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Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
Karolinska Institute.
Karolinska Institute.
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), Paediatric Inflammation Research.
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2018 (English)In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 33, no 4, p. 639-649Article in journal (Refereed) Published
Abstract [en]

Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.

Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.

Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).

Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction 

Place, publisher, year, edition, pages
Springer, 2018. Vol. 33, no 4, p. 639-649
Keywords [en]
Blood pressure, Hydronephrosis, Hypertension, Nitric oxide, Oxidative stress, Ureteral obstruction
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-337796DOI: 10.1007/s00467-017-3848-4ISI: 000427901900012PubMedID: 29196979OAI: oai:DiVA.org:uu-337796DiVA, id: diva2:1170902
Funder
Swedish Research Council, 2016-01381 MC 65X-03522-43-3 AEGPSwedish Heart Lung Foundation, 20140448The Karolinska Institutet's Research FoundationAvailable from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-06-05Bibliographically approved
In thesis
1. High Blood Pressure in Children with Hydronephrosis
Open this publication in new window or tab >>High Blood Pressure in Children with Hydronephrosis
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most common cause of secondary hypertension is intrinsic renal disease, but little is known about the influence of hydronephrosis on blood pressure. In this thesis, the risk of development of hypertension in children with hydronephrosis was studied.

Experimental and clinical studies were combined in order to investigate the risk of developing elevated blood pressure following conservative treatment of hydronephrosis, and to further explore underlying mechanisms. We started with a clinical study in children (study I), which in agreement with previous experimental studies, showed that blood pressure was lowered by surgical management of hydronephrosis. In parallel, an experimental study was conducted (study II) to investigate the involvement of renal sympathetic nerve activity in development of hypertension following induction of hydronephrosis caused by pelvo-ureteric junction obstruction. Renal denervation of the obstructed kidney attenuated hypertension and restored the renal excretion pattern, effects that were associated with reduced activity of both renal NADPH oxidase derived oxidative stress and components of the renin-angiotensin-aldosterone system.

Based on the findings in studies I and II, we continued our studies in children with hydronephrosis, and including two control groups as comparisons with the hydronephrotic group (study III). In the same study, we further investigated potential mechanism(s) of hypertension by analyzing markers of oxidative stress and nitric oxide homeostasis in both urine and blood samples. We demonstrated increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which was restored to normal levels by surgical correction of the obstruction. Finally, in a retrospective cohort study, blood pressure of adult patients undergoing surgical management of hydronephrosis due to pelvo-ureteric junction obstruction was assessed (study IV). Similar to that demonstrated in the pediatric hydronephrotic population, blood pressure was significantly reduced by relief of the obstruction. In addition, blood pressure was increased again if the hydronephrosis recurred, and was reduced again following re-operation.

It is concluded that conservative management of hydronephrosis in children is associated with a risk for development of high blood pressure, which can be reduced or even normalized by relief of the obstruction. The mechanism(s), at least in part, is coupled to increased oxidative stress.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1417
Keywords
Blood pressure, hydronephrosis, hypertension, ambulatory blood pressure monitoring, nitric oxide, oxidative stress, pelvo-ureteric junction obstruction.
National Category
Pediatrics
Research subject
Pediatric Surgery
Identifiers
urn:nbn:se:uu:diva-338678 (URN)978-91-513-0206-5 (ISBN)
Public defence
2018-03-01, Rosénsalen, Akademiska barnsjukhuset ingång 95-96, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2018-02-07 Created: 2018-01-11 Last updated: 2018-03-08

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Al-Mashhadi, Ammar Nadhom FarmanNevéus, TryggveStenberg, ArnePersson, A. Erik G.
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Paediatric SurgeryPaediatric Inflammation ResearchDepartment of Medical Cell Biology
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