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Introduction: Excessive ultrafiltration is associated with intra-dialytic symptoms, loss of residual function, and mortality in haemodialysis patients. A major contributor to excessive ultrafiltration is within-individual variation in pre-dialysis weight and the concept of achieving a fixed target weight by the end of each dialysis session. Haemodialysis protocols which allow variable post-dialysis weight have not been proposed. Methods: Weight variation was observed in haemodialysis patients and healthy controls to estimate the proportion of pre-dialysis weight variation which could be considered natural variation. These estimates were used to derive a novel protocol for setting ultrafiltration, which was evaluated by mathematical modelling. Results: Amongst 20 haemodialysis patients, mean (SD) pre-dialysis weight was 102.74 (0.94)% of target weight after a 2-day gap and 103.50 (0.94)% after a 3-day gap. Amongst 10 healthy individuals, mean (SD) daily weight was 100.0 (0.71)% of average weight. A 4-component model of pre-dialysis weight was derived using these estimates, in which the best estimate of pre-dialysis excess fluid is the midpoint of excess weight and average fluid gain, and used to propose a novel protocol for ultrafiltration setting. In simulations, the novel protocol reduced ultrafiltration variation by more than half (standard deviation 0.6 vs. 1.3% of target weight, p < 0.001), without increasing the variation in post-dialysis fluid excess. Excessive ultrafiltration rates (over 13 mL/h/kg) were far less frequent using this protocol (2.6% vs. 7.5% of sessions, p = 0.001). Conclusion: Considering natural weight variation allows the development of a novel protocol for ultrafiltration in which target weight does not have to be achieved precisely: it is therefore a soft target. This protocol, which is predicted to substantially reduce excessive ultrafiltration variation, is a zero-cost intervention with the potential to improve symptoms and clinical outcome for haemodialysis patients.

Background Dialysis patients are at risk of severe COVID-19. We managed COVID-19 haemodialysis outpatients in dedicated satellite dialysis units. This provided rare opportunity to study early disease progress in community-based patients. We aimed to (1) understand COVID-19 progression, (2) identify markers of future clinical severity and (3) assess associations between dialysis management strategies and COVID-19 clinical outcomes. Methods We conducted a cohort study of all outpatients managed at a COVID-19 haemodialysis unit. We analysed data recorded as part of providing COVID-19 clinical care. We analysed associations between features at diagnosis and the first 3 consecutive haemodialysis sessions in patients who required future hospital admission, and those who had died at 28 days. Results Isolated outpatient haemodialysis was provided to 106 patients over 8 weeks. No patients received antiviral medication or hydroxychloroquine. 21 patients (20%) were admitted at COVID-19 diagnosis. 29 of 85 patients (34%) were admitted after initial outpatient management. 16 patients (15%) died. By multivariate analysis, non-active transplant list status, use of institutional transport, and increased white cell count associated with future hospitalisation and increased age associated with death. Oxygen saturations progressively decreased over the first 3 dialysis sessions in the cohorts who progressed to future hospital admission or death. Mean ultrafiltration volume of the first three haemodialysis sessions was reduced in the same cohorts. Conclusions Outpatient haemodialysis in patients with COVID-19 is safe for patients and staff. Features at the first 3 dialysis sessions can identify individuals at risk of future hospitalisation and death from COVID-19., Graphical abstract

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, many countries have instituted population-wide measures for social distancing. The requirement of patients on dialysis for regular treatment in settings typically not conducive to social distancing may increase their vulnerability to COVID-19. METHODS: Over a 6-week period, we recorded new COVID-19 infections and outcomes for all adult patients receiving dialysis in a large dialysis center. Rapidly introduced control measures included a two-stage routine screening process at dialysis entry (temperature and symptom check, with possible cases segregated within the unit and tested for SARS-CoV-2), isolated dialysis in a separate unit for patients with infection, and universal precautions that included masks for dialysis nursing staff. RESULTS: Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. We observed clustering in specific units and on specific shifts, with possible implications for aspects of service design, and high rates of nursing staff illness. A predictive epidemic model estimated a reproduction number of 2.2; cumulative cases deviated favorably from the model from the fourth week, suggesting that the implemented measures controlled transmission. CONCLUSIONS: The COVID-19 epidemic affected a large proportion of patients at this dialysis center, creating service pressures exacerbated by nursing staff illness. Details of the control strategy and characteristics of this epidemic may be useful for dialysis providers and other institutions providing patient care.

In patients with chronic kidney disease the risk of developing Tuberculosis is increased, while the presentation is often atypical making the diagnosis more difficult. The aim of this study is to describe the presentation of Tuberculosis in dialysis and kidney transplant patients, including the range of diagnostic approaches and the utility of different sample types.In this retrospective study, case records of dialysis and kidney transplant patients were reviewed, including all those treated for Tuberculosis between January 2009 and December 2020.Over 12 years, there were 143 cases of Tuberculosis in 141 patients (aged 17-86, 50.4% male). Tuberculosis was most common in Asian patients (64%) and those receiving hemodialysis (82%), particularly during the first year after dialysis initiation (54% of dialysis cases). Non-pleural/pulmonary disease accounted 40% of cases, and non-organ-specific presenting features were prominent including fever, lymphadenopathy, and weight loss. The diagnosis was confirmed microbiologically or histologically in 87 cases (61%), with low sensitivity observed for many types of samples including sputum (18%) and pleural fluid (12%). Higher sensitivity was observed with tissue samples including bronchoscopic lymph node aspiration (75%) and other lymph node sampling (92%). In the 52 cases where drug sensitivities were available, resistance to a first line treatment, most commonly isoniazid, was seen in 12 cases (23%). Furthermore, 1- and 5-year survival from diagnosis were 78% and 61%, respectively. Baseline variables independently associated with poorer survival were age (OR 1.8 per decade, 95% CI 1.4-2.3), weight loss over 10% (OR 1.9, 95% CI 1.0-3.5), and a non-confirmed diagnosis (OR 1.6, 95% CI 1.2-2.1).Tuberculosis is common in dialysis and kidney transplant patients, particularly during the first year of dialysis. Short-term mortality is high, but the diagnostic sensitivity of many types of samples is low, so that diagnosis is difficult, with treatment often initiated without confirmation. These data highlight the importance of judgment and clinical experience with this complex patient group.

