氯沙坦可降低慢性移植肾肾病移植患者的血浆转化生长因子-β1水平。

Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy.

作者信息

Campistol J M, Iñigo P, Jimenez W, Lario S, Clesca P H, Oppenheimer F, Rivera F

机构信息

Renal Transplant Unit and Hormonal Laboratory, Hospital Clinic, Institut d'Investigació Biomediques August Pi i Sunyer, University of Barcelona, Spain.

出版信息

Kidney Int. 1999 Aug;56(2):714-9. doi: 10.1046/j.1523-1755.1999.00597.x.

DOI:10.1046/j.1523-1755.1999.00597.x

PMID:10432413

Abstract

BACKGROUND

Chronic allograft nephropathy represents the principal cause of graft loss after the first year of transplantation. Transforming growth factor-beta1 (TGF-beta1) is a key factor in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy and other chronic nephropathies. Experimental studies have demonstrated that the angiotensin II receptor antagonist (losartan) could decrease the synthesis of TGF-beta1. The aim of this study was to determine the plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy, and to evaluate the effect of losartan on TGF-beta1 plasma levels and other vasoactive peptides (angiotensin II, plasma renin activity, aldosterone, endothelin-1, and nitrites and nitrates). Angiotensin-converting enzyme genotypes were also determined in all patients.

METHODS

Fourteen transplant patients with chronic allograft nephropathy were included. Treatment with losartan (50 mg) was introduced. Consecutive determinations of TGF-beta1 and other vasoactive peptides were performed during follow-up.

RESULTS

Patients with chronic allograft nephropathy presented higher plasma levels of TGF-beta1 than the control groups. The treatment with losartan significantly decreased the plasma levels of TGF-beta1 (P < 0.05) and endothelin (P < 0.05) in all patients. The decrease of TGF-beta1 was statistically correlated with the blockade of the angiotensin II receptor (P < 0.05). No significant correlation could be demonstrated between angiotensin-converting enzyme genotypes and TGF-beta, endothelin-1, and nitrite-nitrate serum levels.

CONCLUSIONS

This study demonstrates that losartan significantly decreases the plasma levels of TGF-beta1, the most important fibrogenetic factor. These results could play a decisive role in the treatment and prevention of chronic nephropathies, not only graft nephropathy, because the intrinsic pathogenetic mechanism is very similar in all forms, with a crucial roles for the renal renin-angiotensin system and TGF-beta1.

摘要

背景

慢性移植肾肾病是移植术后第一年移植物丢失的主要原因。转化生长因子β1（TGF-β1）是纤维生成的关键因子，参与慢性移植肾肾病及其他慢性肾病的发病机制。实验研究表明，血管紧张素II受体拮抗剂（氯沙坦）可减少TGF-β1的合成。本研究旨在测定慢性移植肾肾病移植患者血浆TGF-β1水平，并评估氯沙坦对TGF-β1血浆水平及其他血管活性肽（血管紧张素II、血浆肾素活性、醛固酮、内皮素-1以及亚硝酸盐和硝酸盐）的影响。同时还测定了所有患者的血管紧张素转换酶基因型。

方法

纳入14例慢性移植肾肾病移植患者，给予氯沙坦（50mg）治疗。随访期间连续测定TGF-β1及其他血管活性肽。

结果

慢性移植肾肾病患者血浆TGF-β1水平高于对照组。氯沙坦治疗使所有患者血浆TGF-β1水平（P<0.05）和内皮素水平（P<0.05）显著降低。TGF-β1的降低与血管紧张素II受体阻断具有统计学相关性（P<0.05）。血管紧张素转换酶基因型与TGF-β、内皮素-1及亚硝酸盐-硝酸盐血清水平之间未显示出显著相关性。