Cardiac complications in autosomal dominant polycystic kidney disease: links to genotype and CKD severity

TL;DR

This study finds that heart issues in a kidney disease are linked to specific genetic mutations and disease severity, which could help personalize treatment.

Contribution

The study identifies novel genotype-phenotype correlations between PKD1 mutations and cardiac complications in ADPKD.

Findings

Left ventricular hypertrophy is independently associated with PKD1 mutations.

Aortic regurgitation correlates with larger kidney size and worse kidney function.

Mitral valve prolapse is linked to truncating PKD1 mutations.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1/PKD2 mutations, features renal and extrarenal manifestations including valvulopathies and left ventricular hypertrophy (LVH), which increase mortality. Associations between these cardiac abnormalities and the ADPKD genotype or disease severity remain poorly defined. We investigated the prevalence and associations of valvulopathies and LVH with renal function, renal size, systemic features and genotype in ADPKD.

This retrospective, single-centre study analysed 154 adult ADPKD patients. Data included echocardiography (LVH, valvulopathies), abdominal ultrasound (renal diameter), cranial magnetic resonance imaging, estimated glomerular filtration rate (eGFR) and genetic testing (PKD1/PKD2 mutations) in 87 patients. Associations were assessed using appropriate statistical tests including logistic regression for multivariable analysis.

Aortic regurgitation was associated with larger mean renal diameter (P = .027) and lower eGFR (P < .001). However, when adjusted for gender and age the associations are no longer significant. Interventricular septal thickness correlated positively with renal diameter (r = +0.32, P < .001) and negatively with eGFR (r = −0.39, P < .001). Left ventricular hypertrophy (LVH, prevalence 30%) was significantly associated with PKD1 mutations (PKD1 non-truncating versus PKD2 adjusted P-value = .011; PKD1 truncating versus PKD2 adjusted P-value = .011), independent of hypertension, age, sex and anaemia (adjusted OR 8.5, P = .008). Mitral valve prolapse was associated with truncating PKD1 mutations (P = .007), independent of hypertension, age, sex and anaemia (adjusted OR 3.950, P = .037). No associations were found with hepatic, pancreatic or intracranial cysts/aneurysms.

This study demonstrates an independent association between LVH and PKD1 mutations and links aortic regurgitation with renal disease severity in ADPKD. These findings highlight genotype–phenotype correlations that may help stratify cardiovascular risk and inform personalized management in ADPKD.

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