Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial

Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness

Lessons learned from EVOLVE for the planning of future global randomized trials in chronic kidney disease

The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism (sHPT) was evaluated in the EVOLVE trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis and reporting of the trial many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting HPT), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower than predicted event rate during the trial, development of a pre-specified analytic plan that accounted for non-adherence and for co-interventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated prior to trial initiation, and interpretation of the benefits to harms ratio for individual patients. It is likely that many of these issues will arise in planning of future trials in chronic kidney disease

Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function.</p> <p>Methods</p> <p>We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min (110 on dialysis). Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan.</p> <p>Results</p> <p>Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events.</p> <p>Conclusion</p> <p>Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.</p

Agricultural chemical exposures and birth defects in the Eastern Cape Province, South Africa A case – control study

BACKGROUND: South Africa is one of the major users of pesticides on the African continent. The Eastern Cape is the second largest province in South Africa. There has been growing concern about the occurrence of certain birth defects which seemed to have increased in the past few years. In this paper we investigate associations between exposure to agricultural chemicals and certain birth defects. Few such studies have been undertaken in the developing world previously. METHODS: Between September 2000 and March 2001 a case – control study was conducted among rural women in the area of the Eastern cape to investigate the association between women's exposure to pesticides and the occurrence of birth defects. Information on birth defects was obtained from the register of the Paediatrics Department at the Cecilia Makiwane Hospital in Mdantsane, one of the largest referral hospitals in the province. The cases were children who were diagnosed with selected birth defects. The controls were children born in the same areas as the cases. Exposure information on the mothers was obtained by interview concerning from their activities in gardens and fields. Data were analysed using conditional logistic regression. RESULTS: A total of 89 case mothers and 178 control mothers was interviewed. Babies with birth defects were seven times more likely to be born to women exposed to chemicals used in gardens and fields compared to no reported exposure (Odds Ratio 7.18, 95% CI 3.99, 13.25); and were almost twice as likely to be born to women who were involved in dipping livestock used to prevent ticks (OR 1.92, 95% CI 1.15, 3.14). They were also 6.5 times more likely to be born to women who were using plastic containers for fetching water (OR 6.5, 95% CI 2.2, 27.9). Some of these containers had previously contained pesticides (OR 1.87, 95% CI 1.06, 3.31). CONCLUSIONS: These findings suggest a link between exposure to pesticides and certain birth defects among the children of rural South African women who work on the land. Education programmes for women alerting them to the dangers to their babies from the use of pesticides and alternative farming methods and elimination of the reuse of pesticide containers are indicated as preventive measures

Transcatheter Aortic Valve Implantation in Dialysis Patients

Background/Aims: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for high-risk patients. However, dialysis patients were excluded from all previous studies. The aim of this study is to compare the outcomes of TAVI for dialysis patients with those for patients with chronic kidney disease (CKD) stages 3 and 4 and to compare TAVI with open surgery in dialysis patients. Methods: Part I: comparison of 10 patients on chronic hemodialysis with 116 patients with non-dialysis-dependent CKD undergoing TAVI. Part II: comparison of transcatheter (n = 15) with open surgical (n = 24) aortic valve replacement in dialysis patients. Results: Part I: dialysis patients were significantly younger (72.3 vs. 82.0 years; p < 0.01). Hospital stay was significantly longer in dialysis patients (21.8 vs. 12.1 days; p = 0.01). Overall 30-day mortality was 3.17%, with no deaths among dialysis patients. Six-month survival rates were similar (log-rank p = 0.935). Part II: patient age was comparable (66.5 vs. 69.5 years; p = 0.42). Patients in the surgical group tended to stay longer in hospital than TAVI patients (29.5 vs. 22.5 days; p = 0.35). Conclusion: TAVI is a safe procedure in patients on chronic hemodialysis. Until new data become available, we find no compelling reason to refuse these patients TAVI. Copyright (C) 2012 S. Karger AG, Base

Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/- 13 years, 57% male, 21% diabetics, mean eGFR 51 +/- 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients

Risk factors of one year increment of coronary calcifications and survival in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.</p> <p>Methods</p> <p>81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.</p> <p>Results</p> <p>Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.</p> <p>Conclusions</p> <p>Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.</p

Ethical challenges in nephrology : a call for action

The American Society of Nephrology, the European Renal Association-European Dialysis and Transplant Association and the International Society of Nephrology Joint Working Group on Ethical Issues in Nephrology have identified ten broad areas of ethical concern as priority challenges that require collaborative action. Here, we describe these challenges - equity in access to kidney failure care, avoiding futile dialysis, reducing dialysis costs, shared decision-making in kidney failure care, living donor risk evaluation and decision-making, priority setting in kidney disease prevention and care, the ethical implications of genetic kidney diseases, responsible advocacy for kidney health and management of conflicts of interest - with the aim of highlighting the need for ethical analysis of specific issues, as well as for the development of tools and training to support clinicians who treat patients with kidney disease in practising ethically and contributing to ethical policy-making. Here, the ASN-ERA-EDTA-ISN Joint Working Group on Ethical Issues in Nephrology highlights ten areas of ethical concern as priority challenges that require collaborative action and discusses the need for development of ethical training and guidance tools to manage these issues

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Pesticide-related illness reported to and diagnosed in Primary Care: implications for surveillance of environmental causes of ill-health

BACKGROUND: In Great Britain (GB), data collected on pesticide associated illness focuses on acute episodes such as poisonings caused by misuse or abuse. This study aimed to investigate the extent and nature of pesticide-related illness presented and diagnosed in Primary Care and the feasibility of establishing a routine monitoring system. METHODS: A checklist, completed by General Practitioners (GP) for all patients aged 18+ who attended surgery sessions, identified patients to be interviewed in detail on exposures and events that occurred in the week before their symptoms appeared. RESULTS: The study covered 59320 patients in 43 practices across GB and 1335 detailed interviews. The annual incidence of illness reported to GPs because of concern about pesticide exposure was estimated to be 0.04%, potentially 88400 consultations annually, approximately 1700 per week. The annual incidence of consultations where symptoms were diagnosed by GPs as likely to be related to pesticide exposure was 0.003%, an annual estimate of 6630 consultations i.e. about 128 per week. 41% of interviewees reported using at least one pesticide at home in the week before symptoms occurred. The risk of having symptoms possibly related to pesticide exposure compared to unlikely was associated with home use of pesticides after adjusting for age, gender and occupational pesticide exposure (OR = 1.88, 95% CI 1.51 - 2.35). CONCLUSION: GP practices were diverse and well distributed throughout GB with similar symptom consulting patterns as in the Primary Care within the UK. Methods used in this study would not be feasible for a routine surveillance system for pesticide related illness. Incorporation of environmental health into Primary Care education and practice is needed