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布地奈德治疗的IgA肾病患者蛋白尿进展中尿生物标志物的预后价值

Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide.

作者信息

Keskinis Christodoulos, Moysidou Eleni, Stai Stamatia, Christodoulou Michalis, Lioulios Georgios, Vamvakas Sotirios-Spyridon, Trivyza Maria Stella, Pateinakis Panagiotis, Papasotiriou Marios, Stangou Maria

机构信息

School of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, Greece.

Department of Nephrology, Papageorgiou Hospital, 56429 Thessaloniki, Greece.

出版信息

Medicina (Kaunas). 2025 Apr 26;61(5):807. doi: 10.3390/medicina61050807.

Abstract

Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m, proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, = 0.004), MMP-9 and uCLU (r = 0.77, = 0.002), and MCP-1 and uCLU (r = 0.65, = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, = 0.03). Higher MCP-1 (r = -0.560, = 0.046) and MMP-9 (r = -0.330, = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, = 0.031) was associated with worsening proteinuria. The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression.

摘要

靶向释放布地奈德(TRB)是首个获批用于针对IgA肾病(IgAN)早期发病机制级联反应的药物。这项前瞻性研究纳入了过去5年内确诊的高加索IgAN患者,这些患者开始了为期10个月的TRB治疗,并在门诊接受随访。所有参与者在至少前6个月一直采用最大支持治疗剂量。在TRB治疗开始时(T0)以及3、6和10个月时(分别为T3、T6和T10)记录肾功能和蛋白尿水平,而在T0和T3时测量尿单核细胞趋化蛋白-1(MCP-1)、基质金属蛋白酶-9(MMP-9)和簇集素(CLU)水平。在所有患者队列中(平均年龄53.24±12.76岁,估计肾小球滤过率(eGFR)52.84±25.93 mL/min/1.73 m²,蛋白尿2.84±1.26 g/24 h),在T0时观察到MMP-9与MCP-1之间存在显著相关性(r = 0.74,P = 0.004),MMP-9与尿CLU之间存在显著相关性(r = 0.77,P = 0.002),以及MCP-1与尿CLU之间存在显著相关性(r = 0.65,P = 0.01)。在T3时,MMP-9与尿CLU(uCLU)之间的显著相关性仍然存在(r = 0.71,P = 0.03)。T0时较高的MCP-1(r = -0.560,P = 0.046)和MMP-9(r = -0.330,P = 0.012)水平与蛋白尿减少相关。相反,T3时簇集素增加(r = 0.599,P = 0.031)与蛋白尿恶化相关。TRB的治疗反应存在异质性,近期诊断(RD)的患者肾功能和蛋白尿有所改善,而诊断时间较长(OD)的患者生物标志物恶化且肾功能下降。因此,早期干预对IgAN患者至关重要。最后,所研究的生物标志物可用于预后监测疾病进展。

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