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终末期肾衰竭及肾移植后的天然血清肿瘤坏死因子拮抗剂

Natural serum TNF antagonists in end-stage renal failure and following renal transplantation.

作者信息

Lambert C, Berthoux P, Vindimian M, Hacini J, Berthoux F

机构信息

Nephrology, Dialysis and Transplantation Department, Hopital Nord, CHRU, St Etienne, France.

出版信息

Nephrol Dial Transplant. 1994;9(12):1791-6.

PMID:7708266
Abstract

TNF is clearly involved in allograft rejection but measurement of serum cytokine levels do not reflect reliably the rejection crisis. TNF induces release of soluble receptor parts that are more stable, are catabolized by kidneys and have inhibitory activity. Thus it is crucial to analyse their kinetics during renal function recovery after transplantation to forecast their potential clinical use in rejection monitoring or treatment. A sequential study was performed in 61 patients undergoing kidney graft, compared to 60 graft patients with long follow-up and 15 healthy controls. Soluble TNF and Il2 receptors were measured by ELISA and TNF was measured by RIA. The sTNF-Rs were markedly increased in renal failure, much more than another soluble cytokine receptor, the sIl2-R. Levels progressively decreased with the recovery of renal function and became directly correlated to the renal function. Normal levels were only reached after some weeks. No significant changes were observed during graft rejection at that stage of renal function but p75 were higher after antilympocyte antiserum and tubular necrosis. High sTNF-R did not seem to minimize rejection risk or gravity. In long-standing recipients, sTNF-R rose in some patients, particularly with glomerulonephritis, and may help in monitoring chronic rejection activity. sTNF-R but not sIl2-R markedly accumulate in ESRF and mask any changes that could be helpful in the monitoring of early graft events. However, increased levels above renal impairment (sTNF-R/SCr) may be clinically relevant in late rejection or glomerulonephritides.

摘要

肿瘤坏死因子(TNF)显然参与同种异体移植排斥反应,但血清细胞因子水平的检测并不能可靠地反映排斥危机。TNF诱导更稳定的可溶性受体部分的释放,这些受体部分由肾脏分解代谢并具有抑制活性。因此,在移植后肾功能恢复期间分析它们的动力学对于预测它们在排斥反应监测或治疗中的潜在临床应用至关重要。对61例接受肾移植的患者进行了一项序贯研究,并与60例长期随访的移植患者和15名健康对照进行了比较。通过酶联免疫吸附测定法(ELISA)检测可溶性TNF和白细胞介素2(Il2)受体,通过放射免疫分析法(RIA)检测TNF。可溶性TNF受体(sTNF-Rs)在肾衰竭时显著升高,比另一种可溶性细胞因子受体可溶性白细胞介素2受体(sIl2-R)升高得多。随着肾功能的恢复,其水平逐渐下降,并与肾功能直接相关。仅在数周后才达到正常水平。在该肾功能阶段的移植排斥反应期间未观察到显著变化,但在抗淋巴细胞抗血清和肾小管坏死之后p75更高。高sTNF-R似乎并未使排斥风险或严重程度降至最低。在长期接受者中,一些患者的sTNF-R升高,尤其是患有肾小球肾炎的患者,其可能有助于监测慢性排斥反应活动。sTNF-R而非sIl2-R在终末期肾衰竭(ESRF)中显著蓄积,并掩盖了可能有助于监测早期移植事件的任何变化。然而,高于肾功能损害水平(sTNF-R/血清肌酐)的升高水平在晚期排斥反应或肾小球肾炎中可能具有临床意义。

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