Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease

Abstract

Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin–angiotensin–aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P < 0.05) at an early stage of the disease.In this study, we showed a high prevalence of PA in ADPKD patients, associated to higher LVMI, HOMA-IR, Hcy, lower FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with ADPKD is recommended.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

“…Several lines of evidence, suggest a hyperactivation of renin-angiotensin-aldosterone system (RAAS), with ectopic production of renin, angiotensinogen , angiotensin-converting enzyme and angiotensin II by cystic epithelium [2, 12]. Angiotensin II seems to represent the main stimulus for the production of aldosterone, and the presence of hyperaldosteronism in ADPKD, could contribute to the development of insulin resistance and endothelial dysfunction, with impaired nitric oxide-related vasorelaxation, and progression of cardiorenal disease [15]. Recently, some authors showed an essential role of the cilia in proper development of the vascular system [16].…”

“…Mutations in PC1 and PC2, transmembranes glicoproteins that are colocalized to the primary cilium of the kidney tubular epithelial cells, cause lower intracellular levels of calcium and increased intracellular cyclic adenosine monophosphate, with aberrant cell proliferation and fluid secretion into cysts [11-13]. ADPKD is a systemic disease, that may involve different organs, showing a high phenotypic variability [14-15], and cardiovascular complications are the major cause of morbidity and mortality, with a cardiac-related death that is estimated to be 1.6- to 3.2-fold higher in these patients than in the general population [16-17]. Currently, there are no prognostic tools to identify ADPKD patients with high cardiovascular risk.…”

Magnetic resonance imaging 3T and total fibrotic volume in autosomal dominant polycystic kidney disease

“…Increased levels of aldosterone and angiotensin II could lead to systemic fibrosis, mitogenesis and stimulate the formation of cysts . Many studies support the evidence of the aldosterone role in determining cardiovascular damage, regardless of angiotensin II and blood pressure . Indeed the hormone could have a fibrotic effect on vascular smooth muscle cells, endothelial cells, cardiomyocytes and renal tissue .…”

“…6 Many studies support the evidence of the aldosterone role in determining cardiovascular damage, regardless of angiotensin II and blood pressure. 5,6,12 Indeed the hormone could have a fibrotic effect on vascular smooth muscle cells, endothelial cells, cardiomyocytes and renal tissue. 24 Our results showed that TFV, was correlated positively also with insulin values, ABI index and LVMI.…”

“…The normal range at rest and with normal sodium diet was 0.2–2.7 ng/mL/h. The determination of plasma aldosterone concentration (PAC) was performed by RIA tests using a commercial kit (Aldosterone Maia Kit, Adaltis Italia S.p.A., Bologna, Italy) …”