Souza Alvaro Assis de, Hesselink Dennis A, Maas Carolien C H M, Stubbs Andrew P, Clahsen-van Groningen Marian, Baan Carla C, Klaveren David van, Boer Karin
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
Clin Transplant. 2025 Sep;39(9):e70299. doi: 10.1111/ctr.70299.
Chemokine levels may predict kidney graft rejection. This study evaluated whether adding early plasma chemokines C-X-C motif ligand 9 (CXCL9) or chemokines C-X-C motif ligand 10 (CXCL10) measurements to a standard-of-care model improves the prediction of the need for antirejection treatment and helps guide biopsy decisions. The benchmark model used recipient and donor age, human leukocyte antigen mismatches, and dialysis need in the first 3 days after transplantation. Plasma CXCL9 or CXCL10 was added, and the extended models were evaluated using likelihood ratio tests (LRTs), area under the receiver operating characteristic curve (ROC-AUC), flexible calibration curves, and net benefit analysis. Model internal validation was performed through bootstrapping. Among 163 consecutively transplanted recipients on standard immunosuppression, 43 (26.4%) required antirejection therapy between Days 3 and 21 posttransplant. The chemokine-extended models outperformed the benchmark (LRT p < 0.01), increasing discriminative ability (delta ROC-AUC of 0.02) and improving calibration. Across the range of risk thresholds for biopsy, the extended models provided better clinical utility, resulting in up to 17 fewer unnecessary biopsies per 100 patients. These findings suggest that adding plasma CXCL9 or CXCL10 to a benchmark model can improve patient care by reducing the number of biopsies in individuals unlikely to require antirejection therapy.
趋化因子水平可能预测肾移植排斥反应。本研究评估了在标准治疗模型中加入早期血浆趋化因子C-X-C基序配体9（CXCL9）或趋化因子C-X-C基序配体10（CXCL10）测量值是否能改善对抗排斥治疗需求的预测，并有助于指导活检决策。基准模型使用了受者和供者年龄、人类白细胞抗原错配情况以及移植后前3天的透析需求。加入血浆CXCL9或CXCL10后，使用似然比检验（LRT）、受试者工作特征曲线下面积（ROC-AUC）、灵活校准曲线和净效益分析对扩展模型进行评估。通过自抽样法进行模型内部验证。在163例接受标准免疫抑制的连续移植受者中，43例（26.4%）在移植后第3天至第21天需要抗排斥治疗。趋化因子扩展模型优于基准模型（LRT p<0.01），提高了判别能力（ROC-AUC增量为0.02）并改善了校准。在活检的一系列风险阈值范围内，扩展模型具有更好的临床实用性，每100例患者可减少多达17次不必要的活检。这些发现表明，在基准模型中加入血浆CXCL9或CXCL10可通过减少不太可能需要抗排斥治疗的个体的活检次数来改善患者护理。
