Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts
Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts
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DOI：
10.1007/s00467-014-3007-0
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发表时间：
2015-02-01
影响因子：
3
通讯作者：
Itabashi, Kazuo
中科院分区：
文献类型：
--
作者：
Hibino, Satoshi;Sasaki, Hiroshi;Itabashi, Kazuo
遗传性肾小管发育不全（RTD）是由编码肾素-血管紧张素系统（RAS）组分的基因突变引起的。RTD的特征是羊水过少、肾衰竭、新生儿低颅和严重低血压。其组织学特征、发病机制和长期预后仍不清楚。我们在此报告一例4岁女性RTD。内分泌分析显示，低血浆肾素活性和高活性肾素浓度之间的差异，提示损失的肾素底物，血管紧张素原（AGT）。直接测序显示AGT基因第5外显子第1,355位核苷酸移码缺失。虽然组织学标志被认为是近端小管的缺失或发育不良，但患者的近端小管功能受损程度最低。在大约一半的肾小球中观察到无肾小球簇的肾小球囊肿。尿浓缩能力和钠重吸收和钾排泄在远端肾单位受到严重影响。尽管近端小管的功能受到轻微影响，但患者的远端肾单位功能受损，可能归因于肾小管发育不良和胎儿低灌注。肾小管的成熟程度和缺血损伤的严重程度可能是RTD临床症状和病理改变的关键决定因素，RAS在其中起着重要作用。
Inherited renal tubular dysgenesis (RTD) is caused by mutations in the genes encoding the components of the renin-angiotensin system (RAS). RTD is characterized by oligohydramnios, renal failure, neonatal hypocalvaria, and severe hypotension. The histological characteristics, underlying mechanism, and long-term prognosis remain poorly known.We describe here a 4-year-old female with RTD. Endocrinologic analysis showed a discrepancy between low plasma renin activity and high active renin concentration, suggesting a loss of the renin substrate, angiotensinogen (AGT). Direct sequencing revealed a frameshift deletion at nucleotide 1,355 in exon 5 in the AGT gene. Although a histological hallmark is regarded to be the absence or poor development of the proximal tubule, the patient does have minimally impaired function of the proximal tubule. Glomerular cysts without glomerular tufts were noted in approximately half of the glomeruli. The urinary concentrating ability and sodium reabsorption and potassium excretion in the distal nephron were severely affected.The patient has an impaired function of the distal nephron despite minimally affected function of the proximal tubule, probably attributed to renal tubular dysgenesis and fetal hypoperfusion. The renal tubular maturity and the severity of ischemic injury may be key determinants of the clinical symptoms and pathological findings in RTD, in which the RAS plays an important role.