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

Introduction Since infammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifer of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. Objective and methods We investigated the efect modifcation by systemic infammation (serum CRP) on the relationship between a surrogate of the flling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantifed by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. Results At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r=0.23, P

AIM The aim of the present study was to evaluate the incidence, risk factors, clinical characteristics and outcomes of acute kidney injury (AKI) in octogenarians admitted to the emergency room, and to compare these parameters with those in a younger group of patients admitted in the same period. METHODS This is a prospective, observational, single-center study that enrolled adult patients admitted to the emergency room of Shaare Zedek Medical Center, Jerusalem, Israel. Patients were stratified by age (≥80 years or

Urinary tract obstructions (UTO) induce tubular injury. The hypothesis explored in this study is that UTO can cause transient proteinuria. The aims of this study were to determine whether patients with UTO have a higher incidence/severity of proteinuria compared with catheterized patients without UTO and whether proteinuria resolves at short term follow-up.This was a prospective, matched case control study that included 100 patients; 50 with acute UTO and 50 controls. Proteinuria was quantified using three consecutive 24-hour urinary collections during a week of hospitalization and its incidence, severity, and quantitative changes were compared between the study groups.Groups were similar by age (83.12±7.94 versus 84.48±9.39 (p=0.44)), major comorbidities, chronic medical treatment and causes of hospitalization. Abnormal proteinuria was observed in all patients with UTO and 94% of the control group. The degree of proteinuria was similar between the groups in the first, second and third 24-hour urine collections (638±419, 828±743, 728±944 vs. 620±639, 648±741, 732±841 mg/24 hours; p=0.88, 0.23 and 0.99, respectively). Proteinuria did not change significantly during a week of in-hospital follow-up in either study group (p=0.19 for trend).This study demonstrated a very high incidence of significant proteinuria in a cohort of hospitalized patients either with or without acute UTO. Proteinuria does not resolve in the early period after the relief of UTO. Future study with longer follow-up is needed to determine if this proteinuria resolves or persists following hospital discharge and if it has long-term prognostic significance.

Nephrology is a young medical specialty that has evolved and expanded during the last 4 decades of the past century, becoming recognized as one of the most innovative and challenging medical specialties. The training of nephrology takes place mainly in public hospitals, and there are important variations in the duration and assessment of training among the European countries. The Union of European Medical Specialties (UEMS) Renal Section and the European Renal Association-European Dialysis and Transplant Association have been working jointly since 2010 to harmonize European nephrology training and more recently to establish the European Certificate in Nephrology (ECN). The first two editions of the ECN were held in early 2017 and 2018. In total, 122 candidates from 26 countries have sat for the exam, with a success rate of 59% (72/122). To date, Switzerland has adopted the exam as their national training assessment and we expect that other countries will join Switzerland in the near future. Fostering the development and importance of the ECN requires that member states work to increase the academic and professional profile of the ECN within their countries. The ECN should be considered a 'quality mark' and a sign of high achievement in nephrology training in Europe. If holding the ECN becomes advantageous for employment or improving scientific careers, the number of candidates will increase and the sustainability of the ECN will be guaranteed. A recent, positive development is the pre-agreement between the UEMS Renal Section, UK Renal Association and Royal Colleges of the UK to adopt a unique pan-European exam beginning in 2020. However, any decision to commence the pan-European exam will depend, in part, on strong candidate enrolment for the ECN 2019 edition. Thus support of the national societies is crucial for the sustainability and growth of a European exam, because of their capacities to influence strategic policies in hospitals, universities and medical associations, with a longer-term aim to increase the professional recognition of the European exam. info:eu-repo/semantics/publishedVersion

The factors that determine prognosis in elderly patients with dialysis-requiring acute kidney injury (AKI-D) is uncertain. The purpose of this study was to examine predictors of in-hospital mortality in these patients.A retrospective, single-center study of hospitalized patients ≥ 70 years old with AKI-D. Clinical and demographic variables were compared between survivors and non-survivors, independent predictors of hospital mortality were identified by logistic regression.Among 137 eligible patients, hospital mortality was 66%; 59% of survivors were dialysis dependent at hospital discharge and 43% of initial survivors died within 1 year post discharge. There was no significant difference in age between survivors (80.2) and non-survivors (80.5) (p = 0.829). Non-survivors had higher rates of altered mental status (68.2 vs. 22.2%, p0.001), hypotension (29.5 vs. 13.6%, p = 0.048), leucopenia/leukocytosis (62.6 vs. 42.2%, p = 0.024), ICU admission (59.3 vs. 34.8%, p = 0.007), mechanical ventilation (64 vs. 21.7% p0.001), hepatic dysfunction (46.2 vs. 21.7%, p = 0.005), a diagnosis of sepsis (64.8 vs. 26.3%, p = 0.04), and treatment with vasopressors (69.8 vs. 35.6%, p0.001). The presence of ≥ 5 of these conditions was associated with90% mortality. Logistic regression showed altered mental status (OR = 7.4, 95% CI = 3.0 - 18.2) and mechanical ventilation (OR = 6.0; 95% CI = 2.5 - 14.6, p0.001) to independently predict hospital mortality.Elderly patients with AKI-D have a very high rate of hospital mortality or dialysis-dependent survival. Acute illness severity predicts poor outcome despite dialysis. The decision to dialyze patients in this setting should not be based on age alone but consider prognosis and expected quality of life. .

