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Background <p>Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients.</p> Materials and methods <p>PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality.</p> Results <p>A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07&#xa0;mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25&#xa0;mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70&#xa0;mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91&#xa0;mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo.</p> Conclusion <p>Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.</p>

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Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on lipid profiles in patients with chronic kidney disease: a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Yun-Hui Huang,
  • Yu-Han Huang,
  • Tzu-Rong Peng,
  • Ta-Wei Wu

摘要

Background

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients.

Materials and methods

PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality.

Results

A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25 mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70 mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91 mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo.

Conclusion

Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.