Division of Nephrology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuo-ku, Saitama-city Saitama, 330-8777, Japan.
Children's Medical Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan.
Clin Exp Nephrol. 2022 May;26(5):453-459. doi: 10.1007/s10157-021-02174-w. Epub 2022 Feb 3.
Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far.
We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS.
At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001).
UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant.
无症状性蛋白尿（ASP）病例不表现为肾病综合征，其病理常表现为局灶节段性肾小球硬化症（FSGS）。然而，到目前为止，尚未对这些病例的特征进行深入研究。
我们回顾性分析了 2003 年至 2019 年间 37 名因持续性孤立性蛋白尿（尿蛋白与肌酐比值：UP/C，>0.2 g/g）而接受肾活检的儿童（中位年龄 9.3 岁）的临床、病理和遗传特征。所有 FSGS 患者（排除继发性 FSGS）均进行靶向下一代测序（NGS）。
在活检时，所有 FSGS 患者（N=14）的 UP/C≥0.5 g/g，FSGS 患者的 UP/C 中位数明显高于肾小球微小病变（MGA）患者（N=23）（1.49 比 0.53 g/g，P<0.001）。在 7 名 FSGS 患者（3 名患者的 TRPC6、WT1、ACTN4 和 INF2 基因，1 名患者的 1 个基因）中发现了致病变异：所有基因变异均为常染色体显性遗传模式的基因。在有遗传 FSGS 的患者中，旁核变异的比例明显高于无遗传 FSGS 的患者（4/7 比 0/7，P<0.05）。Kaplan-Meier 分析显示，在 ASP 诊断后，遗传 FSGS 患者的肾脏存活率明显低于非遗传 FSGS 和 MGA 患者（P<0.001）。
UP/C 是诊断 FSGS 的一个简单且有用的预测参数。无肾病综合征表现的无症状性蛋白尿可能与 FSGS 的常染色体显性病因有关，尤其是在旁核变异患者中。