Background Adverse events and mortality tend to cluster around dialysis sessions, potentially due to the impact of the saw-toothed profile of uraemic toxins such as potassium, peaking pre-dialysis and rapidly dropping during dialysis. Acidosis could be contributing to this harm by exacerbating a rise in potassium. The objectives of this study were to investigate the effects of oral bicarbonate treatment on reducing inter-dialytic potassium gain as well as other clinical consequences of preserving muscle mass and function and reducing intradialytic arrhythmia risk in people on haemodialysis. Methods Open-label randomised controlled trial in a single-centre (London, UK). Forty-three clinically stable adults on haemodialysis were recruited, with a 6 month average pre-dialysis serum bicarbonate level 4 mmol/l. Thirty-three participants completed the study. Oral sodium bicarbonate tablets titrated up to a maximum of 3 g bd (6 g total) in intervention group for 12 weeks versus no treatment in the control group. Outcomes compared intervention versus non-intervention phases in the treated group and equivalent time points in the control group: pre- and post-dialysis serum potassium; nutritional assessments: muscle mass and handgrip strength and electrocardiograms (ECGs) pre and post dialysis. Results Participants took an average of 3.7 ± 0.5 g sodium bicarbonate a day. In the intervention group, inter-dialytic potassium gain was reduced from 1.90 ± 0.60 to 1.69 ± 0.49 mmol/l (p = 0.032) and pre-dialysis potassium was reduced from 4.96 ± 0.62 to 4.79 ± 0.49 mmol/l without dietary change. Pre-dialysis bicarbonate increased from 18.15 ± 1.35 to 20.27 ± 1.88 mmol/l, however with an increase in blood pressure. Nutritionally, lean tissue mass was reduced in the controls suggesting less catabolism in the intervention group. There was no change in ECGs. Limitations are small sample size and unblinded study design lacking a placebo, with several participants failing to achieve the target of 22 mmol/l serum bicarbonate levels due mainly to tablet burden. Conclusion Oral sodium bicarbonate reduced bicarbonate loss and potassium gain in the inter-dialytic period, and may also preserve lean tissue mass. Trial registration The study was registered prospectively on 06/08/2015 with EU Clinical Trials Register EudraCT number 2015-001439-20.

Jugular Tesio lines (TesioCaths; MedCOMP, Harleysville, PA, USA) are frequently used as permanent vascular accesses in haemodialysis patients. During the insertion procedure, arrhythmias are a relatively common complication, usually related to an excessively advanced catheter tip, without major consequences. We present two cases of life-threatening arrhythmias triggered by the Tesio catheter eccentric high-velocity jet of blood resolved after reposition of the catheter without further episodes, despite both lines being inserted under real-time ultrasound and fluoroscopic guidance. We believe dialysis lines should be checked for tip position even when long-standing to prevent relevant complications due to catheter sliding.

BACKGROUND AND OBJECTIVES: Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. RESULTS: Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. CONCLUSIONS: Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.

Introduction There are limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of coronavirus disease 2019 (COVID-19) remains. In this study we delineate the differential risks involved using serologic methods to help define exposure rates. Methods From a cohort of 1433 patients with end-stage kidney disease (ESKD), we analyzed COVID-19 infection rates and outcomes in 299 waitlist patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant program closed due to COVID-19. Results The overall mortality rates in waitlist and transplant populations were equivalent (P = 0.69). However, COVID-19 infection was more commonly diagnosed in the waitlist patients (P = 0.001), who were more likely to be tested by reverse transcriptase polymerase chain reaction (P = 0.0004). Once infection was confirmed, mortality risk was higher in the transplant patients (P = 0.015). The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6%, respectively (P = 0.0001). After adjusting for potential screening bias, the relative risk of death after a diagnosis of COVID-19 remained higher in transplant recipients (hazard ratio = 3.36 [95% confidence interval = 1.19–9.50], P = 0.022). Conclusions Although COVID-19 infection was more common in the waitlist patients, a higher COVID-19‒associated mortality rate was seen in the transplant recipients, resulting in comparable overall mortality rates.

Central venous stenosis is a well-recognized complication of central venous catheter use in hemodialysis patients, which may present with significant swelling of the upper limbs, neck, and face. Here, we describe a renal transplant recipient previously on hemodialysis, who underwent endovascular intervention for central venous stenosis after presenting with facial swelling and exertional dyspnoea. His symptoms continued to progress, however, until the underlying thyroid pathology was recognized. Ruling out the possible mimics of central venous stenosis is important in preventing unnecessary intervention. This case highlights the role of specialty bias in the process of diagnosis.

Background and Aims Despite the now-widespread use of haemodialysis treatment, optimal fluid management in long-term dialysis patients remains challenging. Whilst the between-patient factors affecting target weight and ultrafiltration have been well studied, little is known regarding the within-patient factors affecting these relationships. Method Dialysis data for a group of stable haemodialysis patients, from 4 dialysis units, were analysed over a period of one year. All weights and volumes are expressed as percentage of target weight. Results From 100 patients (aged 28–89, mean 65.4, 54% male) observed over a year, complete data were available for 15530 dialysis sessions, and 13027 combinations of dialysis session plus the following inter-dialytic interval. Mean arterial pressure dropped by 3.5(+/-14.6)mmHg during dialysis, with a significant correlation (p In 87 patients, inter-dialytic fluid gain correlated strongly (p Unsurprisingly, more fluid was gained over longer inter-dialytic intervals: mean(sd) weight at the start of dialysis was 103.2(1.0)% after a 3-day gap and 102.5(1.0)% after a 2-day gap, with this difference being significant (p Conclusion Inter-dialytic fluid gain is strongly dependent on ultrafiltration during the previous dialysis session, and diminishes during the inter-dialytic interval. Large ultrafiltration volumes, which have historically been perceived as the inevitable result of large fluid intakes, are actually a cause of thirst and large fluid intakes in haemodialysis patients. These data, derived from within-patient analyses, strongly challenge our conventional understanding of dialytic fluid management.

Background and objectives Central venous catheters have traditionally provided access for urgent hemodialysis, but are also sometimes advocated as an option for older or more comorbid patients. Adverse effects of this type of dialysis access include central venous stenosis, for which the risk factors and consequences are incompletely understood. Design, setting, participants, & measurements We conducted two studies within the same population cohort, comprising all patients starting hemodialysis in a single center from January 2006 to December 2013. First, patients were retrospectively analyzed for the presence of central venous stenosis; their access outcomes are described and survival compared with matched controls drawn from the same population. Second, a subset of patients with a history of catheter access within this cohort was analyzed to determine risk factors for central venous stenosis. Results Among 2811 patients, central venous stenosis was diagnosed in 120 (4.3%), at a median dialysis vintage of 2.9 (interquartile range, 1.8–4.6) years. Compared with matched controls, patients with central venous stenosis had similar survival (median 5.1 versus 5.2 years; P=0.54). Among a subset of 500 patients, all with a history of catheter use, 34 (6.8%) developed central venous stenosis, at a rate of 2.2 per 100 patient-years. The incidence of central venous stenosis was higher with larger number of previous catheters (relative risk [RR], 2.2; 95% confidence interval [95% CI]. 1.6 to 2.9), pacemaker insertion (RR, 3.9; 95% CI, 1.7 to 8.9), and was lower with older age (RR, 0.7 per decade; 95% CI, 0.6 to 0.8). In a Cox proportional hazards model, the catheter number, pacemaker, and younger age at dialysis initiation were all significant independent risk factors for central venous stenosis. Conclusions Central venous stenosis occurred in a minority of patients on hemodialysis, and was associated with compromised future access, but unchanged survival. Among patients with a history of catheter use, risk related to both the number of catheters and the total catheter duration, although nondialysis factors such as pacemakers were also important. Central venous stenosis risk was lower in older patients, supporting the selective use of tunneled catheters in this group.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: “what does good quality haemodialysis look like?”The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to – most of this is freely available online, at least in summary form.A few notes on the individual sections:This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines “enough” dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term “eKt/V” is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient.This section deals with “non-standard” dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week – this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here.This section deals with membranes (the type of “filter” used in the dialysis machine) and “HDF” (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it’s as good as but not better than regular dialysis.This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this.This section deals with dialysate, which is the fluid used to “pull” toxins out of the blood (it is sometimes called the “bath”). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate.This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects.This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful.This section draws together a few aspects of dialysis which don’t easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered.There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

Eosinophilia is commonly found in patients with clinical reactions to the hemodialysis circuit. With modern membranes, such reactions have become less common, but they may be under diagnosed in patients with subtle symptoms, in whom the presence of eosinophilia is an important diagnostic feature. Two case reports are presented, along with a hemodialysis study of the frequency and clinical associations of eosinophilia. In three hemodialysis facilities, all current hemodialysis patients with persistent eosinophilia (greater than 1 × 10(9) /L for 3 months) were identified. Control patients without eosinophilia (less than 0.5 × 10(9) /L for 3 months) matched for age, gender, and ethnicity were identified from the same facilities. A historical cohort of patients, dialyzing at the same facilities 5 years ago, was screened for the presence of persistent eosinophilia. From 510 patients, 24 cases of persistent eosinophilia were identified (4.7%). The median eosinophil count was 1.75 × 10(9) /L (range 1.1-7.5 × 10(9) /L). The prevalence in a historical cohort 5 years previously was significantly less at 1.5% (P = 0.046). Compared to controls, patients with eosinophilia were more likely to be on an angiotensin converting enzyme inhibitor (41.7% vs. 12.5%, P = 0.049), had a lower C-reactive protein (10 vs. 24 mg/L, P = 0.02) and were more likely to be using a fistula for access (P = 0.049). Over the following 12 months, there was no difference in the mean number of hospital admission days between cases and controls (7.6 vs. 11.5 days, P = 0.54), and no difference in mortality over 29 months (25.0% vs. 29.2%, P = 1.00). Eosinophilia remains not uncommon in hemodialysis patients, and in most cases reflects allergy to components of the dialysis circuit, which is usually subclinical. The overall prognosis for asymptomatic patients appears to be favourable.

BACKGROUND: Hydroxychloroquine (HCQ) is a recommended drug in systemic lupus erythematosus (SLE). It has a long terminal half-life, making it an attractive target for therapeutic drug monitoring. The aim of this study was to establish a relationship between blood HCQ concentration and lupus nephritis activity. METHODS: We conducted a retrospective observational study with data collected from clinical and laboratory records. Inclusion criteria were patients followed in the lupus clinic with biopsy-proven International Society of Nephrology/Renal Pathology Society Classes III, IV or V lupus nephritis on HCQ for at least 3 months (200–400 mg daily) and with HCQ levels measured during treatment. Exclusion criteria were patients on renal replacement therapy at baseline or patients lost to follow-up. RESULTS: In 171 patients, the HCQ level was measured in 1282 samples. The mean HCQ blood level was 0.75 ± 0.54mg/L and it was bimodally distributed. An HCQ level 0.6 mg/L (600 ng/mL) in those patients with lupus nephritis. CONCLUSION: HCQ level monitoring may offer a new approach to identify non-adherent patients and support them appropriately. We propose an HCQ minimum target level of at least 0.6 mg/L to reduce the renal flare rate, but this will require a prospective study for validation.