The increased usage of intravenous iron in hemodialysis patients during recent years has led to increasing concern over the potential development of iron overload. Current methods for detecting iron overload, transferrin saturation, and serum ferritin are neither sensitive nor specific. Labile plasma iron (LPI) represents a component of nontransferrin-bound iron and may be a more accurate indicator of impending iron overload. We studied whether LPI measured can serve as an early indicator of impending iron overload and mortality in hemodialysis patients. Chronic hemodialysis patients from two medical centers in Israel and Poland who received intravenous iron were included. Baseline clinical and laboratory parameters were recorded. LPI was measured before and 48 hours after a single IV administration. Correlation of positive LPI with laboratory parameters and 2-year mortality was evaluated. One hundred and one hemodialysis patients were included in the study. LPI became positive post-administration in 18 (17.8%) patients. Ferritin levels >526 ng/mL and monthly iron doses >250 mg were associated with positive LPI after intravenous iron. At a 2-year follow-up, higher mortality was observed in the positive LPI group (61.1% compared to 25.3%, P ≤ .05), although this effect was not statistically significant after multivariate adjustment. A substantial number of hemodialysis patients have positive LPI after intravenous iron administration. LPI positively correlates with laboratory parameters that are currently in routine clinical use for detecting iron overload and with higher intravenous iron dose. Further studies should be conducted to establish the clinical implications of LPI monitoring in hemodialysis patients.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

The Renal Section of the European Union of Medical Specialists is working towards harmonization and optimization of nephrology training across Europe and its Mediterranean borders. In addition to the need for harmonization of the heterogeneous time dedicated to training, it is necessary to ensure that the learning environment is of a sufficiently high standard to develop skilled specialists. Thus, there is a need to review the core educational infrastructure and resources that should be provided to trainees in order to be considered centres of excellence for nephrology training. This review addresses most of the characteristics and attributes that constitute a high-calibre training centre of excellence, considering that a training centre might not represent a single institution, but a network of institutions that provide a coordinated and complete curriculum to the trainee. The training institution should provide, apart from the classical current nephrological facilities (clinical nephrology, haemodialysis, peritoneal dialysis and transplantation), a number of other complementary facilities, including immunology, nephropathology-with a dedicated and expert renal pathologist-all the specialities of general medicine and general surgery and, in particular, vascular surgery, radiology and interventional radiology specialist services (renal biopsy, renal ultrasound and permanent vascular access) and intensive care unit. In addition to clinical training, a training centre of excellence should offer research facilities to allow trainees the opportunity to be involved in epidemiological, clinical, translational or basic scientific research. The training centres should ideally hold a certification of training accreditation. If the European and its Mediterranean border countries wish to guarantee a high standard of training in nephrology, their national health services need to recognize their responsibility towards the importance of doctor training, providing enough time for educational activities and investing in the resources required for high-standard specialist training.

A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment.To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period.Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS80 and impaired executive function as a Trails A performance time75 seconds and Trails B180 seconds.56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V1.2, p = 0.023), high plasma phosphorus levels (p6 mg/dL, p = 0.034), and hyponatremia (Na135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002).A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Meir Nitzan,1 Itzchak Slotki,2 Linda Shavit2 1Department of Applied Physics/Electro-Optics, Jerusalem College of Technology, 2Department of Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel Abstract: The commonly used techniques for systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurement are the auscultatory Korotkoff-based sphygmomanometry and oscillometry. The former technique is relatively accurate but is limited to a physician’s office because its automatic variant is subject to noise artifacts. Consequently, the Korotkoff-based measurement overestimates the blood pressure in some patients due to white coat effect, and because it is a single measurement, it cannot properly represent the variable blood pressure. Automatic oscillometry can be used at home by the patient and is preferred even in clinics. However, the technique’s accuracy is low and errors of 10–15 mmHg are common. Recently, we have developed an automatic technique for SBP measurement, based on an arm pressure cuff and a finger photoplethysmographic probe. The technique was found to be significantly more accurate than oscillometry, and comparable to the Korotkoff-based technique, the reference-standard for non-invasive blood pressure measurements. The measurement of SBP is a mainstay for the diagnosis and follow-up of hypertension, which is a major risk factor for several adverse events, mainly cardiovascular. Lowering blood pressure evidently reduces the risk, but excessive lowering can result in hypotension and consequently hypoperfusion to vital organs, since blood pressure is the driving force for blood flow. Erroneous measurement by 10 mmHg can lead to a similar unintended reduction of SBP and may adversely affect patients treated to an SBP of 120–130 mmHg. In particular, in elderly patients, unintended excessive reduction of blood pressure due to inaccurate SBP measurement can result in cerebral hypoperfusion and consequent cognitive decline. By using a more accurate technique for automatic SBP measurement (such as the photoplethysmographic-based technique), the optimal blood pressure target can be achieved with lower risk for hypotension and its adverse events. Keywords: oscillometry, hypotension, cognitive impairment, photoplethysmography

Neutrophil-to-lymphocyte ratio (NLR) is considered a readily available biomarker of systemic inflammation. An association between elevated NLR and adverse outcomes in a variety of medical and surgical conditions including CKD has been demonstrated in several studies. In this study, we evaluated the accuracy of single Emergency Department (ED) measurement of NLR for early diagnosis of acute kidney injury (AKI). We prospectively studied 294 patients aged 71.6 ± 17. We measured NLR at presentation to the ED. AKI is defined as a new-onset 1.5-fold or more increase in serum creatinine or a 25% decrease in estimated GFR sustained for at least 3 days despite volume resuscitation. The primary outcome is AKI. Secondary outcome is in-hospital mortality. A multivariate model and ROC analysis were performed to evaluate the association and eventual predictive capacity of NLR for the outcomes. 36 patients (12.2%) developed AKI and 26 (9%) died, 8 (22%) of the AKI group and 17 patients (7%) of the non-AKI group. The Mean NLR is significantly higher in AKI compare to non-AKI patients (11.7 ± 15.2 vs 6.45 ± 7.19, p = 0.048). A multivariate model adjusted for age, gender, blood pressure, plasma albumin and hemoglobin levels confirms that the NLR is higher in AKI patients (p = 0.031). Receiver operating characteristics curve reveals an AUC of 0.715 (95% CI 0.63–0.8) sensitivity 0.78, specificity 0.65, and OR 6.423 (CI 2.659–16.026) for a cutoff value of NLR 5.5. The relation between NLR and in-hospital mortality is not statistically significant (p = 0.92). Single ED measurement of NLR might be a useful tool for early diagnosis of AKI. This finding is particularly important in light of the low cost and widespread availability of NLR, especially compared with other biomarkers currently under study in the context of AKI.

