Patients with mutations in NPHS2 (Podocin) do not respond to standard steroid treatment of nephrotic syndrome
Patients with mutations in NPHS2 (Podocin) do not respond to standard steroid treatment of nephrotic syndrome
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DOI：
10.1097/01.asn.0000113552.59155.72
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发表时间：
2004-03-01
影响因子：
13.6
通讯作者：
Hildebrandt, F
中科院分区：
文献类型：
--
作者：
Ruf, RG;Lichtenberger, A;Hildebrandt, F
肾病综合征（NS）与蛋白尿、低白蛋白血症、水肿和高脂血症有关。类固醇抵抗性NS （SRNS）定义为对标准类固醇治疗的原发性抵抗。在生命的头二十年，它仍然是ESRD最棘手的原因之一。NPHS2基因突变是SRNS的常见原因，约占散发性SRNS病例的20%至30%。基于非常少量的患者，我们怀疑NPHS2纯合子或复合杂合子突变的儿童可能表现出原发性类固醇抵抗，并且肾移植后FSGS复发的风险降低。为了验证这一假设，我们对来自165个不同家族的190例SRNS患者进行了NPHS2突变分析，并对来自120个家族的124例类固醇敏感NS患者进行了对照。165个SRNS家族中有43个（26%）检测到NPHS2纯合或复合杂合突变。相反，在120个类固醇敏感的NS家族中，未观察到NPHS2的纯合或复合杂合突变。20例无NPHS2突变的SRNS患者中有7例（35%）在肾移植中出现FSGS复发，而24例NPHS2纯合子或复合杂合子突变的SRNS患者中只有2例（8%）发生FSGS复发。在接受环孢素A或环磷酰胺治疗的29例NPHS2纯合子或复合杂合子突变患者中，没有一例NS完全缓解。结论是，NPHS2纯合子或复合杂合子突变的SRNS患者对标准类固醇治疗无反应，并且肾移植中FSGS复发的风险降低。由于这些发现可能会影响儿童SRNS的治疗计划，如果患者同意，在开始标准类固醇治疗的第一个疗程的同时进行NPHS2突变分析可能是可取的。
Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very si nail number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.