Nakamura Tsukasa, Inoue Teruo, Sugaya Takeshi, Kawagoe Yasuhiro, Suzuki Tsukasa, Ueda Yoshihiko, Koide Hikaru, Node Koichi
Department of Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan.
Am J Hypertens. 2007 Nov;20(11):1195-201. doi: 10.1016/j.amjhyper.2007.06.003.
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.
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.
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).
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.
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。
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。
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。
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。
