Progression to end-stage renal disease (ESRD) is a major issue for heath care systems both clinically and financially. Given dialysis may not prolong life, and may indeed impair quality of life, alternative options for these patients such as conservative care are urgently needed. We appointed a dialysis charge nurse who had many years of experience of working with patients on dialysis to spearhead the newly set up Conservative Care Programme (CCP) in the Edinburgh Renal Unit. The rationale was to work as part of the renal multidisciplinary team to support patients and their families to make an informed shared decision whether to opt for dialysis or to follow the CCP. From the perspective of the patients, their families and carers we have received positive feedback since starting the CCP - thank you cards; phone calls both to the CCP Nurse Specialist and the renal unit affirming the positive experience patients had during the conservative management of their renal failure. Whilst continuing to provide the best quality of care to renal patients in NHS Lothian and Borders, the number of prevalent dialysis patients in our catchment area has fallen significantly over the last few years as demonstrated by Scottish Renal Registry data. These benefits are potentially applicable to other renal units across the UK.
Abstract Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142 ; EudraCT: 2006-003509-18.
Arterial generalized transfer functions (GTFs) are increasingly used to estimate central pressure from peripheral measurements. Analysis of derived central waveforms may be valuable in the assessment of patients with chronic kidney disease. The aim of this study was to assess whether the GTF is affected by renal disease. Ninety-four subjects with varying degrees of renal function (Kidney Disease Outcomes Quality Initiative stages 1 to 5; 14 controls) had simultaneous measurements of carotid and radial waveforms made by applanation tonometry. GTFs were calculated by Fourier analysis for each subject group. Derived carotid waveforms were obtained by applying an independently generated GTF to the radial waveform. Glomerular filtration rate inversely correlated with central systolic (R = -0.42; P < 0.001), mean (R = -0.34; P < 0.01) and diastolic (R = --0.27, P < 0.01) blood pressures, as well as central augmentation index (R = -0.30; P< 0.01) and carotid-femoral pulse wave velocity (R = -0.33; P < 0.001). Derived waveforms were not significantly different from measured waveforms in terms of systolic blood pressure, augmentation index, maximum slope, or the delay between the incident and reflected waves, although the derived waveforms slightly underestimated the systolic ejection period (-4.4 ± 0.9 ms; P < 0.001). Overall root-mean-square error was 2.4 ± 0.1 mm Hg. No significant relationship existed between the degree of bias of any derived waveform measure and glomerular filtration rate or chronic kidney disease stage (P > 0.16). No significant differences between chronic kidney disease stages were observed in transfer function gain or phase (P > 0.05). We conclude that the peripheral-to-central GTF is not affected by degree of renal dysfunction and can be used with equivalence in patients with varying degrees of chronic kidney disease.
The effect on systemic haemodynamics of BQ‐123, a selective endothelin A (ETA) receptor antagonist, was investigated in healthy men by giving, on separate occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min −1 BQ‐123, each for 15 min, in a randomized, placebo‐controlled, double‐blind study. The response of forearm blood flow to brachial artery infusion of endothelin‐1 (ET‐1; 5 pmol min −1 for 90 min) was also studied using bilateral forearm plethysmography, after systemic pre‐treatment, on separate occasions, with one of two doses of BQ‐123 (300 and 1000 nmol min −1 for 15 min) or placebo. Systemic BQ‐123 dose‐dependently decreased systemic vascular resistance ( P <0.01 for all doses vs placebo) and mean arterial pressure ( P <0.05 for 300 nmol min −1 and P <0.01 for 1000 and 3000 nmol min −1 ) during the 60 min following infusion. There were concurrent increases in heart rate and cardiac index. BQ‐123, when infused systemically for 15 min, appeared to reach a maximum effect at 1000 nmol min −1 . Intra‐brachial ET‐1 infusion, after pre‐treatment with placebo, caused a slow onset progressive forearm vasoconstriction without systemic effects. This vasoconstriction was attenuated by pre‐treatment with BQ‐123 at 300 nmol min −1 and abolished by BQ‐123 at 1000 nmol min −1 ( P <0.01 vs placebo). These effects occurred at concentrations of BQ‐123 in the plasma (510±64 nmol l −1 ) that were ETA receptor selective, and were not accompanied by an increase in plasma ET‐1 that would have indicated ETB receptor blockade. We conclude that ETA‐mediated vascular tone contributes to the maintenance of basal systemic vascular resistance and blood pressure in healthy men. British Journal of Pharmacology (2001) 134 , 648–654; doi: 10.1038/sj.bjp.0704304
The incidence of chronic kidney disease (CKD) is increasing worldwide. Cardiovascular disease is strongly associated with CKD and constitutes one of its major causes of morbidity and mortality. Although current treatments for CKD focus on blood pressure and proteinuria reduction, many CKD patients have ongoing hypertension and residual proteinuria. Newer treatments are needed that not only act on these parameters, but also slow the progression of CKD and improve the cardiovascular risk profile of CKD patients. The endothelins (ETs) are a family of related peptides of which ET-1 is the most powerful endogenous vasoconstrictor and the predominant isoform in the cardiovascular and renal systems. The ET system has been widely implicated in both cardiovascular disease and CKD. ET-1 contributes to the pathogenesis and maintenance of hypertension and arterial stiffness, as well endothelial dysfunction and atherosclerosis. By reversal of these effects, ET antagonists may reduce cardiovascular risk. In CKD patients, antagonism of the ET system may be of benefit in improving renal hemodynamics and reducing proteinuria. ET is likely also involved in the progression of renal disease, and data are emerging that suggest a synergistic role for ET receptor antagonists with angiotensin-converting enzyme inhibitors in slowing CKD progression.
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