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BackgroundThe 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.DescriptionThe 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.ConclusionThe 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.

Introduction Although sodium disturbances are common in hospitalised patients, few studies have specifically investigated the epidemiology of sodium disturbances in the intensive care unit (ICU). The objectives of this study were to describe the incidence of ICU-acquired hyponatraemia and hypernatraemia and assess their effects on outcome in the ICU.

Summary Background and objectives Buttonhole needling is reported to be associated with less pain than standard needling. The purpose of this study was to compare patient perceived pain and fistula complications in buttonhole and standard needling. Design, setting, participants, & measurements In this study, 140 conventional hemodialysis patients were randomly assigned to buttonhole or standard needling. The primary outcome was patient perceived pain with needling at 8 weeks. Fistula complications of hematoma, bleeding postdialysis, and infection were tracked. Results Median pain score at 8 weeks using a visual analog scale from 0 to 10 cm was similar for standard and buttonhole needling (1.2 [0.4–2.4] versus 1.5 [0.5–3.4]; P=0.57). Rate of hematoma formation in standard needling was higher (436 versus 295 of 1000 hemodialysis sessions; P=0.03). Rate of no bleeding postdialysis was 23.6 and 28.3 per 1000 in standard and buttonhole needling, respectively (P=0.40). Rate of localized signs of infection in standard versus buttonhole needling was 22.4 versus 50 per 1000 (P=0.003). There was one episode of Staphylococcal aureus bacteremia during the 8 weeks with buttonhole needling and no episodes with standard needling (P=1.00). Within 12 months of follow-up, another two buttonhole needling episodes developed S. aureus bacteremia, and nine buttonhole needling episodes had needling site abscesses requiring intravenous antibiotics versus zero standard needling episodes (P=0.003). Conclusions Patients had no difference in pain between buttonhole and standard needling. Although fewer buttonhole needling patients developed a hematoma, there was an increased risk of bacteremia and localized signs of infection. Routine use of buttonhole needling is associated with increased infection risk.

Abstract-Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the type I angiotensin II receptor in mediating an increase in arterial pressure associated with a single 6-hour IH exposure. Using a double-blind, placebo-controlled, randomized, crossover study design, we exposed 9 healthy male subjects to sham IH, IH with placebo medication, and IH with the type I angiotensin II receptor antagonist losartan. We measured blood pressure, cerebral blood flow, and ventilation at baseline and after exposure to 6 hours of IH. An acute isocapnic hypoxia experimental protocol was conducted immediately before and after exposure to IH. IH with placebo increased resting mean arterial pressure by 7.9Ϯ1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9Ϯ1.5 mm Hg) or with losartan IH (Ϫ0.2Ϯ2.4 mm Hg; PϽ0.05). Exposure to IH prevented the diurnal decrease in the cerebral blood flow response to hypoxia, independently of the renin-angiotensin system. Finally, in contrast to other models of IH, the acute hypoxic ventilatory response did not change throughout the protocol. IH increases arterial blood pressure through activation of the type I angiotensin II receptor, without a demonstrable impact on the cerebrovascular or ventilatory response to acute hypoxia. (Hypertension. 2010;56:369-377.)Key Words: blood pressure Ⅲ cerebrovascular circulation Ⅲ hypoxia Ⅲ renin Ⅲ physiology P atients with obstructive sleep apnea (OSA) are exposed to chronic intermittent hypoxia (IH), which is thought to be the underlying mechanism that links OSA with an increased risk of cardiovascular disease. 1 The specific pathophysiologic mechanism whereby OSA causes hypertension has not been fully elucidated, but it has been proposed that persistent sympathoexcitation, oxidative stress, and endothelial dysfunction contribute. 2 Central to this concept is the important interaction between the sympathetic nervous system and the renin-angiotensin system (RAS). Renin release from the kidney is tightly controlled by activity in renal sympathetic nerves. 3 In OSA patients, sympathetic nerve activity, 4 the plasma concentration of angiotensin II (ANG-II), 5 and the vasoconstrictor response to ANG-II are elevated. 6 ANG-II has potent vasoconstrictor capabilities through its action on type I ANG-II receptors (AT 1 Rs) located on vascular smooth muscle cells. 7 ANG-II production can also regulate blood volume by increasing aldosterone production. The combined potential for the RAS to be stimulated by IH and its ability to regulate peripheral resistance and blood volume make it a credible pathway through which OSA can lead to the development of systemic hypertension. The role of the RAS in the IH-dependent increase in arterial blood pressure has yet to be addressed in human experiments.The primary objective of this study was to assess the role of the AT 1 R in ...

Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir P ET,O 2 = 45.0 mmHg) alternating with 2 min of normoxia (peak P ET,O 2 = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA.

Background-In healthy humans, continuous treatment with nitroglycerin (GTN) causes nitric oxide synthase dysfunction, probably through the reduced bioavailability of tetrahydrobiopterin. Recent studies proposed that folic acid is involved in the regeneration of tetrahydrobiopterin in different disease states. Therefore, we investigated whether folic acid administration would prevent this phenomenon. We also sought to determine if folic acid supplementation could prevent the development of tolerance to GTN. Methods and Results-On the first visit, 18 healthy male volunteers (aged 19 to 32 years) were randomized to receive either oral folic acid (10 mg once a day) or placebo for 1 week in a double-blind designed study. All subjects also received continuous transdermal GTN (0.6 mg/h). On the second visit, forearm blood flow was measured with venous occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 g/min), N-monomethyl-L-arginine (1, 2, and 4 mol/min), and GTN (11 and 22 nmol/min). Folic acid prevented GTN-induced endothelial dysfunction, as assessed by responses to intraarterial acetylcholine and N-monomethyl-L-arginine (PϽ0.01). Moreover, in the subjects treated with folic acid plus transdermal GTN, responses to intraarterial GTN were significantly greater than those observed after transdermal GTN plus placebo (PϽ0.05). Conclusion-Our data demonstrate that supplemental folic acid prevents both nitric oxide synthase dysfunction induced by continuous GTN and nitrate tolerance in the arterial circulation of healthy volunteers. We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our results confirm the view that oxidative stress contributes to nitrate tolerance.

BackgroundAlthough obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown.MethodsWe studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year.Results858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67).ConclusionNocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function.