BACKGROUND The discovery of hepcidin, the hormone regulating iron absorption and transport, has improved the understanding of anemia and erythropoietin treatment. Excessive hepcidin signaling causes anemia in chronic inflammatory conditions by restricting iron delivery to the bone marrow. Hepcidin is normally eliminated in the urine, and the high levels seen in renal failure are thought to contribute to renal anemia and resistance to erythropoietin. METHODS Clearance of hepcidin by hemodialysis was investigated in this study by measurement of plasma hepcidin before and after a single dialysis session in 204 patients. Results: Dialysis significantly reduced circulating hepcidin (p

Purpose Central venous catheters for maintenance hemodialysis (HD) are designed to attain the required dialysis dose through sustained high blood flow rates (BFR). The authors studied the immediate and long-term performance and complications of two twin-catheter systems, the Tesio catheter (TC) and the LifeCath Twin (LC), to inform clinical practice. Methods This single-center randomized controlled parallel-group trial allocated 80 incident patients (1:1) to receive either a TC (MedComp) or LC (Vygon). Patients were dialyzed to target BFR 450 mL/min and followed up for 12 months. The primary outcome was achievement of target BFR during the first HD session. Secondary outcomes included thrombotic dysfunction, displacement and catheter-related infection. Catheter dysfunction was defined by a BFR ≤ 250 mL/min. Results More LCs reached the primary endpoint (44% vs. 10%, p=0.001) delivering a higher BFR (mean 383±82 vs. 277±79 mL/min, pConclusions The LC can deliver greater BFRs in the first three HD sessions following insertion although this did not translate into differences in performance, dialysis adequacy or complication rates with long-term use. Both catheter types can consistently deliver high BFRs over an extended period of time.

Pleural effusions are common in hemodialysis patients and are associated with significant morbidity. Diagnostic pleural aspiration and subsequent biochemical analysis can be used to differentiate exudates and transudates. In particular, Light's criteria have been validated in the general population although their efficacy in hemodialysis patients is unclear. Furthermore, aspiration is not without risk; we report the case of a life-threatening thoracic bleed as a complication of diagnostic thoracocentesis in a hemodialysis patient, in whom a transudative effusion was misclassified according to Light's criteria. Retrospective examination of a further 22 aspirations in hemodialysis patients suggests that biochemical analysis of pleural fluid in this group is of limited value. Careful clinical and radiological assessment may be of greater value in determining individuals who may benefit from formal drainage, rather than diagnostic aspiration with its attendant risks.

Healthcare costs associated with the provision of dialysis therapy are escalating globally as the number of patients developing end-stage renal disease increases. In this setting, there has been heightened interest in the application and potential benefit of home haemodialysis therapies compared with the conventional approach of thrice weekly, incentre treatments. Increasingly, national healthcare systems are financially incentivising the expansion of home haemodialysis programmes with observational studies demonstrating better patient survival, superior control of circulating volume and blood pressure, greater patient satisfaction and lower running costs compared with incentre dialysis. Nonetheless, increasing the prevalence of home haemodialysis is challenged by the technological complexity of conventional dialysis systems, the need for significant adaptations to the home as well as suboptimal clinician and patient education about the feasibility and availability of this modality. In addition, enthusiasm about frequent as well as nocturnal (extended-hours) haemodialysis has been tempered by results from the recent Frequent Haemodialysis Network randomised controlled trials comparing these schedules with a conventional incentre regime. An increasing emphasis on empowering patient choice and promoting self-management of chronic illness is a powerful driver for the expansion of home haemodialysis programmes in the UK and internationally.

Studying hepcidin in humans is en vogue as demonstrated by an increasing number of publications addressing this key hormone of iron homeostasis over the last decade. As a key regulator of iron transport, hepcidin has been clearly implicated in the pathogenesis of anaemia in chronic kidney disease (CKD), but a more complex pathophysiology is beginning to emerge in which altered iron biology contributes more widely to the complications of uraemia. In CKD, anaemia is caused by a variety of mechanisms, including erythropoietin (EPO) deficiency and resistance and impaired iron metabolism [1]. A (chronic) inflammatory state has been shown to be involved, in part, as a cause or as a consequence of these processes [2]. In particular, disordered iron transport caused by inflammation may accelerate arterial disease, for example by increasing arterial stiffness, thus further enhancing the risk for cardiovascular (CV) events in CKD patients [2–5]. In this issue of Nephrology, Dialysis Transplantation, Neelke van der Weerd and colleagues present intriguing epidemiological data linking hepcidin levels with CV endpoints in haemodialysis (HD) patients [6]. The first reports about hepcidin described its antibacterial and antifungal activities in serum and urine [7, 8], but subsequently focus shifted as its important role in iron metabolism was discovered. Hepcidin 25, an active metabolite, is the key regulator of iron transport, governing intestinal absorption as well as release from the reticuloendothelial system, by its action on the iron export channel, ferroportin: hepcidin leads to internalization of ferroportin, which results in reduced plasma iron and therefore diminished iron availability. Hepcidin synthesis and release themselves are regulated by changes in iron storage, hypoxia and erythropoiesis [9–11]. Although hepcidin can be considered as an acute-phase protein [12] in particular in infectious diseases, levels of the hormone are also elevated in chronic (low grade) inflammation [9, 13]. Hepcidin levels have been described in association with markers of inflammation (e.g. C-reactive protein and interleukin-6), anaemia (e.g. haemoglobin and endogenous EPO) and most strongly with iron status (e.g. ferritin). Both anaemia and chronic inflammation are frequently detected in CKD, which explains the interest about hepcidin in nephrology and especially in the setting of renal anaemia . While insufficient endogenous EPO synthesis in advanced CKD surely represents a major mechanism in the development of renal anaemia [14], a number of reports have shown that EPO levels frequently are within the ‘normal’ range despite being low for the degree of anaemia . The phenomenon of ‘relative EPO deficiency’ is perhaps better described as a ‘blunted EPO response’ and might be insufficient to cause anaemia without the contribution of other mechanisms [15–17]. Further insight comes from the anaemia of chronic disease, with which renal anaemia shares several pathomechanisms, including inflammation and ‘relative’ iron deficiency, that is, insufficient iron availability despite adequate iron stores. In a landmark review article by Weiss [11], these mechanisms were clearly depicted and considered as crucial for the development of anaemia of chronic diseases, which is also frequently described as anaemia of chronic inflammation. A number of publications over the last years have focused on these mechanisms, and a robust body of evidence is developing about the pathophysiologic role of hepcidin in disorders of iron metabolism including renal anaemia. More recently emerging are a small number of studies suggesting a role for hepcidin in the development of CV disease, and as a biomarker and prognostic factor for clinical outcomes, in particular in CKD. IN F O C U S

