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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
Journal of the American Society of Nephrology 06/2014; 25(11). DOI:10.1681/ASN.2013111184 · 9.34 Impact Factor
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