Honkanen E O, Teppo A M, Grönhagen-Riska C
Division of Nephrology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland. eero.honkanen2fimnet.fi
Kidney Int. 2000 Jun;57(6):2343-9. doi: 10.1046/j.1523-1755.2000.00094.x.
Membranous glomerulonephritis (MGN) has, for unknown reasons, an unpredictable and highly variable clinical course. Vascular endothelial growth factor (VEGF) enhances endothelial cell proliferation, angiogenesis, microvascular permeability, and monocyte chemotaxis, and it activates proteinases. In normal kidneys, it is predominantly expressed by glomerular podocytes, where its physiological function and role in development of renal diseases are obscure. This study was designed to evaluate the urinary excretion of VEGF in MGN compared with several other glomerular disease and to asses its relationships to the clinical activity of MGN.
Urinary VEGF was studied during renal biopsy using a sandwich enzyme immunoassay from 30 patients with idiopathic MGN, 8 with minimal change glomerulonephritis, 10 with focal segmental glomerulosclerosis (FSGS), 8 with necrotizing glomerulonephritis associated with systemic vasculitis, and 12 with diabetic nephropathy. In addition, 33 healthy controls were examined. Fifteen patients with MGN were re-evaluated 12 months later, and the evolution of proteinuria was compared with changes in urinary VEGF excretion.
In healthy control subjects, urinary VEGF excretion was 68 +/- 10 (95% CI, 49 to 88) ng/mmol creatinine (UCr). In MGN, the excretion was decreased to 16 +/- 3 (CI, 10 to 23) ng/mmol crea (P < 0.0001, ANOVA), whereas in minimal change glomerulonephritis and diabetic nephropathy, it was unchanged [55 +/- 14 (CI, 24 to 86) and 101 +/- 25 (CI, 45 to 156) ng/mmol UCr, respectively, P = NS]. In vasculitis and FSGS patients, the excretion was higher than normal [184 +/- 68 (CI, 24 to 344), P = 0.01, and 160 +/- 29 (CI 95 to 226), P = 0.002 ng/mmol UCr, respectively]. The excretion did not correlate with serum VEGF, renal function, or proteinuria. In the follow-up of 15 patients, improving MGN (decreasing proteinuria) was associated with increasing VEGF excretion, while persistent disease (no change or increase of proteinuria) was associated with constantly low urinary VEGF excretion. The change in urinary protein excretion over one year correlated inversely with the change in urinary VEGF (r = -0.57, P = 0.026).
MGN is associated with decreased urinary VEGF compared with normal subjects, which is in contrast with other proteinuric diseases. Moreover, decreasing clinical activity (proteinuria) is accompanied by increasing VEGF excretion. Urinary VEGF may serve as an indicator of activity of MGN.
膜性肾小球肾炎（MGN）的临床病程原因不明，不可预测且高度多变。血管内皮生长因子（VEGF）可促进内皮细胞增殖、血管生成、微血管通透性及单核细胞趋化作用，并激活蛋白酶。在正常肾脏中，VEGF主要由肾小球足细胞表达，其生理功能及在肾脏疾病发生中的作用尚不清楚。本研究旨在评估MGN患者尿VEGF排泄情况，并与其他几种肾小球疾病进行比较，同时评估其与MGN临床活动度的关系。
采用夹心酶免疫分析法，对30例特发性MGN患者、8例微小病变性肾小球肾炎患者、10例局灶节段性肾小球硬化（FSGS）患者、8例与系统性血管炎相关的坏死性肾小球肾炎患者、12例糖尿病肾病患者在肾活检时的尿VEGF进行研究。此外，还检查了33名健康对照者。15例MGN患者在12个月后进行复查，比较蛋白尿的变化与尿VEGF排泄的变化。
健康对照者尿VEGF排泄量为68±10（95%可信区间，49至88）ng/mmol肌酐（UCr）。在MGN患者中，排泄量降至16±3（可信区间，10至23）ng/mmol肌酐（P<0.0001，方差分析），而在微小病变性肾小球肾炎和糖尿病肾病患者中，排泄量无变化[分别为55±14（可信区间，24至86）和101±25（可信区间，45至156）ng/mmol UCr，P=无显著性差异]。血管炎和FSGS患者的排泄量高于正常水平[分别为184±68（可信区间，24至344），P=0.01，和160±29（可信区间95至226），P=0.002 ng/mmol UCr]。排泄量与血清VEGF、肾功能或蛋白尿均无相关性。在15例患者的随访中，MGN病情改善（蛋白尿减少）与VEGF排泄增加相关，而病情持续（蛋白尿无变化或增加）与尿VEGF排泄持续降低相关。一年中尿蛋白排泄量的变化与尿VEGF的变化呈负相关（r=-0.57，P=0.026）。
与正常受试者相比，MGN患者尿VEGF排泄减少，这与其他蛋白尿性疾病不同。此外，临床活动度降低（蛋白尿减少）伴随着VEGF排泄增加。尿VEGF可作为MGN活动度的一个指标。
