Keil M, Pec M K, Schenn G, Grünberger T, Kramer G, Függer R, Steininger R, Mühlbacher F, Balcke P, Stockenhuber F
Department of Nephrology, University of Vienna, Ludwig-Boltzmann Institute of Nephrology, Austria.
Nephrol Dial Transplant. 1994;9(7):815-9.
Up to the present the histological diagnosis of rejection through biopsy is still the only possibility for a definite rejection diagnosis. We searched for a reliable non-invasive marker of renal graft rejection. By means of a highly sensitive enzyme-linked immunosorbent assay we investigated the changes in the concentration of serum soluble TNF receptor in kidney graft recipients with different clinical courses according to their graft tolerance. sTNF-R in 19 patients with stable graft function (5.3 +/- 3.2 ng/ml) did not differ significantly from those detected in 22 healty volunteers (4.1 +/- 2.2 ng/ml). In contrast 17 patients suffering from acute graft rejection showed highly significantly increases (23 +/- 8.3 ng/ml, P < 0.0001). These elevated concentrations returned to prerejection rejection values after a 3-day anti-rejection therapy with high-dose methylprednisolone. In 18 patients with an irreversible, chronic kidney graft rejection we could demonstrate significantly increased sTNF-R values (20 +/- 7.9 ng/ml); eight of those patients did not reflect on the anti-rejection therapy, so that the elevated concentrations remained even after the administration of high-dose corticosteroids and ATG. Additionally we found soluble TNF receptor concentrations to be increased earlier than other commonly used biochemical parameters such as creatinine. Soluble TNF-R also proved to be useful for the differentiation of cyclosporin nephrotoxicity. Therefore we believe that the soluble TNF-R and its concentration course may be of diagnostic and prognostic value in kidney graft rejection, as it supports the diagnosis of transplant rejection, indicates the rejection event very early, and reflects the response to anti-rejection therapy.
直到目前，通过活检进行排斥反应的组织学诊断仍然是明确诊断排斥反应的唯一方法。我们寻找一种可靠的肾移植排斥反应非侵入性标志物。通过高灵敏度酶联免疫吸附测定法，我们根据移植耐受性，研究了不同临床病程的肾移植受者血清可溶性肿瘤坏死因子受体浓度的变化。19例移植肾功能稳定患者的可溶性肿瘤坏死因子受体（sTNF-R）浓度（5.3±3.2 ng/ml）与22名健康志愿者检测结果（4.1±2.2 ng/ml）相比，差异无统计学意义。相反，17例发生急性移植排斥反应的患者sTNF-R浓度显著升高（23±8.3 ng/ml，P<0.0001）。经大剂量甲泼尼龙进行3天抗排斥治疗后，这些升高的浓度恢复到排斥反应前的值。在18例发生不可逆慢性肾移植排斥反应的患者中，我们证实sTNF-R值显著升高（20±7.9 ng/ml）；其中8例患者对抗排斥治疗无反应，因此即使给予大剂量皮质类固醇和抗胸腺细胞球蛋白后，升高的浓度仍持续存在。此外，我们发现可溶性肿瘤坏死因子受体浓度比肌酐等其他常用生化参数更早升高。可溶性肿瘤坏死因子受体也被证明有助于区分环孢素肾毒性。因此，我们认为可溶性肿瘤坏死因子受体及其浓度变化过程在肾移植排斥反应中可能具有诊断和预后价值，因为它有助于支持移植排斥反应的诊断，能非常早期地提示排斥反应事件，并反映对抗排斥治疗的反应。
