Feng Shaozhen, Huang Naya, Xue Miaorong, Zhang Puhua, Zhong Zhong, Guo Qunying, Li Zhijian
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China.
J Clin Lab Anal. 2021 Sep 8;35(10):e23995. doi: 10.1002/jcla.23995.
Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes.
Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated.
Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders.
Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.
肾活检仍是诊断和监测IgA肾病（IgAN）的金标准。血管内皮生长因子A（VEGFA）对肾小球细胞的存活至关重要。我们的目的是筛查IgAN患者尿液、循环和肾脏中VEGFA的表达模式，以揭示它们与肾脏病理及预后的关系。
采用酶联免疫吸附测定（ELISA）、实时聚合酶链反应（PCR）和免疫组织化学法测定基线VEGFA水平。评估VEGFA表达与临床病理参数及肾脏预后之间的关联。
与健康对照相比，IgAN患者尿液VEGFA水平明显升高（76.19±63.67 pg/mg肌酐 vs 146.67±232.71 pg/mg肌酐，p = 0.0291），且与血清VEGFA水平无关。通过逐步多因素回归分析，基线尿液VEGFA与性别及肾小管萎缩/间质纤维化显著相关。伴有较高血清肌酐、高血压比例和复发性血尿的男性患者尿液VEGFA水平高于女性患者。在IgAN患者的肾脏中，VEGFA在壁层上皮细胞、足细胞、系膜细胞和肾小管上皮细胞中强烈表达。经过38.53±27.14个月的随访，发现尿液VEGFA水平较高的IgAN患者在调整混杂因素后肾脏替代治疗的肾脏预后较差（风险比[HR]=1.027，p = 0.037）或复合结局较差（HR = 1.023，p = 0.039）。
尿液VEGFA升高可能反映了某些肾脏病理情况，尽管并非完全特异，但仍可作为预测IgAN肾脏进展的有价值的非侵入性指标。
