Early Arterial Stiffness and Inflammatory Bio-Markers in Normotensive Polycystic Kidney Disease Patients

Abstract

Background/Aims: Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. Methods: Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. Results: Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. Conclusion: Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.

Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation

“…Arterial stiffness has been positively associated with levels of different systemic inflammatory markers in healthy individuals [9] and different patient populations [10,11]. One COPD study showed weak correlations with interleukin (IL)-6 and soluble tumour necrosis factor receptor 1 (sTNFR1), but not with sTNFR2 [7].…”

Endothelial Nitric Oxide Synthase Gene Expression Is Associated with Hypertension in Autosomal Dominant Polycystic Kidney Disease

“…Early vascular changes and endothelial dysfunction have been shown in ADPKD patients in our previous studies [8,13]. Moreover, endothelium-dependent relaxation is impaired and endothelial synthase activity is decreased in this population [14,15].…”

“…Although the activation of systemic RAS due to local cyst pressure on the renal vasculature has been a widely accepted hypothesis with regard to the development of hypertension in ADPKD, the evidence of early vascular changes and endothelial dysfunction in normotensive ADPKD patients showed the necessity of further studies in this area [5,13,14,15]. Furthermore, recent studies have shown that intrarenal RAS activation, hyperuricemia, impaired nitric oxide generation, inflammation, and increased oxidative stress could be associated with the development of hypertension in ADPKD patients [8,9,13,15,23]. In addition, genetic predisposition might be related to early occurrence of hypertension.…”

A Link between the Intrarenal Renin Angiotensin System and Hypertension in Autosomal Dominant Polycystic Kidney Disease

“…Although the precise mechanism of hypertension in early ADPKD has not yet been elucidated, early vascular changes have been shown in normotensive ADPKD patients prior to the development of hypertension [28]. Recently, we demonstrated arterial stiffness and inflammation in normotensive ADPKD patients with preserved kidney function that might be a contributing factor for early onset of hypertension [29]. Nevertheless, the pathogenesis of hypertension in ADPKD and the trigger factor remains unclear.…”