Hadeer Zakaria, Noha Alaa Hamdy, Nagy Ah Sayed-Ahmed, Ahmed El-Mallah
{"title":"通过对缺氧诱导因子-2α的新作用，五氧嘧啶可改善血液透析患者的贫血状况：一项随机、双盲、安慰剂对照临床试验。","authors":"Hadeer Zakaria, Noha Alaa Hamdy, Nagy Ah Sayed-Ahmed, Ahmed El-Mallah","doi":"10.1080/00325481.2024.2426448","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>This randomized, double-blind, placebo-controlled clinical trial aimed to prospectively examine the effect of pentoxifylline (PTX) on hypoxia-inducible factor-2 alpha (HIF-2α) and its role in controlling anemia in hemodialysis (HD) patients.</p><p><strong>Methods: </strong>Eighty patients on HD were randomized to receive 400 mg of PTX or placebo twice daily for 6 months. The hemoglobin (Hb) and other hematologic parameters, the weekly erythropoiesis-stimulating agents (ESAs), and the ESA resistance index (ERI) were assessed monthly during the study. The HIF-2α, transforming growth factor-β1 (TGF-β1), and high-sensitivity C-reactive protein (hs.CRP) were measured before and after the intervention.</p><p><strong>Results: </strong>In the pentoxifylline group, an appreciable increase in Hb from 9.7 (9.3, 10.3) g/dl to 10.5 (9.3, 11.4) g/dl and hematocrit (Hct) from 31.3 (29.6, 32.4)% to 33.2 (29.4, 35.9)% was observed after one month of PTX administration, and this effect was maintained over the study time (<i>p</i> < 0.001). This was along with a decrease in the ESA doses required from 8000 (8000, 11500) IU/wk to 4000 (2000, 8000) IU/wk (<i>p</i> < 0.001), and an improvement in the ERI from 11.6 (8.07, 16.97) IU/kg/wk/g/dl to 5.79 (2.01, 10.09) IU/kg/wk/g/dl (<i>p</i> < 0.001). Additionally, the HIF-2α increased significantly at the end of the intervention in patients who received PTX from 3245.35 (2886.8, 4691.56) pg/ml to 7208.75 (5382, 9182.7) pg/ml, while TGF-β1 and hs.CRP decreased significantly from 657.78 (539.78, 1146.62) pg/ml and 88.08 (39.93, 100.4) mg/l to 329.94 (228.67, 793.18) pg/ml and 48.65 (34.44, 84.61) mg/l, respectively. The percent changes in HIF-2α, TGF-β1, and hs.CRP levels in the pentoxifylline group were also statistically significant in comparison with the placebo group.</p><p><strong>Conclusions: </strong>PTX could be a promising agent for correcting anemia in HD patients via increasing HIF-2α levels.</p><p><strong>Clinical trial registration: </strong>Clinicaltrials.gov, February 2023, registry number: NCT05708248.</p>","PeriodicalId":94176,"journal":{"name":"Postgraduate medicine","volume":" ","pages":"847-854"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pentoxifylline improves anemia through its novel effect on hypoxia-inducible factor-2 alpha in hemodialysis patients: a randomized, double-blind, placebo-controlled clinical trial.\",\"authors\":\"Hadeer Zakaria, Noha Alaa Hamdy, Nagy Ah Sayed-Ahmed, Ahmed El-Mallah\",\"doi\":\"10.1080/00325481.2024.2426448\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>This randomized, double-blind, placebo-controlled clinical trial aimed to prospectively examine the effect of pentoxifylline (PTX) on hypoxia-inducible factor-2 alpha (HIF-2α) and its role in controlling anemia in hemodialysis (HD) patients.</p><p><strong>Methods: </strong>Eighty patients on HD were randomized to receive 400 mg of PTX or placebo twice daily for 6 months. The hemoglobin (Hb) and other hematologic parameters, the weekly erythropoiesis-stimulating agents (ESAs), and the ESA resistance index (ERI) were assessed monthly during the study. The HIF-2α, transforming growth factor-β1 (TGF-β1), and high-sensitivity C-reactive protein (hs.CRP) were measured before and after the intervention.