Preoperative anemia adversely affects outcomes of cardiothoracic surgery. However, in patients with CKD, treating anemia to a target of normal hemoglobin has been associated with increased risk of adverse cardiac and cerebrovascular events. We investigated the association between preoperative hemoglobin and outcomes of cardiac surgery in patients with CKD and assessed whether there was a level of preoperative hemoglobin below which the incidence of adverse surgical outcomes increases.This prospective observational study included adult patients with CKD stages 3-5 (eGFR60 ml/min per 1.73 m(2)) undergoing cardiac surgery from February 2000 to January 2010. Patients were classified into four groups stratified by preoperative hemoglobin level:10, 10-11.9, 12-13.9, and ≥ 14 g/dl. The outcomes were postoperative AKI requiring dialysis, sepsis, cerebrovascular accident, and mortality.In total, 788 patients with a mean eGFR of 43.5 ± 3.7 ml/min per 1.73 m(2) were evaluated, of whom 22.5% had preoperative hemoglobin within the normal range (men: 14-18 g/dl; women: 12-16 g/dl). Univariate analysis revealed an inverse relationship between the incidence of all adverse postoperative outcomes and hemoglobin level. Using hemoglobin as a continuous variable, multivariate logistic regression analysis showed a proportionally greater frequency of all adverse postoperative outcomes per 1-g/dl decrement of preoperative hemoglobin (mortality: odds ratio, 1.38; 95% confidence interval, 1.23 to 1.57; P0.001; sepsis: odds ratio, 1.31; 95% confidence interval, 1.14 to 1.49; P0.001; cerebrovascular accident: odds ratio, 1.31; 95% confidence interval, 1.00 to 1.67; P=0.03; postoperative hemodialysis: odds ratio, 1.38; 95% confidence interval, 1.11 to 1.75; P0.01). Moreover, preoperative hemoglobin12 g/dl was an independent risk factor for postoperative mortality (odds ratio, 2.6; 95% confidence interval, 1.1 to 7.3; P=0.04).Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD. Whether outcomes could be improved by therapeutically targeting higher preoperative hemoglobin levels before cardiac surgery in patients with underlying CKD remains to be determined.

Uremic pruritus (UP) affects many patients suffering from chronic kidney disease (CKD) and has a negative impact on quality of life and survival. It has become increasingly evident that central transmission and sensitization processes similar to those observed in chronic pain are important mechanisms of pruritus.To test the potential role of pregabalin in reducing the intensity of UP in CKD patients.We prospectively collected data on CKD patients who suffered from severe intractable pruritus. Patients were asked to record the intensity of pruritus on a visual analogue scale.Twelve patients were studied. The average pretreatment pruritus score was 9.7 ± 0.9 and decreased to 3.7 ± 2.35, 3.2 ± 1.75, and 3 ± 1.5 after one, four, and 24 weeks of treatment, respectively (P0.05). The positive effect of pregabalin was demonstrated during the first week of therapy in six patients. Most patients required 25mg a day. Pregabalin was well tolerated, with somnolence and dizziness developing in two patients.We demonstrated dramatic improvement of long-standing UP after the initiation of pregabalin. We suggest that pregabalin can be used safely in CKD but careful titration of the dose is required to obtain an optimal response and minimize the possible adverse effects.

Background and objectives Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. Design, setting, participants, & measurements In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound–guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre– and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Results Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ -statistics ( κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Conclusions Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Background Vitamin D (Vit D) deficiency plays a central role in the pathogenesis of chronic kidney disease (CKD) complications, both skeletal and nonskeletal. The purpose of this study was to examine whether 25(OH)D levels and supplementation with oral cholecalciferol (Vitamin D3 (Vit D3)) are associated with morbidity and mortality among patients with significant CKD. Methods CKD patients attending the nephrology clinic at Shaare Zedek Medical Center between July 1, 2008 and January 31, 2012, tested at least twice for 25(OH)D levels, were enrolled. Primary endpoints included death, end-stage renal disease (ESRD) requiring start of dialysis, a rise of at least 50% in serum creatinine, or composite endpoints of the above. Results A total of 516 patients were studied, of whom 178, 257, and 81 patients had baseline vitamin D levels 30 ng/mL, respectively. We found an association between baseline 25(OH)D level below 15 ng/mL and renal outcomes (start of dialysis or a rise of at least 50% in serum creatinine) in both crude and multivariate analyses (hazard ratio (HR) 3.17, 95% CI 1.12 - 8.94). Vit D3 supplementation demonstrated beneficial effects on combined renal outcomes and death in univariate analyses (p = 0.02). Moreover, an increment of 10 ng/mL in 25(OH)D levels was associated with a 25% reduction in mortality (HR 0.755 (95% CI 0.54 - 1.00), in crude but not adjusted analyses. Conclusions Significant Vit D deficiency in CKD can serve as a biological marker indicating patients in whom adverse renal outcomes can be anticipated. Moreover, Vit D3 supplementation and rise of serum 25(OH)D levels may have beneficial influence on hard renal outcomes. .

