Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease

Abstract

<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 m<sup>2</sup>. 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.

Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease

“…Regarding the secondary diagnosis of a PKD1 variant in Case 91044, it is interesting to note that CHD, including aortic coarctation, has recently been described in association with PKD1 variants. 31 As in Case 91044, other individuals demonstrated clinical features beyond those usually recognized with the genetic diagnoses. Case 91007 was found to have a well-established pathogenic variant in PTPN11; however, heterotaxy is not the CHD typically found in Noonan syndrome.…”

“…Regarding the secondary diagnosis of a PKD1 variant in Case 91044, it is interesting to note that CHD, including aortic coarctation, has recently been described in association with PKD1 variants. 31…”

Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat

“…According to reports in humans, PLCVC and renal anomalies including PKD, horseshoe kidney, and unilateral absent kidney occur simultaneously ( 5 , 33 , 34 ). In addition, among humans, autosomal-dominant PKD (ADPKD) patients have a higher frequency of congenital heart disease than the general population ( 35 ). This is because polycystin proteins encoded by PKD1 or PKD2 genes may play crucial roles in cardiac development and function.…”

Renal Denervation Helps Preserve the Ejection Fraction by Pre-Serving Endocardial-Endothelial Function During Heart Failure

“…Angiopoietins release from kidney play protective role in heart failure [22]. Also, the congenital heart disease in adults is associated with autosomal dominant polycystic kidney disease [23]. The mitochondrial implication as potential mediator of systemic inflammation, and organ crosstalk in the causation of acute kidney injury has been suggested [24].…”