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• W2055448210 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. 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. Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder and the most common hereditary kidney disease, occurring in approximately 1:1,000 individuals.1Gabow P.A. Autosomal dominant polycystic kidney disease.N Engl J Med. 1993; 329: 332-342Crossref PubMed Scopus (863) Google Scholar Renal manifestations of ADPKD are characterized by gradual cystic expansion resulting in enlarged kidneys ultimately progressing to renal failure in the 5th decade of life.1Gabow P.A. Autosomal dominant polycystic kidney disease.N Engl J Med. 1993; 329: 332-342Crossref PubMed Scopus (863) Google Scholar, 2Torres V.E. Harris P.C. Autosomal dominant polycystic kidney disease: The last 3 years.Kidney Int. 2009; 76: 149-168Crossref PubMed Scopus (453) Google Scholar, 3Chapman A.B. Approaches to testing new treatments in autosomal dominant polycystic kidney disease: Insights from the CRISP and HALT-PKD studies.Clin J Am Soc Nephrol. 2008; 3: 1197-1204Crossref PubMed Scopus (86) Google Scholar Extrarenal manifestations of ADPKD include hypertension, liver cystic disease, intracranial aneurysms, inguinal and ventral hernias, diverticular disease, arachnoid, thyroid, pancreatic and splenic cysts, and abnormalities in the seminal vesicle cysts. The commonest cause of death in ADPKD patients in the postdialysis era is cardiovascular.4Perrone R.D. Ruthazer R. Terrin N.C. Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: Contribution of extrarenal complications to mortality.Am J Kidney Dis. 2001; 38: 777-784Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar, 5Rahman E. Niaz F.A. Al-Suwaida A. et al.Analysis of causes of mortality in patients with autosomal dominant polycystic kidney disease: A single center study.Saudi J Kidney Dis Transpl. 2009; 20: 806-810PubMed Google Scholar Autopsy studies of ADPKD individuals dying because of cardiovascular causes show significant and severe cardiac hypertrophy (>92%) as well as accompanying coronary artery disease (85%). Although cerebrovascular deaths in ADPKD are relatively uncommon, hypertension appears to play an important role in both intracranial and subarachnoid hemorrhage.6Chang M.Y. Kuok C.M. Chen Y.C. et al.Comparison of intracerebral hemorrhage and subarachnoid hemorrhage in patients with autosomal-dominant polycystic kidney disease.Nephron Clin Pract. 2009; 114: c158-c164Crossref PubMed Scopus (10) Google Scholar Hypertension is common and occurs in the majority of adults before the loss of kidney function,7Chapman A.B. Guay-Woodford L.M. Grantham J.J. et al.Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort.Kidney Int. 2003; 64: 1035-1045Crossref PubMed Scopus (316) Google Scholar, 8Chapman A.B. Gabow P.A. Hypertension in autosomal dominant polycystic kidney disease.Kidney Int Suppl. 1997; 61: S71-S73PubMed Google Scholar, 9Schrier R.W. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2009; 20: 1888-1893Crossref PubMed Scopus (111) Google Scholar unlike other renal diseases. Hypertension relates to progressive kidney enlargement and is a significant independent risk factor for progression to ESRD,10Iglesias C.G. Torres V.E. Offord K.P. et al.Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota: 1935-1980.Am J Kidney Dis. 1983; 2: 630-639PubMed Google Scholar, 11Gabow P.A. Johnson A.M. Kaehny W.D. et al.Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease.Kidney Int. 1992; 41: 1311-1319Crossref PubMed Scopus (444) Google Scholar with a diagnosis of hypertension before age 35 identifying the subset of ADPKD patients most likely to progress to renal failure.11Gabow P.A. Johnson A.M. Kaehny W.D. et al.Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease.Kidney Int. 1992; 41: 1311-1319Crossref PubMed Scopus (444) Google Scholar The pathogenesis of hypertension in ADPKD is complex and depends on many interrelated factors that influence each other. Whether hypertension is caused by abnormal endothelial or vascular function related to decreased polycystin expression or secondary to renal cystic expansion and intrarenal ischemia is unclear. Given that cardiovascular causes account for the majority of deaths in ADPKD and that hypertension directly relates to cardiovascular morbidity and mortality, understanding and treating hypertension in ADPKD is worthy of careful attention. Polycystin 1 and 2 are the protein products of the PKD1 and PKD2 genes. Pkd1 expression data from heterozygous and homozygous knockout mouse models as well as isolated endothelial and vascular smooth muscle cells show defects in vascular function. Homozygous mice with a targeted mutation in Pkd1 die in utero at midgestation because of major developmental cardiovascular defects including double outflow right ventricles, disorganized myocardium, and abnormal atrioventricular septation as well as subcutaneous edema and massive peripheral and pericardial hemorrhage caused by focal vascular leaks and rupture of blood vessels.12Boulter C. Mulroy S. Webb S. et al.Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene.Proc Natl Acad Sci U S A. 2001; 98: 12174-12179Crossref PubMed Scopus (255) Google Scholar During embryogenesis, Pkd1 expression is detected first in the neural crest and aorta and later in all major vessels. Pkd1 expression is present in all structures of the heart during embryonic development with the highest expression in the outflow tracts, endocardial cushions, and valve leaflets with lower expression in the myocardium. Cardiac manifestations differ across different Pkd1 mutant mice strains,13Wu G. Markowitz G.S. Li L. et al.Cardiac defects and renal failure in mice with targeted mutations in Pkd2.Nat Genet. 2000; 24: 75-78Crossref PubMed Scopus (299) Google Scholar, 14McGrath J. Somlo S. Makova S. et al.Two populations of node monocilia initiate left-right asymmetry in the mouse.Cell. 2003; 114: 61-73Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar, 15Kim K. Drummond I. Ibraghimov-Beskrovnaya O. et al.Polycystin 1 is required for the structural integrity of blood vessels.Proc Natl Acad Sci U S A. 2000; 97: 1731-1736Crossref PubMed Scopus (270) Google Scholar, 16Lantinga-van Leeuwen I.S. Dauwerse J.G. Baelde H.J. et al.Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease.Hum Mol Genet. 2004; 13: 3069-3077Crossref PubMed Scopus (255) Google Scholar, 17Lu W. Peissel B. Babakhanlou H. et al.Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation.Nat Genet. 1997; 17: 179-181Crossref PubMed Scopus (380) Google Scholar suggesting that the site or type of mutation in human PKD1 may play an important role in cardiac development. Similar to humans with ADPKD, pathologic phenotypes are indistinguishable for Pkd1- and Pkd2-targeted mutant mice; however, Pkd1 and Pkd2 expression patterns (polycystin 1 and 2) differ.13Wu G. Markowitz G.S. Li L. et al.Cardiac defects and renal failure in mice with targeted mutations in Pkd2.Nat Genet. 2000; 24: 75-78Crossref PubMed Scopus (299) Google Scholar Pkd2 plays a central role in nodal cilia,14McGrath J. Somlo S. Makova S. et al.Two populations of node monocilia initiate left-right asymmetry in the mouse.Cell. 2003; 114: 61-73Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar which regulates normal axis determination including the heart. Homozygous mutant embryos show right pulmonary isomerism, randomization of embryonic turning, heart looping, abdominal situs, defects in cardiac septation and focal hemorrhage, and total body edema.13Wu G. Markowitz G.S. Li L. et al.Cardiac defects and renal failure in mice with targeted mutations in Pkd2.Nat Genet. 2000; 24: 75-78Crossref PubMed Scopus (299) Google Scholar, 18Pennekamp P. Karcher C. Fischer A. et al.The ion channel polycystin-2 is required for left right axis determination in mice.Curr Biol. 2002; 4: 938-943Abstract Full Text Full Text PDF Scopus (368) Google Scholar Pkd1 expression appears to be more developmentally regulated than Pkd2 where more constant expression levels are found during embryonic development and throughout the postnatal period. Expression levels of Pkd1 are high throughout the heart in adult mice.12Boulter C. Mulroy S. Webb S. et al.Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene.Proc Natl Acad Sci U S A. 2001; 98: 12174-12179Crossref PubMed Scopus (255) Google Scholar Expression is highest in the aortic outflow tract and atrial appendages and in endothelial and vascular smooth muscle cells of the major vessels including the aorta and intracranial arteries. Notably, Pkd1 is expressed in adult afferent arterioles15Kim K. Drummond I. Ibraghimov-Beskrovnaya O. et al.Polycystin 1 is required for the structural integrity of blood vessels.Proc Natl Acad Sci U S A. 2000; 97: 1731-1736Crossref PubMed Scopus (270) Google Scholar and hypomorphic Pkd1 allele mice, a murine model of ADPKD that survives embryonic development and shows a vascular phenotype show systemic dissecting aneurysms.19Hassane S. Claij N. Lantinga-van Leeuwen I.S. et al.Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model.Arterioscler Thromb Vasc Biol. 2007; 27: 2177-2183Crossref PubMed Scopus (62) Google Scholar In Pkd2+/- mice intracranial vascular abnormalities are observed when hypertension is induced. Both Pkd 1 and 2 are expressed in endothelial and vascular smooth muscle cells of all major vessels. Impaired endothelial-dependent relaxation has been shown from cells of aortas from Pkd1 knockout mice because of a defect in nitric oxide (NO) release from the endothelium correlating with a decrease in Ca2+-dependent endothelial NO syntheses activity.19Hassane S. Claij N. Lantinga-van Leeuwen I.S. et al.Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model.Arterioscler Thromb Vasc Biol. 2007; 27: 2177-2183Crossref PubMed Scopus (62) Google Scholar Interactions between polycystin 1 and 2 have been shown in vascular smooth muscle cells in the sarcoplasmic membrane, suggesting a central role in regulating intracellular Ca2+ levels.20Qian Q. Li M. Cai Y. et al.Analysis of the polycystins in aortic vascular smooth muscle cells.J Am Soc Nephrol. 2003; 14: 2280-2287Crossref PubMed Scopus (78) Google Scholar In Pkd2+/- mice, vascular smooth muscle cells show altered intracellular Ca2+ homeostasis with reduced total intracellular and sarcoplasmic reticulum Ca2+ levels.21Qian Q. Hunter L.W. Li M. et al.Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells.Hum Mol Genet. 2003; 12: 1875-1880Crossref PubMed Scopus (144) Google Scholar Polycystin 2, which is normally conserved in drosophila, when reduced or when haploinsufficiency is present results in altered smooth muscle contractility.22Gao Z. Joseph E. Ruden D.M. et al.Drosophila Pkd2 is haploid-insufficient for mediating optimal smooth muscle contractility.J Biol Chem. 2004; 279: 14225-14231Crossref PubMed Scopus (40) Google Scholar Importantly, recent investigations have shown that stretch-activated channels that respond to significant changes in vascular tone are regulated by polycystin1:2 complexes in vascular smooth muscle cells. Polycystin 1 and 2 colocalize to the cilia of mouse and human vascular endothelial cells.23Nauli S.M. Kawanabe Y. Kaminski J.J. et al.Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1.Circulation. 2008; 117: 1161-1171Crossref PubMed Scopus (354) Google Scholar Normal polycystin 1 and 2 function are required for endothelial cilia to sense fluid shear stress through a complex biochemical cascade involving calcium, calmodulin Akt/PKG, and protein kinase C.15Kim K. Drummond I. Ibraghimov-Beskrovnaya O. et al.Polycystin 1 is required for the structural integrity of blood vessels.Proc Natl Acad Sci U S A. 2000; 97: 1731-1736Crossref PubMed Scopus (270) Google Scholar, 23Nauli S.M. Kawanabe Y. Kaminski J.J. et al.Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1.Circulation. 2008; 117: 1161-1171Crossref PubMed Scopus (354) Google Scholar, 24Abou Alaiwi W.A. Takahashi M. Mell B.R. et al.Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades.Circ Res. 2009; 104: 860-869Crossref PubMed Scopus (234) Google Scholar Normal endothelial cells exposed to fluid shear stress over hours result in polycystin 1 undergoing proteolytic cleavage. Abnormal ciliary polycystin-2 function leads to compromised fluid sensing as well, which impairs the synthesis of NO, a mediator for other downstream signaling pathways involved in vascular smooth muscle relaxation. In response to fluid shear stress, mouse Pkd2-/- endothelial cells lose the ability to generate NO. Therefore, it appears that polycystin 1 and 2 may have a specific shear-sensing role in endothelial cilia. Data from large ADPKD registries indicate that blood pressures are elevated on average by 4 to 6 mm Hg in children as compared with unaffected age- and sex-matched controls. Ten percent to 20% show hypertension or blood pressures greater than the 95th percentile reported for age and sex when measured in the medical office.25Fick-Brosnahan G.M. Tran Z.V. Johnson A.M. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Crossref PubMed Scopus (122) Google Scholar, 26Rizk D. Jurkovitz C. Veledar E. et al.Quality of life in autosomal dominant polycystic kidney disease patients not yet on dialysis.Clin J Am Soc Nephrol. 2009; 4: 560-566Crossref PubMed Scopus (61) Google Scholar Ambulatory blood pressure monitoring (ABPM) shows an increased rate of detection of hypertension compared with office blood pressure measurements (34% vs 16%).26Rizk D. Jurkovitz C. Veledar E. et al.Quality of life in autosomal dominant polycystic kidney disease patients not yet on dialysis.Clin J Am Soc Nephrol. 2009; 4: 560-566Crossref PubMed Scopus (61) Google Scholar Specifically, ADPKD boys show a reduced day:night systolic and diastolic blood pressure ratios versus unaffected age-matched controls,26Rizk D. Jurkovitz C. Veledar E. et al.Quality of life in autosomal dominant polycystic kidney disease patients not yet on dialysis.Clin J Am Soc Nephrol. 2009; 4: 560-566Crossref PubMed Scopus (61) Google Scholar with more than 25% showing a lack of normal nocturnal decline in blood pressure. Whether home blood pressure monitoring is as effective in detecting hypertension in ADPKD children as ABPM has not yet been determined. Elevations in systolic and diastolic blood pressure and left ventricular mass index (LVMI) are found in affected versus unaffected children.25Fick-Brosnahan G.M. Tran Z.V. Johnson A.M. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Crossref PubMed Scopus (122) Google Scholar, 27Ivy D.D. Shaffer E.M. Johnson A.M. et al.Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 1995; 5: 2032-2036PubMed Google Scholar Cardiac valve abnormalities occur with increased frequency in ADPKD children, specifically mitral valve prolapse and aortic insufficiency. ADPKD children show significantly greater LVMI in hypertensive subgroups that associate with systolic or diastolic blood pressure.28Cadnapaphornchai M.A. McFann K. Strain J.D. et al.Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension.Kidney Int. 2008; 74: 1192-1196Crossref PubMed Scopus (86) Google Scholar ADPKD children with increased blood pressure or hypertension show greater kidney volume, greater cyst number, and a greater rate of increase in kidney volume in comparison to age-matched normotensive ADPKD children.25Fick-Brosnahan G.M. Tran Z.V. Johnson A.M. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Crossref PubMed Scopus (122) Google Scholar, 28Cadnapaphornchai M.A. McFann K. Strain J.D. et al.Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension.Kidney Int. 2008; 74: 1192-1196Crossref PubMed Scopus (86) Google Scholar In addition, normotensive children show a significant correlation between kidney volume and systolic and diastolic blood pressures to a greater extent than that observed in ADPKD adults.28Cadnapaphornchai M.A. McFann K. Strain J.D. et al.Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension.Kidney Int. 2008; 74: 1192-1196Crossref PubMed Scopus (86) Google Scholar These observations have been confirmed using ABPM in 58 ADPKD children in whom kidney volume correlates with daytime systolic and nighttime systolic and diastolic blood pressures.29Seeman T. Dusek J. Vondrichova H. et al.Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease.Blood Press Monit. 2003; 8: 107-110Crossref PubMed Scopus (66) Google Scholar Renal concentrating ability, which is decreased in approximately half of ADPKD children, is more often present in those who are hypertensive. Importantly, concentrating ability is inversely associated with ABPM systolic and diastolic pressures and the number of renal cysts.30Seeman T. Dusek J. Vondrak K. et al.Renal concentrating capacity is linked to blood pressure in children with autosomal dominant polycystic kidney disease.Physiol Res. 2004; 53: 629-634PubMed Google Scholar Decreased concentrating ability in ADPKD is associated with increased circulating vasopressin levels31Torres V.E. Role of vasopressin antagonists.Clin J Am Soc Nephrol. 2008; 3: 1212-1218Crossref PubMed Scopus (42) Google Scholar potentially accounting for the elevations in blood pressure seen in ADPKD children. To date, the evaluation of systemic vascular (ie, forearm vascular reactivity) or cardiac (ejection fraction, ventricular relaxation, pulse wave velocity, or carotid wall thickness) function has not been evaluated in ADPKD children. Normotensive ADPKD adults show increased LVMI versus unaffected age and sex-matched controls,32Doulton T.W. Saggar-Malik A.K. He F.J. et al.The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients.J Hypertens. 2006; 24: 939-945Crossref PubMed Scopus (42) Google Scholar and LVMI correlates significantly throughout the range of systolic and diastolic blood pressure in normotensive ADPKD adults.33Chapman A.B. Johnson A.M. Rainguet S. et al.Left ventricular hypertrophy in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 1997; 8: 1292-1297PubMed Google Scholar, 34Valero F.A. Martinez-Vea A. Bardaji A. et al.Ambulatory blood pressure and left ventricular mass in normotensive patients with autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 1999; 10: 1020-1026PubMed Google Scholar Echocardiography in normotensive ADPKD individuals shows increased left and right ventricular mass and volumes with normal ejection fractions and decreased end-diastolic relaxation. Importantly, coronary vascular reserve is diminished in normotensive ADPKD patients compared witt healthy controls.35Turkmen K. Oflaz H. Uslu B. et al.Coronary flow velocity reserve and carotid intima media thickness in patients with autosomal dominant polycystic kidney disease: From impaired tubules to impaired carotid and coronary arteries.Clin J Am Soc Nephrol. 2008; 3: 986-991Crossref PubMed Scopus (36) Google Scholar, 36Ecder T. Schrier R.W. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease.Nat Rev Nephrol. 2009; 5: 221-228Crossref PubMed Scopus (167) Google Scholar In addition, there is an exaggerated diastolic blood pressure response during exercise in normotensive ADPKD individuals suggesting an impaired capacity for exercise-induced vasodilatation.37Martinez-Vea A. Bardaj A. Gutierrez C. et al.Exercise blood pressure, cardiac structure, and diastolic function in young normotensive patients with polycystic kidney disease: A prehypertensive state.Am J Kidney Dis. 2004; 44: 216-223Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Multiple studies have shown increased carotid intimal-medial thickness in normotensive ADPKD patients and is associated with increased levels of urinary albumin excretion.35Turkmen K. Oflaz H. Uslu B. et al.Coronary flow velocity reserve and carotid intima media thickness in patients with autosomal dominant polycystic kidney disease: From impaired tubules to impaired carotid and coronary arteries.Clin J Am Soc Nephrol. 2008; 3: 986-991Crossref PubMed Scopus (36) Google Scholar, 36Ecder T. Schrier R.W. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease.Nat Rev Nephrol. 2009; 5: 221-228Crossref PubMed Scopus (167) Google Scholar, 38Azurmendi P.J. Fraga A.R. Galan F.M. et al.Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function.Nephrol Dial Transplant. 2009; 24: 2458-2463Crossref PubMed Scopus (21) Google Scholar, 39Kocaman O. Oflaz H. Yekeler E. et al.Endothelial dysfunction and increased carotid intima-media thickness in patients with autosomal dominant polycystic kidney disease.Am J Kidney Dis. 2004; 43: 854-860Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, 40Rong S. Jin X. Ye C. et al.Carotid vascular remodelling in patients with autosomal dominant polycystic kidney disease.Nephrology (Carlton). 2009; 14: 113-117Crossref PubMed Scopus (11) Google Scholar Integrated back scatter of the carotid wall, an indirect measure of local tissue fibrosis, shows increased involvement of the carotid arteries in normotensive ADPKD patients versus healthy controls.40Rong S. Jin X. Ye C. et al.Carotid vascular remodelling in patients with autosomal dominant polycystic kidney disease.Nephrology (Carlton). 2009; 14: 113-117Crossref PubMed Scopus (11) Google Scholar Endothelial-dependent relaxation is impaired in normotensive ADPKD individuals before the loss of kidney function.41Wang D. Iversen J. Wilcox C.S. et al.Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease.Kidney Int. 2003; 64: 1381-1388Crossref PubMed Scopus (123) Google Scholar Two relatively noninvasive methods that measure endothelial function, forearm brachial artery dilation in response to shear stress42Turgut F. Oflaz H. Namli S. et al.Ambulatory blood pressure and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease.Ren Fail. 2007; 29: 979-984Crossref PubMed Scopus (12) Google Scholar and ex vivo exposure of resistance vessels to increasing doses of acetylcholine,41Wang D. Iversen J. Wilcox C.S. et al.Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease.Kidney Int. 2003; 64: 1381-1388Crossref PubMed Scopus (123) Google Scholar have been tested in patients with ADPKD. Both show a diminished capability of the endothelium to respond appropriately to vasodilatory stressors. Brachial artery dilatory capacity is reduced approximately 10% to 30%39Kocaman O. Oflaz H. Yekeler E. et al.Endothelial dysfunction and increased carotid intima-media thickness in patients with autosomal dominant polycystic kidney disease.Am J Kidney Dis. 2004; 43: 854-860Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar and is associated with abnormal circadian blood pressure patterns in ADPKD.42Turgut F. Oflaz H. Namli S. et al.Ambulatory blood pressure and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease.Ren Fail. 2007; 29: 979-984Crossref PubMed Scopus (12) Google Scholar This abnormality is further exaggerated in hypertensive ADPKD patients (see later). Importantly, impaired brachial artery dilation in response to shear stress is not associated with albuminuria as has been shown with increased LVMI in ADPKD.38Azurmendi P.J. Fraga A.R. Galan F.M. et al.Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function.Nephrol Dial Transplant. 2009; 24: 2458-2463Crossref PubMed Scopus (21) Google Scholar Acetylcholine-induced endothelial-dependent relaxation is impaired in subcutaneous vessels from gluteal region in ADPKD patients.43Wang D. Iversen J. Strandgaard S. Endothelium-dependent relaxation of small resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2000; 11: 1371-1376PubMed Google Scholar This impairment is not caused by a decreased ability of vascular smooth muscle cells to respond to NO but rather defective NO generation from diminished NO synthase activity.41Wang D. Iversen J. Wilcox C.S. et al.Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease.Kidney Int. 2003; 64: 1381-1388Crossref PubMed Scopus (123) Google Scholar, 43Wang D. Iversen J. Strandgaard S. Endothelium-dependent relaxation of small resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2000; 11: 1371-1376PubMed Google Scholar Hypertension is common in ADPKD and occurs before the loss of kidney function in >60% of affected individuals7Chapman A.B. Guay-Woodford L.M. Grantham J.J. et al.Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consor" @default.
