Data_Sheet_1_Urinary Properdin and sC5b-9 Are Independently Associated With Increased Risk for Graft Failure in Renal Transplant Recipients.PDF

The pathophysiology of late kidney-allograft failure remains complex and poorly understood. Activation of filtered or locally produced complement may contribute to the progression of renal failure through tubular C5b-9 formation. This study aimed to determine urinary properdin and sC5b-9 excretion and assess their association with long-term outcome in renal transplant recipients (RTR).Methods: We measured urinary properdin and soluble C5b-9 in a well-defined cross-sectional cohort of RTR. Urinary specimens were taken from a morning urine portion, and properdin and sC5b-9 were measured using an enzyme-linked-immunosorbent assay (ELISA). Cox proportional hazard regression analyses were used to investigate prospective associations with death-censored graft failure.Results: We included 639 stable RTR at a median [interquartile range] 5.3 (1.8–12.2) years after transplantation. Urinary properdin and sC5b-9 excretion were detectable in 161 (27%) and 102 (17%) RTR, respectively, with a median properdin level of 27.6 (8.6–68.1) ng/mL and a median sC5b-9 level of 5.1 (2.8–12.8) ng/mL. In multivariable-adjusted Cox regression analyses, including adjustment for proteinuria, urinary properdin (HR, 1.12; 95% CI 1.02–1.28; P = 0.008) and sC5b-9 excretion (HR, 1.34; 95% CI 1.10–1.63; P = 0.003) were associated with an increased risk of graft failure. If both urinary properdin and sC5b-9 were detectable, the risk of graft failure was further increased (HR, 3.12; 95% CI 1.69–5.77; P < 0.001).Conclusions: Our findings point toward a potential role for urinary complement activation in the pathogenesis of chronic allograft failure. Urinary properdin and sC5b-9 might be useful biomarkers for complement activation and chronic kidney allograft deterioration, suggesting a potential role for an alternative pathway blockade in RTR.

晚期肾脏同种异体移植的病理生理学复杂且理解不足。过滤或局部产生的补体激活可能通过形成管状C5b-9途径，导致肾衰竭的进展。本研究旨在确定尿液中 Properdin 和 sC5b-9 的排泄情况，并评估其与肾脏移植受体（RTR）长期预后之间的关联。方法：我们在定义明确的横断面队列中测量了 RTR 的尿液 Properdin 和可溶性 C5b-9。晨尿样本被采集，并使用酶联免疫吸附测定（ELISA）来测量 Properdin 和 sC5b-9。采用 Cox 比例风险回归分析，以探究与死亡截断的移植物失败的前瞻性关联。结果：我们纳入了 639 名在移植后中位 [四分位距] 5.3（1.8–12.2）年稳定的 RTR。161 名（27%）和 102 名（17%）RTR 的尿液 Properdin 和 sC5b-9 可检测，其中 Properdin 中位水平为 27.6（8.6–68.1）ng/mL，sC5b-9 中位水平为 5.1（2.8–12.8）ng/mL。在多变量调整后的 Cox 回归分析中，包括对蛋白尿的调整，尿液 Properdin（HR，1.12；95% CI 1.02–1.28；P = 0.008）和 sC5b-9 排泄（HR，1.34；95% CI 1.10–1.63；P = 0.003）与移植物失败风险增加相关。如果尿液 Properdin 和 sC5b-9 均可检测，移植物失败的风险进一步增加（HR，3.12；95% CI 1.69–5.77；P < 0.001）。结论：我们的研究结果指向了尿液补体激活在慢性同种异体移植病源发生中的潜在作用。尿液 Properdin 和 sC5b-9 可能是补体激活和慢性肾脏同种异体移植恶化的有用生物标志物，暗示了在 RTR 中阻断替代途径的潜在作用。