Ozcan Seyda Gul, Eren Necmi, Dincer Mevlut Tamer, Atli Zeynep, Bolayirli Murat, Ergul Metin, Ozer Hakan, Turkmen Kultigin, Trabulus Sinan, Seyahi Nurhan
Cerrahpasa Medical Faculty, Department of Nephrology, Istanbul University- Cerrahpasa, Istanbul, Turkey.
Kocaeli Medical Faculty, Department of Nephrology, Kocaeli University, Kocaeli, Turkey.
BMC Nephrol. 2025 May 26;26(1):258. doi: 10.1186/s12882-025-04189-x.
Fabry disease is a rare lysosomal storage disorder. The genotypic and phenotypic heterogeneity of the disease complicates the prediction of disease activity. This study aimed to evaluate the association between multiple plasma biomarkers and disease activity in Fabry disease.
A cross-sectional analysis was conducted involving 87 Fabry patients, 46 chronic kidney disease (CKD) patients, and 41 healthy controls. Plasma levels of KIM-1, MCP-1, YKL-40, TNFR-1, TNFR-2, and cystatin-C were measured using ELISA. eGFR was calculated using creatinine and creatinine-cystatin C-based CKD-EPI formulas. Fabry patients on renal replacement therapy were analyzed as a subgroup. Primary analyses focused on 62 Fabry patients receiving enzyme replacement therapy.
Although eGFR (cr) did not differ significantly between Fabry patients and healthy controls, eGFR(cr-cys) was significantly lower in Fabry patients. After adjusting for age, gender, and BMI, MCP-1 and TNFR-2 levels were significantly lower in Fabry patients than in CKD patients. Among Fabry patients, those with renal involvement, had significantly higher MCP-1 levels than those without. While KIM-1 and YKL-40 did not differ significantly between groups, both were significantly elevated in patients with Lyso-Gb3 > 4 ng/mL and positively correlated with Lyso-Gb3.
MCP-1, TNFR-2, YKL-40, and cystatin C may serve as potential biomarkers for different aspects of Fabry disease activity. Further investigation into the associated pathogenic pathways may support the development of novel diagnostic tools or targeted therapies.
法布里病是一种罕见的溶酶体贮积症。该疾病的基因型和表型异质性使疾病活动的预测变得复杂。本研究旨在评估多种血浆生物标志物与法布里病疾病活动之间的关联。
进行了一项横断面分析，纳入了87例法布里病患者、46例慢性肾脏病（CKD）患者和41例健康对照。使用酶联免疫吸附测定法（ELISA）测量血浆中肾损伤分子-1（KIM-1）、单核细胞趋化蛋白-1（MCP-1）、几丁质酶3样蛋白1（YKL-40）、肿瘤坏死因子受体1（TNFR-1）、肿瘤坏死因子受体2（TNFR-2）和胱抑素C的水平。使用基于肌酐和肌酐-胱抑素C的慢性肾脏病流行病学合作（CKD-EPI）公式计算估算肾小球滤过率（eGFR）。将接受肾脏替代治疗的法布里病患者作为一个亚组进行分析。主要分析集中于62例接受酶替代治疗的法布里病患者。
尽管法布里病患者与健康对照之间的eGFR（基于肌酐）无显著差异，但法布里病患者的eGFR（基于肌酐-胱抑素C）显著更低。在调整年龄、性别和体重指数后，法布里病患者的MCP-1和TNFR-2水平显著低于CKD患者。在法布里病患者中，有肾脏受累的患者的MCP-1水平显著高于无肾脏受累的患者。虽然KIM-1和YKL-40在各组之间无显著差异，但在溶血型葡萄糖基神经酰胺（Lyso-Gb3）>4 ng/mL的患者中两者均显著升高，且与Lyso-Gb3呈正相关。
MCP-1、TNFR-2、YKL-40和胱抑素C可能作为法布里病疾病活动不同方面的潜在生物标志物。对相关致病途径的进一步研究可能有助于新型诊断工具或靶向治疗的开发。
