Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations
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DOI：
10.3390/jcm9010146
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Mochizuki, Toshio
中科院分区：
文献类型：
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作者：
Kataoka, Hiroshi;Fukuoka, Hinata;Mochizuki, Toshio
具有 PKD1 突变的常染色体显性多囊肾病 (ADPKD) 患者，特别是具有截短突变的患者，预后较差。然而，不同突变类型的疾病进展差异尚不清楚。本研究对 ADPKD 患者的肾脏预后进行了比较研究，根据基因型（PKD1 与 PKD2 突变）、突变类型（截短突变：无义突变、移码突变、剪接突变和大缺失；非截短突变：替换和框内缺失）和突变位置进行分类。共有 123 名就诊的患者入组。具有 PKD1 剪接、PKD1 移码和 PKD2 剪接突变的患者的肾脏预后较差。尽管存在截短突变，但具有无义突变的患者的肾脏预后相对有利。五分之三的 PKD2 突变患者在 58 岁之前需要肾脏替代治疗。总之，我们发现肾脏预后根据 PKD1 和 PKD2 突变类型的不同而不同，并且对于 PKD1 截短突变患者中的无义突变患者有利。还证实，PKD2 突变患者的肾脏预后并不总是有利。突变类型的详细评估可能有助于预测 ADPKD 患者的肾脏预后。
Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. However, the differences in disease progression with different mutation types are unclear. Here, a comparative study was conducted on the renal prognosis of patients with ADPKD who were categorized based on genotype (PKD1 versus PKD2 mutation), mutation type (truncating mutation: nonsense, frameshift, splicing mutation, and large deletion; non-truncating mutation: substitution and in-frame deletion), and mutation position. A total of 123 patients visiting our hospital were enrolled. Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.