Erythropoietin receptor agonist(Ligand Pharmaceuticals, Inc.)

Erythropoiesis-stimulating agents (ESA) are used to treat anemia in hemodialysis (HD) patients. We investigated the role of inflammation and accumulation of environmental toxins (perfluorinated chemicals (PFCs), such as perfluorooctanoic acid and perfluorooctane sulfonate) in the erythropoietic response of HD patients who receive a fixed monthly continuous erythropoietin receptor activator (CERA) dosage. Forty-five patients underwent three successive phases of ESA treatment for two months each (phase one: 100 µg CERA once monthly; phase two: 50 µg CERA twice monthly; phase three: 100 µg CERA once monthly). Patient data were collected to determine the association of various factors with erythropoietic response (change in hematocrit). Liquid chromatography-tandem mass spectrometry was used to analyze perfluorinated chemicals. Twenty-eight patients exhibited a poor erythropoietic response that was significantly associated with: age > 80 years, initial hematocrit > 36%, glucose > 200 mg/dL, alanine aminotransferase > 21 U/L, c-reactive protein > 1 mg/dL, interleukin-6 > 10 ng/mL, lactate dehydrogenase ≤ 190 U/L, and chloride ≤ 93 mEq/L. There was also a borderline significant association between inflammation and PFCs, although PFCs failed to show any impact on ESA response. Age, glucose, chloride, liver function, and inflammation may be associated with cost-effective fixed CERA dosage administered at an increased frequency.

The World Anti-Doping Agency (WADA) has recently implemented dried blood spots (DBSs) as a matrix for doping control. However, specifications regarding the analysis of the class of prohibited substances called erythropoietin receptor agonists (ERAs) from DBSs are not yet described. The aim of this study was to find optimal conditions (sample volume, storage) to sensitively detect endogenous erythropoietin (EPO) and prohibited ERAs from DBSs and compare detection limits to WADA-stipulated minimum required performance levels (MRPLs) for ERAs in serum/plasma samples. Venous whole blood was spotted onto Whatman 903 DBS cards with primarily 60 μL of blood, but various volumes from 20 to75 μL were tested. All samples were immunopurified with MAIIA EPO Purification Gel kit (EPGK) and analysed with SAR-PAGE and Western blot. 60 μL-DBSs allowed the detection of the four main ERAs (BRP, NESP, CERA, and EPO-Fc) at concentrations close to WADA's MRPLs described for 500 μL of serum/plasma. Different storage temperatures, from -20°C to 37°C, were evaluated and did not affect ERA detection. A comparison of the detection of endogenous EPO from the different anti-doping matrices (urine, serum, and DBSs produced from upper-arm capillary blood), from five participants for six weeks was performed. Endogenous EPO extracted from DBSs showed intra-individual variations in male and female subjects, but less than in urine. Doping controls would benefit from the stability of ERAs on DBSs: it can be a complementary matrix for ERA analysis, particularly in the absence of EPO signals in urine.