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects. Fil: Macdougall, Iain C.. King's College Hospital Nhs Foundation Trust; Reino Unido Fil: Bircher, Andreas J.. Universitatsspital Basel; Suiza Fil: Eckardt, Kai Uwe. Universitat Erlangen-nuremberg; Alemania Fil: Obrador, Gregorio T.. Universidad Panamericana; México Fil: Pollock, Carol A.. The University Of Sydney; Australia. Royal North Shore Hospital; Australia Fil: Stenvinkel, Peter. Karolinska University Hospital; Suecia Fil: Swinkels, Dorine W.. Radboud University Nijmegen Medical Centre; Países Bajos Fil: Wanner, Christoph. Universitatsklinikum Wurzburg; Alemania Fil: Weiss, Günter. Medizinische Universitat Innsbruck; Austria Fil: Chertow, Glenn M.. University Of Stanford; Estados Unidos Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The multidrug-resistance 1 (MDR-1) P-glycoprotein (Pgp) is a transmembrane transporter system, which actively pumps cytotoxic drugs out of the cell. MDR-1 acquired in vitro differs from MDR-1 acquired in vivo, but has important consequences on the cellular phenotype and metastatic behavior. Here we report that the human colonic cancer cell line HT29 (MDR-1 negative) is more malignant than its MDR-1 overexpressing variant (HT29 MDR-1 positive). HT29 MDR-1 negative cells produce undifferentiated signet ring carcinomas when implanted subcutaneously into SCID mice, while HT29 MDR-1 positive cells form tumors with tubular structures, but without signet ring cells. Immunohistochemical proliferation marker analysis revealed that the MDR-1 positive cells proliferate much more slowly than the MDR-1 negative cells. MDR-1 overexpression results in a less differentiated phenotype at the cellular level (absence of mucin producing cells) but in a more differentiated phenotype at the tissue level (tubule formation). In addition, lectin binding patterns including that of Helix pomatia agglutinin (HPA), an indicator of metastatic potential, differed between the two cell lines. HT29 MDR-1 positive cells had less HPA binding sites than HT29 MDR-1 negative counterparts and metastasized less frequently in SCID mice. As slow proliferation, low degree of differentiation and multidrug-resistance is a hallmark of cancer stem cells and all were present in MDR-1 positive tumors, it is attractive to speculate that they represent a stem cell rich tumor. As shown by global gene expression analyses, genes involved, e.g. in cell adhesion, glycosylation and signal transduction, were deregulated in MDR-1 positive tumors compared to MDR-negative tumors. Overexpression of E-cadherin and carcinoembryonic antigen-related cell adhesion molecules 1 (CEACAM1) may provide clues to the mechanisms responsible for the reduced metastatic potential of MDR-1 overexpressing tumors. Since drug treatment shifted the cells towards a less metastatic phenotype in this in vivo model, it seems conceivable to achieve this using drug treatment also in a clinical situation.

Introduction The prevalence of heparin-induced antibodies (HIA) varies widely among reported series, but is generally higher in cardiac surgery than hemodialysis patients. This study was designed to explore the reasons behind the different prevalence of HIA in these two populations. Methods Blood samples from all hemodialysis and cardiac surgery patients in our hospital were examined for HIA. Heparin-induced thrombocytopenia (HIT) was suspected when platelet count was 50% decline in platelet count in the cardiac surgery group. Results 79 hemodialysis and 40 cardiac surgery patients were studied. HIA prevalence was significantly higher in cardiac surgery than in hemodialysis patients (65% v 10.1%, respectively, PConclusions Prevalence of HIA was significantly lower in hemodialysis as compared with cardiac surgery patients. Our data suggest that the observed difference in HIA prevalence was either population dependent, or due to different timing of heparin administration in the two groups.

INTRODUCTION AND AIMS Recent studies have suggested that aldosterone has many effects in addition to its ability to cause the kidney to retain sodium. To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN. METHODS 220 chronic hemodialysis patients underwent initial screening. Of these, 8 patients were followed for 8 weeks and their blood pressure, weight, plasma potassium, aldosterone levels and plasma renin activity were recorded. After a 4 week run in period, each patient received eplerenone 25 mg twice daily for another 4 weeks. RESULTS Administration of eplerenone for 4 weeks decreased predialysis systolic blood pressure from 166 ± 14 to 153 ± 10 mmHg (p < 0.05). Eplerenone had no effect on diastolic blood pressure, potassium, predialysis weight, intradialytic weight gain, plasma aldosterone or PRA. CONCLUSION Eplerenone significantly reduces systolic blood pressure in oligo-anuric hypertensive hemodialysis patients without effect on plasma aldosterone concentrations or plasma renin activity. Plasma potassium increases minimally after 4 weeks of therapy, a finding that raises some concern for long-term eplerenone use in chronic hemodialysis.

Background Catheter thrombosis is common and results in inadequate dialysis treatment and, frequently, in catheter loss. Since dialysis treatment runs on a strict schedule, occluded catheters need to be restored in a timely and cost effective manner. We present a new shortened protocol of urokinase infusion that allows hemodialysis to be performed within 90 minutes. Methods To chronic hemodialysis patients, who developed complete catheter occlusion, urokinase was infused simultaneously through both lumens of the catheter (125,000 units to each lumen) over 90 minutes. Technical success was defined as restoring blood pump speed to at least 250 ml/min. We determined the average time from catheter placement to first clot event (primary patency PP), recurrent clot event after urokinase treatment (secondary patency SP), catheter salvage rate and cause for removal. Results 37 catheters developed total thrombosis and urokinase was used to restore patency one or more times (total 47 treatments). Catheter salvage rate was 97 %. The average time of PP was 152 ± 56 days (7 - 784 days). Nine patients (30%) developed recurrent occlusion and the average time of SP was 64 ± 34 days (2 - 364 days). One catheter was removed because of dysfunction due to thrombosis. Other catheters were removed due to infection, fistula maturation or fell out spontaneously. Hemodialysis was performed immediately after treatment with blood speed of 250 ml/min in all patients. Conclusion Our protocol is highly effective, short, and allows to restore patency of totally occluded central venous catheters with minimal disruption of the dialysis session.

Enoxaparin, a low molecular weight heparin, has been shown to be a safe and effective anticoagulant to prevent clotting in the extracorporeal circulation during hemodialysis. Enoxaparin also possesses antiproliferative properties, and reduces neointimal proliferation following vascular injury in animals. Use of enoxaparin during hemodialysis may be associated with decreased myointimal proliferation and diminished vascular access stenosis or failure.The aim of our study was to test the efficacy of enoxaparin to reduce the incidence of recurrent vascular access stenosis in chronic hemodialysis patients.Twenty-nine hemodialysis patients who suffered from recurrent arteriovenous (A-V) access stenosis were studied retrospectively to compare the incidence of vascular access procedures before and during enoxaparin administration. Enoxaparin was administered intravenously as a single bolus at the start of hemodialysis.Twenty-eight patients (14 male) were analyzed. Ten required a new fistula during the study period. Observed treatment times (years/patient) were 1.20 ± 0.87 for unfractionated heparin (UFH) and 3.04 ± 2.19 for enoxaparin (P = 0.0001). Angiographic procedure rates (procedures/year) were 1.76 ± 0.92 in the UFH group and 1.30 ± 1.01 in the enoxoparin group (P = 0.0786). There were no significant differences in time to first stenosis between the two groups (P = 0.5315). One patient receiving enoxaparin developed upper gastrointestinal bleeding and a second patient sustained a subdural hematoma after a fall.Our study demonstrated a trend toward a decreased number of angiographic procedures for maintaining A-V access patency in selected chronic hemodialysis patients treated with enoxaparin in comparison with UFH as anticoagulant during dialysis.

