氯沙坦对免疫抑制治疗耐药的原发性局灶节段性肾小球硬化患者的疗效。

Efficacy of losartan in patients with primary focal segmental glomerulosclerosis resistant to immunosuppressive treatment.

作者信息

Usta M, Ersoy A, Dilek K, Ozdemir B, Yavuz M, Güllülü M, Yurtkuran M

机构信息

Department of Nephrology, Uludağ University Medical School, Bursa, Turkey.

出版信息

J Intern Med. 2003 Mar;253(3):329-34. doi: 10.1046/j.1365-2796.2003.01071.x.

Abstract

OBJECTIVES

Angiotensin II may play an important role in the progression of renal disease. Currently, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are commonly used for renoprotection. To our knowledge, there is no study investigating this effect of angiotensin II receptor antagonists in patients with primary focal segmental glomerulosclerosis (FSGS) in the literature. The aim of this study was to evaluate the effects of losartan on proteinuria and renal function in patients with FSGS refractory to immunosuppressive treatment.

DESIGN

Twenty-three normotensive patients with FSGS proven through renal biopsy were included in the study. Thirteen of them, five men and eight women, were given losartan in a dose of 50 mg day(-1) during 12 months, and 10, four men and six women, were in the control group. Mean arterial blood pressure (MAP), 24-h urine protein excretion, serum total protein and albumin levels were determined just before the start of treatment as well as after 1, 6 and 12 months of the study. In addition, serum creatinine, creatinine clearance (CrCl), cholesterol and triglyceride levels were determined at the beginning and end of the study.

RESULTS

Age, gender and baseline levels of proteinuria, serum albumin, total protein, creatinine, CrCl and MAPs were similar in the two groups. Nephrotic range of proteinuria was present in five of 13 patients (38.4%) in the losartan group and in four of 10 patients (40%) in the control group. In the losartan group, 24-h proteinuria had decreased from 3.6 +/- 0.5 g to 2.3 +/- 0.5 g after 1 month, to 2.4 +/- 0.7 g after 6 months and to 1.9 +/- 0.7 g after 12 months. In the control group, a significant increase in proteinuria compared with the baseline value was noticed after 12 months. Proteinuria levels were significantly higher in the control group than in the losartan group after 6 and 12 months. Whilst total protein and albumin levels increased in the losartan group, they did not change significantly in the control group. The total protein levels after 6 and 12 months, and albumin levels after 6 months were significantly higher in the losartan group than in the control group. No significant change was observed between the baseline and the 12-month creatinine and CrCl levels of the groups when intra- and inter-group comparisons were made. Furthermore, serum cholesterol levels of the losartan group were reduced significantly. The changes in MAP values did not reach significant levels in either of the groups. There was no correlation between the percentage changes in MAP and in proteinuria of the losartan group after 12 months.

CONCLUSIONS

Angiotensin II receptor antagonists may be an alternative therapy in FSGS patients who are resistant to immunosuppressive therapy.

摘要

目的

血管紧张素II可能在肾脏疾病进展中起重要作用。目前,血管紧张素转换酶(ACE)抑制剂和血管紧张素II受体拮抗剂常用于肾脏保护。据我们所知,文献中尚无研究调查血管紧张素II受体拮抗剂对原发性局灶节段性肾小球硬化(FSGS)患者的这种作用。本研究的目的是评估氯沙坦对免疫抑制治疗无效的FSGS患者蛋白尿和肾功能的影响。

设计

本研究纳入了23例经肾活检证实的血压正常的FSGS患者。其中13例,5例男性和8例女性,在12个月期间给予50mg/日(-1)的氯沙坦,10例,4例男性和6例女性,作为对照组。在治疗开始前以及研究的1、6和12个月后测定平均动脉压(MAP)、24小时尿蛋白排泄量、血清总蛋白和白蛋白水平。此外,在研究开始和结束时测定血清肌酐、肌酐清除率(CrCl)、胆固醇和甘油三酯水平。

结果

两组患者的年龄、性别以及蛋白尿、血清白蛋白、总蛋白、肌酐、CrCl和MAP的基线水平相似。氯沙坦组13例患者中有5例(38.4%)出现肾病范围蛋白尿,对照组10例患者中有4例(40%)出现。氯沙坦组中,24小时蛋白尿在1个月后从3.6±0.5g降至2.3±0.5g,6个月后降至2.4±0.7g,12个月后降至1.9±0.7g。对照组中,12个月后与基线值相比蛋白尿显著增加。6个月和12个月后,对照组的蛋白尿水平显著高于氯沙坦组。氯沙坦组总蛋白和白蛋白水平升高,而对照组无显著变化。氯沙坦组6个月和12个月后的总蛋白水平以及6个月后的白蛋白水平显著高于对照组。组内和组间比较时,两组的基线和12个月时的肌酐和CrCl水平无显著变化。此外,氯沙坦组的血清胆固醇水平显著降低。两组的MAP值变化均未达到显著水平。12个月后氯沙坦组的MAP变化百分比与蛋白尿变化百分比之间无相关性。

结论

血管紧张素II受体拮抗剂可能是对免疫抑制治疗耐药的FSGS患者的一种替代治疗方法。

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