Andrulli Simeone, Manenti Lucio, Reggiani Francesco, Pisani Isabella, Giannese Domenico, Vischini Gisella, Valsecchi Giovanni, Godeas Giulia, Gigliotti Giuseppe, Esposito Pasquale, De Giovanni Paola, Murtas Corrado, Casuscelli Chiara, Caruso Sabrina, Rossini Michele, Andrulli Giovanni, Quaglia Marco, Aucella Filippo, Buscaroli Andrea, Rossi Giovanni Maria, Mattozzi Francesca, Di Renzo Brigida, Zanchelli Fulvia, Bruno Francesca, Sciri Raffaela, Manes Massimo, Torres Diletta Domenica, Garozzo Maurizio, Lazzarin Roberta, Corbani Valentina, Fontana Francesco, Calatroni Marta, Incerti Monia, Bini Claudia, Infante Barbara, D'Angio' Pierluigi, Di Martino Margherita, Rigotti Angelo, Gesualdo Loreto
Associazione Italiana Ricercare per Curare ODV ETS (AIRpC), Lecco, Italy.
Nephrology Unit, Azienda Sociosanitaria Liguria 5, La Spezia, Italy.
Front Immunol. 2025 Sep 12;16:1655825. doi: 10.3389/fimmu.2025.1655825. eCollection 2025.
The role of complement in the long-term renal survival of patients with lupus nephritis (LN) remains poorly understood. Recent studies suggest its potential impact; however, long-term data are lacking.
This multicenter, observational, retrospective study aimed at investigating the influence of complement levels on long-term renal outcomes in LN patients. We evaluated whether isolated C3 hypocomplementemia (i-LowC3), defined as serum low C3 (≤80 mg/dL) and normal C4 (>10 mg/dL) six months after kidney biopsy is associated with subsequent risk of chronic kidney disease (CKD), End Stage Kidney Disease (ESKD) or death.
445 patients with LN were studied (median follow-up 4.9 years). Based on six-month C3/C4 levels, patients were categorized into i-LowC3 (91 patients) and controls (354 patients). Over the first six months, serum C3 and C4 levels increased by a median of 20 mg/dL and 5 mg/dL, respectively. i-LowC3 was significantly associated with twice the risk of a poor outcome, including CKD, ESKD, composite outcome of CKD or death and ESKD or death, with lower survival rates for all these outcomes compared to controls (P < 0.001). Multivariate Cox regression analysis revealed a lower risk of CKD and CKD or death with increases in C3 levels during the first six months, while i-LowC3 was associated with an independent higher risk for these outcomes.
The trajectory of serum C3 levels within the first six months appears to predict long-term renal prognosis of LN patients. These findings support the use of i-LowC3 as a low-cost, readily available biomarker to guide early treatment of LN patients.
补体在狼疮性肾炎（LN）患者长期肾脏存活中的作用仍未得到充分了解。近期研究提示了其潜在影响；然而，缺乏长期数据。
这项多中心、观察性、回顾性研究旨在调查补体水平对LN患者长期肾脏结局的影响。我们评估了孤立性C3低补体血症（i-LowC3），定义为肾活检后6个月血清C3低水平（≤80mg/dL）且C4正常（>10mg/dL），是否与随后慢性肾脏病（CKD）、终末期肾病（ESKD）或死亡风险相关。
对445例LN患者进行了研究（中位随访时间4.9年）。根据6个月时的C3/C4水平，患者被分为i-LowC3组（91例患者）和对照组（354例患者）。在最初6个月期间，血清C3和C4水平分别中位数升高20mg/dL和5mg/dL。i-LowC3与不良结局风险增加两倍显著相关，包括CKD、ESKD、CKD或死亡的复合结局以及ESKD或死亡，与对照组相比，所有这些结局的生存率均较低（P<0.001）。多变量Cox回归分析显示，最初6个月期间C3水平升高与CKD以及CKD或死亡风险降低相关，而i-LowC3与这些结局的独立高风险相关。
最初6个月内血清C3水平的变化轨迹似乎可预测LN患者的长期肾脏预后。这些发现支持将i-LowC3作为一种低成本、易于获得的生物标志物，以指导LN患者的早期治疗。
