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The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease.
Am J Physiol Renal Physiol. 2004 Oct; 287(4):F775-88.AJ

Abstract

Hypertension is a common complication of autosomal dominant polycystic kidney disease (ADPKD), often present before the onset of renal failure. A role for the renin-angiotensin system (RAS) has been proposed, but studies of systemic RAS have failed to show a correlation between plasma renin activity and blood pressure in ADPKD. Ectopic renin expression by cyst epithelium was first reported in 1992 (Torres VE, Donovan KA, Sicli G, Holley KE, Thibodeau ST, Carretero OA, Inagami T, McAteer JA, and Johnson CM. Kidney Int 42: 364-373, 1992). It is not known, however, whether other RAS components are also expressed by cysts in ADPKD. We show that, in addition to renin, angiotensinogen (AGT) is produced by some cysts and dilated tubules. Angiotensin-converting enzyme, ANG II type 1 receptor, and ANG II peptide are also present within cysts and in many tubules; and some cyst fluids contain high ANG II concentrations. Additionally, cyst-derived cells in culture continue to express the components of the RAS at both the protein and mRNA levels. We further show that renin is expressed primarily in cysts of distal tubule origin and in cyst-derived cells with distal tubule characteristics, whereas AGT is expressed primarily in cysts of proximal tubule origin and in cyst-derived cells with proximal tubule characteristics. Renin production by cyst-derived cells appears to be regulated by extracellular Na+ concentration. Based on these observations, we propose a model of an autocrine/paracrine RAS in polycystic kidney disease, whereby overactivity of the intrarenal system results in sustained increases in intratubular ANG II concentrations.

Authors+Show Affiliations

Department of Pediatrics and Pediatric Research Institute, Saint Louis University, St. Louis, Missouri 07920, USA. mloghman@att.netNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15187005

Citation

Loghman-Adham, Mahmoud, et al. "The Intrarenal Renin-angiotensin System in Autosomal Dominant Polycystic Kidney Disease." American Journal of Physiology. Renal Physiology, vol. 287, no. 4, 2004, pp. F775-88.
Loghman-Adham M, Soto CE, Inagami T, et al. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol. 2004;287(4):F775-88.
Loghman-Adham, M., Soto, C. E., Inagami, T., & Cassis, L. (2004). The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. American Journal of Physiology. Renal Physiology, 287(4), F775-88.
Loghman-Adham M, et al. The Intrarenal Renin-angiotensin System in Autosomal Dominant Polycystic Kidney Disease. Am J Physiol Renal Physiol. 2004;287(4):F775-88. PubMed PMID: 15187005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. AU - Loghman-Adham,Mahmoud, AU - Soto,Carlos E, AU - Inagami,Tadashi, AU - Cassis,Lisa, Y1 - 2004/06/08/ PY - 2004/6/10/pubmed PY - 2004/10/27/medline PY - 2004/6/10/entrez SP - F775 EP - 88 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 287 IS - 4 N2 - Hypertension is a common complication of autosomal dominant polycystic kidney disease (ADPKD), often present before the onset of renal failure. A role for the renin-angiotensin system (RAS) has been proposed, but studies of systemic RAS have failed to show a correlation between plasma renin activity and blood pressure in ADPKD. Ectopic renin expression by cyst epithelium was first reported in 1992 (Torres VE, Donovan KA, Sicli G, Holley KE, Thibodeau ST, Carretero OA, Inagami T, McAteer JA, and Johnson CM. Kidney Int 42: 364-373, 1992). It is not known, however, whether other RAS components are also expressed by cysts in ADPKD. We show that, in addition to renin, angiotensinogen (AGT) is produced by some cysts and dilated tubules. Angiotensin-converting enzyme, ANG II type 1 receptor, and ANG II peptide are also present within cysts and in many tubules; and some cyst fluids contain high ANG II concentrations. Additionally, cyst-derived cells in culture continue to express the components of the RAS at both the protein and mRNA levels. We further show that renin is expressed primarily in cysts of distal tubule origin and in cyst-derived cells with distal tubule characteristics, whereas AGT is expressed primarily in cysts of proximal tubule origin and in cyst-derived cells with proximal tubule characteristics. Renin production by cyst-derived cells appears to be regulated by extracellular Na+ concentration. Based on these observations, we propose a model of an autocrine/paracrine RAS in polycystic kidney disease, whereby overactivity of the intrarenal system results in sustained increases in intratubular ANG II concentrations. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/15187005/The_intrarenal_renin_angiotensin_system_in_autosomal_dominant_polycystic_kidney_disease_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00370.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -