#3329 Autonomic modulation in normotensive ADPKD patients

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Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, leading to progressive loss of kidney function. Arterial hypertension (AH) is one of the most common and early-onset extrarenal manifestation, whose pathogenesis is multifactorial. Autonomic dysregulation is associated with an increased risk for all cardiovascular events in the general population, having already been described among ADPKD patients with AH and reduced renal function. The present study aimed to investigate cardiovascular autonomic regulation in ADPKD before the development of AH. Method Cardiovascular autonomic modulation parameters at rest, baroreflex sensitivity (BRS), and cardiovascular reactivity were evaluated in young patients (18 to 40 years old) with ADPKD, normotensive, and with preserved renal function. The control group consisted of healthy individuals, matched by age, sex, and body mass index (BMI). Heart rate (HR), blood pressure (BP) variability (HRV and BPV), and spontaneous BRS during the 5-minute rest were determined. The analysis of BRS during the Valsalva maneuver (VM) and cardiovascular reactivity during and after sympathoexcitatory maneuvers using the Stroop test, Cold pressor test (CPT), and Handgrip (HG) were also evaluated. Cardiovascular monitoring was performed using the Finapres device. ADPKD patients were classified according to Mayo Clinic imaging criteria (MIC) as between slow or rapid progressors. Results A total of 37 individuals were evaluated, 18 with ADPKD (11F/7M, 27.7 ± 6.4 years) and 19 controls (9F/10M, 25.7 ± 3.8 years), with no statistical differences in the distributions of sex, age, and mean BMI and estimated glomerular filtration rate (eGFR). HRV and BPV did not reveal statistical differences in either the time or frequency domains, demonstrating that the sympathovagal balance was similar among groups. The values of spontaneous BRS and the ones presented during the VM were similar between groups, suggesting an adequate baroreflex response at rest and to the sudden drop in blood pressure. Cardiovascular reactivity during sympathoexcitatory maneuvers revealed no differences between groups. The results of all these tests also did not show statistical differences between subgroups of ADPKD patients with slow versus rapid progression. Serum markers of inflammation, endothelial function, and hormones, such as neuropeptide Y and angiotensinogen did not differ between ADPKD and controls. However, urinary angiotensinogen and albuminuria levels were significantly higher in ADPKD. Conclusion In summary, the present study did not demonstrate cardiovascular autonomic dysregulation in normotensive ADPKD patients with preserved renal function, nor in those patients with ADPKD who were rapid progressors according to the Mayo Clinic Classification in relation to slow progressors. Serum markers of endothelial function and inflammation were not different between ADPKD patients and controls, nor between those with rapid or slow progressors. Higher levels of albuminuria and urinary angiotensinogen were observed in ADPKD patients, and a direct correlation between these parameters was observed, suggesting activation of the intrarenal Renin–Angiotensin System (RAS), already in the early stages of the disease. These findings suggest a complex interaction between the RAS and sympathetic nervous system in the regulation of albuminuria, although further studies are needed to clarify the exact mechanisms underlying this interaction in ADPKD.

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