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目的:观察来氟米特联合中小剂量糖皮质激素治疗原发性难治性肾病综合征患者的临床效果及其对血白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)水平的影响。方法:选取43例原发性难治性肾病综合征患者,予以口服来氟米特加小剂量的糖皮质激素,来氟米特起始剂量为50mg.d-1顿服,服用3d后减量至20mg.d-1顿服,至少服药6个月;泼尼松的起始剂量为0.8mg.kg-1.d-1(最大剂量40mg.d-1)顿服,4~6周后逐步减量,总疗程为1年。20例健康成人作为正常对照组。观察治疗前后24h尿蛋白定量、血胆固醇、血肌酐、血清白蛋白水平;采用酶联免疫吸附试验(ELISA)检测治疗前和治疗6个月时IL-8、TNF-α、VEGF水平。结果:治疗6个月时24h尿蛋白定量、血胆固醇较治疗前显著下降(P<0.01);血清白蛋白水平较治疗前显著升高(P<0.01);血肌酐水平治疗前后无统计学意义(P>0.05);治疗6个月时IL-8、TNF-α、VEGF指标较治疗前显著降低(P<0.01);较正常对照组无显著差异(P>0.05)。Spearman相关分析显示,血VEGF水平与24h尿蛋白定量呈正相关(r=0.726,P=0.025)。结论:来氟米特联合中小剂量糖皮质激素能显著降低难治性肾病综合征患者的尿蛋白,升高血清白蛋白水平,并持续稳定肾功能;其机制可能是通过抑制炎症介质的释放下调VEGF水平,改善肾病中炎症和内皮细胞功能紊乱,阻止系膜病变继续进展。
Objective: To observe the clinical effect of leflunomide combined with small and medium dose glucocorticoid on patients with primary refractory nephrotic syndrome and its effect on serum interleukin-8 (IL-8), tumor necrosis factor-α (TNF- α), vascular endothelial growth factor (VEGF) levels. Methods: Forty-three patients with primary refractory nephrotic syndrome were enrolled. Patients received oral leflunomide plus a small dose of glucocorticoid. The initial dose of leflunomide was 50 mg.d-1 for Dayton, The dose of prednisone was 0.8mg.kg-1.d-1 (the maximum dose of 40mg.d-1) Dayton clothing, 4 to 6 weeks After gradual reduction, the total course of treatment for 1 year. Twenty healthy adults served as normal control group. Urinary protein, blood cholesterol, serum creatinine and serum albumin were observed 24h before and after treatment. The levels of IL-8, TNF-α and VEGF were measured before and 6 months after treatment by enzyme-linked immunosorbent assay (ELISA). Results: After 6 months of treatment, urinary protein excretion and serum cholesterol were significantly decreased (P <0.01), serum albumin level was significantly higher than before treatment (P <0.01), serum creatinine level was not statistically significant (P> 0.05). The indexes of IL-8, TNF-α and VEGF at 6 months after treatment were significantly lower than those before treatment (P <0.01), no significant difference compared with the normal control group (P> 0.05). Spearman correlation analysis showed that the level of serum VEGF was positively correlated with the urinary protein excretion in 24h (r = 0.726, P = 0.025). Conclusion: Leflunomide combined with small and medium dose glucocorticoids can significantly reduce urinary protein in patients with refractory nephrotic syndrome, increase serum albumin levels and continue to stabilize renal function; its mechanism may be through inhibition of the release of inflammatory mediators VEGF levels, improve inflammation and endothelial cell dysfunction in renal disease, to prevent the continued progress of mesangial lesions.