尿蛋白可能代表腎臟移植失敗


  November 26, 2008 — 根據發表於11月26日美國腎臟學會期刊的觀念驗證研究結果,一種非侵犯式的尿蛋白分析,可以正確辨識腎臟移植失敗的病患。
  
  西班牙巴塞隆納大學的Luis F. Quintana等人寫道,儘管有適當的免疫抑制治療,超過50%的腎臟移植因為慢性移植器官失能而失敗,非侵犯方式可以診斷慢性移植器官失能,而更早介入,因而改善移植器官效用。
  
  研究者使用質譜儀分析32名慢性移植器官失能病患與18名對照組的尿多肽類型。在這32名慢性移植器官失能(CAD)病患中,14人有單純的腎間質纖維化(interstitial fibrosis)及腎小管萎縮(tubular atrophy),18人有慢性活性抗體媒介排斥;控制組包括8名穩定的移植病患與10名健康個案。
  
  非教導型階層分群法顯示這四種臨床狀況之間有相對不錯的樣本區隔;再者,單純的腎間質纖維化及腎小管萎縮之蛋白質體組成,與慢性活性抗體媒介排斥組不同。使用獨立確認設定確認這些結果。
  
  利用這兩組之間可以最清楚區分的14種蛋白質離子,將可以正確分類單純的腎間質纖維化及腎小管萎縮之100%的蛋白質,與慢性活性抗體媒介排斥之100%的蛋白質。
  
  研究作者寫道,本研究建立了一個模式,有兩個組織病灶與顯著不同的移植結果有關,邁向設計特定的、非侵犯的慢性移植器官失能診斷工具;在腎臟移植之後的各時間點併用協定移植物切片與蛋白質體分析,可以提供有關發生CAD機轉的更準確資訊。此資訊將相當有助於及早診斷CAD以及進行治療和預防,以免導致移植物失效。
  
  主要的研究限制是樣本數不夠。
  
  研究作者結論表示,需要包括更大與更多樣移植族群的其他研究來確認我們的資料;若後續研究可再現這些模式,將表示個別蛋白質之辨識邁出一大步,將這個複雜的過程轉為臨床生化檢查。
  
  Fondo de Investigaciones Sanitarias與巴塞隆納Hospital Clinic之Emili Letang Fellowship獎金資助本研究。作者宣稱沒有相關資金上的往來。
  
  J Am Soc Nephrol. 線上出版於2008年11月26日。

Urine Proteins May Identify Failure of Kidney Transplantation

By Laurie Barclay, MD
Medscape Medical News

November 26, 2008 — 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.

    
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