Erythropoiesis-stimulating agents (ESAs) increase hemoglobin levels, reduce transfusion requirements, and have been the standard of treatment for anemia in patients with chronic kidney disease (CKD) since 1989. Many safety concerns have emerged regarding the use of ESAs, including an increased occurrence of cardiovascular events and vascular access thrombosis. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitors are a new class of agents for the treatment of anemia in CKD. These agents work by stabilizing the HIF complex and stimulating endogenous erythropoietin production even in patients with end-stage kidney disease. HIF-PH inhibitors improve iron mobilization to the bone marrow. They are administered orally, which may be a more favorable route for patients not undergoing hemodialysis. By inducing considerably lower but more consistent blood erythropoietin levels than ESAs, HIF-PH inhibitors may be associated with fewer adverse cardiovascular effects at comparable hemoglobin levels, although this has yet to be proved in long-term clinical trials. One significant concern regarding the long-term use of these agents is their possible effect on tumor growth. There are 4 such agents undergoing phase 2 and 3 clinical trials in the United States; this report provides a focused review of HIF-PH inhibitors and their potential clinical utility in the management of anemia of CKD.

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OBJECTIVE-We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers.METHODS-In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age.RESULTS-Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores.CONCLUSIONS-Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to Copyright © 2008 by the American Academy of Pediatrics. All rights reserved.Address correspondence to Madhusmita Misra, MD, MPH, Massachusetts General Hospital, Neuroendocrine Unit, BUL 457, 55 Fruit St, Boston, MA 02114. mmisra@partners.org. The authors have indicated they have no financial relationships relevant to this article to disclose.Drs Christo and Prabhakaran contributed equally to this work. NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2011 November 4. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. Keywordsadolescents; athletes; bone density; bone-turnover markers; insulin-like growth factor I Amenorrhea has been reported to occur in 23.5% of high school athletes, 1 although the prevalence may vary depending on the type, intensity, and duration of exercise, as well as the athlete's nutritional status. [1][2][3][4] In particular, activities such as gymnastics, running track, ballet, diving, swimming, and cheerleading are common among high school girls, require a thin physique, and are as...