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Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and gamma-ENaC abundance in rat kidney
Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.ORCID iD: 0000-0002-9170-2168
Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
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2018 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 315, no 3, p. F547-F557Article in journal (Refereed) Published
Abstract [en]

Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that 1) in pediatric patients with UPJO the RAAS is activated before surgical relief of the obstruction; 2) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na transporters; and 3) the injured UPJO kidney allows aberrant filtration of plasminogen, leading to proteolytic activation of the epithelial Na channel gamma-subunit (gamma-ENaC). Hydronephrosis resulting from UPJO in pediatric patients and rats was associated with increased urinary plasminogen-to-creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone, and urine soluble prorenin receptor did not differ significantly before or after surgery, or compared with controls. Increased plasmin-to-plasminogen ratio was seen in UPJO rats. Intact gamma-ENaC abundance was not changed in UPJO kidney, whereas low-molecular cleavage product abundance increased. The Na-Cl cotransporter displayed significantly lower abundance in the UPJO kidney compared with the nonobstructed contralateral kidney. The Na-K-ATPase alpha-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC , 2018. Vol. 315, no 3, p. F547-F557
Keywords [en]
ENaC, hydronephrosis, NCC, plasmin
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-364250DOI: 10.1152/ajprenal.00635.2017ISI: 000444017300003PubMedID: 29767556OAI: oai:DiVA.org:uu-364250DiVA, id: diva2:1258452
Funder
Swedish Research Council, 2016-01381Swedish Heart Lung Foundation, 20140448Swedish Heart Lung Foundation, 20170124The Karolinska Institutet's Research FoundationAvailable from: 2018-10-24 Created: 2018-10-24 Last updated: 2018-10-24Bibliographically approved

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