Sleep‐Disordered Breathing and 24‐Hour Ambulatory Blood Pressure Monitoring in Renal Transplant Patients: Longitudinal Study

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Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198

Design and implementation of the canadian kidney disease cohort study (CKDCS): A prospective observational study of incident hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).</p> <p>Methods/Design</p> <p>The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.</p> <p>Preliminary Results</p> <p>Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.</p> <p>Discussion</p> <p>The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.</p

PHYSIOLOGICAL RESPONSE OF MAPLE AND BIRCH ROOTS TO RHIZOSPHERE HYPOXIA

The purpose of this study was to determine if internal aeration of roots by lower stems, changes in gross morphology of lower stems, or both, contribute to flood tolerance of certain tree species. Greenhouse-grown seedlings of red maple (Acer rubrum L.) and river birch (Betula nigra L.) tolerated at least 30 days of flooding, whereas sugar maple (Acer saccharum Marsh) and European birch (Betula pendula Roth) were intolerant. Flood treatment induced lenticel intumescences and adventitious root formation on red maple stems, but only adventitious roots formed on river birch stems. Stem morphology of sugar maple and European birch was unchanged by flooding. Flood stress decreased oxygen consumption capacity of excised roots from both tolerant and intolerant species. Exclusion of oxygen from the lower stems of red maple and river birch prevented lenticel intumescence and adventitious root formation, but flood tolerance and root respiration capacity were unchanged. Neither internal aeration nor changes in stem morphology appear to account for flood tolerance of red maple and river birch. In the second part of this study, several biochemical and physiological responses of river and European birch roots to hypoxia were compared in order to determine root metabolic activity under low oxygen tension. Although hypoxia decreased total adenosine phosphate and adenosine triphosphate contents in roots from both species, river birch roots contained greater quantities of these nucleotides after 18 days of treatment. Adenylate energy charge of river birch roots decreased between 6 and 12 days of hypoxia, whereas energy charge of European birch roots decreased significantly after only one day. In vitro activity of cytochrome c oxidase and oxygen consumption capacity of excised roots from both birch species decreased under hypoxia. In vitro activity of alcohol dehydrogenase from roots of both species increased after 1 day of hypoxia. However, alcohol dehydrogenase activity from river birch roots increased 25 fold by 6 days of hypoxia, whereas that in European birch roots decreased back to control levels. Metabolic adaptation within the root, rather than internal aeration, appears to be responsible for tolerance of river birch to hypoxia

Vitamin D and methylarginines in chronic kidney disease (CKD).

BACKGROUND:Vitamin D associates with the plasma concentration of the endogenous inhibitor of the nitric oxide system asymmetric dimethyl arginine (ADMA) and cross-sectional studies in CKD patients treated with the vitamin D receptor activator paricalcitol show that plasma ADMA is substantially less than in those not receiving this drug. METHODS:In the frame of a randomized, double-blind, placebo controlled trial, the Paracalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY), we investigated whether vitamin D receptor activation by paricalcitol (2 μg/day x 12 weeks) affects the plasma concentration of ADMA and symmetric dimethyl arginine (SDMA) in 88 patients with stage 3 to 4 CKD. RESULTS:Paricalcitol produced the expected small rise in serum calcium and phosphate and a marked PTH suppression. However, ADMA [Paricalcitol: baseline 0.75 μMol/L (95%CI: 0.70-0.81), 12 week 0.72 μMol/L (95%CI: 0.66-0.78); Placebo: baseline 0.75 μMol/L (95%CI: 0.70-0.90) 12 weeks 0.70 μMol/L (95%CI: 0.66-0.74)] and SDMA [Paricalcitol: baseline 0.91 μMol/L (95%CI: 0.82-1.00), 12 week 0.94 μMol/L (95%CI: 0.82-0.1.06); Placebo: baseline 0.91 μMol/L (95%CI: 0.82-1.06) 12 weeks 0.99 μMol/L (95%CI: 0.88-1.10)] remained unchanged during the trial and 2 weeks after stopping these treatments. CONCLUSIONS:Paricalcitol does not modify plasma ADMA and SDMA in patients with stage 3-4 CKD. The apparent beneficial effects of paricalcitol on ADMA registered in cross-sectional studies is likely attributable to confounding by indication rather than to a true effect of this drug on ADMA metabolism