Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain.
Department of Clinical Biochemistry, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain.
Ann Transplant. 2021 Mar 9;26:e929491. doi: 10.12659/AOT.929491.
BACKGROUND Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-g-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. MATERIAL AND METHODS A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. RESULTS Banff scores 't', 'i', 'g', and 'ptc' were significantly related to urinary CXCL10 levels. Multivariate analysis showed that 't' (ß=0.107, P=0.001) and 'ptc' (ß=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799-11.646, P=0.001) after multivariate regression analysis. CONCLUSIONS DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.
需要非侵入性的移植物排斥生物标志物来优化肾移植受者的管理和结局。IFN-γ相关趋化因子 CXCL10 的尿排泄与临床和亚临床 T 细胞介导的移植物炎症明显相关，但与抗体介导的损伤的关系尚未完全阐明。此外，影响尿 CXCL10 排泄水平的变量尚不清楚。
前瞻性分析了 151 例肾移植活检（92 例监测活检和 59 例指征活检）和 151 例活检前匹配的尿液样本。根据 2017 年 Banff 分类标准定义 T 细胞介导的排斥反应（TCMR）和抗体介导的排斥反应（AbMR）。通过 ELISA 测量尿 CXCL10 水平，并通过尿肌酐校正。
Banff 评分“t”、“i”、“g”和“ptc”与尿 CXCL10 水平显著相关。多变量分析显示“t”（β=0.107，P=0.001）和“ptc”（β=0.093，P=0.002）与尿 CXCL10 显著相关。供体特异性抗体（DSA）与移植后 1 年尿 CXCL10 的高排泄有关（优势比[OR]17.817，P=0.003）。尿 CXCL10 对 AbMR 具有良好的鉴别能力（AUC-ROC 0.760，P=0.001）。多变量回归分析后，尿 CXCL10 的第三 tertile 仍与 AbMR 显著相关（OR 4.577，95%置信区间 1.799-11.646，P=0.001）。
DSA 是唯一与高尿 CXCL10 水平明显相关的变量。尿 CXCL10 是 AbMR 和 TCMR 的良好非侵入性候选生物标志物，提供了与肾功能和其他通常用于监测肾移植的变量无关的信息。
