Background and objectives Roxadustat , an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD.Design, setting, participants, & measurements The 145 patients with nondialysis CKD and hemoglobin #10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of $1.0 g/dl from baseline and hemoglobin of $11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/ severity of adverse events.Results Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (6SD) of 1.83 (60.09) g/dl (P,0.001). Overall mean total cholesterol level was reduced by a mean (6SD) of 26 (630) mg/dl (P,0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported.Conclusions In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.

The preparation, properties, and crystal structures of 12 trichromium extended metal atom chain (EMAC) compounds of the type Cr(3)(L)(4)X(2) (L = equatorial ligands dipyridylamide (dpa) or di-4,4'-ethyl-2,2'-pyridylamide (depa), and X = axial ligands, e.g., halide or pseudohalide ions) with large variations in metal-metal distances are reported here. These complexes, which belong to a broad class of fundamentally interesting trinuclear molecules over which the electrons may or may not be delocalized, pose significant theoretical and experimental challenges which are dealt with in this report. Complexes with strongly donating axial or equatorial ligands tend to favor a symmetrical (D(4)) molecular structure, while more weakly donating ligands give rise to unsymmetrical (C(4)) structures; the physical properties of these two classes of compounds are discussed fully, and important comparisons with a reported DFT model of the electronic structures of the compounds are made.