Berthoux Francois, Suzuki Hitoshi, Mohey Hesham, Maillard Nicolas, Mariat Christophe, Novak Jan, Julian Bruce A
Department of Nephrology, Dialysis, and Renal Transplantation, University North Hospital, Saint Etienne, France;
Division of Nephrology, Department of Internal Medicine, Juntendo University, Tokyo, Japan.
J Am Soc Nephrol. 2017 Jun;28(6):1943-1950. doi: 10.1681/ASN.2016060670. Epub 2017 Mar 2.
A prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor-based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1-specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1-specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; =0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; =0.05). Normalized Gd-IgA1-specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1-specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN.
目前缺乏预测肾移植后IgA肾病(IgAN)复发的生物标志物。我们对96例接受首次肾移植的原发性IgAN患者(79例男性;92例死亡供者;平均年龄48.1岁)进行了为期10年的随访,这些患者均接受基于钙调神经磷酸酶抑制剂的免疫抑制治疗,观察其死亡、移植肾失功及临床病理复发(CPR,临床证据明确且活检证实)情况。采用时间依赖性Cox回归分析和受试者工作特征曲线,我们评估了移植时或原发性IgAN诊断时(仅30例患者)血清中半乳糖缺陷型IgA1(Gd-IgA1,自身抗原)以及Gd-IgA1特异性IgG和IgA自身抗体水平的预后意义。总体而言,13例患者死亡,34个移植肾失功(17例因CPR),34例患者在平均5.8年后发生CPR。与健康对照者(n = 30)相比,患者在诊断时和移植时血清Gd-IgA1水平显著升高,但该水平与任何结局均无关联。患者在诊断时和移植时标准化(而非总)血清Gd-IgA1特异性IgG自身抗体水平也显著升高,且移植时该水平与CPR风险较高相关(相对风险,2.68;95%置信区间,1.26至5.71;P = 0.01;受试者工作特征曲线下面积,0.62;95%置信区间,0.51至0.74;P = 0.05)。在多变量分析中,标准化Gd-IgA1特异性IgG自身抗体水平仍是CPR的独立危险因素。血清Gd-IgA1特异性IgA自身抗体水平在诊断和移植之间未发生变化,也不能预测结局。本研究强调了IgAN患者移植后标准化血清IgG抗聚糖自身抗体水平的预后价值。