Fujimoto Keiji, Haraguchi Takatoshi, Kumano Sho, Yamazaki Keita, Miyatake Nobuhiko, Nomura Kanae, Mukai Kiyotaka, Okino Kazuaki, Hayashi Norifumi, Adachi Hiroki, Yokoyama Hitoshi, Iida Yasuo, Furuichi Kengo
Department of Nephrology, Kanazawa Medical University School of Medicine, Ishikawa 920-0293, Japan.
Department of Mathematics, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Int J Nephrol. 2022 Aug 9;2022:2718810. doi: 10.1155/2022/2718810. eCollection 2022.
This retrospective exploratory study aimed to identify early clinical indicators of kidney prognosis in primary nephrotic syndrome (NS). Univariate Cox proportional hazards regression analysis identified clinical parameters in the 2-month period after initiating immunosuppressive therapy (IST); it predicted 40% reduction in the estimated glomerular filtration rate (eGFR) in 36 patients with primary NS. Time-dependent receiver operating characteristic curve analysis was used to evaluate the performance of the predictors for the cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST. The mean follow-up period was 71.9 months. The eGFR was reduced by 40% in four patients. Significant predictors for time to 40% reduction in the eGFR were as follows: an increase in the serum soluble urokinase plasminogen activator receptor (s-suPAR) 2 months after initiating IST (Δs-suPAR (2M); hazard ratio (HR) for every 500 pg/mL increase: 1.36, =0.006), s-suPAR at 2 months after initiating IST (s-suPAR (2M); HR for every 500 pg/mL increase: 1.13, =0.015), urinary protein-to-creatinine ratio (u-PCR) (u-PCR (2M); HR for every 1.0 g/gCr increase: 2.94, =0.003), and urinary liver-type fatty acid-binding protein (u-L-FABP) (u-L-FABP (2M); HR for every 1.0 g/gCr increase: 1.14, =0.006). All four factors exhibited high predictive accuracy for cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST, with areas under the receiver operating characteristic curve of 0.92 for Δs-suPAR (2M), 0.87 for s-suPAR (2M), 0.93 for u-PCR (2M), and 0.93 for u-L-FABP (2M). These findings suggest that Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) could be useful indicators of initial therapeutic response for predicting kidney prognosis in primary NS.
这项回顾性探索性研究旨在确定原发性肾病综合征(NS)患者肾脏预后的早期临床指标。单因素Cox比例风险回归分析确定了开始免疫抑制治疗(IST)后2个月内的临床参数;该分析预测了36例原发性NS患者的估计肾小球滤过率(eGFR)降低40%的情况。采用时间依赖性受试者工作特征曲线分析来评估预测指标对IST开始后长达8年eGFR降低40%累积发生率的预测性能。平均随访期为71.9个月。4例患者的eGFR降低了40%。eGFR降低40%的时间的显著预测指标如下:开始IST后2个月血清可溶性尿激酶型纤溶酶原激活物受体(s-suPAR)升高(Δs-suPAR(2M);每增加500 pg/mL的风险比(HR):1.36,P=0.006),开始IST后2个月的s-suPAR(s-suPAR(2M);每增加500 pg/mL的HR:1.13,P=0.015),尿蛋白与肌酐比值(u-PCR)(u-PCR(2M);每增加1.0 g/gCr的HR:2.94,P=0.003),以及尿肝型脂肪酸结合蛋白(u-L-FABP)(u-L-FABP(2M);每增加1.0 g/gCr的HR:1.14,P=0.006)。所有这四个因素对IST开始后长达8年eGFR降低40%的累积发生率均表现出较高的预测准确性,Δs-suPAR(2M)的受试者工作特征曲线下面积为0.92,s-suPAR(2M)为0.87,u-PCR(2M)为0.93,u-L-FABP(2M)为0.93。这些发现表明,Δs-suPAR(2M)、s-suPAR(2M)、u-PCR(2M)和u-L-FABP(2M)可能是预测原发性NS患者肾脏预后的初始治疗反应的有用指标。