Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Division of Nephrology, Department of Internal and Public Medicine, University of Bari, Bari, Italy.
Nephron Clinical Practice (Impact Factor: 1.4). 08/2009; 113(2):c71-5. DOI: 10.1159/000228537
Source: PubMed


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.
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.
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).
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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    ABSTRACT: Hypertension is common and occurs in a majority of autosomal dominant polycystic kidney disease (ADPKD) patients before the loss of kidney function. Hypertension relates to progressive kidney enlargement and is a significant independent risk factor for progression to ESRD. The pathogenesis of hypertension in ADPKD is complex and dependent on many factors that influence each other. Pkd1 and Pkd2 expression levels are highest in the major vessels and are present in the cilia of endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin 1 or 2 expression is associated with abnormal vascular structure and function. Pkd1/Pkd2 deficiency results in reduced nitric oxide (NO) levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Ten percent to 20% of ADPKD children show hypertension and the majority of adults are hypertensive before any loss of kidney function. Cardiac abnormalities such as left ventricular hypertrophy and carotid intimal wall thickening are present before the development of hypertension in ADPKD. The activation of the renin-angiotensin-aldosterone system occurs in ADPKD because of decreased NO production as well as bilateral cyst expansion and intrarenal ischemia. With increasing cyst size, further activation of the RAAS occurs, blood pressure increases, and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to ESRD. The inhibition of the angiotensin aldosterone system is possible with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. However, interventional studies have not yet shown benefit in slowing progression to renal failure in ADPKD. Currently, large multicenter studies are being performed to determine the beneficial effects of RAAS inhibition both early and late in ADPKD.
    Preview · Article · Mar 2010 · Advances in chronic kidney disease
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    ABSTRACT: Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
    Preview · Article · Jun 2014 · Journal of the American Society of Nephrology
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is correlated with an increased frequency of both intracranial aneurysms (ICANs), and arterial hypertension (AH). The aim of our study was to search for the association between blood pressure (BP) and ICANs in ADPKD patients. Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for ICANs with magnetic resonance angiography of the brain, and ambulatory blood pressure monitoring (ABPM). ICANs were diagnosed in 10 patients (ICAN(+) group), while in 58 were not (ICAN(-) group). The nighttime maximum diastolic blood pressure (DBP), maximum increase in DBP from measurement to measurement (positive delta of DBP) at night, and the standard deviation of the daytime mean arterial pressure were significantly higher in ICAN(+) compared to ICAN(-) patients. Additionally, in a subgroup of patients after 45 years-of-age, ICAN(+) patients had significantly higher maximum 24-hour and daytime systolic blood pressure, maximum 24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of DBP compared to ICAN(-) cases. Development of ICANs in hypertensive ADPKD patients is accompanied with higher values of some BP parameters measured by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed by ABPM, especially those after 45 years-of-age, should become candidates for screening for ICANs. © 2015 S. Karger AG, Basel.
    No preview · Article · Dec 2014 · Kidney and Blood Pressure Research