Impact of HIF-prolyl hydroxylase inhibitors on VEGF expression and vascular adverse events in chronic kidney disease: a meta-analysis of 34 randomized controlled trials.
Seyed Mahdi Montazer, Amirali Asadi, Amirali Taghipour et al.
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In 30 seconds
This meta-analysis of 34 randomized controlled trials assessed VEGF levels and VEGF-related adverse outcomes with hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in people with chronic kidney disease. Across 26 trials reporting VEGF, treatment was associated with a modest increase in levels (SMD = 0.23; 95% CI: 0.07-0.39). Peripheral edema was the most consistent adverse signal, with increased risk (log RR = 0.22; 95% CI: 0.09-0.35). The analysis found no significant associations with cancer, diabetic retinopathy, or thrombosis; dialysis status moderated the VEGF response.
Key findings
- HIF-PHI treatment was associated with higher VEGF levels (SMD = 0.23; 95% CI: 0.07-0.39).
- Peripheral edema risk increased with HIF-PHIs (log RR = 0.22; 95% CI: 0.09-0.35).
- No significant associations were found for cancer, diabetic retinopathy, or thrombosis.
- VEGF elevation was greater in dialysis-dependent patients.
Why it matters
The findings identify peripheral edema as a consistent adverse-event signal alongside the modest VEGF increase, while offering no evidence of increased cancer, retinal disease, or thrombosis in the analyzed trials. This helps frame safety monitoring for HIF-PHIs, but the absence of detected harm in these data does not establish long-term safety.
What to keep in mind
The abstract does not report follow-up duration; its conclusion limits the absence of oncologic or retinal harm to the short term.