抗氧化剂（Probucol）联合缬沙坦治疗IgA肾病的临床研究

发布时间：2019-01-06 04:53

【摘要】：研究背景和目的以往研究显示血管紧张素受体拮抗剂(ARB)和抗氧化治疗均能减少IgA肾病患者的蛋白尿排泄率,延缓疾病进展。本研究拟通过多中心、随机、开放标签、平行对照研究,探讨联合应用抗氧化剂普罗布考(Probucol)和血管紧张素受体拮抗剂缬沙坦对高危IgA肾病患者疾病进展的影响。探讨联合应用2种药物对IgA肾病患者24小时蛋白尿的影响及用药安全性。方法本研究在5个中心75例经肾活检确诊IgA肾病而且24小时尿蛋白)1.0g/24小时的患者进入筛选,经筛选后69例入组,随机进入治疗组(Probucol750mg/d+缬沙坦160mg/d)或对照组(缬沙坦160mg/d)；其中1人退出研究,测定患者的血、尿的氧化应激指标,收集患者的临床病理资料并随访3年。统计分析方法：利用SPSS18.0软件进行统计学分析,数据均采用均数±标准差(x±s)来描述。治疗组与对照组基线情况采用独立样本t检验进行分析；采用配对t检验比较后续治疗时期与基线时期的相关指标的差异,根据比较次数校正检验水准,P0.007被定义为有统计学差异。治疗组和对照组随访基线主要观察终点和次要观察终点的比较采用重复测量的方差分析。P0.05被定义为有统计学差异。结果共68例患者完成研究,其中治疗组33人,对照组35人。入组时两组患者的基础血压、血肌酐水平、24小时蛋白尿排泄水平、肝功能、血钾、血胆固醇及诊断时体内的氧化应激指标及抗氧化指标水平(血、尿丙二醛,超氧化物歧化酶SOD,总抗氧化能力T-AOC)均相当(P0.05),基线病理评分没有统计学差异。治疗组和对照两组分别有23和20例患者达到主要观察终点。其中治疗组患者24小时尿蛋白下降50%所需时间较对照组短。两组的中位终点时间分别为8.13和19.63个月(χ2=5.476,P=-0.019)。两组患者第一年24小时蛋白尿排泄率明显降低,分别从基线的1391.21±534.91mg/24h和1466.54±638.81mg/24h降至1010.04±421.20mg/24h和1048.39±639.55mg/24h(与基线比较F=11.74,P0.001)。随访2年时,治疗组24小时尿蛋白排泄率定量为968.98±338.98mg/24h(与基线比较F=11.74,P0.001)。而对照组24小时尿蛋白排泄率为1237.13±720.41mg/24h(与基线比较F=4.411,P=0.009)。但随访3年后治疗组和对照两组24小时蛋白尿排泄率分别为1365.68±395.31mg/24h和1357.20±427.19mg//24h(与基线比较F=1.101,P=-0.298)。治疗组和对照组eGFR分别从基线的54.83±13.11ml/min和57.75±10.36ml/min升高至56.70±9.92和58.61±8.47ml/min(F=0.225,P=0.862)。随访1年时,治疗组血清胆固醇水平显著比对照组低,分别为4.37±0.94mmol/L和4.87±0.80mmol/L(t=02.376,p=0.020)。随访3年过程中均未见AST和ALT升高。没有一例患者进入终末期肾病。结论probucol联合缬沙坦治疗高危的IgA肾病患者安全,能在短期内更快降低24小时尿蛋白水平,但经长期随访(3年)并不能持续降低这类患者24小时尿蛋白排泄率,但患者肾功能保持稳定。这一疗法能否改善高危IgA肾病的远期预后还有待于进一步的观察。
[Abstract]:Background and objective previous studies have shown that both angiotensin receptor antagonist (ARB) and antioxidant therapy can reduce proteinuria excretion rate in patients with IgA nephropathy and delay the progression of the disease. The purpose of this study was to investigate the effects of combination of antioxidant probucol (Probucol) and angiotensin receptor antagonist valsartan on the progression of high risk IgA nephropathy patients in a multicenter, randomized, open label, parallel controlled study. To investigate the effect of combined use of two drugs on 24-hour proteinuria in patients with IgA nephropathy and its safety. Methods in this study, 75 patients with IgA nephropathy diagnosed by renal biopsy and 24 hours urine protein) 1.0g/24 hour were selected in 5 centers, and 69 patients were enrolled after screening. Probucol750mg/d valsartan 160mg/d or control group (valsartan 160mg/d) were randomly assigned to the treatment group. One of them withdrew from the study to measure the oxidative stress index of blood and urine, collect the clinicopathological data of the patient and follow up for 3 years. Statistical analysis method: the data were all described by mean 卤standard deviation (x 卤s) using SPSS18.0 software. The baseline data of the treatment group and the control group were analyzed by independent sample t-test. A paired t test was used to compare the relative indexes between the follow-up treatment period and the baseline period, and P0.007 was defined as having statistical difference according to the comparison times calibration test level. The treatment group and the control group follow up the baseline main observation end point and the secondary observation end point comparison uses the repeated measurement variance analysis. P0.05 is defined as having the statistical difference. Results A total of 68 patients completed the study, including 33 patients in the treatment group and 35 in the control group. The basic blood pressure, serum creatinine level, 24 hour proteinuria excretion level, liver function, blood potassium, blood cholesterol, oxidative stress index and antioxidant index (blood, urine malondialdehyde) in the two groups at the time of entering the group. The total antioxidant capacity of superoxide dismutase (SOD,) T-AOC was equal (P0.05), and there was no statistical difference in baseline pathological score. In the treatment group and the control group, 23 and 20 patients reached the main observation end point, respectively. In the treatment group, the time required to reduce urinary protein by 50% in 24 hours was shorter than that in the control group. The median end point time of the two groups was 8.13 and 19.63 months (蠂 ~ 2 = 5.476 ~ (-0.019). In the first year, the excretion rate of proteinuria decreased from 1391.21 卤534.91mg/24h and 1466.54 卤638.81mg/24h in the baseline to 1010.04 卤421.20mg/24h and 1048.39 卤639.55mg/24h in the first year, respectively. At 2 years follow-up, the 24 hour urinary protein excretion rate in the treatment group was 968.98 卤338.98mg/24h. The urinary protein excretion rate in the control group was 1237.13 卤720.41mg/24h (compared with baseline: 4.411P0. 009). However, after 3 years follow-up, the 24-hour proteinuria excretion rates of the treatment group and the control group were 1365.68 卤395.31mg/24h and 1357.20 卤427.19mg//24h, respectively. The eGFR of the treatment group and the control group increased from 54.83 卤13.11ml/min and 57.75 卤10.36ml/min to 56.70 卤9.92 and 58.61 卤8.47ml/min, respectively. The serum cholesterol levels in the treatment group were significantly lower than those in the control group (4.37 卤0.94mmol/L and 4.87 卤0.80mmol/L, respectively). No increase in AST and ALT was observed during the 3-year follow-up. None of the patients went into end-stage nephropathy. Conclusion probucol combined with valsartan in the treatment of high risk IgA nephropathy patients is safe and can decrease the urinary protein level of 24 hours more quickly in the short term, but it can not continuously decrease the 24 hour urinary protein excretion rate after long-term follow-up (3 years). But the patient's renal function remained stable. Whether this therapy can improve the long-term prognosis of high-risk IgA nephropathy remains to be further observed.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R692.3

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