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN.We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)50 mg/mmol or partial remission (PR) if PCR50 mg/mmol but non-nephrotic and50% reduction.A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode.The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality. We examined the effect of water treatment component replacement on declining ESA responsiveness in the absence of chemical or microbiological standards failure. Pre-emptive renewal of the water treatment system supplying 802 standard-flux haemodialysis patients resulted in a significant rise in haemoglobin from (mean ± SD) 12.1 ± 1.2 to 12.3 ± 1.0 g/dl (p < 0.0001), accompanied by a significant decrease in prescribed dose of darbepoetin alfa from 47.9 ± 27.3 to 44.7 ± 27.6 μg/week (p < 0.0001). ESA responsiveness improved significantly from 0.060 ± 0.041 to 0.055 ± 0.040 μg/kg/g·dl-1 (p < 0.0001) and the number of patients no longer requiring ESA therapy increased threefold. These benefits were derived in the absence of haemolysis or significant changes in water quality. Renewal of water system components should be conducted even in the absence of proven microbiological and chemical failure.

Background: There are no prospective randomized controlled trials describing the outcome of acute interstitial nephritis (AIN) treated with steroids, and retrospective studies are limited. Methods: We identified adult patients with a diagnosis of AIN without glomerular pathology over a 14-year period. Treated patients all received oral prednisolone and three also recieved IV methylprednisolone. Data were collected retrospectively on estimated glomerular filtration rate (eGFR), change in eGFR from time of biopsy, dependence on renal replacement therapy (RRT) and mortality, and outcomes were analysed according to the treatment prescribed. Results: A total of 187 eligible patients with AIN were identified and 158 were treated with steroids. There was no difference in median eGFR or dependence on RRT at the time of biopsy. Steroid-treated patients had significantly higher eGFR at all time points post-biopsy up to 24 months, when median eGFR was 43 mL/min in the steroid-treated group and 24 mL/min in the untreated group (P = 0.01). Fewer patients in the steroid-treated group were dialysis dependent by 6 months (3.2% versus 20.6%, P = 0.0022) and 24 months (5.1% versus 24.1%, P = 0.0019). Conclusions: This large retrospective study suggests a benefit of steroids in treatment of AIN with greater improvement in eGFR and fewer patients progressing to end-stage renal disease.

Analyses of national registry-based datasets have demonstrated the association of longer haemodialysis treatment times with lowered mortality risk.We performed a prospective cohort study of 451 incident haemodialysis patients and examined the effect of targeting higher dialysis dose with extended treatment time, on 10-year patient outcomes.Mean treatment time (TT) was 233 ± 22.8 minutes (median 235, range 180-296). Overall patient survival was 95% at 1 year, 75% at 3 years, 56% at 5 years and 25% at 10 years. Increasing TT was associated with incremental 10-year patient survival (TT/=241 minutes 39.7%, TT 226-240 minutes 19.6% and TT/=225 minutes 14.7%; p0.001). Single pool Kt/V and TT were strong independent predictors of patient survival in Cox multivariate analysis (p0.0001). At 10 years, each 0.1-unit increase in spKt/V and 20-minute increase in TT were associated with a 20% and 32% decrease in the relative risk of death, respectively. Survival benefits of higher dialysis dose and longer TT were cumulative, with highest survival exhibited by patients achieving both Kt/V1.6 and TT/=241 minutes, and lowest survival exhibited by patients receiving Kt/V1.2 and TT/=225 minutes.Extended treatment times are associated with higher patient survival irrespective of dialysis dose. Further study of extended treatment time and effect on patient outcomes is needed.

Objectives: This study sought to understand the prevalence and clinical relevance of iron deficiency in patients with idiopathic pulmonary arterial hypertension (IPAH).Background: Iron availability...

The use of central venous catheters for long-term hemodialysis has been associated with increased mortality and high prevalence of infection and venous stenosis. However, because central venous catheters still constitute a significant proportion of vascular access in prevalent populations, even in the Fistula-First era, the authors examined the long-term patient outcomes and performance of this vascular access type to inform current clinical practice.The authors conducted a retrospective cohort study of 433 patients on maintenance hemodialysis in a dialysis program from January 1999 through April 2008 all using twin-catheter Tesio Caths (TCs) (MedCOMP, Harleysville, Pennsylvania). Written and electronic records were examined with respect to laboratory indices as well as mortality, access-related infection, need for thrombolytic infusion, access revision and dialysis adequacy.A total of 759 TCs were inserted with 552,035 catheter days follow-up. Thirty-six percent of insertions were in patients incident to dialysis (90 days). Mean single-pool Kt/V was 1.6 ± 0.3. Cumulative cohort survival rates were 85%, 72%, and 48% at 1, 2, and 5 years, respectively. No patients died as a result of lack of vascular access. Cumulative assisted primary access site patencies were 76%, 62%, and 42% at 1, 2, and 5 years, respectively. The prevalence of symptomatic central venous stenosis was 5%. Catheter-related bacteremia occurred at a rate of 0.34 per 1,000 catheter days.Appropriate use of TCs with protocolized care can deliver effective long-term hemodialysis with good adequacy and rates of access-related infection approaching those seen with arteriovenous grafts.