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• W2055448210 date "2010-03-01" @default.
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• W2055448210 title "Hypertension in Autosomal Dominant Polycystic Kidney Disease" @default.
• W2055448210 cites W106821638 @default.
• W2055448210 cites W1783360620 @default.
• W2055448210 cites W1933284538 @default.
• W2055448210 cites W1964323043 @default.
• W2055448210 cites W1969212379 @default.
• W2055448210 cites W1970019484 @default.
• W2055448210 cites W1975348834 @default.
• W2055448210 cites W1978553685 @default.
• W2055448210 cites W1980677775 @default.
• W2055448210 cites W1985685880 @default.
• W2055448210 cites W1998739441 @default.
• W2055448210 cites W1999095798 @default.
• W2055448210 cites W2002859651 @default.
• W2055448210 cites W2003784194 @default.
• W2055448210 cites W2005068861 @default.
• W2055448210 cites W2005153420 @default.
• W2055448210 cites W2006771871 @default.
• W2055448210 cites W2012159432 @default.
• W2055448210 cites W2012933903 @default.
• W2055448210 cites W2013853671 @default.
• W2055448210 cites W2016023852 @default.
• W2055448210 cites W2022633987 @default.
• W2055448210 cites W2025185391 @default.
• W2055448210 cites W2025455982 @default.
• W2055448210 cites W2028464499 @default.
• W2055448210 cites W2030927065 @default.
• W2055448210 cites W2032340185 @default.
• W2055448210 cites W2032669447 @default.
• W2055448210 cites W2033244214 @default.
• W2055448210 cites W2036935323 @default.
• W2055448210 cites W2038787817 @default.
• W2055448210 cites W2039890339 @default.
• W2055448210 cites W2048168245 @default.
• W2055448210 cites W2050080410 @default.
• W2055448210 cites W2053805783 @default.
• W2055448210 cites W2059086984 @default.
• W2055448210 cites W2062454696 @default.
• W2055448210 cites W2065840941 @default.
• W2055448210 cites W2071729123 @default.
• W2055448210 cites W2083275457 @default.
• W2055448210 cites W2098567649 @default.
• W2055448210 cites W2103557245 @default.
• W2055448210 cites W2110300199 @default.
• W2055448210 cites W2112127063 @default.
• W2055448210 cites W2113588019 @default.
• W2055448210 cites W2118994076 @default.
• W2055448210 cites W2121300543 @default.
• W2055448210 cites W2123474135 @default.
• W2055448210 cites W2125720034 @default.
• W2055448210 cites W2128219017 @default.
• W2055448210 cites W2128428095 @default.
• W2055448210 cites W2129253605 @default.
• W2055448210 cites W2132018948 @default.
• W2055448210 cites W2132710360 @default.
• W2055448210 cites W2141313696 @default.
• W2055448210 cites W2142545397 @default.
• W2055448210 cites W2142630332 @default.
• W2055448210 cites W2145441966 @default.
• W2055448210 cites W2146420434 @default.
• W2055448210 cites W2148543606 @default.
• W2055448210 cites W2150782716 @default.
• W2055448210 cites W2153747318 @default.
• W2055448210 cites W2160121026 @default.
• W2055448210 cites W2162195477 @default.
• W2055448210 cites W2165323293 @default.
• W2055448210 cites W2166718853 @default.
• W2055448210 cites W2170006225 @default.
• W2055448210 cites W2198923824 @default.
• W2055448210 cites W2254486459 @default.
• W2055448210 cites W2312400976 @default.
• W2055448210 cites W2332099696 @default.
• W2055448210 cites W2412854658 @default.
• W2055448210 cites W2413521904 @default.
• W2055448210 cites W3021964512 @default.
• W2055448210 cites W4249200213 @default.
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