Tasic Velibor, Gucev Zoran, Polenakovic Momir
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2015;36(3):5-12. doi: 10.1515/prilozi-2015-0073.
Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt's group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis.
肾病综合征的定义为大量蛋白尿、低白蛋白血症、水肿和高脂血症同时出现。根据对强化类固醇治疗的反应，可将其分为类固醇敏感型或类固醇抵抗型（SRNS）。SRNS通常会进展为终末期肾衰竭。根据北美儿科肾脏试验和协作研究，SRNS是20岁前导致终末期肾病的第二大常见原因。不幸的是，大多数患者没有治愈性治疗方法。大多数SRNS患者具有局灶节段性肾小球硬化的组织学表现。有趣的是，遗传性SRNS患者肾移植复发的风险低于无遗传背景的患者。几十年来，SRNS的病因和发病机制一直是个谜。39个显性或隐性SRNS基因的发现有助于更好地理解肾小球足细胞和裂孔膜的功能。希尔德布兰特团队表明，仅四个基因（NPHS1、NPHS2、LAMB2或WT1）中一个基因的隐性突变就能解释85%在3个月大时发病以及66%在1岁时发病的SRNS病例。同一团队使用了下一代测序等现代诊断技术，对一大群国际SRNS患者（n = 1783个家庭）进行了检测。诊断面板包括21个隐性遗传模式基因和6个显性遗传模式基因。在1783个25岁前出现症状的SRNS家庭中，29.5%（526个家庭）检测到单基因病因。在某些情况下，确定致病单基因突变可能具有重要的治疗意义。这对携带辅酶Q10生物合成基因（COQ2、COQ6、ADCK4或PDSS2）突变的患者非常重要。对于这些患者，可能需要使用辅酶Q10进行治疗。此外，PLCE1隐性突变患者可能对类固醇或环孢素A治疗完全有反应。CUBN患者可能从维生素B12治疗中获益。致病突变的检测对于家族遗传咨询和产前诊断也可能非常重要。