Background. The incidence of subdural haematoma (SDH) is high in haemodialysis (HD), with data suggesting an increasing incidence over time. The prognosis remains poor with 40% mortality at 30 days. The extent of this problem in non-US populations has not been described in the literature. Methods. We conducted a retrospective, single-centre UK study of non-traumatic SDH in patients established on maintenance HD between 1 January 2002 and 1 June 2009. Results. The prevalence of SDH was 0.4% at our centre with an overall annual incidence of 189 per 100 000 patients. SDH was associated with increased patient age (mean 71.3 ± 8.5 years) but not associated with a higher prevalence of major comorbid conditions and antiplatelet or anticoagulant use. Mortality was high (46% at 30 days, 58% at 1 year). We did not observe a trend to increasing prevalence of this condition over time. Conclusions. SDH has a higher (>20 times) incidence in HD patients than in the general population and is associated with high mortality. Although the prevalence in this study was lower than in published US studies, the incidence rate is similar. Further studies to validate prognostic criteria that guide decisions regarding surgery are required.

Expression of hepcidin, the key hormone governing iron transport, is reduced by anemia in a manner which appears dependent on increased bone marrow activity. The temporal associations between plasma hepcidin and other iron parameters were examined in healthy humans after erythropoietin administration and venesection. Profound hepcidin suppression appeared abruptly 24 hours after subcutaneous erythropoietin (P=0.003), and was near maximal at onset, with peak (mid-afternoon) levels reduced by 73.2%, gradually recovering over the following two weeks. Minor changes in circulating iron, soluble transferrin receptor and growth differentiation factor-15 were observed after the reduction in hepcidin. Similar but more gradual changes in these parameters were observed after reducing hematocrit by removal of 250 mL blood. These human studies confirm the importance of a rapidly responsive marrow-hepcidin axis in regulating iron supply in vivo, and suggest that this axis is regulated by factors other than circulating iron, soluble transferrin receptor or growth differentiation factor-15.

Hepcidin is a critical inhibitor of iron export from macrophages, enterocytes, and hepatocytes. Given that it is filtered and degraded by the kidney, its elevated levels in renal failure have been suggested to play a role in the disordered iron metabolism of uremia, including erythropoietin resistance. Here, we used a novel radioimmunoassay for hepcidin-25, the active form of the hormone, to measure its levels in renal disease. There was a significant diurnal variation of hepcidin and a strong correlation to ferritin levels in normal volunteers. In 44 patients with mild to moderate kidney disease, hepcidin levels were significantly elevated, positively correlated with ferritin but inversely correlated with the estimated glomerular filtration rate. In 94 stable hemodialysis patients, hepcidin levels were also significantly elevated, but this did not correlate with interleukin-6 levels, suggesting that increased hepcidin was not due to a general inflammatory state. Elevated hepcidin was associated with anemia, but, intriguingly, the erythropoietin dose was negatively correlated with hepcidin, suggesting that erythropoietin suppresses hepcidin levels. This was confirmed in 7 patients when hepcidin levels significantly decreased after initiation of erythropoietin treatment. Our results show that hepcidin is elevated in renal disease and suggest that higher hepcidin levels do not predict increased erythropoietin requirements.

To date there have been few published immunoassays for the important iron regulator hepcidin. This study describes a novel competitive radioimmunoassay (RIA) for the bioactive hepcidin peptide. A rabbit anti-hepcidin polyclonal antibody was produced using synthetic hepcidin radiolabelled with 125I to produce a competitive RIA. Normal patient (n=47) samples were collected and assayed for hepcidin to determine a reference range. Other patient groups collected were ulcerative colitis (UC; n=40), iron deficiency anaemia (IDA; n=15), chronic kidney disease not requiring dialysis (CKD; n=45) and chronic kidney disease requiring dialysis (HCKD; n=94). Detection limit of the assay was determined as 0.6 ng/mL. Intra-assay precision was 5 ng/mL (7.2%) and 50 ng/mL (5.8%), interassay precision was 5 ng/mL (7.6%) and 50 ng/mL (6.7%). Analytical recovery was 98% (5 ng/mL), 94% (10 ng/mL) and 97% (50 ng/mL). The assay was linear up to 200 ng/mL. No demonstrable cross-reactivity with human insulin, glucagon I, angiotensinogen I, beta-defensin 1-4, alpha-defensin-1 and plectasin was observed. There was significant correlation (r=0.96, P < or = 0.0001) between the hepcidin RIA and an established hepcidin SELDI-TOF-MS method. Analysis of the normal human samples gave a reference range of 1.1-55 ng/mL for hepcidin. Further statistical evaluation revealed a significant difference between male and female hepcidin levels. There was significant correlation between hepcidin and ferritin in the control group (r=0.6, P < or = 0.0001). There was also a significant difference between the normal and disease groups (P < or = 0.0001). Healthy volunteers (n=10) showed a diurnal increase in plasma hepcidin at 4.00 pm compared to 8.00 am. A robust and optimised immunoassay for bioactive hepcidin has been produced and the patient sample results obtained further validates the important role of hepcidin in iron regulation, and will allow further investigation of this important peptide and its role in iron homeostasis.

Advances in the understanding of appetite are leading to a refined concept of disease cachexia and point to novel therapeutic strategies based on the manipulation of appetite. The complex social and psychological short-term influences on appetite obscure the fact that over the longer term appetite is tightly regulated by physiological considerations; the homeostatic control of energy balance. Like obesity, which is now viewed as a disorder of homeostasis, cachexia can be seen as an adaptive response to the disease state that becomes harmful when prolonged. Several lines of evidence implicate a disorder of appetite regulation in the pathogenesis of cachexia. As the only known circulating mediator of increased appetite the peptide hormone ghrelin has attracted attention as a potential therapy. Trials in patients with various chronic illnesses, including cancer and kidney failure, have demonstrated short-term increases in energy intake. Trials in patients with emphysema and heart failure have also shown benefits in clinical outcomes such as lean body mass and exercise capacity, and longer-term trials using oral analogues are being undertaken. As well as improving nutrition, ghrelin has a number of other actions that may be useful, including an anti-inflammatory effect; of interest since many cachexias are associated with inappropriate immune activation. The manipulation of appetite, in particular by ghrelin agonism, is emerging as an exciting potential therapy for disease cachexia. Future research should focus on the ascertainment of clinically-relevant outcomes, and further characterisation of the non-nutritional effects of this pathway.

