The effects of nocturnal hemodialysis compared to conventional hemodialysis on change in left ventricular mass: Rationale and study design of a randomized controlled pilot study

BACKGROUND: Nocturnal hemodialysis (NHD) is an alternative to conventional three times per week hemodialysis (CvHD) and has been reported to improve several health outcomes. To date, no randomized controlled trial (RCT) has compared NHD and CvHD. We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular (LV) mass, as measured by cardiac magnetic resonance imaging (cMR). METHODOLOGY/DESIGN: All patients in Alberta, Canada, expressing an interest in performing NHD are eligible for the study. Patients enrolled in the study will be randomized to either NHD or CvHD for a six month period. All patients will have a full clinical assessment, including collection of biochemical and cMR data at baseline and at 6 months. Both groups of patients will be monitored biweekly to optimize blood pressure (BP) to a goal of <130/80 mmHg post-dialysis using a predefined BP management protocol. The primary outcome is change in LV mass, a surrogate marker for cardiac mortality, measured at baseline and 6 months. The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography. Secondary outcomes include BP control, anemia, mineral metabolism, health-related quality of life, and costs. DISCUSSION: To our knowledge, this study will be the first RCT evaluating health outcomes in NHD. The impact of NHD on LV mass represents a clinically important outcome which will further elucidate the potential benefits of NHD and guide future clinical endpoint studies

Overview of the Alberta Kidney Disease Network

<p>Abstract</p> <p>Background</p> <p>The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.</p> <p>Description</p> <p>The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.</p> <p>Conclusion</p> <p>The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.</p

Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

<p>Abstract</p> <p>Background</p> <p>Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis.</p> <p>Methods</p> <p>This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC).</p> <p>Results</p> <p>Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy.</p> <p>Conclusions</p> <p>A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.</p

Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii

In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii

Assessing Creatinine Clearance from Modification of Diet in Renal Disease Study Equations in the ADEMEX Cohort: Limitations and Potential Applications

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine and dialysate collections provide accepted means to assess adequacy in peritoneal dialysis (PD). Recent publications suggest that creatinine clearance (CrCl) estimated from the Modification of Diet in Renal Disease (MDRD) equations (eCrCl) accurately approximates measured CrCl (mCrCl) derived from 24-hour collections of urine and dialysate and might serve as an alternative means to assess small-solute clearance and adequacy in PD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Post hoc analysis of data from patients enrolled in ADEMEX was used to assess agreement between mCrCl and eCrCl derived by four- and six-variable MDRD equations (4V-MDRDE and 6V-MDRDE, respectively). Additionally, associations among mCrCl, eCrCl, and survival were determined. RESULTS: Acceptable precision was observed between mCrCl and 4V-MDRDE-eCrCl and 6V-MDRDE-eCrCl for the entire cohort. Precision was markedly diminished when analysis was limited to functionally anuric patients with mCrCl \u3c 12 ml/min per 1.73 m². Although there was no association between survival and mCrCl, for every 1-ml/min per 1.73 m² increase in 4V- and 6V-MDRDE-eCrCl, there was a 6% and 4% increase in risk of death, respectively. There was a negative association between MDRDE-eCrCl and creatinine appearance rates, suggesting MDRDE-eCrCl is significantly confounded by individual differences in muscle mass. CONCLUSIONS: MDRDE-eCrCl provides demographically comparable values to 24-hour urine and dialysate collections across the ADEMEX cohort. However, MDRDEs should not be used to assess small-solute removal or adequacy in individual PD patients or to predict outcome in any cohort of patients over narrow ranges of limited clearance