Supplementary Material for: Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease

<b><i>Introduction:</i></b> Autosomal dominant polycystic kidney disease (ADPKD) is caused mainly by pathogenic variants in <i>PKD1</i> or <i>PKD2</i> encoding the polycystin-1 and -2 proteins. Polycystins have shown to have an essential role in cardiac development and function in animal models. In the current study, we describe the clinical association between ADPKD and congenital heart disease (CHD). <b><i>Methods:</i></b> Medical records from Mayo Clinic were queried for all patients with confirmed ADPKD and CHD between 1993 and 2020. CHD was categorized into left-to-right shunt, obstructive, and complex lesions. Patent foramen ovale, mitral valve prolapse, and bicuspid aortic valve anomalies were excluded. <b><i>Results:</i></b> Twenty-five out of 1,359 (1.84%) ADPKD patients were identified to have CHD. Of these, 84% were Caucasians and 44% were males. The median (Q1–Q3) age (years) at CHD diagnosis was 12.0 (2.0–43.5). Fourteen patients (56%) had left-to-right shunt lesions, 6 (24%) had obstructive lesions and 5 (20%) complex lesions. Seventeen patients (68%) had their defects surgically corrected at a median age (Q1–Q3) of 5.5 (2.0–24.7). Among 13 patients with available genetic testing, 12 (92.3%) had <i>PKD1</i> pathogenic variants, and none had <i>PKD2</i>. The median (Q1–Q3) age at last follow-up visit was 47.0 (32.0–62.0) and median (Q1–Q3) eGFR was 35.8 (11.4–79.0) mL/min/1.73 m². Three patients (12%) died; all of them had left-to-right shunt lesions. <b><i>Discussion/Conclusion:</i></b> We observed a higher CHD frequency in ADPKD than the general population (1.84 vs. 0.4%). While only <i>PKD1</i> pathogenic variants were identified in this cohort, further studies are needed to confirm this novel finding and understand the role of polycystins in the development of the heart and vessels.

<b><i>引言：</i></b> 常染色体显性遗传性多囊肾病（Autosomal dominant polycystic kidney disease, ADPKD）主要由编码多囊蛋白-1和多囊蛋白-2的<i>PKD1</i>或<i>PKD2</i>基因的致病变异引发。已有研究证实，多囊蛋白在动物模型的心脏发育与功能维持中发挥关键作用。本研究旨在探讨ADPKD与先天性心脏病（Congenital heart disease, CHD）之间的临床关联。<b><i>方法：</i></b> 本研究检索了梅奥诊所（Mayo Clinic）1993年至2020年间所有确诊为ADPKD合并先天性心脏病的患者的医疗记录。将先天性心脏病分为左向右分流型、梗阻型及复杂型三类，并排除卵圆孔未闭、二尖瓣脱垂及二叶主动脉瓣畸形病例。<b><i>结果：</i></b> 本研究共纳入1359例ADPKD患者，其中25例（1.84%）合并先天性心脏病。该亚组患者中84%为白种人，44%为男性。先天性心脏病确诊时的中位年龄（四分位间距Q1~Q3）为12.0岁（2.0~43.5岁）。14例（56%）为左向右分流型病变，6例（24%）为梗阻型病变，5例（20%）为复杂型病变。17例（68%）患者接受了手术矫治，手术时的中位年龄（四分位间距Q1~Q3）为5.5岁（2.0~24.7岁）。在13例具备完整基因检测数据的患者中，12例（92.3%）携带<i>PKD1</i>致病变异，无患者携带<i>PKD2</i>致病变异。末次随访时的中位年龄（四分位间距Q1~Q3）为47.0岁（32.0~62.0岁），中位估算肾小球滤过率（estimated glomerular filtration rate, eGFR）为35.8（11.4~79.0）mL/min/1.73 m²。共有3例（12%）患者死亡，均为左向右分流型病变患者。<b><i>讨论与结论：</i></b> 本研究发现，ADPKD患者的先天性心脏病患病率（1.84%）高于普通人群（0.4%）。本队列中仅检出<i>PKD1</i>致病变异，后续仍需开展更多研究以验证这一新发现，并阐明多囊蛋白在心脏与血管发育中的作用机制。