxidative stress, as measured by AOPP levels, in dialysis patients receiving intravenous iron. Our findings could identify dialysis patients who are at higher risk from iron supplementation via measurement of NGAL levels.

Purpose To analyze the maternal and obstetric outcomes of patients with Alport syndrome.Methods We describe the pregnancy course of 8 pregnancies of three family members with the autosomal dominant (the rarest) form of Alport syndrome. We also analyzed 10 previously reported pregnancies with other Alport mutations in order to explore risk factors for unfavorable obstetric outcomes and maternal renal deterioration.Results In 13 pregnancies (72 %), renal function did not deteriorate permanently. All of these women had pre-pregnancy mild chronic kidney disease (CKD stage G1). In all of them, only a transient increase in proteinuria was recorded and in one case there was a transient decrease in the estimated glomerular filtration rate. In four other pregnancies (22 %), renal function deteriorated following pregnancy. All of them were complicated with pre-eclampsia. One woman had pre-pregnancy CKD-G2A3 and chronic hypertension. Two women had CKD-G1A3 of whom one had pre-pregnancy proteinuria near the nephrotic range. In the fourth case, renal function deterioration was reported without information on the exact pre-pregnancy renal function. In the last case, CKD-G2 was reported after pregnancy without information on CKD stage prior to pregnancy. Severe proteinuria did not imply a permanent renal function deterioration if it developed during pregnancy. Ten pregnancies ended with preterm birth (56 %). Two stillbirths were reported (11 %); however, only one was attributed to maternal health deterioration.Conclusion Data regarding pregnancy outcomes in Alport syndrome is limited. The outcome seems favorable when pre-pregnancy kidney function is normal or near normal and when chronic hypertension/pre-eclampsia is absent.

Background. Circulating cell-free DNA (CFD) appears following cell damage and DNA release, and increases in hemodialysis (HD) patients particularly following HD. We hypothesized that CFD is an integrative marker of tissue damage and can be an independent predictor for all-cause mortality in HD patients.Methods. In a prospective study, CFD levels before and after HD were evaluated in 31 chronic HD patients with no acute disease, using the reported rapid non-cumbersome inexpensive fluorometric assay developed in our laboratory. Follow-up levels were assessed at 18 months in 22 patients. All-cause mortality was a primary endpoint.Results. During 42 months of follow-up, 13 of the 31 (41.9%) patients died. The decedents were older than the survivors (mean age 69.9 versus 61.5 years, P = 0.06), but did not differ in end-stage renal disease (ESRD) duration, gender, albumin and hemoglobin, diabetes mellitus and weight. Post-dialysis CFD levels were significantly lower in survivors (median 688 versus 880 ng/mL, P = 0.01). The sensitivity and specificity of CFD levels of 850 ng/mL to predict 42 months (3.5 years) mortality were 73 and 75%, respectively, and the area under the receiver-operating characteristic curve was 0.77 [95% confidence interval (CI) 0.60-0.94]. The Cox proportional hazard regression model showed that CFD higher than 850 ng/mL adjusted for age, ESRD duration, weight and creatinine (stepwise model) was highly predictive of all-cause death with a hazard ratio of 8.0 (95% CI 2.3-28.5, P = 0.001).Conclusions. Post-dialysis CFD level is an independent predictor of all-cause mortality in patients undergoing HD. We propose that CFD detection is an inexpensive applicable tool for identifying patients at risk and their followup.

To describe the clinical manifestations and response to therapy of adult patients with tubulointerstitial nephritis and uveitis (TINU) syndrome and to provide suggested work-up and treatment. We retrospectively examined medical records of all adult patients suffering from TINU at Soroka University Medical Center (SUMC) over the past 15 years. Characteristics of ocular and nephrologic manifestations were investigated with particular attention given to age, presenting signs and symptoms, treatment and course of disease. Five adult patients (median age 44 years) were diagnosed with TINU syndrome and followed from 1991–2006 at SUMC. As renal involvement was present at initial evaluation in all patients, they were all treated with steroids. They all suffered from moderate to severe ocular inflammation and most of them relapsed; they also suffered from TINU-related non-specific symptoms. The uveitis in our adult patients was more severe than previously reported. Renal failure and TINU-related non-specific symptoms were observed in all patients and led to the diagnosis of TINU and to systemic therapy which is more aggressive than the usual therapy for uvetis. Thus, early suspicion and diagnosis of TINU may help to direct the appropriate therapy for the degree of uveitis observed in these patients.

