Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs' Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.

Parenteral vitamin D is associated with improved survival among long-term hemodialysis patients. Among nondialyzed patients with chronic kidney disease (CKD), oral activated vitamin D reduces parathyroid hormone levels, but the impact on clinical outcomes is unknown. We evaluated associations of oral calcitriol use with mortality and dialysis dependence in 1418 nondialysis patients with CKD and hyperparathyroidism in the Veterans' Affairs Consumer Health Information and Performance Sets database. Incident calcitriol users and nonusers were selected on the basis of stages 3 to 4 CKD, hyperparathyroidism, and the absence of hypercalcemia before calcitriol use and then were matched by age and estimated kidney function. During a median follow-up of 1.9 yr, 408 (29%) patients died and 217 (16%) initiated long-term dialysis. After adjustment for demographics; comorbidities; estimated kidney function; medications; and baseline levels of parathyroid hormone, calcium, and phosphorous, oral calcitriol use was associated with a 26% lower risk for death (95% confidence interval 5 to 42% lower; P ϭ 0.016) and a 20% lower risk for death or dialysis (95% confidence interval 1 to 35% lower; P ϭ 0.038). The association of calcitriol with improved survival was not statistically different across baseline parathyroid hormone levels. Calcitriol use was associated with a greater risk for hypercalcemia. In conclusion, oral calcitriol use is associated with lower mortality in nondialysis patients with CKD. Chronic kidney disease (CKD) affects Ͼ10% of American adults and leads to disturbances in vitamin D and mineral metabolism. [1][2][3][4] The kidneys play an important role in converting 25-hydroxyvitamin D to calcitriol, the most biologically potent vitamin D metabolite, under regulation by parathyroid hormone (PTH) and phosphate. 5,6 A decline in calcitriol levels and a rise in serum PTH levels are among the first detectable mineral metabolism disturbances in CKD. 2,7,8 In clinical trials of predialysis patients with CKD, oral calcitriol or its analogues lowered serum PTH levels. 9 -11 A body of evidence suggests potential health benefits of vitamin D beyond reducing PTH levels. 12 Activated vitamin D binds to the vitamin D receptor to influence a diverse genetic response. 13 In renal and nonrenal populations, lower 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels have been associated with cardiovascular risk factors, including higher renin levels, inflammation, albuminuria, and glucose intolerance. 14 -17 In observational studies of long-term hemodialysis patients, intravenous vitamin D treatment has been associated with improved survival. 18 -21 Given biologic plausibility for an effect of oral calcitriol on survival and lack of clinical outcome data pertaining to this commonly prescribed CKD medication, we evaluated associations of oral calcitriol use with mortality and dialysis dependence in 1418 patients with stages 3 to 4 CKD and hyperparathyroidism.

Although exercise is often recommended for managing osteoarthritis (OA), limited evidence-based exercise options are available for older adults with OA. This study compared the effects of Hatha yoga (HY) and aerobic/strengthening exercises (ASE) on knee OA. Randomized controlled trial with three arms design was used: HY, ASE, and education control. Both HY and ASE groups involved 8 weekly 45-min group classes with 2–4 days/week home practice sessions. Control group received OA education brochures and weekly phone calls from study staff. Standardized instruments were used to measure OA symptoms, physical function, mood, spiritual health, fear of falling, and quality of life at baseline, 4 and 8 weeks. HY/ASE adherences were assessed weekly using class attendance records and home practice video recordings. Primary analysis of the difference in the change from baseline was based on intent-to-treat and adjusted for baseline values. Eight-three adults with symptomatic knee OA completed the study (84% female; mean age 71.6 ± 8.0 years; mean BMI 29.0 ± 7.0 kg/m2). Retention rate was 82%. Compared to the ASE group at 8 weeks, participants in the HY group had a significant improvement from baseline in perception of OA symptoms (−9.6 [95% CI −15.3, −4]; p = .001), anxiety (−1.4 [95% CI −2.7, −0]; p = .04), and fear of falling (−4.6 [−7.5, −1.7]; p = .002). There were no differences in class/home practice adherence between HY and ASE. Three non-serious adverse events were reported from the ASE group. Both HY and ASE improved symptoms and function but HY may have superior benefits for older adults with knee OA.

Objective To evaluate the effects of exenatide on body mass index (BMI) and cardiometabolic risk factors in adolescents with severe obesity. Design Three-month, randomized, double-blind, placebo-controlled, multicenter clinical trial followed by a three-month open label extension. Setting An academic medical center and an outpatient pediatric endocrinology clinic. Patients Twenty-six adolescents (age 12–19 years) with severe obesity (BMI ≥ 1.2 times the 95th percentile or ≥ 35 kg/m2). Intervention All patients received lifestyle modification counseling and were equally randomized to exenatide or placebo injection, twice per day. Main Outcome Measures The primary endpoint was the mean percent change in BMI measured at baseline and three-months. Secondary endpoints included absolute change in BMI, body weight, body fat, blood pressure, hemoglobin A1c, fasting glucose, fasting insulin, and lipids at three-months. Results Twenty-two patients completed the trial. Exenatide elicited a greater reduction in percent change in BMI compared to placebo (−2.70%, 95% CI (−5.02, −0.37), P = 0.025). Similar findings were observed for absolute change in BMI (−1.13 kg/m2, 95% CI (−2.03, −0.24), P = 0.015) and body weight (−3.26 kg, 95% CI (−5.87, −0.66), P = 0.017). Although not reaching the level of statistical significance, reduction in systolic blood pressure was observed with exenatide. During the open label extension, BMI was further reduced in those initially randomized to exenatide (cumulative BMI reduction of 4%). Conclusions These results provide preliminary evidence supporting the feasibility, safety, and efficacy of glucagon-like peptide-1 receptor agonist therapy for the treatment of severe obesity in adolescents. Trial Registration This study is registered on the www.clinicaltrials.gov website (ClinicalTrials.gov identifier: NCT01237197).