Introduction: Contrast-induced acute kidney injury (CI-AKI) is one of the leading causes of hospital-acquired acute kidney injury. Multiple clinical studies have proposed several preventive strategies. Aims: To examine the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine (NAC) for preventive hydration after cardiac catheterization. Methods: We conducted a prospective, single-center trial. Patients with chronic kidney disease (CKD) stage III–IV undergoing cardiac catheterization were allocated to receive either an infusion of 0.9% sodium chloride and oral NAC or 154 mEq/L sodium bicarbonate. Main: Outcome measure CI-AKI, defined as an increase of 25% or 0.3 mg/dL or more in plasma creatinine within 2 days of contrast administration. Results: Ninety-three patients were allocated to one of the two groups: 42 patients in the saline plus NAC group and 51 patients in the bicarbonate group. There were no statistically significant differences between the groups in the most important clinical and procedural characteristics. Baseline plasma creatinine levels, estimated glomerular filtration rate, incidence of diabetes mellitus, hypertension, congestive heart failure, and contrast medium volume were similar. Mean plasma creatinine concentration was 1.76 ± 0.54 mg/dL in the saline and NAC group and 1.9 ± 1 mg/dL in the bicarbonate group (P = 0.23). The rate of CI-AKI was 9.8% in the bicarbonate group and 8.4% in the saline plus NAC group. No patient required renal replacement therapy. Conclusion: Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI-AKI in patients with CKD stage III–IV undergoing cardiac catheterization.

Study Objective. To evaluate the safety and efficacy by measuring antifactor Xa levels, of enoxaparin 1 mg/kg subcutaneously once every 24 hours in patients with severe renal failure. Design. Prospective study. Setting. Emergency, internal medicine, geriatrics, and cardiology departments of a medical center in Israel. Patients. Nineteen patients with stage 4 or 5 chronic kidney disease who required full anticoagulation. Intervention. Patients received enoxaparin 1 mg/kg subcutaneously every 24 hours for 2 or more days, as determined by a treating physician. Measurements and Main Results. Data on patients' demographic and clinical characteristics were collected. Blood samples for peak and trough antifactor Xa levels were obtained during the enoxaparin treatment period. Of the 19 study patients, 14 (74%) had peak antifactor Xa levels within the recommended range for full anticoagulation of 0.5-1.0 U/ml after their first enoxaparin dose; no concentration exceeded 1.0 U/ml. The mean peak antifactor Xa level was not significantly different after the first enoxaparin dose compared with the second and third doses. The mean ± SD trough antifactor Xa level, thought to be an indicator of drug accumulation, was 0.12 ± 0.12 U/ml; its clinical significance and target range are still unknown. No major bleeding events were noted. Conclusion. Enoxaparin 1 mg/kg once every 24 hours in patients with stage 4 or 5 chronic kidney disease who required full anticoagulation was safe, and this dose did not exceed recommended concentrations. The significance of enoxaparin trough levels remains unclear and should be investigated in future studies. Other dosing regimens of enoxaparin for specific patient populations should also be assessed for safety and efficacy.

The practice of intravenous iron supplementation has grown as nephrologists have gradually moved away from the liberal use of erythropoiesis-stimulating agents as the main treatment for the anemia of CKD. This approach, together with the introduction of large-dose iron preparations, raises the future specter of inadvertent iatrogenic iron toxicity. Concerns have been raised in original studies and reviews about cardiac complications and severe infections that result from long-term intravenous iron supplementation. Regarding the iron preparations specifically, even though all the currently available preparations appear to be relatively safe in the short term, little is known regarding their long-term safety. In this review we summarize current knowledge of iron metabolism with an emphasis on the sources and potentially harmful effects of labile iron, highlight the approaches to identifying labile iron in pharmaceutical preparations and body fluids and its potential toxic role as a pathogenic factor in the complications of CKD, and propose methods for its early detection in at-risk patients.

The Renal Section of the European Union of Medical Specialists is working towards harmonization and optimization of nephrology training across Europe and its Mediterranean borders. In addition to the need for harmonization of the heterogeneous time dedicated to training, it is necessary to ensure that the learning environment is of a sufficiently high standard to develop skilled specialists. Thus, there is a need to review the core educational infrastructure and resources that should be provided to trainees in order to be considered centres of excellence for nephrology training. This review addresses most of the characteristics and attributes that constitute a high-calibre training centre of excellence, considering that a training centre might not represent a single institution, but a network of institutions that provide a coordinated and complete curriculum to the trainee. The training institution should provide, apart from the classical current nephrological facilities (clinical nephrology, haemodialysis, peritoneal dialysis and transplantation), a number of other complementary facilities, including immunology, nephropathology—with a dedicated and expert renal pathologist—all the specialities of general medicine and general surgery and, in particular, vascular surgery, radiology and interventional radiology specialist services (renal biopsy, renal ultrasound and permanent vascular access) and intensive care unit. In addition to clinical training, a training centre of excellence should offer research facilities to allow trainees the opportunity to be involved in epidemiological, clinical, translational or basic scientific research. The training centres should ideally hold a certification of training accreditation. If the European and its Mediterranean border countries wish to guarantee a high standard of training in nephrology, their national health services need to recognize their responsibility towards the importance of doctor training, providing enough time for educational activities and investing in the resources required for high-standard specialist training.

