Cardiovascular Autonomic Control in Normotensive Patients with Autosomal Dominant Polycystic Kidney Disease

Key Points Systemic arterial hypertension is a frequent early onset manifestation in autosomal dominant polycystic kidney disease (ADPKD) contributing to progression. Assessment of cardiovascular autonomic function in young patients with ADPKD before hypertension or renal decline revealed no abnormalities. Findings showed no autonomic dysfunction, but high urinary angiotensinogen suggests early intrarenal renin angiotensin-aldosterone system activation in normotensive patients with ADPKD. Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, leading to progressive renal function loss. Systemic arterial hypertension is a frequent early-onset extrarenal manifestation with an incompletely understood pathogenesis. Therefore, this study investigated cardiovascular autonomic control at rest and during physiological sympathetic stimulation, along with humoral and urinary molecules involved in BP regulation, in young patients with ADPKD before hypertension and renal dysfunction onset. Methods Eighteen normotensive patients with ADPKD (11 female/7 male, 27.7±6.4 years) and 19 age- and sex-matched healthy controls (9 female/10 male, 25.7±3.8 years) participated in this study. Based on Mayo Clinic imaging criteria, patients with ADPKD were classified as rapid or slow progressors. Heart rate variability, BP variability, and spontaneous baroreflex sensitivity (BRS) were assessed at rest, with BRS further evaluated during the Valsalva maneuver. Cardiovascular reactivity to sympathoexcitation was examined using the cold pressor test, Stroop test, and static handgrip exercise. Neuropeptide Y, angiotensinogen (AGT), and inflammatory and endothelial function markers were measured in blood, whereas monocyte chemoattractant protein-1, AGT, and albumin were analyzed in urine. Results Heart rate variability, BP variability, BRS, and cardiovascular reactivity did not differ between patients and controls or between rapid and slow progressors. Serum markers and urinary monocyte chemoattractant protein-1 were also not different between groups. However, urinary AGT and albumin levels were significantly higher in patients. Conclusions These findings suggest that cardiovascular autonomic dysregulation, systemic inflammation, and endothelial dysfunction are absent in early-stage ADPKD, whereas intrarenal renin-angiotensin-aldosterone system is overactivated and potentially plays a key role in triggering hypertension.