Merhi Basma, Bayliss George, Gohh Reginald Y
Basma Merhi, George Bayliss, Department of Medicine, Division of Kidney Disease and Hypertension, Rhode Island Hospital, Brown University School of Medicine, Providence, RI 02903, United States.
World J Transplant. 2015 Dec 24;5(4):251-60. doi: 10.5500/wjt.v5.i4.251.
Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B mRNAs, FOXP3 mRNA, CXCL9/CXCL10 and miRNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.
尽管近几十年来引入了强效免疫抑制药物,但急性排斥反应仍占所有移植失败病例的12%,并且通常与晚期移植失败风险增加相关。目前急性排斥反应的检测依赖于频繁监测血清肌酐,随后进行诊断性肾活检。这种策略存在缺陷,因为血清肌酐的改变是晚期临床事件,而且往往已经发生了显著的不可逆组织学损伤。此外,活检是有创操作,本身存在固有风险。发现非侵入性尿液生物标志物以帮助诊断急性排斥反应一直是大量研究的主题。我们在此回顾关于尿液生物标志物的文献,重点关注特定标志物穿孔素和颗粒酶B mRNA、FOXP3 mRNA、CXCL9/CXCL10和微小RNA。这些及其他生物标志物尚未在临床环境中广泛应用,但我们对文献的回顾表明,生物标志物可能与活检结果相关,并提供排斥反应的重要早期指标,从而实现更快速的治疗和更好的移植存活率。