Background Labile plasma iron (LPI) associated with iron supplementation has been implicated in complications found in dialysis patients. As LPI can potentially catalyse oxygen radical generation, we determined the presence of labile iron in the parenteral preparations and the frequency of occurrence of LPI in dialysis patients. Design The capacity to donate iron to apotransferrin (apo-) or to the chelator desferrioxamine (DFO) was measured with fluorescein-Tf (Fl-Tf) and Fl-DFO, respectively. Those probes undergo quenching upon binding to iron. Iron-catalysed generation of oxidant species was determined with dihydrorhodamine. Plasma nontransferrin-bound iron (NTBI), here termed LPI, was determined by mobilization of iron from low-affinity binding sites with oxalate, followed by its quantification with Fl-Tf in the presence of Ga(III). Results Normal individuals and most (80%) dialysis patients, analysed at least 1 week after iron supplementation showed no detectable ( 0·2 µm), in some cases weeks after iron administration. LPI levels correlated best (r2 = 0·9) with Tf saturation. The iron preparations contained 2–6% low molecular weight and redox-active iron, most of which is chelated by Tf. Conclusions Parenteral iron formulations contain a small but significant fraction of redox-active iron, most of which is scavenged by apo-Tf within

INTRODUCTION Colistin (polymyxin E) was developed ~ 60 years ago but was rarely used in clinical practice during the last 20 years because of concerns related to high rates of nephrotoxicity. However, it was recently reintroduced to clinical practice in many parts of the world for the treatment of multi-drug resistant gram-negative bacilli. In the current study, we evaluated the predictive capacity of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of acute kidney injury (AKI) in geriatric patients with urinary tract infection (UTI) receiving colistin therapy. METHODS We studied 116 patients aged 80.7 ± 12 treated with colistin who suffered from UTI. Urinary NGAL was measured at baseline and 1 - 2 hours after the second dose of colistin. The primary outcome was AKI. Secondary outcome was in-hospital morbidity and mortality. RESULTS 52 patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without changes in renal function during hospitalization and the remaining 48 patients (41%) had normal kidney function. The mean duration of colistin therapy was 9.1 ± 4.8 days. At baseline, urine NGAL was 405 ± 452 g/l in ATN, 285 ± 256 g/l in prerenal azotemia, 390 ± 468 g/l in CKD and 347 ± 877 g/l in normal kidney function patients (difference non-significant). We were unable to demonstrate statistically significant increments of urine NGAL following colistin administration in either ATN or non-ATN patient groups. Urine NGAL was not correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity 0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar results were obtained for secondary outcomes. CONCLUSIONS Our data suggest limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large clinical setting of geriatric patients hospitalized for UTI and receiving the potentially nephrotoxic colistin. This finding is likely due to the powerful influence of UTI on NGAL levels in both patients with normal kidney function and those with a wide spectrum of acute or chronic kidney diseases.

Nontransferrin-bound iron (NTBI) appears in the serum of individuals with iron overload and in a variety of other pathologic conditions. Because NTBI constitutes a labile form of iron, it might underlie some of the biologic damage associated with iron overload. We have developed a simple method for NTBI determination, which operates in a 96-well enzyme-linked immunosorbent assay format with sensitivity comparable to that of previous assays. A weak ligand, oxalic acid, mobilizes the NTBI and mediates its transfer to the iron chelator deferoxamine (DFO) immobilized on the plate. The amount of DFO-bound iron, originating from NTBI, is quantitatively revealed in a fluorescence plate reader by the fluorescent metallosensor calcein. No NTBI is found in normal sera because transferrin-bound iron is not detected in the assay. Thalassemic sera contained NTBI in 80% of the cases (range, 0.9-12.8 μmol/L). In patients given intravenous infusions of DFO, NTBI initially became undetectable due to the presence of DFO in the sera, but reappeared in 55% of the cases within an hour of cessation of the DFO infusion. This apparent rebound was attributable to the loss of DFO from the circulation and the possibility that a major portion of NTBI was not mobilized by DFO. NTBI was also found in patients with end-stage renal disease who were treated for anemia with intravenous iron supplements and in patients with hereditary hemochromatosis, at respective frequencies of 22% and 69%. The availability of a simple assay for monitoring NTBI could provide a useful index of iron status during chelation and supplementation treatments.

The labile iron pool (LIP) of animal cells has been implicated in cell iron regulation and as a key component of the oxidative-stress response. A major mechanism commonly implied in the downregulation of LIP has been the induced expression of ferritin (FT), particularly the heavy subunits (H-FT) that display ferroxidase activity. The effects of H-FT on LIP and other physiological parameters were studied in murine erythroleukemia (MEL) cells stably transfected with H-FT subunits. Clones expressing different levels of H-FT displayed similar concentrations of total cell iron (0.3 ± 0.1 mmol/L) and of reduced/total glutathione. However, with increasing H-FT levels the cells expressed lower levels of LIP and reactive oxygen species (ROS) and ensuing cell death after iron loads and oxidative challenges. These results provide direct experimental support for the alleged roles of H-FT as a regulator of labile cell iron and as a possible attenuator of the oxidative cell response. H-FT overexpression was of no apparent consequence to the cellular proliferative capacity. However, concomitant with the acquisition of iron and redox regulatory capacities, the H-FT–transfectant cells commensurately acquired multidrug resistance (MDR) properties. These properties were identified as increased expression of MDR1 mRNA (by reverse transcription polymerase chain reaction [RT-PCR]), P-glycoprotein (Western immunoblotting), drug transport activity (verapamil-sensitive drug efflux), and drug cytotoxicity associated with increased MDR1 or PgP. Although enhanced MDR expression per se evoked no significant changes in either LIP levels or ROS production, it might be essential for the survival of H-FT transfectants, possibly by expediting the export of cell-generated metabolites.

