Department of Pediatrics, University of Washington, Seattle, WA.
Division of Nephrology, Seattle Children's Hospital, Seattle, WA.
Transplantation. 2018 Dec;102(12):2072-2079. doi: 10.1097/TP.0000000000002310.
The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear.
One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection.
Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA.
The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.
新产生的供体特异性抗体（dnDSA）的发展与肾移植中的排斥和移植物丢失有关，目前建议对所有肾移植受者进行 DSA 筛查。然而，在所有接受肾移植的患者中，通过筛查检测到 dnDSA 的临床意义仍不清楚。
2007 年 12 月 1 日至 2013 年 12 月 31 日期间，103 名年龄在 18 岁以下的患者接受了首次单独的肾移植，在移植后 2 年内每 3 个月进行一次 DSA 筛查，如有临床指征则进行额外检测。在没有活检证实排斥反应的情况下，不给予针对 DSA 的治疗。
20 名（19%）患者在筛查试验中首次检测到 dnDSA，13 名（13%）患者在因病因检测中首次检测到 dnDSA。移植后平均随访时间为 4.4 年。筛查检测到的 dnDSA 与 3 年内排斥反应的风险增加、微血管炎症和 2 年协议活检中的 C4d 染色有关。在 Cox 比例风险回归中，筛查检测到的 dnDSA 与估计肾小球滤过率下降 30%的时间无关（调整后的危险比，0.88；95%置信区间[CI]，0.30-2.00；P=0.598）或移植物丢失。因病因检测首次检测到 dnDSA 与移植物功能下降的风险增加 2.8 倍相关（95%CI，1.08-7.27；P=0.034）和移植物丢失的风险增加 7.34 倍相关（95%CI，1.37-39.23；P=0.020）与未发生 dnDSA 的患者相比。
dnDSA 首次检测的临床情况会影响 dnDSA 与移植物功能之间的关系。需要进一步的研究来阐明 dnDSA 筛查在儿科肾移植中的作用。
