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根据发表于11月26日美国肾脏学会期刊的观念验证研究结果，一种非侵犯式的尿蛋白分析，可以正确辨识肾脏移植失败的病患。
西班牙巴塞隆纳大学的Luis F. Quintana等人写道，尽管有适当的免疫抑制治疗，超过50%的肾脏移植因为慢性移植器官失能而失败，非侵犯方式可以诊断慢性移植器官失能，而更早介入，因而改善移植器官效用。
研究者使用质谱仪分析32名慢性移植器官失能病患与18名对照组的尿多肽类型。在这32名慢性移植器官失能(CAD)病患中，14人有单纯的肾间质纤维化（interstitial fibrosis）及肾小管萎缩（tubular atrophy），18人有慢性活性抗体媒介排斥；控制组包括8名稳定的移植病患与10名健康个案。
非教导型阶层分群法显示这四种临床状况之间有相对不错的样本区隔；再者，单纯的肾间质纤维化及肾小管萎缩之蛋白质体组成，与慢性活性抗体媒介排斥组不同。使用独立确认设定确认这些结果。
利用这两组之间可以最清楚区分的14种蛋白质离子，将可以正确分类单纯的肾间质纤维化及肾小管萎缩之100%的蛋白质，与慢性活性抗体媒介排斥之100%的蛋白质。
研究作者写道，本研究建立了一个模式，有两个组织病灶与显著不同的移植结果有关，迈向设计特定的、非侵犯的慢性移植器官失能诊断工具；在肾脏移植之后的各时间点并用协定移植物切片与蛋白质体分析，可以提供有关发生CAD机转的更准确资讯。此资讯将相当有助于及早诊断CAD以及进行治疗和预防，以免导致移植物失效。
主要的研究限制是样本数不够。
研究作者结论表示，需要包括更大与更多样移植族群的其他研究来确认我们的资料；若后续研究可再现这些模式，将表示个别蛋白质之辨识迈出一大步，将这个复杂的过程转为临床生化检查。
Fondo de Investigaciones Sanitarias与巴塞隆纳Hospital Clinic之Emili Letang Fellowship奖金资助本研究。作者宣称没有相关资金上的往来。
J Am Soc Nephrol. 线上出版于2008年11月26日。
Urine Proteins May Identify Failure of Kidney Transplantation
By Laurie Barclay, MD
Medscape Medical News
A noninvasive test that analyzes proteins in the urine can correctly identify patients whose transplanted kidneys are failing, according to the results of a proof-of-concept study reported in the November 26 issue of the Journal of the American Society of Nephrology.
"Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction," write Luis F. Quintana, from the University of Barcelona in Spain, and colleagues. "A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life."
The investigators used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction and in 18 control subjects. Of the 32 patients with chronic allograft dysfunction (CAD), 14 had pure interstitial fibrosis and tubular atrophy, and 18 had chronic active antibody-mediated rejection. The control subjects consisted of 8 stable transplant recipients and 10 healthy subjects.
Unsupervised hierarchical clustering demonstrated good segregation of samples in groups that corresponded relatively well to these 4 clinical conditions. Furthermore, the composition of the proteome in the group with pure interstitial fibrosis and tubular atrophy differed from that of the chronic active antibody-mediated rejection group. These results were confirmed in an independent validation set.
Using the 14 protein ions that best discriminated between these 2 groups allowed correct classification of 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection.
"This study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction," the study authors write. "The combination of protocol graft biopsies with simultaneous proteomic analyses at different times after renal transplantation could provide more accurate information on the exact mechanisms involved in the development of CAD. This information could be very helpful not only for an early diagnosis of CAD but also in the treatment and prevention of the leading cause of graft loss."
The main study limitation was small sample size.
"Additional studies including a larger and more diverse transplant recipient population are required to confirm our data," the study authors conclude. "Reproduction of these patterns in future studies would represent a step forward in identifying each protein and in translating this relatively intricate procedure into a biochemical test of clinical utility."
The Fondo de Investigaciones Sanitarias and an Emili Letang Fellowship award from Hospital Clinic in Barcelona supported this study. The authors have disclosed no relevant financial relationships.
J Am Soc Nephrol. Published online November 26, 2008.