The labile iron pool (LIP) harbors the metabolically active and regulatory forms of cellular iron. We assessed the role of intracellular ferritin in the maintenance of intracellular LIP levels. Treating K562 cells with the permeant chelator isonicotinoyl salicylaldehyde hydrazone reduced the LIP from 0.8 to 0.2 μmol/L, as monitored by the metalo-sensing probe calcein. When cells were reincubated in serum-free and chelator-free medium, the LIP partially recovered in a complex pattern. The first component of the LIP to reappear was relatively small and occurred within 1 hour, whereas the second was larger and relatively slow to occur, paralleling the decline in intracellular ferritin level (t½= 8 hours). Protease inhibitors such as leupeptin suppressed both the changes in ferritin levels and cellular LIP recovery after chelation. The changes in the LIP were also inversely reflected in the activity of iron regulatory protein (IRP). The 2 ferritin subunits, H and L, behaved qualitatively similarly in response to long-term treatments with the iron chelator deferoxamine, although L-ferritin declined more rapidly, resulting in a 4-fold higher H/L-ferritin ratio. The decline in L-ferritin, but not H-ferritin, was partially attenuated by the lysosomotrophic agent, chloroquine; on the other hand, antiproteases inhibited the degradation of both subunits to the same extent. These findings indicate that, after acute LIP depletion with fast-acting chelators, iron can be mobilized into the LIP from intracellular sources. The underlying mechanisms can be kinetically analyzed into components associated with fast release from accessible cellular sources and slow release from cytosolic ferritin via proteolysis. Because these iron forms are known to be redox-active, our studies are important for understanding the biological effects of cellular iron chelation.

INTRODUCTION All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. The LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied for the first time NTBI correlations with markers of iron status and inflammation in prevalent hemodialyzed patients. MATERIAL AND METHODS Complete blood count, urea, serum lipids, fasting glucose, creatinine, ferritin, serum iron, total iron binding capacity (TIBC) were studied by standard laboratory method. The NTBI was assessed commercially available kits from Aferrix Ltd in Tel Aviv, Israel. A test result of 0.6 units of LPI or more indicates a potential for iron-mediated production of reactive oxygen species in the sample. RESULTS Patients with LPI units ≥ 0.6 had higher serum iron, erythropoiesis stimulating agents (ESA) dose, ferritin, high-sensitivity C-reactive protein (hsCRP), hepcidin and lower hemojuvelin. In hemodialyzed patients NTBI correlated with hsCRP (r = 0.37, p < 0.01), ferritin (r = 0.41, p < 0.001), IL-6 (r = 0.43, p < 0.001). In multivariate analysis predictors of NTBI were hemoglobin and alkaline phosphatase, explaining 58% of the variability. CONCLUSIONS Elevated NTBI in HD may be due to disturbed iron metabolism. Anemia and liver function might also contribute to the presence of NTBI in this population.

While dialysis historically began as treatment intended for younger patients, it has, over time, increasingly been extended to treat elderly patients with a high comorbidity burden. Data on the outcomes of dialysis in these patients show that in some cases it confers no benefit and may be associated with functional decline. We describe a 101-year-old male patient with chronic kidney disease (CKD), admitted to the intensive care unit (ICU) with exacerbation of heart failure and sepsis. He experienced acute deterioration of renal function, with oliguria and acidosis. The patient’s healthcare proxy insisted that dialysis be initiated despite his extremely advanced age, citing the patient’s devout religious beliefs. He underwent 56 dialysis treatments over the course of ∼4 months after which he died as a result of septic and cardiogenic shock. Our case is unique, in that it may represent the oldest individual ever reported to start haemodialysis. It illustrates the ever-growing clinical and ethical challenges posed by the treatment of renal failure in the geriatric population.

BACKGROUND AND OBJECTIVES Hypoparathyroidism in patients with functioning kidneys leads to hyperphosphatemia. This paper reviews data suggesting that hypoparathyroidism in patients on maintenance dialysis leads to hypophosphatemia. DESIGN Clinical data in two patients on dialysis with hypoparathyroidism following parathyroid surgery; literature review of dialysis patients with hypoparathyroidism following parathyroid surgery. RESULTS In the patients presented both here and in the literature, hypoparathyroidism in dialysis patients is associated with persistent hypophosphatemia or decrease in serum phosphorus from its pre-surgery level. CONCLUSION In patients on maintenance dialysis, persistent hypoparathyroidism post-parathyroidectomy may lead to chronic hypophosphatemia, in contrast to the hyperphosphatemia usually associated with hypoparathyroidism. Proposed mechanisms for this paradoxical phenomenon include ongoing phosphorus deposition into bone (Hungry Bone Syndrome), phosphorus deposition into soft tissue and/or diminished intestinal phosphorus absorption or increased intestinal phosphorus loss.

Background The proportion of elderly individuals is growing and the prevalence of chronic kidney disease (CKD) among elderly people undergoing cardiac surgery is increasing constantly. The aim of this study was to determine the influence of different degrees of preoperative renal dysfunction on postoperative outcomes in patients older than 80 years of age. Methods This is an observational study that included adult patients undergoing cardiac surgery in which data were collected prospectively. Patients were divided into groups according to their preoperative plasma creatinine and eGFR levels. Results From February 1997 to January 2010, 318 octogenarians underwent cardiac surgery. Of these, 140 patients (44%) had abnormal preoperative creatinine levels. A significantly higher incidence of postoperative sepsis (4% vs. 17%, p 0.03), CVA (1% vs. 6%, p 0.03), and prolonged hospital stay (16 ± 13 vs. 20 ± 16 days, p 0.04) were detected in patients with preoperative kidney dysfunction. Subgroup analysis revealed that preoperative CKD stage IV (eGFR 15–30 ml/min/1.73 m2) but not CKD stage III (eGFR 30–60 ml/min/1.73 m2) and preoperative creatinine > 1.8 mg/dl were independently associated with increased incidence of postoperative CVA (OR 4; 95% CI 0.07–0. 8, p = 0.05 for eGFR, and OR 7.8; 95% CI 1.2–60, p = 0.003 for creatinine). However, no significant increment in postoperative mortality with decreasing eGFR or increasing preoperative creatinine was demonstrated. Conclusions A substantial increase in the risk of postoperative CVA and sepsis, but not mortality, was demonstrated in octogenarians with advanced but not mild degrees of preoperative CKD. Compared to younger patients, a high burden of comorbidities in octogenarians may have a greater influence on outcomes post cardiac surgery than impaired renal function. Our data may provide a rationale for modified risk stratification in octogenarian candidates for cardiac surgery.

