Elevation of serum von Willebrand factor and anti‐endothelial cell antibodies in patients with immunoglobulin A nephropathy are associated with intrarenal arterial lesions

Jiang, Lei; Liu, Gang; Wang, Su‐Xia; Zou, Wan-zhong; Zhao, Minghui

doi:10.1111/j.1440-1797.2008.00983.x

Cited by 11 publications

(13 citation statements)

References 24 publications

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“…Plasma levels of vWF were determined using ELISA as previously described[16]. Briefly, ELISA plates were coated with rabbit anti-human vWF polyclonal antibodies (DAKO, Denmark) at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

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Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

et al. 2014

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BackgroundEndothelial 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.MethodsInitially, 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.ResultsVEGF/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).ConclusionsThe 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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Section: Methodsmentioning

confidence: 99%

“…Our previous studies found that the prevalence of anti-endothelial cell antibodies (AECA) was higher in IgAN patients with severe intra-renal arterial lesions and malignant hypertension[16], [17]. AECA cannot explain all of the endothelial dysfunction in patients with IgAN.…”

Section: Introductionmentioning

confidence: 99%

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

et al. 2014

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“…36 Therefore, we assumed that variants in CFHR5 SCR8-9 would have a similar influence and might be associated with endothelial injury. Although we now have considerable evidence regarding endothelial injury in IgAN, [37][38][39] the underlying mechanism is still unknown. Additional functional studies are required to clarify whether our identified variants in SCR8-9 of CFHR5 influence its binding to endothelial cells and what their genetic mechanisms are in IgAN.…”

Section: Discussionmentioning

confidence: 99%

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Zhai

Meng

Zhu

et al. 2016

JASN

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A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants.

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“…Various autoantibodies, such as antiendothelial cell antibodies (AECAs) [24], antiphospholipid antibodies, antidouble-stranded DNA antibodies, antioxLDL antibodies, and antiapolipoprotein A-I antibodies [25], could directly or indirectly affect the endothelial cells and cause chronic vessel wall damage as circulating or local immune complexes, and might contribute to the pathogenesis of atherosclerosis by causing injury to the endothelium and altering the metabolism of lipoproteins involved in atherogenesis.…”

Section: Vascular Inflammationmentioning

confidence: 99%

Diverse vascular lesions in systemic lupus erythematosus and clinical implications

Tan

Yu²,

Liu³

2014

Current Opinion in Nephrology and Hypertension

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Elevation of serum von Willebrand factor and anti‐endothelial cell antibodies in patients with immunoglobulin A nephropathy are associated with intrarenal arterial lesions

Abstract: Intrarenal arterial lesions are associated with endothelial cell damage in IgAN, and vWF is a useful serological biomarker of severe intrarenal arterial lesions. AECA, especially IgG-AECA, may play an important role in the pathogenesis of intrarenal arterial damage in IgAN.

Cited by 11 publications

References 24 publications

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Diverse vascular lesions in systemic lupus erythematosus and clinical implications

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