Urine exoglycosidases are potential markers of renal tubular injury in children with ureteropelvic junction obstruction

Taranta-Janusz, Katarzyna; Zalewska-Szajda, Beata; Chojnowska, Sylwia; Wasilewska, Anna

doi:10.1111/apa.13068

Cited by 8 publications

(18 citation statements)

References 28 publications

(32 reference statements)

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“…The quantitative urine protein analysis was performed using commercially available human sandwich enzyme-linked immunosorbent assay (ELISA) kits in 32 (84.2%) studies. Fourteen (36.8%) studies compared patients undergoing pyeloplasty [surgical group (SG)] with patients with mild non-obstructive dilatation not requiring surgery [non-surgical group (NSG)] and healthy children [reference group (RG)] (9,10, [14][15][16][17][18]20,22,27,29,[31][32][33]. Seven (18.4%) articles analysed urine biomarker concentrations in patients undergoing surgery (SG) and related them with patients conservatively treated (NSG) (6,19,21,28,36,37,41).…”

Section: Resultsmentioning

confidence: 99%

Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review

Paraboschi¹,

Mantica²,

Dalton³

et al. 2020

Transl Androl Urol

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Antenatal hydronephrosis is a common finding detected on prenatal ultrasound. Although hydronephrosis will spontaneously resolve in the majority of newborns, there is a significant amount of cases that will worsen with the risk of a progressive and permanent loss of renal function. There is an increasing concern among experts that the current criteria for evaluation of clinically significant obstructions are limited.Our aim is to provide a systematic review of the available literature on biomarkers of renal injury, potential targets for diagnosis and prognosis of children with hydronephrosis. The main search was conducted in the electronic databases from inception through March 2019 using various combinations of the keywords: pelvicureteric [All Fields] AND junction [All Fields] AND obstruction [All Fields] AND "biomarkers" [MeSH Terms] OR "biomarkers" [All Fields] OR "biomarker" [All Fields]. To broaden the research, additional articles were identified through hand-searching review of the references reported in each study previously selected.Histopathological studies, studies with no control group or with participants suffering from concomitant urological diseases and articles published in language other than English were excluded. Data on study design, sample size, average patient age, hydronephrosis definition used, surgical indication, duration and pattern of follow-up, details on biomarker studied, diagnostic test characteristics, area under the curve (AUC) on receiver operating characteristic (ROC) analysis with the best cut-off (BCO) values, sensitivity, specificity and outcomes were all collected. 38 articles analysing 41 biomarkers were selected. The most frequent proteins investigated were neutrophil gelatinase-associated lipocalin (NGAL) (n=9; 23.7%), monocyte chemotactic peptide-1 (MCP1) (n=8; 21.1%), transforming growth factor β1 (TGFβ1) (n=7; 18.4%), epidermal growth factor (EGF) (n=6; 15.8%) and kidney injury molecule 1 (KIM 1) (n=6; 15.8%). Twenty-seven (71.1%) studies evaluated the effect of pyeloplasty on voided urine biomarker concentrations, comparing their values before and after surgery. Twelve (31.6%) studies investigated the correlation between preoperative biomarker concentration and the anterior posterior renal pelvis diameter (DAP) while 20 (52.6%) studies investigated the correlation between preoperative biomarker concentration with the split renal function (SRF) measured on nuclear medicine assessments. ROC curves were used to investigate the performance of urinary biomarkers in the total patient data set in 27 (71.1%) studies. Some biomarkers offer promising results. However, a critic analysis of the published studies demonstrates bias and lack of consistency suggesting that larger multicentre and carefully designed prospective studies are still needed to evaluate the clinical usefulness of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive hydronephrosis.

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Section: Resultsmentioning

confidence: 99%

Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review

Paraboschi¹,

Mantica²,

Dalton³

et al. 2020

Transl Androl Urol

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“…They showed that urinary NGAL levels correlate with DRF in the affected kidney in patients with unilateral UPJO, and could thus be used as a sensitive biomarker of kidney injury in children with UPJO. In addition, Katarzyna et al demonstrated higher renal activities of exoglycosidases, which are indicative of renal tubular damage, in children with UPJO (12). Finally, increasing urinary procollagen III N-terminal propeptide protein levels were also shown to be associated with worsening obstruction in children (27).…”

Section: Discussionmentioning

confidence: 98%

“…Multiple non-invasive urinary biomarkers have been evaluated for the identification of pathologic changes associated with UPJO (10)(11)(12). Several approaches, such as capillary electrophoresis and mass spectrometry, radioimmunoassay, and ELISA have been used to identify potential biomarkers (10,13,14).…”

