Trautmann Agnes, Schnaidt Sven, Lipska-Ziętkiewicz Beata S, Bodria Monica, Ozaltin Fatih, Emma Francesco, Anarat Ali, Melk Anette, Azocar Marta, Oh Jun, Saeed Bassam, Gheisari Alaleh, Caliskan Salim, Gellermann Jutta, Higuita Lina Maria Serna, Jankauskiene Augustina, Drozdz Dorota, Mir Sevgi, Balat Ayse, Szczepanska Maria, Paripovic Dusan, Zurowska Alexandra, Bogdanovic Radovan, Yilmaz Alev, Ranchin Bruno, Baskin Esra, Erdogan Ozlem, Remuzzi Giuseppe, Firszt-Adamczyk Agnieszka, Kuzma-Mroczkowska Elzbieta, Litwin Mieczyslaw, Murer Luisa, Tkaczyk Marcin, Jardim Helena, Wasilewska Anna, Printza Nikoleta, Fidan Kibriya, Simkova Eva, Borzecka Halina, Staude Hagen, Hees Katharina, Schaefer Franz
Division of Pediatric Nephrology, University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
Institute of Medical Biometry and Informatics, University of Heidelberg, Germany.
J Am Soc Nephrol. 2017 Oct;28(10):3055-3065. doi: 10.1681/ASN.2016101121. Epub 2017 May 31.
We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.
我们研究了基因、组织病理学和早期治疗反应信息在预测原发性类固醇抵抗性肾病综合征患儿长期肾脏预后中的价值。从PodoNet注册中心，我们获得了1354例患者（发病年龄>3个月且<20岁）的纵向临床信息：612例有强化免疫抑制（IIS）反应记录，1155例有肾活检结果，212例有明确的基因诊断。我们使用多变量Cox回归模型评估终末期肾病（ESRD）的危险因素。疾病发作后12个月内蛋白尿完全缓解和部分缓解的儿童分别占24.5%和16.5%，基于钙调神经磷酸酶抑制剂的方案缓解率最高。IIS抵抗、完全缓解和部分缓解的儿童10年无ESRD生存率分别为43%、94%和72%；有基因诊断的儿童为27%；微小病变性肾小球病和局灶节段性肾小球硬化（FSGS）组织病理学表现的儿童分别为79%和52%。弥漫性系膜硬化的5年无ESRD生存率为21%。IIS反应性、基因诊断的存在、初始活检时的FSGS或弥漫性系膜硬化以及发病时的年龄、血清白蛋白浓度和慢性肾脏病（CKD）分期影响ESRD风险。我们的研究结果表明，对初始IIS的反应性和遗传性足细胞病的检测分别是类固醇抵抗性肾病综合征患儿长期预后良好和不良的预后指标。多药耐药散发性疾病患儿的肾脏生存率高于遗传性疾病患儿。此外，当建立基因诊断时，组织病理学发现可能仍具有预后相关性。
