WT1基因检测时机对Wilms肿瘤合并慢性肾脏疾病预后影响的回顾性队列研究

目的 分析在Wilms肿瘤合并慢性肾脏疾病(CKD)的患儿中WT1基因检测对诊断和长期预后的影响。方法 检索上海市肾脏发育与儿童肾脏病研究中心儿童肾脏病基因检测数据库,2001年1月1日至2018年12月31日明确WT1基因突变、年龄<18岁患儿,或Wilms肿瘤合并CKD 2~5期或肾病综合征或有蛋白尿的连续病例。按进展为终末期肾衰竭(ESRD)之前是否明确WT1基因突变分为早诊断组和晚诊断组,以ESRD为终点比较两组的预后。结果 22例患儿明确WT1基因的常染色体显性遗传突变,分别位于第8~9外显子/内含子。依据临床分型,10例为Denys-Drash综合征,3例为Fraiser综合征,9例表型为孤立型肾病综合征,5例合并假两性畸形。随访终点进入ESRD有15例,7例进入CKD 2~4期。应用生存曲线分析证实,早诊断组较晚诊断组进入ESRD病程显著延迟(P=0.011)。结论 在儿童Wilms肿瘤、肾病综合征/蛋白尿、慢性肾功能损害的患儿中,在肾功能进展恶化之前及早明确WT1基因突变,不仅有助于临床诊断分型,还能显著延缓进入ESRD病程。

Retrospective cohort study of the effect of WT1 gene detection time on the prognosis of children with Wilms tumor and chronic kidney disease

Objective To explore the WT1 mutation-induced nephrotic syndrome (NS), proteinuria or Wilms tumor in children and its long-term renal prognosis.Methods We analyzed the clinical features in patients with NS, proteinuria or Wilms tumor since from January 2001 to December 2018 in our medical center. Patients were divided by genotypes or divided into two subgroups of early detection and late detection of WT1.Results Twelve different mutations were detected in 22 patients, which all located between exon 8 and exon 9, including diagnosis of Denys-Drash syndrome (10 cases), Fraiser syndrome (3 cases) and isolated NS (9 cases). Five cases presented with pseudohermaphroditism. During follow up, 15 cases progressed into end stage renal disease (ESRD) and 5 cases into CKD 2-4 stage. Patients in early detection group had a significant longer duration of ESRD progression compared with the patients in late detection group by Kaplan-Meier survival analysis (P=0.011).Conclusion Detection of WT1 mutations should be performed in children with Wilms tumor, proteinuria/NS or chronic kidney disease. Early detection of WT1 mutations before developing into ESRD could help to delay the ESRD progression.