Immunosuppression and Renal Outcome in Congenital and Pediatric Steroid-Resistant Nephrotic Syndrome
Immunosuppression and Renal Outcome in Congenital and Pediatric Steroid-Resistant Nephrotic Syndrome
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DOI：
10.2215/cjn.01190210
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发表时间：
2010-11-01
影响因子：
9.8
通讯作者：
Konrad, Martin
中科院分区：
文献类型：
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作者：
Buescher, Anja K.;Kranz, Birgitta;Konrad, Martin
背景和目标：足细胞基因突变与类固醇耐药型肾病综合征（SRNS）相关，主要影响年轻人群。迄今为止，尚不清楚这些患者是否受益于加强免疫抑制与环孢素A（CsA）。本研究的目的是评估足细胞基因缺陷对先天性肾病综合征（CNS）和儿童SRNS的影响，对CsA治疗的疗效和肾功能的保护。设计，设置，参与者和测量：在91名CNS/SRNS患者中进行基因分型，无论表现年龄或对CsA的反应如何。在52%的家族中鉴定出突变（11个NPHS 1，17个NPHS 2，11个WT 1，1个LAMB 2，3个TRPC 6）。68%的非遗传性SRNS患者对CsA有反应，其中大多数达到完全缓解。相比之下，没有一个患有遗传性CNS/SRNS的患者经历了完全缓解，只有两个（17%）达到了部分缓解，这两个都受到WT 1突变的影响。平均随访时间为8.6年（终末期肾病29%比71%）后，非遗传性疾病儿童的肾功能保护明显更好。结论：在我们的人群中，突变检测率很高（52%）。大多数遗传性CNS/SRNS患者没有从CsA中获益，与非遗传性患者相比，缓解率明显较低，并迅速进展为终末期肾衰竭。这些数据强烈支持这样的想法，即不暴露CNS/SRNS患者与足细胞功能相关的遗传缺陷，以加强免疫抑制与CsA。Clin J Am Soc Nephrol 5：2075-2084，2010. doi：10.2215/CJN.01190210
Background and objectives: Mutations in podocyte genes are associated with steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups. To date, it is unclear whether these patients benefit from intensified immunosuppression with cyclosporine A (CsA). The aim of this study was to evaluate the influence of podocyte gene defects in congenital nephrotic syndrome (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal function.Design, settings, participants, & measurements: Genotyping was performed in 91 CNS/SRNS patients, irrespective of age at manifestation or response to CsA.Results: Mutations were identified in 52% of families (11 NPHS1, 17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with nongenetic SRNS responded to CsA, most of them achieved complete remission. In contrast, none of the patients with genetic CNS/SRNS experienced a complete remission and only two (17%) achieved a partial response, both affected by a WT1 mutation. Preservation of renal function was significantly better in children with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29% versus 71%).Conclusions: The mutation detection rate in our population was high (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with significantly lower response rates compared with nongenetic patients and showed rapid progression to end-stage renal failure. These data strongly support the idea not to expose CNS/SRNS patients with inherited defects related to podocyte function to intensified immunosuppression with CsA. Clin J Am Soc Nephrol 5: 2075-2084, 2010. doi: 10.2215/CJN.01190210