半乳糖凝集素 3 与肾移植受者晚期移植物失功风险：一项为期 10 年的前瞻性队列研究。
Galectin-3 and Risk of Late Graft Failure in Kidney Transplant Recipients: A 10-year Prospective Cohort Study.
机构信息
Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Radiology, Clinical Hospital of the University of Chile, University of Chile, Santiago, Chile.
出版信息
Transplantation. 2021 May 1;105(5):1106-1115. doi: 10.1097/TP.0000000000003359.
BACKGROUND
Galectin-3 may play a causal role in kidney inflammation and fibrosis, which may also be involved in the development of kidney graft failure. With novel galectin-3-targeted pharmacological therapies increasingly coming available, we aimed to investigate whether galectin-3 is associated with risk of late graft failure in kidney transplant recipients (KTR).
METHODS
We studied adult KTR who participated in TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study, recruited in a university setting (2001-2003). Follow-up was performed for a median of 9.5 (interquartile range, 6.2-10.2) years. Overall and stratified (Pinteraction < 0.05) multivariable-adjusted Cox proportional-hazards regression analyses were performed to study the association of galectin-3 with risk of graft failure (restart of dialysis or retransplantation).
RESULTS
Among 561 KTR (age 52 ± 12 y; 54% males), baseline median galectin-3 was 21.1 (interquartile range, 17.0-27.2) ng/mL. During follow-up, 72 KTR developed graft failure (13, 18, and 44 events over increasing tertiles of galectin-3). Independent of adjustment for donor, recipient, and transplant characteristics, galectin-3-associated with increased risk of graft failure (hazard ratios [HR] per 1 SD change, 2.12; 95% confidence interval [CI], 1.63-2.75; P < 0.001), particularly among KTR with systolic blood pressure ≥140 mmHg (HR, 2.29; 95% CI, 1.80-2.92; P < 0.001; Pinteraction = 0.01) or smoking history (HR, 2.56; 95% CI, 1.95-3.37; P < 0.001; Pinteraction = 0.03). Similarly, patients in the highest tertile of galectin-3 were consistently at increased risk of graft failure.
CONCLUSIONS
Serum galectin-3 levels are elevated in KTR, and independently associated with increased risk of late graft failure. Whether galectin-3-targeted therapies may represent novel opportunities to decrease the long-standing high burden of late graft failure in stable KTR warrants further studies.
背景
半乳糖凝集素-3 可能在肾脏炎症和纤维化中起因果作用，这也可能与肾脏移植物衰竭的发展有关。随着新型半乳糖凝集素-3 靶向药物治疗的不断出现，我们旨在研究半乳糖凝集素-3 是否与肾移植受者（KTR）晚期移植物衰竭的风险相关。
方法
我们研究了参加 TransplantLines 胰岛素抵抗和炎症生物库和队列研究的成年 KTR，该研究是在一所大学环境中进行的（2001-2003 年）。中位随访时间为 9.5 年（四分位距，6.2-10.2 年）。进行了总体和分层（Pinteraction < 0.05）多变量调整的 Cox 比例风险回归分析，以研究半乳糖凝集素-3 与移植物衰竭（重新开始透析或再次移植）风险的关系。
结果
在 561 名 KTR（年龄 52 ± 12 岁；54%为男性）中，基线中位半乳糖凝集素-3 为 21.1（四分位距，17.0-27.2）ng/ml。在随访期间，72 名 KTR 发生了移植物衰竭（递增三分位组中分别有 18、44 和 72 个事件）。无论是否调整供体、受者和移植特征，半乳糖凝集素-3 与移植物衰竭风险增加相关（每 1 SD 变化的危险比[HR]，2.12；95%置信区间[CI]，1.63-2.75；P < 0.001），尤其是在收缩压≥140mmHg 的 KTR 中（HR，2.29；95% CI，1.80-2.92；P < 0.001；Pinteraction = 0.01）或有吸烟史的 KTR 中（HR，2.56；95% CI，1.95-3.37；P < 0.001；Pinteraction = 0.03）。同样，半乳糖凝集素-3 三分位最高组的患者始终处于移植物衰竭风险增加的状态。
结论
血清半乳糖凝集素-3 水平在 KTR 中升高，与晚期移植物衰竭风险增加独立相关。半乳糖凝集素-3 靶向治疗是否可能为稳定 KTR 中晚期移植物衰竭的高负担提供新的机会，值得进一步研究。
Zotero 插件