Dataset Information

Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction.

ABSTRACT:

Importance

Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-invasive way to enhance surgical decision making for patients and urologists.

Objective

We sought to develop a predictive model to identify UPJO patients at risk for reduced renal function.

Design

Prospective cohort study.

Setting

Pre-operative urine samples were collected in a prospectively enrolled UPJO biomarker registry at our institution. Urinary MMP-2, MMP-7, TIMP-2, and NGAL were measured as well as clinical characteristics including hydronephrosis grade, differential renal function, t1/2, and UPJO etiology.

Participants

Children who underwent pyeloplasty for UPJO.

Main outcome measurement

Primary outcome was reduced renal function defined as MAG3 function <40%. Multivariable logistic regression was applied to identify the independent predictive biomarkers in the original Training cohort. Model validation and generalizability were evaluated in a new UPJO Testing cohort.

Results

We included 71 patients with UPJO in the original training cohort and 39 in the validation cohort. Median age was 3.3 years (70% male). By univariate analysis, reduced renal function was associated with higher MMP-2 (p = 0.064), MMP-7 (p = 0.047), NGAL (p = 0.001), and lower TIMP-2 (p = 0.033). Combining MMP-7 with TIMP-2, the multivariable logistic regression model predicted reduced renal function with good performance (AUC = 0.830; 95% CI: 0.722-0.938). The independent testing dataset validated the results with good predictive performance (AUC = 0.738).

Conclusions and relevance

Combination of urinary MMP-7 and TIMP-2 can identify reduced renal function in UPJO patients. With the high sensitivity cutoffs, patients can be categorized into high risk (aggressive management) versus lower risk (observation).

SUBMITTER: Wang HS

PROVIDER: S-EPMC9282603 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction.

Wang Hsin-Hsiao S HS Cho Patricia S PS Zhi Hui H Kostel Stephen A SA DiMartino Shannon S Dagher Adelle M AM Davis Kylie H KH Cabour Lily D LD Shimmel Ashley A Lee James J Froehlich John W JW Zurakowski David D Moses Marsha A MA Lee Richard S RS

PloS one 20220714 7

<h4>Importance</h4>Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-invasive way to enhance surgical decision making for patients and urologists.<h4>Objective</h4>We sought to develop a predictive model to identi ...[more]

PMID: 35834547

Similar Datasets

Project description:Introduction and objectiveReliable urinary biomarker proteins would be invaluable in identifying children with ureteropelvic junction obstruction (UPJO) as the existing biomarker proteins are inconsistent in their predictive ability. Therefore, the aim of this study was to identify consistent and reliable urinary biomarker proteins in children with UPJO.MethodsTo identify candidate biomarker proteins, total protein from age-restricted (<2 years) and sex-matched (males) control (n = 22) and UPJO (n = 21) urine samples was analyzed by mass spectrometry. Proteins that were preferentially identified in UPJO samples were selected (2-step process) and ranked according to their diagnostic odds ratio value. The top ten proteins with highest odds ratio values were selected and tested individually by ELISA. The total amount of each protein was normalized to urine creatinine and the median with interquartile ranges for control and UPJO samples was determined. Additionally, fold change (UPJO/Control) of medians of the final panel of 5 proteins was also determined. Finally, we calculated the average + 3(SD) and average + 4(SD) values of each of the 5 proteins in the control samples and used it as an arbitrary cutoff to classify individual control and UPJO samples.ResultsIn the first step of our selection process, we identified 171 proteins in UPJO samples that were not detected in the majority of the control samples (16/22 samples, or 72.7%). Of the 171 proteins, only 50 proteins were detected in at least 11/21 (52.4%) of the UPJO samples and hence were selected in the second step. Subsequently, these 50 proteins were ranked according to the odds ratio value and the top 10 ranked proteins were validated by ELISA. Five of the 10 proteins - prostaglandin-reductase-1, ficolin-2, nicotinate-nucleotide pyrophosphorylase [carboxylating], immunoglobulin superfamily-containing leucine-rich-repeat-protein and vascular cell adhesion molecule-1 were present at higher levels in the UPJO samples (fold-change of the median protein concentrations ranging from 2.9 to 9.4) and emerged as a panel of biomarkers to identify obstructive uropathy. Finally, the order of prevalence of the 5 proteins in UPJO samples is PTGR1>FCN2>QPRT>ISLR>VCAM1.ConclusionIn summary, this unique screening strategy led to the identification of previously unknown biomarker proteins that when screened collectively, may reliably distinguish between obstructed vs. non-obstructed infants and may prove useful in identifying informative biomarker panels for biological samples from many diseases.

