Roxadustat for treatment of erythropoietin-hyporesponsive anemia in a hemodialysis patient:A case report

BACKGROUND Hyporesponsiveness to erythropoiesis-stimulating agents(ESAs)is a prevalent problem in patients with chronic kidney disease.It is associated with increased morbidity and mortality in patients who undergo dialysis.A significant proportion of patients do not respond to iron supplementation and conventional ESAs.We report a case of severe ESA hyporesponsiveness-related anemia that was successfully treated with oral roxadustat.CASE SUMMARY A 59-year-old Chinese woman had high blood glucose for 25 years,maintenance hemodialysis for 7 years,and recurrent dizziness and fatigue for more than 2 years.Laboratory tests showed severe anemia(hemoglobin level of 54 g/L),though bone marrow biopsy,fluorescence in situ hybridization,and hemolysis tests were within normal ranges.We initially administered first-line therapies and other adjuvant treatments,such as blood transfusions,ESAs,and adequate dialysis,but the patient did not respond as anticipated.Her erythropoietinresistant anemia was probably not only due to chronic renal insufficiency.The patient received the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat(100 mg,three times weekly).After 12 wk of treatment,the patient’s hemoglobin increased significantly,and her symptoms were alleviated.During the follow-up period,adverse drug reactions were controllable and tolerable.CONCLUSION Oral roxadustat is effective and tolerable for the treatment of ESA hyporesponsiveness-related anemia in patients undergoing hemodialysis.

Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats

BACKGROUND： Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin（PGI2） in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.METHODS： Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride（CCl4） corn oil solution combined with intermittent drinking of 5% alcohol, and agematched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1α（6-keto-PGF1α, a stable metabolite of PGI2） was tested via enzyme immunoassays and the expression of cyclooxygenase（COX） in mesenteric arteries was detected by Western blotting.RESULTS： In parallel with the increase of plasma 6-ketoPGF1α, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3＇, 5＇-cyclic monophosphothioate（Rp-cAMPS） partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats.Indomethacin significantly decreased the plasma 6-keto-PGF1α.Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats,whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.CONCLUSION： Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributedto the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.