Section: Introductionmentioning

confidence: 99%

“…Several approaches, such as capillary electrophoresis and mass spectrometry, radioimmunoassay, and ELISA have been used to identify potential biomarkers (10,13,14). Previous studies have shown that the concentrations of urine biomarkers are associated with the severity of hydronephrosis and decrease following pyeloplasty (12,15). Proteins can be secreted or shed into the urine from a number of cellular sources following UPJO-induced renal tissue damage, and may represent useful non-invasive biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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Matrix Remodeling-Associated Protein 5 in Urinary Exosomes as a Potential Novel Marker of Obstructive Nephropathy in Children With Ureteropelvic Junction Obstruction

et al. 2020

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Recent investigations have described the use of urinary matrix remodeling-associated protein 5 (MXRA5) as a novel biomarker of kidney impairment in the setting of chronic kidney disease. In this study, we aimed to evaluate the possible clinical application of urinary MXRA5 as a useful non-invasive marker in the urine from the affected renal pelvis and bladder of children with ureteropelvic junction obstruction (UPJO). We conducted a prospective cohort study of patients aged <12 months with prenatally diagnosed unilateral UPJO who underwent dismembered pyeloplasty in 2018 or 2019, and a sex-and age-matched control group of healthy children. Blood urea nitrogen and creatinine levels were normal in all the patients. The whole urine and urinary exosomal concentrations of MXRA5 were measured by enzyme-linked immunosorbent assay. The correlations between bladder/renal pelvic MXRA5 levels and differential renal function (DRF) in the affected kidney were also determined. A total of 35 UPJO patients and 12 controls were enrolled in the study. There was no significant difference in whole-urine MXRA5 level between the controls and UPJO patients. However, the exosomal MXRA5 level was significantly lower in the controls than in patients with UPJO (p < 0.05). There were non-significant correlations between bladder and renal pelvis whole-urine MXRA5 levels and DRF (R 2 = 0.1115, p = 0.05 and R 2 = 0.3313, p = 0.0502, respectively). The strongest correlation was between exosomal MXRA5 level in the renal pelvis and DRF (R 2 = 0.8128, p < 0.0001). Urinary exosomal MXRA5 level was significantly higher in children with UPJO than controls. Higher urinary exosomal MXRA5 levels were significantly correlated with lower DRF in the affected kidney in children with UPJO.

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“…Given the need for a sensitive method to control specific changes in renal function in patients with urinary tract obstruction and to identify MCP-1 as a urinary biomarker (8), the present study was conducted to assess the level of urinary cytokine MCP-1 in children with urinary tract obstruction compared to healthy children.…”

Section: Introductionmentioning

confidence: 99%

Mean Urinary Cytokine MCP-1 in Children with Urinary Tract Obstruction and Healthy Children

Sadeghi‐Bojd¹,

Alijani²,

Mahdavian³

2018

Nephro-Urol Mon

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Background and Objectives: Hydronephrosis is defined as varying degrees of dilatation in renal pelvis and calyxes, which leads to renal parenchymal atrophy together with obstruction of urinary flow. The present study was conducted to compare levels of urinary cytokine MCP-1 in children with urinary obstruction and healthy children attending Ali-Asghar hospital of the city of Zahedan. Methods: The present case-control study recruited 20 children with obstructive hydronephrosis, 20 children with non-obstructive hydronephrosis, and 30 healthy children as the control group that matched in terms of gender and age and were selected by the convenience sampling method. Urine samples were taken from these children, and urinary creatinine and MCP-1 levels were measured. Data were analyzed with the SPSS-21 software using analysis of variance (ANOVA), Kruskal-Wallis, and Mann-Whitney tests. Results: Mean MCP-1 level was 542.56 ng/L in the obstructive hydronephrosis group, 424.7 ng/L in the non-obstructive hydronephrosis, and 335.97 ng/L in the control group. Mean MCP-1 to creatinine ratio was 58.94 in the obstructive hydronephrosis group, 39.58 in non-obstructive hydronephrosis, and 33.1 in the control group. Mean MCP-1 and MCP-1 to creatinine ratio was significantly higher in the obstructive hydronephrosis group compared with non-obstructive hydronephrosis and control groups (P < 0.05). No significant difference was found in MCP-1 and MCP-1 to creatinine ratio between patients with unilateral and bilateral obstructive hydronephrosis (P < 0.05). Conclusions: The present study results showed that MCP-1 could be a marker for renal tubular injury in patients with obstructive hydronephrosis.

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Urine exoglycosidases are potential markers of renal tubular injury in children with ureteropelvic junction obstruction

Abstract: Our findings demonstrated that children with UPJO showed increased renal activities of assessed exoglycosidases, which correlated positively with the urine albumin/creatinine ratio. A larger multicentre study is required to confirm the clinical applications of these observations.

Cited by 8 publications

References 28 publications

Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review

Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review

Matrix Remodeling-Associated Protein 5 in Urinary Exosomes as a Potential Novel Marker of Obstructive Nephropathy in Children With Ureteropelvic Junction Obstruction

Mean Urinary Cytokine MCP-1 in Children with Urinary Tract Obstruction and Healthy Children

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