Candidate Urinary Biomarker Discovery in Ureteropelvic Junction Obstruction: A Proteomic Approach

Mesrobian, H.-G. O.; Mitchell, Michael E.; See, William A.; Halligan, Brian D.; Carlson, Brian E.; Greene, Andrew S.; Wakim, Bassam T.

doi:10.1016/j.juro.2010.03.061

Cited by 26 publications

(22 citation statements)

References 22 publications

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“…In addition, many proteins that were implicated in obstructive nephropathy in a prior study (8) were also statistically significant in this study, with the same quantitative trends. Elevated proteins included angiotensin; albumin; keratin 8; keratin 9; lectin, galactoside-binding, sol- uble, 3 binding protein; macrophage inhibitory factor; myosin heavy chain 7; serpin peptidase inhibitor; clade A member 1; and transferrin.…”

Section: Discussionsupporting

confidence: 80%

“…(5,6,8,12) However, these studies were differently focused, exclusively analyzing the low molecular weight peptidome (Ͻ 10kDa) or had a low degree of proteomic coverage. Points of merit in the current study include: (1) very well defined, age-and sexmatched severe disease and control cohorts (Table I) to provide definitive insight into the pathophysiology of clinically significant renal obstruction; (2) unique access to urine directly from the diseased kidney (KU); and (3) the deepest profiling of the UPJO urinary proteome to date.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that the urinary proteome may contain clinically significant biomarkers of UPJO (5)(6)(7)(8)(9). However, these studies either focused on the low molecular weight peptidome or achieved limited proteomic depth.…”

mentioning

confidence: 99%

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Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction Obstruction

Froehlich

Kostel

Cho

et al. 2016

Molecular & Cellular Proteomics

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Prenatal hydronephrosis is a common condition that may spontaneously resolve after birth. However, this condition can result in renal damage and requires surgical correction in a number of cases. Preventing renal damage is paramount, but existing diagnostic technology is invasive, exposes infants to radiation, is costly, and is often indeterminate. A better understanding of the pathophysiology of renal obstruction as reflected in the urinary proteome may provide new insights into the disease that could potentially alter the clinical management of hydronephrosis. We performed a quantitative proteomics study of urine that was surgically obtained from eight clinically significant, unilaterally obstructed infants versus eight healthy controls, with the goal of identifying quantitatively varying proteins and the biological networks associated with them. Notably, urine was obtained from both the obstructed kidney and the bladder. Over 1100 proteins were identified, and a total of 76 quantitatively varying proteins were identified. Proteins involved in oxidative stress, inflammation, and renal disease pathways showed the most significant abundance differences. This study gives a deeper understanding of the critical proteomic changes associated with renal obstruction and represents the deepest proteomic profile of renal obstruction to date.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction Obstruction

Froehlich

Kostel

Cho

et al. 2016

Molecular & Cellular Proteomics

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“…There were only 6 children in the study group of children >1 year (5 for operation and 1 no operation), which is a weakness of the study, and it is therefore necessary with further and larger studies to clarify whether age-specific urinary proteome patterns will be able to identify older children requiring pyeloplasty for treatment of UPJO [55]. Mesrobian et al confirmed the presence of significant differences in the urinary proteome in UPJO compared to age-matched normal individuals [56]. Their study comprised 25 newborns presenting with unilateral grade 4 hydronephrosis secondary to UPJO followed for at least 12 months, and a control group of 21 healthy newborns (normal ultrasound).…”

Section: Urinary Proteome Analysismentioning

confidence: 99%

Urinary biomarkers in prenatally diagnosed unilateral hydronephrosis

Madsen

Nørregaard

Frøkiær

et al. 2011

Journal of Pediatric Urology

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“…Regarding the pediatric nephrourology setting, there have been various attempts to identify noninvasive diagnostic markers of congenital renal obstruction and vesicoureteral reflux (VUR) [14][15][16]. For instance, Furness et al [17] have shown fourfold elevated TGF-β1 levels in children with upper urinary tract obstruction.…”

Section: Introductionmentioning

confidence: 99%

Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

et al. 2011

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This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n = 47), urinary tract malformations (n = 35), and dysplastic kidneys (n = 18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p = 0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

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Candidate Urinary Biomarker Discovery in Ureteropelvic Junction Obstruction: A Proteomic Approach

Cited by 26 publications

References 22 publications

Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction Obstruction

Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction Obstruction

Urinary biomarkers in prenatally diagnosed unilateral hydronephrosis

Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

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