HIF-2 inhibitor, erythrocytosis, and pulmonary hypertension

Prchal, Josef T.

doi:10.1182/blood.2020010323

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…Additionally, subgroup analysis based on the type of control intervention further revealed a higher risk of hypertension associated with oral roxadustat treatment of anemia in CKD patients when compared to the placebo group, but no statistically significant difference was observed when compared with ESA group. HIF transcription factors are also known to contribute to the development of pulmonary hypertension, suggesting that HIF-PHIs have a complex effect on vasculature [ 55 ]. This is supported by our finding of an inconsistent risk of hypertension in the roxadustat group relay on whether it was compared with the placebo or ESA group.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis

Tian,

Wang,

Liu

et al. 2024

Renal Failure

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This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis

Tian,

Wang,

Liu

et al. 2024

Renal Failure

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“…Therefore, these authors hypothesized that the up-regulation of Hypoxia inducible factors (HIF) signaling in granulocytes and platelets, perhaps with an additional contribution of augmented inflammation, plays a central role in the development of thrombosis in PV and ET. In a pivotal study, Prchal and colleagues quantitated mRNA of these HIF-regulated prothrombotic genes: THBS1, SERPINE1, ITGA2B, PTGS2, SELP, PDGFA, and ITGB3 131,132. They analyzed granulocytes from 16 CE subjects (8 iron deficient) and platelets from 12 CE subjects (7 iron deficient).…”

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confidence: 99%