Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome
Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome
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DOI：
10.2215/cjn.07370715
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发表时间：
2016-02-01
影响因子：
9.8
通讯作者：
Weber, Stefanie
中科院分区：
文献类型：
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作者：
Buescher, Anja K.;Beck, Bodo B.;Weber, Stefanie
背景与目的先天性肾病综合征（CNS）和激素抵抗性肾病综合征（SRNS）治疗要求高，肾脏预后差。许多致病基因突变已被确定在SRNS影响肾足细胞。在高通量测序技术的时代，非遗传性SRNS患者经常逃避科学的兴趣。我们在这里提出了德国CNS/SRNS随访研究的长期数据，重点关注非遗传性与遗传性疾病患者对环孢菌素A（CsA）的反应。设计、设置、参与者和测量收集了8所大学儿科肾脏病单位治疗的231例CNS/SRNS患者的横截面和纵向临床数据，中位观察时间为113个月（四分位数范围，50-178）。结果突变检出率为57%（CNS为97%，SRNS为41%），其中85%的突变是通过3个单基因（NPHS 1、NPHS 2和WT 1）的分析确定的，分别占CNS突变总数的92%和SRNS突变总数的79%。在中位治疗期2.5个月后，78%的非遗传性SRNS患者观察到疾病缓解; 82%的非遗传性SRNS患者在治疗6个月内有反应，98%的非遗传性SRNS和CsA诱导的完全缓解（正常白蛋白血症和无蛋白尿）患者维持正常的肾功能。相反，遗传性SRNS与66%的患者的高ESRD率相关。只有3%的患者与遗传性SRNS经历了CsA治疗后完全缓解和16%的患者与遗传性SRNS经历了部分缓解。结论CsA的疗效是高的非遗传性SRNS，在绝大多数患者的肾功能良好的预后。在这些非遗传性SRNS患者中，应给予CsA至少6个月。在遗传性SRNS中，对CsA的反应较低，仅限于特殊患者。
Background and objectives Treatment of congenital nephrotic syndrome (CNS) and steroid resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease.Design, setting, participants, & measurements Cross sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50-178). Genotyping was performed systematically in all patients.Results The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy.Conclusions The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.