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Background: Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. Methods: One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years. Results: In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases. Conclusions: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl. [ABSTRACT FROM AUTHOR]

Darbepoetin alfa is a novel erythropoiesisstimulating protein with a two- to threefold longer halflife than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 µg/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal halflife of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients. [ABSTRACT FROM AUTHOR]

Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl.Background.The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI™) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipar™) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca× P) was investigated in subjects on dialysis with secondary HPT.Methods.Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180 mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca× P levels.Results.Cinacalcet-treated subjects were more likely to achieve a mean iPTH≤300 pg/mL (31.8 pmol/L) than were control subjects on traditional therapy (56% vs. 10%,P<0.001). Cinacalcet-treated subjects were more likely to achieve concentrations of serum calcium within 8.4 to 9.5 mg/dL (2.10–2.37 mmol/L) and serum phosphorus within 3.5 to 5.5 mg/dL (1.13–1.78 mmol/L) than were control subjects (49% vs. 24% and 46% vs. 33%,P<0.001 for each). Cinacalcet also improved achievement of Ca× P<55 mg2/dL2 (4.44 mmol2/L2) and concurrent achievement of Ca× P<55 mg2/dL2 (4.44 mmol2/L2) and iPTH≤300 pg/mL (31.8 pmol/L) (65% vs. 36% and 41% vs. 6%,P<0.001 for each).Conclusion.In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca× P. [ABSTRACT FROM AUTHOR]