BACKGROUND:Patients with end-stage renal disease are at high risk of mycobacterial infection.OBJECTIVES:To analyze the difficulties in reaching an accurate diagnosis of tuberculosis in dialysis patients.METHODS:We conducted a retrospective follow-up of patients who attended our peritoneal and hemodialysis units during the 10 year period 1995-2005.RESULTS:Our dialysis unit diagnosed 10 cases of tuberculosis caused by Mycobacterium tuberculosis and 9 cases of Mycobacterium other than tuberculosis. In the former group, five patients had Mycobacterium in the sputum, which was diagnosed by intraabdominal mass biopsy in one, culture of the gastric juices in one, and pleural fluid culture or pleural biopsy in three. One of these patients was suffering from pleural TB as well as Potts disease. Of the patients with Mycobacterium other than tuberculosis, five were diagnosed by sputum cultures, three by urine cultures and one in peritoneal fluid. Differences in treatment and outcome were also reviewed.CONCLUSIONS:The diagnosis of TB in dialysis patients should be approached with a high index of suspicion. It is clear that extensive diagnostic procedures are required to ensure an accurate diagnosis of the disease. Tuberculosis incurs a significant added burden due to the need for isolation of infected patients within the dialysis unit. Treatment of patients with Mycobacterium other than tuberculosis should be addressed individually.

Background: Recent studies have demonstrated correlation between inflammation to plasma troponin (cTnI) levels elevation and atrial fibrillation (AF) in noncardiac surgery settings. The goal of this prospective study was to examine the relation between inflammation associated parameters (IAPs) to post cardiac surgery cTnI elevation and AF. Methods: A single post CABG cTnI measurement was assessed in 156 consecutive patients. Clinical, operative and postoperative data, IAPs (hypophosphatemia, preoperative statin treatment, immediate postoperative fever, and prolonged mechanical ventilation) and in-hospital AF episodes were prospectively recorded. Results: Mean cTnI level was 14.4 +/- 12.4 ng/mL. In the two in-hospital deaths (1.2%) cTnI concentration was less than 12 ng/mL. Cardiac troponin-I levels were significantly higher in patients not preoperatively treated with statins (21.6 +/- 4.1 vs. 13.3 +/- 0.9, p = 0.05), in patients who needed intraoperative cardioversion (16.7 +/- 2.2 vs. 12.2 +/- 0.9, p = 0.07), in patients with postoperative hypophosphatemia (16.9 +/- 10.0 vs. 11.1 +/- 13.7, p = 0.04), postoperative fever (18.6 +/- 3.0 vs. 13.7 +/- 1.0, p = 0.07) and postoperative respiratory complications (23.9 +/- 4.3 vs. 13.5 +/- 1.0, p = 0.04). Step-wise logistic regression analysis revealed the following parameters as independently associated with elevated cTnI levels: preoperative statin treatment (CI 95% -15.9; -1.7, p = 0.02), intraoperative ventricular arrhythmia (CI 95% -0.7; 13.8, p = 0.08), hypophosphatemia (CI 95% 0.9; 8.6, p = 0.02), postoperative fever (CI 95% 0.9; 11.0, p = 0.02), and postoperative respiratory complications (CI 95% 0.1; 0.5, p = 0.01). Of the 156 patients, 50 (32.1%) had postoperative AF. The first episode of AF occurred between postoperative day 1 and 6 (mean-day 2). Mean duration of AF was 21.8 +/- 8.1 hours. Postoperative AF was significantly associated with age above 75 (50% vs. 29.4%, p = 0.01), hypertension (37% vs. 18%, p = 0.02), preoperative calcium channel blockers treatment (44% vs. 26%, p = 0.02), furosamide treatment (58% vs. 30%, p = 0.05), and preoperative left atrial diameter above 40 mm (56% vs. 29%, p = 0.01). Postoperatively, AF was significantly associated with postoperative renal failure (70% vs. 29%, p = 0.01), respiratory complications (61% vs. 29%, p = 0.02), and prolonged hospital stay (OR 1.1; CI 1.0-1.3; p < 0.05). No association was found between troponin levels and postoperative AF. Multivariable analysis found only left atrial enlargement and prolonged hospital stay independently associated with AF. Conclusions: A significant correlation between clinical IAPs and cTnI plasma level elevation was found after cardiac surgery. There was no correlation between these parameters and postoperative AF, and there was no correlation between postoperative plasma cTnI levels and the occurrence of AF. Preoperative treatment with statins may be beneficial in reducing postoperative inflammatory response but further study has to be carried out.

