Oxymetholone

Nephrotic syndrome associated with myelodysplastic syndromes (MDSs) is rare, and collapsing glomerulopathy (CG) in this condition is extremely uncommon. We report a case of CG in a 62-year-old man who presented with generalized edema, severe anemia, acute kidney injury, and nephrotic-range proteinuria. Laboratory tests showed hypoalbuminemia and elevated serum creatinine, whereas kidney ultrasound showed normal-sized kidneys with increased parenchymal echogenicity. Kidney biopsy confirmed a diagnosis of CG, and subsequent bone marrow biopsy showed myelodysplastic syndromes with isolated 5q deletion (MDS-del(5q)) and low blast count. The patient was treated with oxymetholone, erythropoietin, and lenalidomide. Despite treatment, his kidney function deteriorated, leading to kidney failure with replacement therapy. To our knowledge, CG is a rare cause of nephrotic syndrome in patients with MDS, particularly in those with MDS-del(5q), and has not been previously reported. This case underscores the importance of considering hematologic malignancies, including MDS, in the differential diagnosis of CG, especially when accompanied by cytopenias. Early recognition of the underlying etiology is essential for guiding treatment and may offer the opportunity to modify disease progression.

In vitro metabolic models provide a means to circumvent the ethical concerns associated with human administration research, allowing for preliminary predictions of human metabolism while generating high concentrations of metabolites for characterization. As S1.1-class anabolic androgenic steroids on the World Anti-Doping Agency (WADA) Prohibited List, oxymetholone and methasterone have consistently appeared in the top 20 substances identified in adverse analytical findings (AAFs) in recent years, reflecting their persistent abuse patterns in sports. Given their exogenous nature, the metabolites of these steroid hormones fall within the scope of doping control, making metabolic studies a crucial aspect of anti-doping research. In this study, human liver S9 fractions were employed as a model for the characterization and metabolic profiling of oxymetholone and methasterone via gas chromatography-orbitrap-high-resolution mass spectrometry (GC-Orbitrap-HRMS). The full scan mode of GC-Orbitrap-HRMS was utilized to detect free and two conjugated fractions of metabolites, comparing these with control groups to confirm the metabolites during in vitro incubation. Possible metabolite structures were inferred from EI mass spectra, and the metabolic pathways for both drugs were discussed. In vitro, three oxymetholone and five methasterone metabolites were identified, and among them, two metabolites, OMT-M3 (2α,17α-methyl-5ξ-androstan-3α,6β,17β-triol) and MTS-M3 (2α,17α-dimethyl-5ξ-androstane-3α,12ξ,16ξ,17β-tetrol), were characterized as novel metabolites based on recent human in vivo metabolic studies. These metabolites exhibited diverse metabolic pathways, and their structures were corroborated through complementary in vitro and in vivo metabolic analyses. This study provides a comprehensive evaluation of the applicability of the human liver S9 model in the metabolic studies of anabolic steroids in vitro, verifying novel human metabolites and providing valuable insights for future research in this field.