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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进展性IgA肾病患者的临床效果及其对尿血管细胞黏附分子(VCAM)-1水平的影响。方法符合条件的3个月内接受肾脏活组织检查、蛋白尿>1.0g/d、Lee氏Ⅱ～Ⅳ级的IgA肾病患者随机入组来氟米特+糖皮质激素治疗组(LEF组)和糖皮质激素治疗组(激素组)。LEF组予口服来氟米特联合泼尼松治疗,来氟米特的起始剂量为40mg/d顿服,3d后减量至20mg/d顿服;泼尼松的起始剂量为0.8mg.kg-1.d-1(最大剂量40mg/d)顿服,4～6周后逐步减量,总疗程为1年。激素组予口服泼尼松治疗,起始剂量为1mg.kg-1.d-1(最大剂量60mg/d)顿服,8～12周后逐步减量。采用酶联免疫吸附试验(ELISA)检测治疗前和治疗6个月时尿VCAM-1水平。结果共36例患者入选,LEF组和激素组各18例。LEF组治疗6个月时的尿VCAM-1水平中位数为23.5ng/L(6.1～332.3ng/L),24h尿蛋白中位数为1.1g(0.3～2.0g),显著低于治疗前的44.9ng/L(14.1～560.4ng/L,P=0.017)和2.4g(1.4～4.0g,P<0.01),血清肌酐的差异无统计学意义(P>0.05)。激素组治疗6个月时的尿VCAM-1水平中位数为10.8ng/L(3.8～78.4ng/L),虽低于治疗前的22.6ng/L(4.5～632.9ng/L),但差异无统计学意义(P=0.068),治疗6个月时的24h尿蛋白中位数为0.4g(0.1～1.1g),显著低于治疗前的2.6g(1.7～3.1g,P=0.001),血清肌酐的差异无统计学意义(P>0.05)。Spearman相关分析结果显示,尿VCAM-1水平与血清肌酐值相关(r=0.236,P=0.046)。结论来氟米特联合中小剂量糖皮质激素治疗进展性IgA肾病的临床效果与大剂量激素治疗相仿,抑制VCAM-1的表达可能是其治疗机制之一。
Objective To observe the clinical effect of leflunomide combined with small and medium dose glucocorticoid on patients with progressive IgA nephropathy and its effect on the level of vascular cell adhesion molecule (VCAM) -1. Methods Patients with IgA nephropathy who received renal biopsy and proteinuria> 1.0g / d within 3 months were eligible for leflunomide + glucocorticoid therapy (LEF group) and Glucocorticoid treatment group (hormone group). LEF group was treated with oral leflunomide combined with prednisone, leflunomide starting dose of 40mg / d Dayton clothes, 3d reduced to 20mg / d Dayton clothing; prednisone starting dose of 0.8mg .kg-1.d-1 (the maximum dose of 40mg / d Dayton clothing, 4 to 6 weeks after gradual reduction, the total course of treatment of 1 year. The hormone group was treated with oral prednisone, the initial dose of 1mg.kg-1.d-1 (maximum dose of 60mg / d) Dayton clothing, gradually reduced after 8 to 12 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to detect urinary VCAM-1 levels before and 6 months of treatment. Results A total of 36 patients were enrolled, 18 in each of the LEF group and the hormone group. The urinary VCAM-1 level at 6 months after treatment in LEF group was 23.5ng / L (6.1-332.3ng / L), and the median of 24-hour urinary protein was 1.1g (0.3-2.0g), which was significantly lower than that of treatment There were no significant differences in serum creatinine before treatment (44.9ng / L, 14.1 ~ 560.4ng / L, P = 0.017) and 2.4g (1.4 ~ 4.0g, P <0.01). The urinary VCAM-1 level in the hormone group at 6 months was 10.8 ng / L (3.8-78.4 ng / L), which was lower than that of 22.6 ng / L (4.5-632.9 ng / L) before treatment The difference was not statistically significant (P = 0.068). The median urinary protein in 24 hours after treatment was 0.4g (0.1-1.1g) at 6 months, which was significantly lower than 2.6g before treatment (1.7-3.1g, P = 0.001 ), Serum creatinine difference was not statistically significant (P> 0.05). Spearman correlation analysis showed that the level of urinary VCAM-1 was correlated with serum creatinine (r = 0.236, P = 0.046). Conclusion The clinical effect of leflunomide combined with small and medium dose glucocorticoid on progressive IgA nephropathy is similar to that of high dose hormone therapy. Suppression of VCAM-1 expression may be one of its therapeutic mechanisms.