Background: Although there are increasing numbers of long-term survivors on dialysis, there is remarkably little information about their medical and social wellbeing. Methods: A group of 46 current survivors of long-term dialysis at a single centre were identified and asked to complete a structured interview; selected routine blood tests were also reviewed. The group’s background and renal replacement history are described, along with frequencies of various complications. Results: Younger age and non-diabetic renal disease are associated with longer survival. Substantial morbidity accumulated over the time on dialysis, particularly vascular disease (57%) which was strongly linked to smoking history, as well as musculoskeletal complications (78%) and nutritional decline (80%). Encapsulating peritoneal sclerosis developed in 4 patients, after between 9 and 13 years of peritoneal dialysis. Conclusions: Despite accumulating morbidity, a surprisingly stable and socially well-adjusted group is revealed, with low rates of hospital admission in the majority. The pattern of complications may be influenced by modality choices.

Large-bore dual lumen in-dwelling venous catheters are used in hemodialysis. These catheters are usually locked with heparin after the treatment. This study addressed the underappreciated postdialysis coagulopathy that can result. Thirty-six patients were included: 7 dialyzed through arterio-venous fistulae, 29 through in-dwelling venous catheters. The latter group was further subdivided according to whether they received heparin or heparin-free dialysis. To assess the heparin lock, a full-dose heparin lock as well as a much weaker heparin lock and a citrate lock were used. To assess the coagulopathy, blood was taken 1 hr after dialysis. The activated partial thromboplastin time (APTT) and anti-Xa level was measured. Additionally, 6 venous catheters were removed and the amount of fluid expelled upon locking with saline was measured. Clotting from the patient group with arterio-venous fistulae was normal following dialysis. The patients with in-dwelling venous catheters and heparin locks had significantly deranged clotting; 6 out of 10 patients had abnormal APTT results. All patients with catheters, heparin-free dialysis, and heparin locks had deranged clotting (7 out of 7). The rate decreased significantly when heparinized saline was used as a lock. A subset of patients had a citrate lock rather than a heparin lock; the clotting results normalized in all but one patient. An in vitro study demonstrated immediate leakage of fluid from the end of the ports upon locking. Significant postdialysis anticoagulation can occur after dialysis, which can be attributed to the heparin line locks. This risk is considerably reduced when a citrate lock is used instead.

In their review, Siddiky and colleagues suggest that arteriovenous fistulas for haemodialysis “offer the best short, intermediate and long term options for renal replacement therapy.”1 Although they have many advantages, one of the few rigorous systematic reviews in vascular access emphasises the often overlooked complication of primary non-function (the fistula never works).2 This occurs …

Background: Fistula maturation is a complex multifactorial process with the effect of diabetes on vessel augmentation during fistula formation remaining unclear. Variation in results has reflected in a range of clinical practice with regard to patient selection and fistula formation and so requires more study. The aim of our study was to compare outcomes of diabetic and non-diabetic patients undergoing formation of a new upper limb arteriovenous fistula (AVF) to assess whether diabetes has a prognostic effect on outcome. Methods: A retrospective cohort study analysing 339 patients looking at both radiocephalic and brachiocephalic fistula formation in diabetic and non-diabetic patients was designed, with the primary outcome being fistula failure and then time taken to mature. Results: No difference was found between diabetic and non-diabetic patients in terms of fistula failure or time to mature. Conclusions: With AVF remaining the best access for dialysis, diabetic patients should not be discouraged from being offered AVF formation as they have equivalent outcomes to non-diabetic patients.

Much of the high mortality seen in chronic renal failure is due to a form of vascular disease which, unlike the overnutrition vascular disease of the general population, is closely associated with the development of malnutrition. Various micronutrient deficiencies occur, and are commonly treatment related, but a specific syndrome of energy malnutrition associated with unexplained activation of inflammatory mediators, is a common and early feature of renal failure, which is frequently refractory to nutritional supplementation. Many abnormalities of appetite hormones have been found in renal failure, and like obesity, renal malnutrition is increasingly understood as a disorder of appetite homeostasis, which therefore would respond best to manipulation of the appetite regulatory system—for example by administration of ghrelin. Reduced clearance by failing kidneys leads to accumulation of ghrelin, with elevated circulating levels of total ghrelin; however, a reduction in the acyl fraction has been found. Acyl ghrelin administration has been shown to increase energy intake in animal models of renal failure, and promising results have also been found with daily subcutaneous injections in dialysis patients over the course of a week. In addition, ghrelin is thought to have an anti-inflammatory effect, which may be therapeutically relevant in a syndrome in which inappropriate inflammation is a prominent feature.

Summary Background and objectives Recent interest has focused on wait listing patients without pretreating coronary artery disease to expedite transplantation. Our practice is to offer coronary revascularization before transplantation if indicated. Design, setting, participants, & measurements Between 2006 and 2009, 657 patients (427 men, 230 women; ages, 56.5 ± 9.94 years) underwent pretransplant assessment with coronary angiography. 573 of 657 (87.2%) patients were wait listed; 247 of 573 (43.1%) patients were transplanted during the follow-up period, 30.09 ± 11.67 months. Results Patient survival for those not wait listed was poor, 83.2% and 45.7% at 1 and 3 years, respectively. In wait-listed patients, survival was 98.9% and 95.3% at 1 and 3 years, respectively. 184 of 657 (28.0%) patients were offered revascularization. Survival in patients (n = 16) declining revascularization was poor: 75% survived 1 year and 37.1% survived 3 years. Patients undergoing revascularization followed by transplantation (n = 51) had a 98.0% and 88.4% cardiac event–free survival at 1 and 3 years, respectively. Cardiac event–free survival for patients revascularized and awaiting deceased donor transplantation was similar: 94.0% and 90.0% at 1 and 3 years, respectively. Conclusions Our data suggest pre-emptive coronary revascularization is not only associated with excellent survival rates in patients subsequently transplanted, but also in those patients waiting on dialysis for a deceased donor transplant.

