Renal Vascular Resistance and Renin-Angiotensin System in the Pathogenesis of Early Hypertension in Autosomal Dominant Polycystic Kidney Disease

Ramunni, Alfonso; Saracino, A.; Esposito, Tommaso; Saliani, M.T.; Coratelli, P

doi:10.1291/hypres.27.221

Cited by 14 publications

(14 citation statements)

References 29 publications

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“…In support of the idea of a defective endothelium-dependent relaxation sustained by a reduced NO synthesis, in a previous work we found an increased intrarenal vascular resistance in patients with ADPKD still unaffected by hypertension or renal failure [29]. In these subjects, the normal values of circulating renin led us to hypothesize that, at least under baseline conditions, PRA was not involved in the increase in RVR, thus upholding the notion of a reduced NO synthesis [30].…”

Section: Discussionsupporting

confidence: 73%

Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Ramunni¹,

Brescia²,

Quaranta³

et al. 2009

Nephron Clin Pract

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Background/Aims: An endothelial dysfunction has been described in autosomal dominant polycystic kidney disease (ADPKD) before the development of hypertension and renal impairment. The aim of this work was to verify the existence of a microvascular reactivity in the early stages of ADPKD. Methods: Fifteen ADPKD normotensive patients with normal renal function underwent laser Doppler examination of the cutaneous microcirculation in basal conditions and after the warm test, as well as evaluation of plasma concentrations of some endothelial activation parameters [total cholesterol and fractions, fibrinogen, von Willebrand factor, Lp(a)]. The results were compared with those in 15 healthy subjects, 15 essential hypertensive patients and 15 hypertensive ADPKD patients with normal renal function. Results: Both basal and post-warm-test values were significantly lower in normotensive ADPKD subjects than controls (3.2 ± 1 vs. 5.8 ± 1.3 AU, p = 0.0001; 35.2 ± 10.9 vs. 50.5 ± 10.8 AU, p = 0.005, respectively). All evaluated parameters were within normal limits and comparable between normotensive ADPKD subjects and controls, except for LDL cholesterol (125 ± 18 vs. 101 ± 22 mg/dl, p = 0.01) and Lp(a), which was significantly higher in the ADPKD subjects (52.2 ± 36 vs. 6.0 ±4 mg/dl, p = 0.0006). Conclusion: Our study confirms the existence of a systemic microcirculation defect in ADPKD. The presence of high levels of Lp(a) could contribute to causing the high incidence of cardiovascular events in ADPKD.

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Section: Discussionsupporting

confidence: 73%

Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Ramunni¹,

Brescia²,

Quaranta³

et al. 2009

Nephron Clin Pract

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“…Conversely, in our study, we have not revealed a significant difference in IMT and ABI, indexes of subclinical atherosclerosis, perhaps because ADPKD patients are still in the early stages of disease. Indeed, endothelial dysfunction is an early and potentially reversible manifestation of atherosclerosis, with multifactorial etiology [52-54], and it develops in ADPKD patients, preceding the renal failure [55-56]. Atherosclerosis has been considered to play a key role in the early phases of cardiovascular disease found in ADPKD [57-59].…”

Section: Discussionmentioning

confidence: 99%

“…Three to five reproducible and consecutive waveforms with similar aspect from each kidney were obtained. These measurements were used to calculate the average RI value for each kidney, and then the average RI value for each patient was calculated as the mean of the RI in the left and right kidney [29]. We determined the peak systolic velocity and end-diastolic velocity (centimeters/second) to calculate the RRI as = [1-(end-diastolic velocity ÷ maximal systolic velocity)] x 100 [30-31].…”

Section: Methodsmentioning

confidence: 99%

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai

Mastroluca

Matino

et al. 2017

Kidney Blood Press Res

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Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O₂ uptake (V’O₂max), and O₂ uptake at lactic acid threshold (V’O₂@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V’O₂max, V’O₂max/Kg and V’O₂max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V’O₂@LT, V’O₂ @LT%, V’O₂@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

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“…Several studies have shown higher renovascular resistance in hypertensive [24][25][26] and normotensive 35 ADPKD patients compared to controls, and it has been suggested this may be indicative of increased intra-renal RAS activity. However, renovascular resistance is also increased in individuals with essential hypertension, 42 and may be no higher in ADPKD subjects than in matched essential hypertensive subjects.…”

Section: Renovascular Resistancementioning

confidence: 99%

“…Many of these studies can be criticised because the ADPKD patients were not matched with the control subjects for BP [22][23][24][25][26] and renal function. 23,24 It is likely that the raised BP itself and the expansion of extra-cellular fluid volume that occurs, particularly in those with renal impairment, will tend to suppress PRA and it is, therefore, not appropriate to use healthy …”

mentioning

confidence: 99%

Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease

Lawson

Doulton

MacGregor

2006

J Renin Angiotensin Aldosterone Syst

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Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance.There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension.A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.

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Renal Vascular Resistance and Renin-Angiotensin System in the Pathogenesis of Early Hypertension in Autosomal Dominant Polycystic Kidney Disease

Cited by 14 publications

References 29 publications

Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease

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