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September 5, 2025Open Access

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

DRDaniel Ribeiro da RochaUniversidade Federal de São Paulo AAAna Carolina AnauateFundação de Apoio à Universidade Federal de São Paulo MOMilene Subtil OrmanjiFundação de Apoio à Universidade Federal de São Paulo

Key Points

Cardiovascular autonomic dysregulation was absent in early-stage ADPKD patients without hypertension.
Heart rate variability, blood pressure variability, and baroreflex sensitivity showed no significant differences between patients and controls.
Urinary levels of angiotensinogen and albumin were significantly elevated in ADPKD patients compared to healthy controls.
These findings suggest that the overactive renin-angiotensin-aldosterone system may contribute to hypertension onset.

Abstract

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 blood pressure (BP) regulation, in young ADPKD patients before hypertension and renal dysfunction onset. Methods: Eighteen normotensive ADPKD patients (11F/7M, 27.7 ± 6.4 years) and 19 age- and sex-matched healthy controls (9F/10M, 25.7 ± 3.8 years) participated in the study. Based on Mayo Clinic imaging criteria, ADPKD patients were classified as rapid or slow progressors. Heart rate variability (HRV), BP variability (BPV), 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, while monocyte chemoattractant protein-1 (MCP-1), AGT, and albumin were analyzed in urine. Results: HRV, BPV, BRS, and cardiovascular reactivity did not differ between patients and controls or between rapid and slow progressors. Serum markers and urinary MCP-1 were also no difference 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 RAAS is overactivated and potentially plays a key role in triggering hypertension.

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