</p><p><strong>Results: </strong>In the pentoxifylline group, an appreciable increase in Hb from 9.7 (9.3, 10.3) g/dl to 10.5 (9.3, 11.4) g/dl and hematocrit (Hct) from 31.3 (29.6, 32.4)% to 33.2 (29.4, 35.9)% was observed after one month of PTX administration, and this effect was maintained over the study time (<i>p</i> < 0.001). This was along with a decrease in the ESA doses required from 8000 (8000, 11500) IU/wk to 4000 (2000, 8000) IU/wk (<i>p</i> < 0.001), and an improvement in the ERI from 11.6 (8.07, 16.97) IU/kg/wk/g/dl to 5.79 (2.01, 10.09) IU/kg/wk/g/dl (<i>p</i> < 0.001). Additionally, the HIF-2α increased significantly at the end of the intervention in patients who received PTX from 3245.35 (2886.8, 4691.56) pg/ml to 7208.75 (5382, 9182.7) pg/ml, while TGF-β1 and hs.CRP decreased significantly from 657.78 (539.78, 1146.62) pg/ml and 88.08 (39.93, 100.4) mg/l to 329.94 (228.67, 793.18) pg/ml and 48.65 (34.44, 84.61) mg/l, respectively. The percent changes in HIF-2α, TGF-β1, and hs.CRP levels in the pentoxifylline group were also statistically significant in comparison with the placebo group.</p><p><strong>Conclusions: </strong>PTX could be a promising agent for correcting anemia in HD patients via increasing HIF-2α levels.</p><p><strong>Clinical trial registration: </strong>Clinicaltrials.gov, February 2023, registry number: NCT05708248.</p>\",\"PeriodicalId\":94176,\"journal\":{\"name\":\"Postgraduate medicine\",\"volume\":\" \",\"pages\":\"847-854\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Postgraduate medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/00325481.2024.2426448\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Postgraduate medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/00325481.2024.2426448","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/10 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Pentoxifylline improves anemia through its novel effect on hypoxia-inducible factor-2 alpha in hemodialysis patients: a randomized, double-blind, placebo-controlled clinical trial.
Objectives: This randomized, double-blind, placebo-controlled clinical trial aimed to prospectively examine the effect of pentoxifylline (PTX) on hypoxia-inducible factor-2 alpha (HIF-2α) and its role in controlling anemia in hemodialysis (HD) patients.
Methods: Eighty patients on HD were randomized to receive 400 mg of PTX or placebo twice daily for 6 months. The hemoglobin (Hb) and other hematologic parameters, the weekly erythropoiesis-stimulating agents (ESAs), and the ESA resistance index (ERI) were assessed monthly during the study. The HIF-2α, transforming growth factor-β1 (TGF-β1), and high-sensitivity C-reactive protein (hs.CRP) were measured before and after the intervention.
Results: In the pentoxifylline group, an appreciable increase in Hb from 9.7 (9.3, 10.3) g/dl to 10.5 (9.3, 11.4) g/dl and hematocrit (Hct) from 31.3 (29.6, 32.4)% to 33.2 (29.4, 35.9)% was observed after one month of PTX administration, and this effect was maintained over the study time (p < 0.001). This was along with a decrease in the ESA doses required from 8000 (8000, 11500) IU/wk to 4000 (2000, 8000) IU/wk (p < 0.001), and an improvement in the ERI from 11.6 (8.07, 16.97) IU/kg/wk/g/dl to 5.79 (2.01, 10.09) IU/kg/wk/g/dl (p < 0.001). Additionally, the HIF-2α increased significantly at the end of the intervention in patients who received PTX from 3245.35 (2886.8, 4691.56) pg/ml to 7208.75 (5382, 9182.7) pg/ml, while TGF-β1 and hs.CRP decreased significantly from 657.78 (539.78, 1146.62) pg/ml and 88.08 (39.93, 100.4) mg/l to 329.94 (228.67, 793.18) pg/ml and 48.65 (34.44, 84.61) mg/l, respectively. The percent changes in HIF-2α, TGF-β1, and hs.CRP levels in the pentoxifylline group were also statistically significant in comparison with the placebo group.
Conclusions: PTX could be a promising agent for correcting anemia in HD patients via increasing HIF-2α levels.
Clinical trial registration: Clinicaltrials.gov, February 2023, registry number: NCT05708248.
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