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Updated: Jun 21, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
The soluble VEGF receptor sFlt1 contributes to endothelial dysfunction in CKD
Giovana S Di Marco1, Stefan Reuter, Uta Hillebrand
1Department of Internal Medicine D, University Clinics Münster, Münster, Germany.
Insights
Elevated soluble VEGF receptor 1 (sFlt-1) in chronic kidney disease (CKD) patients is linked to endothelial dysfunction and reduced blood vessel formation. This finding suggests sFlt-1 may indicate cardiovascular risk in CKD.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Vascular Biology
Background:
- Endothelial dysfunction is a key factor in the elevated cardiovascular risk observed in patients with chronic kidney disease (CKD).
- The soluble VEGF receptor 1 (sFlt-1), an antagonist of vascular endothelial growth factor (VEGF), is investigated for its potential role in CKD-associated endothelial dysfunction and impaired angiogenesis.
Purpose of the Study:
- To investigate the association between plasma sFlt-1 levels and endothelial dysfunction in patients with CKD.
- To explore the functional impact of sFlt-1 on angiogenesis, endothelial cell apoptosis, and nitric oxide generation in the context of CKD.
Main Methods:
- Plasma sFlt-1 levels were measured in 130 CKD patients (stages 3-5) and 56 controls.
- Multivariate regression analysis identified associations between sFlt-1, renal function, and von Willebrand factor (vWF).
- In vitro and in vivo assays (CAM assay, endothelial cell cultures, rat model) assessed the functional effects of sFlt-1 and its inhibition.
Main Results:
- CKD patients exhibited significantly higher plasma sFlt-1 levels compared to controls.
- sFlt-1 levels were independently associated with renal function and vWF levels.
- Both recombinant sFlt-1 and CKD patient serum demonstrated antiangiogenic properties, induced endothelial cell apoptosis, and reduced nitric oxide generation, effects reversed by anti-sFlt-1 antibody.
Conclusions:
- Excessive sFlt-1 is associated with endothelial dysfunction and impaired angiogenesis in CKD.
- Monocytes are identified as a potential source of increased sFlt-1 in CKD patients.
- Elevated sFlt-1 may serve as a predictive marker for cardiovascular risk in the CKD population.
Abstract:
Endothelial dysfunction contributes to the increased cardiovascular risk that accompanies CKD. We hypothesized that the soluble VEGF receptor 1 (sFlt-1), a VEGF antagonist, plays a role in endothelial dysfunction and decreased angiogenesis in CKD. We enrolled 130 patients with CKD stages 3 to 5 and 56 age- and gender-matched control patients. Plasma sFlt-1 levels were higher in patients with CKD and, after multivariate regression analyses, exclusively associated with renal function and levels of vWF, a marker of endothelial dysfunction. Compared with serum from control patients, both recombinant sFlt-1 and serum from patients with CKD had antiangiogenic activity in the chick chorioallantoic membrane (CAM) assay, induced endothelial cell apoptosis in vitro, and decreased nitric oxide generation in two different endothelial cell lines. Pretreating the sera with an antibody against sFlt-1 abrogated all of these effects. Furthermore, we observed increased sFlt1 levels in 5/6-nephrectomized rats compared with sham-operated animals. Finally, using real-time PCR and ELISA, we identified monocytes as a possible source of increased sFlt-1 in patients with CKD. Our findings show that excess sFlt-1 associates with endothelial dysfunction in CKD and suggest that increased sFlt-1 may predict cardiovascular risk in CKD.
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