Sgambat Kristen, Clauss Sarah, Moudgil Asha
Department of Nephrology, Children's National Hospital, Washington, DC, United States.
Department of Cardiology, Children's National Hospital, Washington, DC, United States.
Front Pediatr. 2020 Jan 31;8:17. doi: 10.3389/fped.2020.00017. eCollection 2020.
The presence of circulating donor specific anti-HLA antibodies (dnDSA) has been implicated in an immune-mediated form of accelerated systemic arteriosclerosis in adult heart and kidney transplant recipients, however this has not been previously investigated in pediatric kidney transplant recipients. Carotid intima-media thickness (CIMT) is a reliable method for detection of arteriosclerosis. We hypothesized that children who develop dnDSA after kidney transplant would have increased CIMT compared with those who remain dnDSA negative. A prospective, controlled pilot cohort study of 38 transplant patients and 20 healthy controls was conducted to investigate the association between CIMT and development of dnDSA after kidney transplant. CIMT, anthropometrics, blood pressure and lipid panel were measured at 1, 18, and 30 months post-transplant. DSA was checked at 6, 12, 18, 24 and 30 months post-transplant. CIMT of DSA positive transplant recipients was compared to DSA negative and controls. Of the 38 transplant recipients, 7 patients developed dnDSA by 18-30 months post-transplant. Among 5 dnDSA positive patients who did not receive treatment for DSA prior to CIMT measurement (n=6 observations), the median CIMT was 0.505 mm (95% CI 0.454-0.560 mm) at 18-30 months post-transplant, compared to 0.455 mm (95% CI 0.440-0.470) in DSA negative transplant recipients ( = 54 observations of 30 patients) and 0.450 mm (95% CI 0.436-0.460) in the healthy controls (20 observations of 20 patients). Presence of dnDSA was independently associated with a 7.8% increase in CIMT compared to those without dnDSA (p=0.006), after adjusting for race, hypertension, dyslipidemia, and abdominal obesity. Development of dnDSA was associated with increased CIMT, an indicator of arteriosclerosis, in a cohort of dnDSA positive pediatric kidney transplant recipients. The association between dnDSA and CIMT was independent of traditional CV risk factors, including hypertension, dyslipidemia, and abdominal obesity.
循环供体特异性抗人白细胞抗原抗体（dnDSA）的存在与成年心脏和肾脏移植受者免疫介导的加速性系统性动脉硬化有关，然而此前尚未在小儿肾脏移植受者中进行过研究。颈动脉内膜中层厚度（CIMT）是检测动脉硬化的可靠方法。我们推测，肾移植后出现dnDSA的儿童与dnDSA仍为阴性的儿童相比，其CIMT会增加。我们开展了一项前瞻性、对照性队列研究，纳入38例移植患者和20例健康对照，以调查肾移植后CIMT与dnDSA发生之间的关联。在移植后1个月、18个月和30个月测量CIMT、人体测量指标、血压和血脂水平。在移植后6个月、12个月、18个月、24个月和30个月检查DSA。将DSA阳性移植受者的CIMT与DSA阴性受者及健康对照进行比较。在38例移植受者中，7例患者在移植后18 - 30个月出现dnDSA。在5例CIMT测量前未接受DSA治疗的dnDSA阳性患者中（共6次观察），移植后18 - 30个月时CIMT中位数为0.505毫米（95%置信区间0.454 - 0.560毫米），而DSA阴性移植受者（30例患者的54次观察）为0.455毫米（95%置信区间0.440 - 0.470），健康对照（20例患者的20次观察）为0.450毫米（95%置信区间0.436 - 0.460）。在对种族、高血压、血脂异常和腹型肥胖进行校正后，与未出现dnDSA的患者相比，dnDSA的存在与CIMT增加7.8%独立相关（p = 0.006）。在dnDSA阳性的小儿肾脏移植受者队列中，dnDSA的出现与CIMT增加有关，CIMT是动脉硬化的一个指标。dnDSA与CIMT之间的关联独立于传统心血管危险因素，包括高血压、血脂异常和腹型肥胖。
