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氯沙坦对肾移植受者心血管风险和移植物损伤生物标志物的短期影响。

Short-term Effects of Losartan on Cardiovascular Risk and Allograft Injury Biomarkers in Kidney Transplant Recipients.

机构信息

Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland.

Department of Transplantology and Surgery, District Public Hospital, Poznań, Poland.

出版信息

Transplant Proc. 2022 May;54(4):981-988. doi: 10.1016/j.transproceed.2022.02.012. Epub 2022 Mar 26.

Abstract

BACKGROUND

There is a controversy over the renoprotective and cardioprotective effects of renin-angiotensin-aldosterone system blockade in kidney transplant recipients (KTRs). The aim of the study was to evaluate the short-term effects of losartan on allograft injury, cardiovascular risk biomarkers and safety of the treatment in KTRs.

METHODS

An interim analysis of a prospective, open, multicenter, controlled clinical trial CELART (Cardiovascular Effects of Losartan After Renal Transplantation) was performed. KTRs were allocated to losartan (L) 50 to 100 mg or standard hypotensive treatment (ST) group to reach target blood pressure (BP) <140/90 mm Hg. The short-term effects of the therapy were evaluated after 6 months: estimated glomerular filtration rate (eGFR), albuminuria, the intrarenal fibrosis biomarkers: urine excretion of transforming growth factor β-1 (TGFβ-1) and procollagen type III amino terminal propeptide (PIIINP), cardiac biomarker: serum concentration of N-terminal-pro-B-type natriuretic peptide (NT-proBNP), 24-hour ambulatory BP measurement, and hemoglobin and potassium concentrations.

RESULTS

At baseline the groups did not differ with respect to age, primary nephropathy, comorbidity, immunosuppressive therapy, albuminuria, and graft function. A total of 61 (L group) and 73 (ST group) patients reached the target BP and completed protocol at 6 months. After 6 months of therapy there were no significant differences in changes of eGFR, albuminuria, hemoglobin and potassium concentrations, urine excretion of PIIINP, and TGFβ-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP.

CONCLUSIONS

Losartan shows minimal adverse effects and no influence on graft function and biomarkers of graft fibrosis. It may have a positive effect on cardiovascular risk in KTRs. Further interim analyses of the CELART study will be conducted.

摘要

背景

肾素-血管紧张素-醛固酮系统阻滞剂在肾移植受者(KTR)中的肾脏保护和心脏保护作用存在争议。本研究旨在评估氯沙坦对同种异体移植物损伤、心血管风险生物标志物的短期影响以及治疗的安全性。

方法

对一项前瞻性、开放、多中心、对照临床试验 CELART(肾移植后氯沙坦对心血管的影响)进行了中期分析。将 KTR 随机分配至氯沙坦(L)组 50-100mg 或标准降压治疗(ST)组以达到目标血压(BP)<140/90mmHg。治疗 6 个月后评估短期疗效:估算肾小球滤过率(eGFR)、蛋白尿、肾内纤维化生物标志物:转化生长因子β-1(TGFβ-1)和 III 型前胶原氨基末端肽(PIIINP)的尿排泄量、心脏生物标志物:血清 N-末端-pro-B 型利钠肽(NT-proBNP)浓度、24 小时动态血压测量以及血红蛋白和钾浓度。

结果

基线时,两组在年龄、原发性肾病、合并症、免疫抑制治疗、蛋白尿和移植物功能方面无差异。共有 61 名(L 组)和 73 名(ST 组)患者达到目标血压并在 6 个月时完成方案。治疗 6 个月后,两组间 eGFR、蛋白尿、血红蛋白和钾浓度、PIIINP 和 TGFβ-1 的尿排泄量均无显著差异。L 组血清 NT-proBNP 浓度有下降趋势。

结论

氯沙坦显示出最小的不良反应,对移植物功能和移植物纤维化生物标志物无影响。它可能对 KTR 的心血管风险有积极影响。CELART 研究的进一步中期分析将进行。

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