The leading cause of the high morbidity and mortality in hemodialysis (HD) patients is cardiovascular disease (CVD), followed by infections. A combination of patho-physiological processes is involved in the development and progression of vascular disease in HD patients including volume-overload/hypertension, atherosclerosis, calcification and thrombosis. A vicious circle of inflammation and oxidative stress, augmented by iatrogenic effects of HD lines, dialyzers and water contribute to the severity of atherosclerosis and possibly of vascular calcification. Specific metabolic risk factors include increased homocysteine levels, abnormal lipid profile and insulin resistance. The iatrogenic effect of associated therapy such as intravenous (IV) iron administration, active vitamin D derivatives, calcium containing phosphate binders, high dialysate Na concentration and possibly heparin, may add to the detrimental effects of uremia and co-morbid diseases. Potential mechanisms for iatrogenic processes may include effects of IV iron on protein oxidation and leucocyte adhesion to endothelial cells, as well as adverse effects of anticoagulation such as sub-clinical heparin induced thrombocytopenia (HIT). Preventive measures require a multidirectional approach to improve dialysis delivery and volume/blood pressure control, and to minimize adverse effects of current common essential therapies. Keywords: Adhesion, advanced oxidative protein products (AOPP), anemia, atherosclerosis, blood volume, calcification, diabetes mellitus, endothelial dysfunction, heparin, heparin induced thrombocytopenia

During a 12-month surveillance period, haemodialysis (HD) patients in southern Israel were categorised according to the type of vascular access site (VAS), i.e., arteriovenous (AV) fistula, synthetic AV graft, and cuffed or non-cuffed vascular catheters. Endpoints, expressed as cases/100 patient-months, were: incidence of hospital admission; antibiotic therapy; bloodstream infection (BSI); and VAS infection. These were compared to Centers for Disease Control (CDC) surveillance data, overall and by VAS type. In total, 2568 patient-months were analysed. The VAS distribution differed significantly from CDC data for fistulas (72% vs. 31%), grafts (12% vs. 41%), cuffed catheters (11% vs. 25%) and non-cuffed catheters (5% vs. 3%) (p < 0.0001 in all cases). Of 151 admissions, 32% resulted from infection, for which 112 antibiotic courses (22% vancomycin) were given. There were 16 BSIs, three involving resistant strains. The incidences of admission, antibiotic therapy, BSI and VAS infection were significantly lower overall, compared to CDC rates, as were most VAS-specific endpoints. These differences may be explained by VAS type distribution, although other factors may also be involved. Reporting regional or national surveillance data may allow a standardised comparison of the incidence of HD-associated infections.

Hepatitis C (HCV) is common in developing countries, where blood sampling and expensive sophisticated methods for detection are less available. Hemodialysis patients have high prevalence of HCV and may resemble sick populations in developing countries in relation to immunosuppression and antibodies production. For these reasons anti-HCV antibodies were assayed in saliva of hemodialysis patients by ImmunoComb II assay that is less laborious, relatively inexpensive and easy to perform If the findings are confirmed by larger studies this method may be useful especially in developing countries. Serum and saliva samples were obtained from 37 hemodialysis patients and assayed by ImmunoComb II kit. In positive PCR patients the saliva test had 100% sensitivity, which was as good as serum anti-HCV Axsym testing. Saliva testing had a similar or better specificity than the serum method.

Renal vein thrombosis (RVT) may present as an acute or chronic event, the latter being more common, and patients are usually asymptomatic. Acute RVT is more frequent in younger patients and is characterized by a sudden onset of severe flank pain associated with marked costovertebral angle tenderness and macroscopic haematuria. RVT is a known complication of the nephrotic syndrome. Other causes of acute RVT include membranous nephropathy and amyloidosis, trauma, oral contraceptive drugs, dehydration (mostly in infants) and steroid administration [1].