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Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited nephropathy due to mutations in PKD1 or PKD2 genes. In addition to kidney involvement, ADPKD is also characterized by extrarenal manifestations including the presence of cysts in other organs, intracranial aneurysms, arterial hypertension, valvulopathies and left ventricular hypertrophy (LVH). Cardiac abnormalities are an important cause of morbidity and mortality in ADPKD patients. Limited data on the association between these cardiovascular manifestations with phenotypic (both renal and systemic) and genotypic features of ADPKD are currently available. In this study we report the prevalence of the main cardiac abnormalities (valvulopathies, with a focus on aortic, mitral, tricuspid valve regurgitation, mitral prolapse, and LVH) observed in a large cohort of ADPKD patients, and investigated their association with renal diameter, renal function, other systemic manifestations such as pancreatic cysts, intracranial cysts, intracranial aneurysm and genotype. Method This retrospective study was conducted at the A. Gemelli Hospital, Rome in a single-center cohort of 129 ADPKD patients, who had previously undergone echocardiogram, abdominal ultrasound, brain MRI, and blood tests, between January 2018 and July 2023. Genetic testing was performed in 58 of the 129 patients. For the statistical analysis the average bilateral renal diameter of each patient was used. An interventricular septum cut-off thickness of 11 mm was used to define left ventricular hypertrophy. Non-parametric (Mann–Whitney and Spearman) and chi-square tests were applied as appropriate. Results In our cohort of 129 patients, the prevalence of valvulopathies was the following: 68% of mitral regurgitation, 22% of mitral prolapse, 20% of aortic regurgitation and 56% of tricuspid regurgitation. Left ventricular hypertrophy was identified in 28% of the entire cohort. We found that in ADPKD patients with aortic regurgitation, renal diameters are larger (p = 0.027) and the eGFR is lower (p 0.01) than in patients without this echocardiographic abnormality (Fig. 1a,b). In the subset of genotyped ADPKD patients (58), mutations in PKD 1 were associated with mitral prolapse (p = 0.02). Interventricular septal thickness, regardless of the presence of hypertrophy was positively correlated (Fig. 1c) with renal diameter (p = 0.001 r = +0.289) and negatively (Fig. 2a) with eGFR (p 0.001 r = −0.422). Both correlations, also adjusted for arterial hypertension, remained statistically significant (p = 0.008, coefficient r = +0.235 and p 0.001, coefficient r = −0.304, respectively). In addition, patients with LVH featured a larger renal diameter (p = 0.03), and a lower eGFR (p 0.001) (Fig. 2b-c). Moreover LVH was associated with the presence of PKD1 mutations (p = 0.03). Neither valvulopathies nor LVH were associated with other systemic manifestations of the disease. Conclusion We show for the first time an association of LVH with ADPKD genotype (specifically mutations in PKD1) and the association of a specific valvulopathy (aortic regurgitation) with the renal phenotype of ADPKD patients. To date only one study found an association of another valvulopathy, mitral regurgitation, with mutations in PKD1 1. Heart valves disease and LVH are risk factors for the subsequent development of further cardiovascular complications therefore understanding the pathogenetic mechanisms responsible for the higher incidence of these abnormalities in ADPKD would be useful to identify high-risk subgroups of patients and tailor personalised interventions.
Condello et al. (Wed,) studied this question.