Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies

Abstract

Introduction: Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). Experimental evidence suggests an important role of the polycystins in cardiac development and myocardial function. To determine whether ADPKD may predispose to the development of cardiomyopathy, we have evaluated the coexistence of diagnoses of ADPKD and primary cardiomyopathy in our patients.

Methods: Clinical data were retrieved from medical records for patients with a coexisting diagnosis of ADPKD and cardiomyopathies evaluated at the Mayo Clinic (1984-2015).

Results: Among the 58 of 667 patients with available echocardiography data, 39 (5.8%) had idiopathic dilated cardiomyopathy (IDCM), 17 (2.5%) had hypertrophic obstructive cardiomyopathy, and 2 (0.3%) had left ventricular noncompaction. Genetic data were available for 19, 8, and 2 cases of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction, respectively. PKD1 mutations were detected in 42.1%, 62.5%, and 100% of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction cases, respectively. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (15%). In at least 1 patient from 3 IDMC families and 1 patient from a hypertrophic obstructive cardiomyopathy family, the cardiomyopathy did not segregate with ADPKD, suggesting that the PKD mutations may be predisposing factors rather than solely responsible for the development of cardiomyopathy.

Discussion: Coexistence of ADPKD and cardiomyopathy in our tertiary referral center cohort appears to be higher than expected by chance. We suggest that PKD1 and PKD2 mutations may predispose to primary cardiomyopathies and that genetic interactions may account for the observed coexistence of ADPKD and cardiomyopathies.

Keywords: ADPKD; cardiomyopathies; hypertrophic cardiomyopathy; idiopathic dilated cardiomyopathy; left ventricular noncompaction; polycystic kidney.

Figure 1

Study flow chart. ADPKD, autosomal polycystic kidney disease; CKD, chronic kidney disease; CMP, cardiomyopathy; EF, ejection fraction; HOCM, hypertrophic obstructive cardiomyopathy; ICD-9, International Classification of Diseases, Revision 9; IDCM, idiopathic dilated cardiomyopathy; LVNC, left ventricular noncompaction.

Figure 2

Chest and abdominal computed tomography (CT) scan in a patient with autosomal dominant polycystic kidney disease (ADPKD) and idiopathic dilated cardiomyopathy (IDCM). The patient is a 72-year-old man with ADPKD who was diagnosed with IDCM at age 58. His left ventricular ejection fraction (LVEF) was estimated at 21% at the time of this imaging. He previously underwent biventricular implantable cardiac device placement. His chest CT scan showed cardiomegaly with left ventricular enlargement (dashed lines, panels a and b). His total kidney volume was 2031 ml as measured on the CT scan of the abdomen (arrows, panels c and d).

Figure 3

Cardiac magnetic resonance imaging (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD) and hypertrophic obstructive cardiomyopathy (HOCM). (a) A 63-year-old female patient with ADPKD had cardiac MRI findings consistent with asymmetric left ventricular hypertrophy, measuring 21 mm in the basal anterior septum (marked with an asterisk). (b) A 58-year-old male patient with ADPKD had cardiac MRI, which revealed the sigmoid morphologic subtype of hypertrophic cardiomyopathy and maximal end-diastolic myocardial thickness of 19 mm at the basal anterior septum (marked with an asterisk).

Figure 4

Echocardiogram of patient with autosomal dominant polycystic kidney disease (ADPKD) and left ventricular noncompaction (LVNC). (a) A 54-year-old male patient with ADPKD who had findings consistent with noncompaction cardiomyopathy on echocardiographic evaluation. Noncompaction is noted at the apex and extends past the mid portion of the myocardium without significant impact on ejection fraction. (b) A 58-year-old female patient with ADPKD who was found to have noncompaction on echocardiographic evaluation. Noncompaction is limted to the apical myocardium only but with impact on left ventricular diastolic function.