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奥美沙坦和替莫卡普利对免疫球蛋白A肾病正常血压患者尿肝型脂肪酸结合蛋白水平的有益影响。

Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy.

作者信息

Nakamura Tsukasa, Inoue Teruo, Sugaya Takeshi, Kawagoe Yasuhiro, Suzuki Tsukasa, Ueda Yoshihiko, Koide Hikaru, Node Koichi

机构信息

Department of Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan.

出版信息

Am J Hypertens. 2007 Nov;20(11):1195-201. doi: 10.1016/j.amjhyper.2007.06.003.

Abstract

BACKGROUND

Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated.

METHODS

Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings.

RESULTS

Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05).

CONCLUSIONS

The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy.

摘要

背景

肝型脂肪酸结合蛋白(L-FABP)是肾小管间质损伤的临床生物标志物,在慢性肾脏病(CKD)进展中起重要作用,包括免疫球蛋白A(IgA)肾病。血管紧张素受体阻滞剂(ARB)与血管紧张素转换酶抑制剂(ACEI)联合治疗对CKD的影响尚未阐明。

方法

24例血压正常的IgA肾病患者被随机分配接受奥美沙坦10毫克/天、替莫卡普利2毫克/天或两种药物联合治疗。在治疗3个月前后测量尿L-FABP水平以及8-羟基脱氧鸟苷(8-OHdG)和蛋白质排泄量。还通过组织病理学结果评估慢性指数和活动指数。

结果

IgA肾病患者尿L-FABP和8-OHdG水平高于年龄和性别匹配的健康对照(分别为122.5±25.5对6.4±3.8微克/克肌酐,P<.001;以及22.6±4.4对4.8±1.4纳克/毫克肌酐,P<.01)。尿L-FABP水平与8-OHdG水平(基线时,P=.0001;3个月后,P=.008)及蛋白尿严重程度(基线时,P=.0015;3个月后,P=.0001)相关。与奥美沙坦单药治疗组(P<.05)和替莫卡普利单药治疗组(P<.05)相比,联合治疗组治疗3个月后尿L-FABP和8-OHdG水平、蛋白质排泄量及活动指数的降低百分比更大。

结论

数据表明,在血压正常的IgA肾病患者中,与使用ARB或ACEI单药治疗相比,ARB加ACEI联合治疗对肾损伤具有更大的有益作用。

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