Arias-Cabrales Carlos E, Riera Marta, Pérez-Sáez María José, Gimeno Javier, Benito David, Redondo Dolores, Burballa Carla, Crespo Marta, Pascual Julio, Rodríguez Eva
Department of Nephrology, Hospital del Mar, Barcelona, Catalunya, Spain.
Institut Hospital del Mar d'Investigacions Mèdiques, IMIM, Barcelona, Catalunya, Spain.
Clin Kidney J. 2020 Oct 10;14(4):1190-1196. doi: 10.1093/ckj/sfaa147. eCollection 2021 Apr.
Ischaemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients.
We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies ( = 12) and a control group of 1-year protocol biopsies without tissue damage ( = 4) were stained for C5b-9, C3b and FH.
SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142 mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0-7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients.
Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.
缺血再灌注（I/R）损伤是移植肾延迟功能恢复（DGF）的一个相关原因。补体激活参与实验性I/R损伤，但肾移植（KT）患者的数据较少。我们研究了膜攻击复合物（C5b-9）作为可溶性成分（SC5b-9）的动态变化以及DGF患者中C3b、补体因子H（FH）和C5b-9的组织学沉积模式。
我们评估了59例受者的SC5b-9水平：38例移植肾功能立即恢复者和21例发生DGF者。在KT术前及术后7天测量SC5b-9。对DGF肾活检标本（n = 12）和一组无组织损伤的1年方案活检对照组标本（n = 4）进行C5b-9、C3b和FH染色。
DGF患者的SC5b-9显著升高（第0天：6621±2202 mAU/L vs第7天：9626±4142 mAU/L；P = 0.006），而非DGF患者则保持稳定。第0 - 7天升高>5%是区分DGF与非DGF患者的更佳临界值（敏感性 = 81%）。此外，SC5b-9升高与DGF持续时间及更差的移植肾功能相关，且与DGF的发生独立相关。在肾小管上皮细胞基底膜观察到SC5b-9、C3b和FH染色。与对照组患者相比，DGF肾活检标本显示高强度染色更频繁、阳性染色的肾小管数量更多以及SC5b-9、C3b和FH阳性染色的肾小管周长更大。
在发生DGF的患者中，SC5b-9水平以及肾小管上皮细胞基底膜中的SC5b-9、C3b和FH沉积均高度表达。SC5b-9水平升高可能作为DGF严重程度的一个标志物。
