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HIV 感染患者的微量白蛋白尿和高血压:替米沙坦的初步研究。

Microalbuminuria and hypertension in HIV-infected patients: a preliminary study of telmisartan.

机构信息

Infectious Diseases Clinic, "G. d'Annunzio" University, School of Medicine, Chieti, Italy.

出版信息

Eur Rev Med Pharmacol Sci. 2012 Apr;16(4):491-8.

Abstract

BACKGROUND

There is increasing evidence of hypertension and microalbuminuria in HIV-infected patients, and these are two important risk factors for renal and cardiovascular disease. Anti-hypertensive drugs inhibiting the renin-angiotensin system exert an antiproteinuric effect. Telmisartan, an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist that is approved for the treatment of hypertension, appears to exert a nephroprotective effect independent of blood pressure reduction in the general population.

OBJECTIVE

The aim of this preliminary study was to evaluate possible nephroprotective effects of telmisartan in hypertensive HIV-positive patients with microalbuminuria.

PATIENTS AND METHODS

Caucasian male patients with HIV infection (n=13) receiving stable combined antiretroviral therapy (without therapeutic changes for > 12 months) and a recent diagnosis of grade 1 hypertension were treated with daily oral telmisartan 80 mg for 6 months. Patients had suppressed viremia and a CD4 cell count > 300 cells/mL for 6 months, and microalbuminuria > 5 mg/dL. Systolic and diastolic blood pressure (SBP, DBP), triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), microalbuminuria, Modification of Diet Renal Disease-Glomerular Filtration Rate (MDRD-GFR), vascular endothelial growth factor (VEGF) and endothelin-1 were measured at baseline and at one, three and six months. All statistical analyses were performed using SAS 9.2.

RESULTS

A significant reduction of microalbuminuria (p < 0.001) with stable MDRD-GFR was observed, although the main indices of renal function showed no substantial change. A significant reduction in mean SBP and DBP was observed at T1 and confirmed at T3 and T6 (SBP p < 0.001 and DBP p < 0.001), and there was BP normalization. Metabolic assessments showed an improvement in lipid parameters, and a significant decrease in insulin resistance assessed by the homeostasis model assessment index-insulin resistance (HOMA-IR) (p = 0.04). In addition, there was a statistically significant reduction in ESR (p = 0.02) and a non significant reduction in CRP. Other results included a significant reduction in serum VEGF and endothelin-1 levels (p < 0.001).

CONCLUSIONS

From these preliminary findings, telmisartan has demonstrated efficacy in the control of hypertension and microalbuminuria in HIV-infected patients. Decreased microalbuminuria with stable MDRD-GFR may be indicative of a nephroprotective effect of telmisartan; mechanisms causing microalbuminuria in patients with HIV could be related to infection, chronic inflammation, and endothelial dysfunction. The decreased endothelin-1 and VEGF levels in patients in this study may be related to an endothelial protective effect of telmisartan. This study reports the first observation of renal and endothelial protective effects of telmisartan in HIV-positive patients.

摘要

背景

越来越多的证据表明,HIV 感染者中存在高血压和微量白蛋白尿,这两个因素都是肾脏和心血管疾病的重要危险因素。抑制肾素-血管紧张素系统的抗高血压药物具有降低蛋白尿的作用。替米沙坦是一种血管紧张素 II 受体阻滞剂和过氧化物酶体增殖物激活受体 γ(PPARγ)的部分激动剂,已被批准用于治疗高血压,它似乎在一般人群中具有独立于降压作用的肾脏保护作用。

目的

本初步研究旨在评估替米沙坦对合并微量白蛋白尿的 HIV 阳性高血压患者可能具有的肾脏保护作用。

患者和方法

13 名接受稳定联合抗逆转录病毒治疗(>12 个月无治疗性改变)且近期诊断为 1 级高血压的白人男性 HIV 感染者,每天口服替米沙坦 80mg 治疗 6 个月。患者具有抑制性病毒血症和 CD4 细胞计数>300 个细胞/mL,且微量白蛋白尿>5mg/dL。在基线和 1、3、6 个月时测量收缩压(SBP)、舒张压(DBP)、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、C 反应蛋白(CRP)、红细胞沉降率(ESR)、微量白蛋白尿、改良肾脏病饮食肾小球滤过率(MDRD-GFR)、血管内皮生长因子(VEGF)和内皮素-1。所有统计分析均使用 SAS 9.2 进行。

结果

观察到微量白蛋白尿显著降低(p<0.001),同时 MDRD-GFR 稳定,尽管主要肾功能指标没有明显变化。T1 时 SBP 和 DBP 显著降低(p<0.001 和 p<0.001),并在 T3 和 T6 时得到确认,且血压正常化。代谢评估显示血脂参数得到改善,胰岛素抵抗评估的稳态模型评估指数-胰岛素抵抗(HOMA-IR)显著降低(p=0.04)。此外,ESR 显著降低(p=0.02),CRP 虽无统计学意义,但也有所降低。其他结果包括 VEGF 和内皮素-1 水平显著降低(p<0.001)。

结论

从这些初步发现来看,替米沙坦在控制 HIV 感染者的高血压和微量白蛋白尿方面具有疗效。MDRD-GFR 稳定的微量白蛋白尿降低可能提示替米沙坦具有肾脏保护作用;HIV 患者微量白蛋白尿的发生机制可能与感染、慢性炎症和内皮功能障碍有关。本研究中患者的内皮素-1 和 VEGF 水平降低可能与替米沙坦的内皮保护作用有关。本研究首次报道了替米沙坦在 HIV 阳性患者中的肾脏和内皮保护作用。

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