Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA NephropathyReportar como inadecuado




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Background

Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor vWF level, is a common manifestation in IgA nephropathy IgAN. However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor-Soluble fms-like tyrosine kinase-1 VEGF-sFlt-1 has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration.

Methods

Initially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF-sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor sFlt-1 was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN.

Results

VEGF-sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers 0.33±0.27 vs. 0.43±0.22, p = 0.02 in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated 101.18±25.19 vs. 79.73±18.85 pg-ml, p<0.001, but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients 93.40±39.78 vs. 71.92±15.78 pg-ml, p<0.001. Plasma sFlt-1 levels in IgAN patients correlated with proteinuria severe >3.5 g-d vs. moderate 1–3.5 g-d vs. mild <1 g-d proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg-ml; severe vs. mild: p<0.001, moderate vs. mild p = 0.001, severe vs. moderate: p = 0.014, hypertension with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg-ml, p = 0.015 and vWF levels r = 0.161, p = 0.021.

Conclusions

The present study found elevated sFlt-1 in IgAN patients and further identified its correlation with proteinuria, hypertension and vWF levels. These results suggested that elevated sFlt-1 contributes to endothelial injury in IgAN.



Autor: Ya-Ling Zhai, Li Zhu , Su-Fang Shi, Li-Jun Liu, Ji-Cheng Lv, Hong Zhang

Fuente: http://plos.srce.hr/



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