This study sought to understand the prevalence and clinical relevance of iron deficiency in patients with idiopathic pulmonary arterial hypertension (IPAH).Iron availability influences the pulmonary vascular response to hypoxia in humans and may be significant in the pathogenesis of IPAH.Iron deficiency, defined by raised levels of soluble transferrin receptor (sTfR), was investigated in 98 patients with IPAH. Hepcidin and erythropoietin (EPO) levels were also measured. The effect of bone morphogenetic protein (BMP) receptor knockdown on BMP-6-stimulated hepcidin production was assessed in human hepatoma HepG2 cells. Relationships between sTfR and exercise capacity, functional class, and all-cause mortality were analyzed.Circulating sTfR levels were raised in 63% of IPAH patients, indicating significant iron deficiency. Consistent with this, iron, ferritin, and transferrin saturation levels were reduced and red cell distribution width increased, without overt anemia. Hepcidin correlated inversely with sTfR and positively with increasing ferritin. Hepcidin was inappropriately raised in IPAH independent of the inflammatory marker interleukin-6. EPO levels were also raised and correlated inversely with hepcidin. BMP receptor-type 2 (BMPR2) knockdown in HepG2 cells increased BMP-6-stimulated hepcidin expression. sTfR increased with World Health Organization functional class (p0.05), correlated negatively with exercise capacity (p = 0.027), and values28.1 nmol/l independently predicted survival (p = 0.011).Iron deficiency is common in IPAH patients and associated with disease severity and poor clinical outcome. Inappropriately raised hepcidin levels, which impair iron absorption from the gut, may be a factor.

BACKGROUND Vascular access for haemodialysis is achieved by tunnelled central venous catheter (CVC) in at least 23% of prevalent patients in the UK, Canada and the USA. Use of CVCs is associated with an increased incidence of venous stenosis that can progressively limit future vascular access routes. Lack of conventional venous access routes mandates the use of alternative strategies such as the translumbar approach. METHODS We retrospectively analysed patients at our centre requiring translumbar inferior vena caval CVCs (TesioCath) for haemodialysis in the period 1999-2008. Written and electronic records capturing dialysis adequacy and complications, hospital admissions and laboratory data were examined. RESULTS Thirty-nine pairs of translumbar CVCs were inserted in 26 patients with 15 864 catheter days follow-up, mean patient age 61.9 +/- 12.1 years, 31% diabetic, 15% with ischaemic heart disease. All insertions were successful. Insertion of one CVC was associated with a self-limiting retroperitoneal haematoma. No patients died of a catheter-related cause or through lack of vascular access. Cumulative assisted primary catheter site patency was 81% at 6 months and 73% at 1 year (median 18.5 months). Good dialysis adequacy was achieved throughout (mean single-pool Kt/V 1.5 +/- 0.4). The incidence of access-related infection was 2.84/1000 catheter days (exit site infection rate 2.02/1000 catheter days; catheter-related bacteraemia rate 0.82/1000 catheter days). Catheter dysfunction (need for thrombolytic infusion or catheter change) led to 0.88 admissions per 1000 catheter days. CONCLUSION Translumbar inferior vena caval CVCs can offer relatively safe and effective long-term haemodialysis access in patients with no other options.

Background and objectives: Treatment without catheter replacement (catheter salvage) has been described for bacteremia associated with tunneled venous catheters in hemodialysis patients, but few data are available on which to base an estimation of the likelihood of treatment success. Design, setting, participants, & measurements: In a prospective cohort study, all cases of catheter-associated bacteremia that occurred in a large dialysis center were identified during a 12-mo period. Catheter salvage was attempted according to a standard protocol in all cases in which a favorable early response to antibiotic therapy was seen, and patients were followed for at least 6 mo. Bacteremias, catheter changes, and all major clinical events were recorded. Results: During a period covering 252,986 catheter days, 208 episodes were identified involving 133 patients, 74% of which were selected for attempted salvage. Salvage was successful in 66.1% of incident bacteremias with a very low complication risk (0.9%). Some bacteremias, however, recurred as late as 6 mo after the initial infection; salvage was less likely to be successful in treating recurrences. Conclusions: Appropriately used catheter salvage can be successful in approximately two thirds of cases; however, recurrences continue to occur up to 6 mo later and are unlikely to be cured without catheter replacement.

Advances in the understanding of appetite are leading to a refined concept of disease cachexia and point to novel therapeutic strategies based on the manipulation of appetite. The complex social and psychological short-term influences on appetite obscure the fact that over the longer term appetite is tightly regulated by physiological considerations; the homeostatic control of energy balance. Like obesity, which is now viewed as a disorder of homeostasis, cachexia can be seen as an adaptive response to the disease state that becomes harmful when prolonged. Several lines of evidence implicate a disorder of appetite regulation in the pathogenesis of cachexia. As the only known circulating mediator of increased appetite the peptide hormone ghrelin has attracted attention as a potential therapy. Trials in patients with various chronic illnesses, including cancer and kidney failure, have demonstrated short-term increases in energy intake. Trials in patients with emphysema and heart failure have also shown benefits in clinical outcomes such as lean body mass and exercise capacity, and longer-term trials using oral analogues are being undertaken. As well as improving nutrition, ghrelin has a number of other actions that may be useful, including an anti-inflammatory effect; of interest since many cachexias are associated with inappropriate immune activation. The manipulation of appetite, in particular by ghrelin agonism, is emerging as an exciting potential therapy for disease cachexia. Future research should focus on the ascertainment of clinically-relevant outcomes, and further characterisation of the non-nutritional effects of this pathway.