Background/Aims: Cardiovascular morbidity and mortality are high in patients with chronic kidney disease. We evaluated the influence of small differences in preoperative kidney function on mortality and complications following cardiac surgery. Methods: This is an observational study that included adult patients undergoing cardiac surgery. Preoperative estimated glomerular filtration rate (eGFR) was estimated by the 4-component Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on preoperative creatinine levels. For analysis, patients were divided into groups according to their preoperative creatinine (0.2 mg/dl increments) and eGFR levels (15–30 ml/min/1.73 m2 decrements). Results: Data on 5,340 patients were analyzed. A significant increase in postoperative mortality was demonstrated with preoperative creatinine at high-normal versus low-normal values (OR 1.7, 95% CI: 1–2.5; p = 0.02). For preoperative creatinine >1.2 mg/dl, adjusted OR for in-hospital mortality increased stepwise with every 0.2-mg/dl increment of creatinine. In addition, a statistically significant increment of mortality was detected with every 15-ml/min/1.73 m2 decrement in preoperative eGFR. Conclusions: Minimal changes of preoperative kidney function are associated with a substantial increase in the risk of mortality and morbidity following cardiac surgery. Even within the ‘normal’ range, minimal increases in serum creatinine levels are associated with increased risk of adverse events postoperatively.

Cl- channel and Na(+)-K(+)-2Cl- cotransport activities were studied in various cystic fibrosis transmembrane conductance regulator (CFTR)-expressing cells with the aim of assessing integrative patterns of regulation of Cl- secretion. Human colonic HT-29 cells express relatively high levels of CFTR and cotransporter but relatively low Cl- channel activity. These cells showed commensurate activations of both transport systems evoked by short-term (minutes) or long-term (hours) exposures to adenosine 3',5'-cyclic monophosphate (cAMP). However, unlike in the case of CFTR and Cl- channels, long-term induction of cotransporter did not depend on de novo protein synthesis or changes in number of transporters. The patterns of activation of both transporters were also examined in CFTR-deficient cell lines (CFPAC and the viral-transfected CFPAC-PLJ) and in the viral CFTR-transfected derivative (CFPAC-4.7). All these cells displayed relatively low basal cotransport activity and a correspondingly low number of transporters, whereas only CFPAC-4.7 cells showed short-term (but not long-term) activatable Cl- channels. However, irrespective of the presence or absence of CFTR in CFPAC cells, neither short- nor long-term cAMP exposures induced significant cotransporter activation. Our studies with the various epithelial cell lines indicate that expression of CFTR activity per se is not sufficient for stimulation of cotransporter activity. Moreover, despite apparent correction of CFTR levels in CFPAC cells by gene transfer, the apparent Cl- secretory capacity might be limited by the low cotransport activity, such as that found in CFPAC cells, with obvious implications for proposed gene therapy of cystic fibrosis.

Introduction: We tested the hypothesis that urinary and serum neutrophil gelatinase-associated lipocalins (NGAL) early after non-cardiac major surgery predict postoperative acute kidney injury (AKI), complications and mortality. Methods: We studied 74 patients undergoing orthopedic, vascular and abdominal surgery lasting ≧2 h. NGAL was measured in preoperative, as well as 2- and 6-hour postoperative samples. The primary outcome was AKI. Secondary outcome was postoperative infection and death. Results: 10 patients (13.5%) developed AKI, 19 (26%) reached secondary outcomes, of whom 5 (7%) died. Serum NGAL was significantly higher in patients with diabetes and chronic kidney disease (CKD). No significant correlation was detected between serum or urine NGAL and subsequent development of AKI. Urine NGAL at 6 h and serum NGAL at 2 and 6 h were strongly correlated with postoperative infection and death (p = 0.004, p = 0.013 and p = 0.001, respectively). Conclusions: Our data suggest that in the general surgical population, NGAL could serve as a potent early biomarker for postoperative infection, and that the presence of CKD and diabetes mellitus is associated with higher levels of NGAL and may influence its predictive value.

The role of N-acetylcysteine (NAC) to protect against contrast-induced nephropathy (CN) in patients with pre-existing renal insufficiency remains controversial despite several randomized controlled trials and meta-analyses. The potential reasons of inconsistency may be due to differences in definition, type and dose of contrast medium, imaging procedures, and the frequency of other potential causes of acute renal injury. Renal function before contrast administration is a major determinant of deterioration in function after administration.We conducted a retrospective review of patients with Stage III Chronic Kidney Disease (CKD) who underwent cardiac catheterization from January 2000 through January 2004 in our hospital. The incidence of CN was examined in patients pretreated and not pretreated with NAC.From January 2000 to January 2004, 189 patients with Stage III CKD underwent cardiac catheterization. All patients received 0.45% or 0.9% saline hydration prior to catheterization. NAC was given prior to 83 catheterizations and not given prior to 57. Eleven of 57 patients (19.3%) not pretreated with NAC developed acute renal injury (ARI) while 6 of 83 who received NAC (7.2%) developed ARI (p0.05). Nineteen patients underwent more than one cardiac catheterization, but there was no pattern to their potential for multiple episodes of ARI irrespective of prophylactic NAC administration.In our study NAC offered significant protection against ARI in patients with Stage III CKD. No overt risk factor for multiple episodes of ARI was observed, nor was the occurrence of ARI after first cardiac catheterization predictive of ARI after a subsequent catheterization.

To the Editor: Jhaveri et al.1 provide a comprehensive review of glomerular diseases seen with malignancy and its treatments, including chemotherapy-induced thrombotic microangiopathy (TMA). However, they have overlooked evidence for renal TMA after pegylated liposomal doxorubicin (PLD) for ovarian cancer.