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Elevated soluble VEGF receptor sFlt-1 correlates with endothelial injury in IgA nephropathy #MMPMID25007257
Zhai YL; Zhu L; Shi SF; Liu LJ; Lv JC; Zhang H
PLoS One 2014[]; 9 (7): e101779 PMID25007257show ga
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.
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PLoS+One 2014 ; 9 (7): e101779
