Neutrophils rapidly undergo spontaneous apoptosis, but this process can be considerably delayed by exposure to a variety of agents such as pro-inflammatory cytokines. The anti-apoptotic protein of the Bcl-2 family, Mcl-1, plays a key role in the regulation of neutrophil apoptosis. The protein has some unusual properties compared with other family members, including an extremely high turnover rate. Many factors, such as cytokines and local oxygen concentrations, can regulate cellular levels of Mcl-1 via transcription and post-transcriptional modification, control the survival time of neutrophils within tissues and thereby influence the inflammatory response.

Our prospective study is the first and currently the largest observational study of a multidisciplinary approach in the management of NDT patients. SCG was an independent prognostic factor in predicting survival. In those patients who chose not to dialyse, SCG provides a potentially useful indication of expected prognosis.

Substance abuse has been increasing steadily in the UK and some other countries. Recent evidence suggests more than 40% of young people have tried illicit drugs at some time. There are numerous medical consequences to recreational drug use, and a physician should always consider substance abuse in any unexplained illness. The renal complications of drug abuse are also becoming more frequent, and may encompass a spectrum of glomerular, interstitial and vascular diseases. Although some substances are directly nephrotoxic, a number of other mechanisms are also involved. These effects are often chronic and irreversible, but occasionally acute with possible recovery. The rapid growth of illicit drug use is clearly a major public health problem. We review the commonly used substances of abuse and their associations with renal disease.

In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Improvement in end-of-life-care is required for patients dying with chronic kidney disease (CKD). The UK government now recommends that tools such as the Liverpool Care Pathway for the Dying Patient (LCP) be used to enhance the care of those patients dying with CKD. The LCP was originally developed for patients dying with terminal cancer, however has been shown to be transferable to patients dying with heart failure or stroke. On this background, in 2005 a UK National Renal LCP Steering Group was formed. The aim was to determine whether or not the generic LCP was transferable to patients dying with CKD. An Expert Consensus sub-group was established to produce evidence-based prescribing guidelines to allow safe and effective symptom control for patients dying with renal failure. These guidelines were finalised by the Expert Consensus group in August 2007 and endorsed by the Department of Health in March 2008. A literature search on symptom control and end-of-life care in renal failure was performed. A summary of the evidence was presented at a National Steering Group meeting. Opinions were given and provisional guidelines discussed. A first draft was produced and individually reviewed by all members of the Expert Group. Following review, amendments were made and a second draft written. This was presented to the entire National Steering Group and again individual comments were taken into consideration. A third and fourth draft were written and individually reviewed, before the guidelines were finalised by the Expert Consensus group. Patients dying with advanced CKD suffer symptoms similar to patients dying of cancer. The Renal LCP prescribing guidelines aim to control the same symptoms as the generic LCP: pain, dyspnoea, terminal restlessness and agitation, nausea and respiratory tract secretions. The evidence for the production of the guidelines is discussed and how a consensus was reached. A summary of the guidelines is given and the complete guidelines document is available via the Marie Curie Palliative Care Institute, Liverpool website.

The link between increased QT dispersion and cardiac death in subjects with diabetes and arterial disease is well recognised. Corrected QT dispersion was studied in subjects with end stage renal failure on haemodialysis. Thirty one stable, chronic subjects on haemodialysis had 12-lead electrocardiograms (ECGs) taken before and after a single haemodialysis session. The QT interval was measured manually in each and the corrected QT and corrected QT dispersion calculated. Serum concentrations of potassium, calcium, and magnesium were measured at the same time as ECG acquisition. Corrected QT dispersion increased from a mean (SEM) 90.6 (5.8) to 117.7 (10.2) ms (p=0.002). Serum potassium and magnesium decreased from 5.0 (0.14) to 3.5 (0.09) mmol/l and 0.95 (0.04) to 0.89 (0.09) mmol/l respectively, while serum calcium increased from 2.56 (0.04) to 2.77 (0.04) mmol/l. Intradialytic weight fell by a mean of 2.1 kg. There was no significant correlation between the change in QTc dispersion and the changes in measured serum anions or the subjects' weight during dialysis. Corrected QT dispersion was higher in subjects on haemodialysis than previously suggested normal values, and was significantly increased by haemodialysis. This reflects increased inhomogeneous ventricular repolarisation, which may lead to an increased risk of arrhythmias and sudden death. Studies looking at QT dispersion in subjects on dialysis should standardise the timing of ECG recordings taken with respect to dialysis.C ardiovascular disease is a major cause of mortality and morbidity among subjects on haemodialysis. Cardiovascular death is responsible for up to 50% of deaths among subjects on dialysis. 1 Cardiac arrhythmias are frequent among the haemodialysis population, particularly during and immediately after a dialysis session. 2-5 These arrhythmias may be caused by the rapid changes in intracellular and extracellular electrolytes during the dialysis session, in hearts that are susceptible due to both myocardial ischaemia and intramyocardiocytic fibrosis. 6 7 A reliable way of predicting subjects at risk of ventricular arrhythmias would be an extremely useful tool for the dialysis physician.Recently, dispersion of the QT interval has emerged as an important predictor of ventricular arrhythmias. The QT dispersion is simply the difference between the shortest and longest QT interval on a standard surface 12-lead electrocardiograph. 8 This is a non-invasive measurement of myocardial repolarisation inhomogeneity and hence predisposition to re-entry arrhythmias. 9 A QT dispersion above 80 ms reflects a loss of synchronisation in the repolarisation process. 10 In clinical studies, a wide QT dispersion has been shown to be a risk factor for cardiac arrhythmia after myocardial infarction, 11 congestive cardiac failure, 12 peripheral vascular disease, 13 and drug induced arrhythmiogenicity. 14 It has also been shown that a wide QT dispersion can narrow when congestive cardiac failure is treated with enalapril 15 and after successful thrombolysis for acut...

BackgroundSome patients with end-stage renal failure (ESRF) are unlikely to benefit from dialysis and conservative management (CM) is offered as a positive alternative. Understanding the trajectory of illness by health care professionals may improve end-of-life care.MethodsWe aimed to describe the trajectory of functional status within our CM population through a prospective, observational study using the objective Timed Up and Go (TUG) test and subjective Barthel Index (BI) and health-related quality of life (HRQoL) [EuroQol 5D-5L (EQ-5D-5L)] measurements and correlating them with demographic and laboratory data and with sentinel events.ResultsThere was a significant increase in TUG scores over the 6 months prior to death {2.24 [95% confidence interval (CI) 1.16–4.32], P = 0.017} and a significant decrease in EQ-5D-5L [−0.19 (95% CI −0.33 to −0.06), P = 0.006]. The only significant associations with mortality were serum albumin [hazard ratio (HR) 0.81 (95% CI 0.67–0.97), P = 0.024] and male gender [HR 5.94 (95% CI 1.50–23.5), P = 0.011].ConclusionsWe have shown there is a significant decline in functional status in the last 6 months before death in the CM population. Of interest, there was a significant relationship of lower serum albumin with functional decline and risk of death. We hope that with improved insight into disease trajectories we can improve our ability to identify and respond to the changes in needs of these patients, facilitate complex and sensitive end-of-life discussions and improve end-of-life care.

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