Increased prevalence of kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.

IF 4.8 2区 医学 Q1 TRANSPLANTATION
Mónica Furlano, Melissa Pilco-Teran, Marc Pybus, Víctor Martínez, Miriam Aza-Carmona, Asunción Rius Peris, Vanessa Pérez-Gomez, Gerson Berná, Jaime Mazon, Jonathan Hernández, Leonor Fayos de Arizón, Elizabet Viera, Ignasi Gich, Hugo Vergara Pérez, Elena Gomá-Garcés, José Luis Albero Dolon, Elisabet Ars, Roser Torra
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引用次数: 0

Abstract

Background: Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3/COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4-related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4 and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3/COL4A4 genes is assessed in this study.

Methods: We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, estimated glomerular filtration rate (eGFR) and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population.

Results: Half of the individuals with P/LP variants in COL4A3/COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (P < .001). No association was found between KC and proteinuria, sex or causative gene.

Conclusions: Individuals with COL4A3/COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals.

携带杂合子 COL4A3 或 COL4A4 致病变体的人患肾囊肿的几率增加。
背景:COL4A3/COL4A4基因杂合致病/可能致病(P/LP)变异体(又称常染色体显性Alport综合征或COL4A3/COL4A4相关疾病)患者的临床变异性很大;许多患者无症状或表现为微量血尿,而另一些患者则可能出现蛋白尿和慢性肾脏疾病(CKD)。单纯性肾囊肿(KC)在普通人群中的发病率因年龄而异,晚期 CKD 患者很容易患上这种疾病。在小规模队列中描述了杂合子 COL4A3、COL4A4 和 COL4A5 P/LP 变异与 KC 之间可能存在的关联。本研究评估了一个多中心队列中 COL4A3/COL4A4 基因杂合子 P/LP 变异个体中是否存在 KC:我们通过超声波评估了157名未接受肾脏替代治疗的COL4A3(40.7%)或COL4A4(53.5%)基因P/LP变异者中是否存在KC。分析了 KC 的存在与年龄、蛋白尿、eGFR 和致病基因之间的关联。KC的患病率与普通人群中的历史病例系列进行了比较:结果:一半 COL4A3/COL4A4 P/LP 变体患者出现 KC,这一比例明显高于普通人群。只有3.8%(6/157)的患者患有囊性肾病。年龄和 eGFR 与 KC 的存在有关联(p 结论:与普通人群相比,COL4A3/COL4A4 P/LP变异体的患者更容易患上KC,而且KC的出现与年龄和eGFR有关。蛋白尿、性别或致病基因都不会影响这些人是否出现 KC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nephrology Dialysis Transplantation
Nephrology Dialysis Transplantation 医学-泌尿学与肾脏学
CiteScore
10.10
自引率
4.90%
发文量
1431
审稿时长
1.7 months
期刊介绍: Nephrology Dialysis Transplantation (ndt) is the leading nephrology journal in Europe and renowned worldwide, devoted to original clinical and laboratory research in nephrology, dialysis and transplantation. ndt is an official journal of the [ERA-EDTA](http://www.era-edta.org/) (European Renal Association-European Dialysis and Transplant Association). Published monthly, the journal provides an essential resource for researchers and clinicians throughout the world. All research articles in this journal have undergone peer review. Print ISSN: 0931-0509.
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