Renal Tissue Endothelin in Long-Term Complete Ureteric Obstruction in the Young Rat

Josephson, Staffan; Hemsén, Anette

doi:10.1159/000282636

Cited by 14 publications

(7 citation statements)

References 17 publications

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“…In progressive obstructive nephropathy, renal tubules dilate and tubular epithelial cells 44 The Journal of Clinical Investigation | January 1999 | Volume 103 | Number 1…”

Section: Discussionmentioning

confidence: 99%

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Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

et al. 1999

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A novel approach was employed to assess the contribution of the renin-angiotensin system (RAS) to obstructive nephropathy in neonatal mice having zero to four functional copies of the angiotensinogen gene (Agt). Two-day-old mice underwent unilateral ureteral obstruction (UUO) or sham operation; 28 days later, renal interstitial fibrosis and tubular atrophy were quantitated. In all Agt genotypes, UUO reduced ipsilateral renal mass and increased that of the opposite kidney. Renal interstitial collagen increased after UUO linearly with Agt expression, from a fractional area of 25% in zero-copy mice to 54% in two-copy mice. Renal expression of transforming growth factor-β1 was increased by ipsilateral UUO in mice expressing Agt, but not in zero-copy mice. However, the prevalence of atrophic tubules due to UUO did not vary with Agt expression. Blood pressure was not different in all groups, except for a reduction in sham zero-copy mice. We conclude that a functional RAS is not necessary for compensatory renal growth. This study demonstrates conclusively that angiotensin regulates at least 50% of the renal interstitial fibrotic response in obstructive nephropathy, an effect independent of systemic hemodynamic changes. Angiotensininduced fibrosis likely is a mechanism common to the progression of many forms of renal disease.

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“…In progressive obstructive nephropathy, renal tubules dilate and tubular epithelial cells 44 The Journal of Clinical Investigation | January 1999 | Volume 103 | Number 1…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, all Agt genotypes were normotensive after UUO in the present study. The maintenance of normotension by UUO in the zero-copy mice may relate to the production of other vasoconstrictors, such as endothelin, which are generated by the hydronephrotic kidney (44).…”

Section: Figurementioning

confidence: 99%

Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

et al. 1999

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“…Endothelin‐1. Endothelin‐1 (ET‐1) is a potent vasoconstrictor that has been implicated in the tissue damage and dysfunction associated with UUO (Josephson & Hemsen 1994; Feldman et al. 2000) and UPJ obstruction (Taha et al.…”

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confidence: 99%

Congenital ureteropelvic junction obstruction: human disease and animal models

Klein

Gonzalez

Miravète

et al. 2010

International Journal of Experimental Pathology

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Summary Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin–angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short‐coming is the absence of data on the impact of UPJ obstruction on long‐term adult renal function to elucidate whether these animal data are also valid in humans.

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“…[29] ET-1 has been implicated in the tissue damage and dysfunction associated with UUO. [30] Kelleher et al [31] demonstrated that ET-1 has a predominant role in the development of preglomerular arteriolar stenosis in the obstructed upper urinary tract. Additionally, results have suggested that ET-1 may play a role in the progression of interstitial fibrosis after ureteral ligation.…”

Section: Resultsmentioning

confidence: 99%

Role of urinary biomarkers in the diagnosis of congenital upper urinary tract obstruction

Shokeir¹

2008

Indian J Urol

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Background:Congenital obstructive uropathy constitutes a significant cause of morbidity in children. Currently, there is no reference standard for the diagnosis of renal obstruction in children. The noninvasive measurement of biomarkers in voided urine has considerable appeal as a potential application in children with congenital obstructive nephropathy. The aim of the present review is to explore the current role of biomarkers in the diagnosis and follow-up of obstructive uropathy in children.Materials and Methods:The literature database (PubMed) was searched from inception to May 2007 regarding the role of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.Results:The review included 23 experimental and 33 prospective controlled clinical studies. Several cytokines, peptides, enzymes and microproteins were identified as major contributors to or ensuing from obstruction-induced renal fibrosis and apoptosis. The most important biomarkers were transforming growth factor-β1 (TGFβ1), epidermal growth factor (EGF), endothelin-1 (ET-1), urinary tubular enzymes [N-acetyl-β-D-glucosaminidase (NAG), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP)], and microproteins [β2-microglobulin (β2M), microalbumin (M. Alb) and micrototal protein (M.TP)]. All biomarkers showed different degrees of success but the most promising markers were TGFβ1, ET-1 and a panel of tubular enzymes. These biomarkers showed sensitivity of 74.3% to 100%, specificity of 80% to 90% and overall accuracy of 81.5% to 94% in the diagnosis of congenital obstructive uropathy in children. Moreover, some of the markers were valuable in differentiation between dilated non-obstructed kidneys in need of conservative management and obstructed kidneys in need of surgical correction. Some studies demonstrated that urinary biomarkers are helpful in the evaluation of success of treatment of children with congenital renal obstruction. Some limitations of the previous studies include lack of different types of controls and small sample size. Larger studies with variable controls are invited to confirm the clinical usefulness of biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.Conclusion:Urinary biomarkers are a promising tool that could be used as a noninvasive assessment of congenital renal obstruction in children.

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Renal Tissue Endothelin in Long-Term Complete Ureteric Obstruction in the Young Rat

Cited by 14 publications

References 17 publications

Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

Congenital ureteropelvic junction obstruction: human disease and animal models

Role of urinary biomarkers in the diagnosis of congenital upper urinary tract obstruction

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