Document Detail


Hypertension in autosomal dominant polycystic kidney disease.
MedLine Citation:
PMID:  20219618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Arlene B Chapman; Konrad Stepniakowski; Frederic Rahbari-Oskoui
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Advances in chronic kidney disease     Volume:  17     ISSN:  1548-5609     ISO Abbreviation:  Adv Chronic Kidney Dis     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-11     Completed Date:  2010-06-07     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101209214     Medline TA:  Adv Chronic Kidney Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-63     Citation Subset:  IM    
Copyright Information:
2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers / therapeutic use*
Humans
Hypertension, Renal* / drug therapy,  etiology,  pathology
Polycystic Kidney, Autosomal Dominant* / complications,  drug therapy,  pathology
Renin-Angiotensin System / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
T32 DK007656/DK/NIDDK NIH HHS; U01 DK056956/DK/NIDDK NIH HHS; U01 DK056956-01/DK/NIDDK NIH HHS; U01 DK056956-02/DK/NIDDK NIH HHS; U01 DK056956-03/DK/NIDDK NIH HHS; U01 DK056956-04/DK/NIDDK NIH HHS; U01 DK056956-04S1/DK/NIDDK NIH HHS; U01 DK056956-04S2/DK/NIDDK NIH HHS; U01 DK056956-05/DK/NIDDK NIH HHS; U01 DK056956-05S1/DK/NIDDK NIH HHS; U01 DK056956-06/DK/NIDDK NIH HHS; U01 DK056956-07/DK/NIDDK NIH HHS; U01 DK056956-08/DK/NIDDK NIH HHS; U01 DK056956-09/DK/NIDDK NIH HHS; U01 DK056956-10/DK/NIDDK NIH HHS; U01 DK062408/DK/NIDDK NIH HHS; U01 DK062408-01/DK/NIDDK NIH HHS; U01 DK062408-01S1/DK/NIDDK NIH HHS; U01 DK062408-02/DK/NIDDK NIH HHS; U01 DK062408-03/DK/NIDDK NIH HHS; U01 DK062408-04/DK/NIDDK NIH HHS; U01 DK062408-05/DK/NIDDK NIH HHS; U01 DK062408-05S1/DK/NIDDK NIH HHS; U01 DK062408-06/DK/NIDDK NIH HHS; U01 DK062408-07/DK/NIDDK NIH HHS; U01 DK062408-08/DK/NIDDK NIH HHS; U01 DK062408-08S1/DK/NIDDK NIH HHS; U01 DK56956/DK/NIDDK NIH HHS; U01 DK62408/DK/NIDDK NIH HHS; UL1 RR025008/RR/NCRR NIH HHS; UL1 RR025008/RR/NCRR NIH HHS; UL1 RR025008-01/RR/NCRR NIH HHS; UL1 RR025008-02/RR/NCRR NIH HHS; UL1 RR025008-02S1/RR/NCRR NIH HHS; UL1 RR025008-03/RR/NCRR NIH HHS; UL1 RR025008-03S1/RR/NCRR NIH HHS; UL1 RR025008-03S2/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers
Comments/Corrections

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