Project description: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: pelvic-ureteric [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.

Project description:BackgroundRobotic-assisted laparoscopic pyeloplasty (RALP) has been gaining acceptance among paediatric urologists.ObjectiveTo compare surgical variables and clinical outcomes, including complications and success rate, with RALP using the transperitoneal (T-RALP) and retroperitoneal (R-RALP) approaches.Design setting and participantsWe performed a multicentre, prospective, cohort study (NCT03274050) between November 2016 and October 2021 in three paediatric urology teaching centres (transperitoneal approach, n = 2; retroperitoneal approach, n = 1). The diagnosis of ureteropelvic junction obstruction (UPJO) was confirmed by renal ultrasound and mercaptoacetyltriglycine-3 renal scan or uro-magnetic resonance imaging with functional evaluation. The exclusion criteria were children <2 yr old, persistent UPJO after failed pyeloplasty, and horseshoe and ectopic kidney.InterventionWe performed dismembered pyeloplasty using running monofilament 6-0 absorbable suture.Outcome measurements and statistical analysisWe assessed intra- and postoperative morbidity (primary outcome) and success (secondary outcome). Data were expressed as medians and interquartile range (25th and 75th percentiles) for quantitative variables, and analysed comparatively.Results and limitationsWe operated on 106 children (T-RALP, n = 53; R-RALP, n = 53). Preoperative data were comparable between groups (median age 9.1 [6.2-11.2] yr; median weight 26.8 [21-40] kg). Set-up time (10 vs 31 min), anastomotic time (49 vs 73 min), and console time (97 vs 153 min) were significantly shorter with T-RALP than with R-RALP (p < 0.001). No intraoperative complications occurred. No conversion to open surgery was necessary. The median hospital stay was longer after T-RALP (2 d) than after R-RALP (1 d; p < 0.001). Overall, postoperative complication rates were similar. No failure had occurred at the mean follow-up of 25.4 (15.1-34.7) mo.ConclusionsIn selected children, RALP is safe and effective using either the transperitoneal or the retroperitoneal approach, with a shorter hospital stay after R-RALP.Patient summaryIn our multicentre, prospective study, we compared the results and complications of robotic-assisted laparoscopic pyeloplasty (RALP) using the transperitoneal and retroperitoneal approaches. We found that RALP is safe and effective using either approach, with a shorter hospital stay after R-RALP.

Project description:IntroductionWe compare open pyeloplasty (OP) versus laparoscopic pyeloplasty (LP) in children in a multicenter, prospective, case-control study.Materials and methodsFrom May 2007 to March 2009, a program was established at Hospital Garrahan, the reference center, to perform LP with a mentoring surgeon that would attend the institution once a month. Every new case of ureteropelvic junction obstruction (UPJO) diagnosed in the reference institution was offered to participate in the study. If the patient was enrolled, it was scheduled for LP. The following patient diagnosed with UPJO was operated on with open technique and served as a case-control. In three other facilities, patients were only offered LP and had a matched control open case at the reference institution. The first end point of the study was patient recovery: analgesia requirement and length of hospitalization (LOH). The second end point of the study was resolution of UPJO in long-term follow-up for the two techniques. Demographic data, surgical time, perioperative complications, analgesia requirement, analgesia score during hospitalization, LOH, and outcome were recorded. Both groups received the same postoperative indications for pain control. Parents were asked to assess pain in their children every 4 h postoperatively and to complete a pain scale chart to which the nurses were blinded.ResultsFifteen OP and 15 LP were compared. Groups were similar with regard to sex, age, weight, and laterality. Mean surgical time was longer in LP than in OP group (mean 188 versus 65 min) (p < 0.01). Hospitalization was shorter for LP group with a mean of 1.9 versus 2.5 days for OP group (p < 0.05). Postoperative analgesia requirement was significantly higher in the OP group with a mean use of morphine of 1.7 versus 0.06 mg/kg in the LP group (p < 0.05). Pain scores were similar in both the groups. At a mean follow-up of 58 months there were no failures.ConclusionIn this prospective comparative cohort, LP was a longer procedure than OP. Both procedures had the same efficacy and complication rates, but patients undergoing LP needed fewer narcotics for pain control and had a shorter hospitalization.

Dataset Information

Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction.

Importance

Objective

Design

Setting

Participants

Main outcome measurement

Results

Conclusions and relevance

Publications

Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets