Introduction Cystic expansion damaging the parenchyma is thought to lead to end-stage kidney disease (ESKD) in autosomal dominant polycystic kidney disease (ADPKD). Here we characterized genotypic and phenotypic attributes of ADPKD at time of ESKD. Methods This is a retrospective cross-sectional study of patients with ADPKD with ESKD evaluated at Mayo Clinic with available abdominal computed tomography (CT) or magnetic resonance imaging (MRI). Kidney volumes were measured (total kidney volume adjusted for height [HtTKV]), Mayo Image Class (MIC) calculated, ADPKD genotype determined, and clinical and laboratory features obtained from medical records. Results Differences in HtTKV at ESKD were associated with patient age and sex; older patients and women had smaller HtTKV at ESKD. HtTKV at ESKD was observed to be 12.3% smaller with each decade of age ( P < 0.01); but significant only in women (17.8%, P < 0.01; men 6.9%, P = 0.06). Patients with onset of ESKD at <47, 47–61, or >61 years had different characteristics, with a shift from youngest to oldest in male to female enrichment, MIC from 1D/1E to 1B/1C, likely fully penetrant PKD1 mutations from 95% to 42%, and presence of macrovascular disease from 8% to 40%. Macrovascular disease was associated with smaller kidneys in female patients. Conclusion HtTKV at ESKD was smaller with advancing age in patients with ADPKD, particularly in women. These novel findings provide insight into possible underlying mechanisms leading to ESKD, which differ between younger and older individuals. Cystic growth is the predominant mechanism in younger patients with ESKD, whereas aging-related factors, including vascular disease, becomes potentially important as patients age.

<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.

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