The role of urinary TIMP1 and MMP9 levels in predicting vesicoureteral reflux in neonates with antenatal hydronephrosis

Mohammadjafari, Hamid; Rafiei, Alireza; Abedi, Mohammad Reza; Aalaee, Abdolrasul; Abedi, Ehsan

doi:10.1007/s00467-013-2693-3

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Urinary biomarkers are candidates for assessment of kidney injury and have been studied widely for this purpose [ 9 , 10 ]. Theoretically, these markers could be used for the early diagnosis of kidney damage in cases with obstruction [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, andN-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

et al. 2014

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PurposeAntenatal hydronephrosis (AH) is found in 0.5%-1% of neonates. The aim of the study was to assess the urinary concentrations of 3 biomarkers, endothelin-1 (ET-1), monocyte chemotactic peptide-1 (MCP-1), and N-acetyl-glucosaminidase (NAG) in severely hydronephrotic neonates.Materials and MethodsNeonates with a history of prenatal hydronephrosis were enrolled in the prospective study in 2 groups. Group 1 included neonates with severe forms of obstruction requiring surgical intervention and group 2 included neonates with milder forms of obstruction without any functional impairment. Fresh voided urinary levels of ET-1, MCP-1, and NAG were measured and their ratios to urinary Cr were calculated.ResultsFourty-two neonates were enrolled into the 2 groups: group 1, 24 patients (21 male, 3 female); group 2, 18 neonates (16 male, 2 female). There were no statistically significant differences between urinary ET-1, NAG, MCP-1 values, and ET-1/Cr and NAG/Cr ratios in groups 1 and 2. The urinary MCP-1/Cr ratio was significantly higher in group 1 than in group 2. For comparison of groups 1 and 2, the cut-off values were measured as 0.5709 ng/mg (sensitivity, 75%; specificity, 67%; positive predictive value [PPV], 71%; negative predictive value [NPV], 71%), 0.927 ng/mg (sensitivity, 77%; specificity, 72%; PPV, 77%; NPV, 72%), and 1.1913 IU/mg (sensitivity, 62%; specificity, 67%; PPV, 68%; NPV, 60%) for ET-1/Cr, MCP-1/Cr, and NAG/Cr ratios, respectively.ConclusionsThe urinary MCP-1/Cr ratio is significantly elevated in neonates with severe obstruction requiring surgical intervention. Based upon these results, urinary MCP-1/Cr may be useful in identification of severe obstructive hydronephrosis in neonates.

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Section: Introductionmentioning

confidence: 99%

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, andN-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

et al. 2014

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“…Abedi and Mohammadjafari [ 45 ] postulated that urinary MMP-9 and TIMP-1 may be markers of renal scarring in children with urinary tract infections. Other authors [ 46 ] suggested the usefulness of the measurement of urinary MMP-9 excretion and the urinary MMP-9/TIMP-1 ratio for the prediction of vesicoureteral reflux in neonates with antenatal HN. Tian et al [ 47 ] reported that urinary MMP-9 and TIMP-1 may be noninvasive biomarkers in children with UPJO.…”

Section: Discussionmentioning

confidence: 99%

Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis

Bieniaś

Sikora

2020

Disease Markers

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Renal tubulointerstitial fibrosis caused by congenital ureteropelvic junction obstruction (UPJO) may lead to the development of obstructive nephropathy (ON) and the impairment of kidney function. Hence, the identification of early biomarkers of this condition might be of assistance in therapeutic decisions. This study evaluates serum and urinary metalloproteinases MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 as potential biomarkers of ON in children with congenital unilateral hydronephrosis (HN) caused by UPJO. Forty-five (45) children with congenital HN of different grades of severity and twenty-one (21) healthy controls were enrolled in the study. Urinary and serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using specific ELISA kits. The urinary excretions were expressed as biomarker/creatinine (Cr) ratios. To evaluate the extracellular matrix remodelling process activity, the serum and urinary MMP-1, -2, -9/TIMP-1, -2 ratios were also calculated. In comparison with the controls, patients with HN, independent of the grade, showed significantly increased median serum MMP-9, TIMP-1, and TIMP-2, median urinary MMP-9/Cr, and TIMP-2/Cr ratios. Lower median values of serum MMP-2/TIMP-1, MMP-9/TIMP-1 in patients with HN were also revealed. Additionally, higher urinary MMP-2/Cr, lower urinary MMP-2/TIMP-2, and lower serum MMP-9/TIMP-2 ratios were observed in patients with HN grades 3 and 4. Patients with ON diagnosed by renal scintigraphy had a significantly higher median serum MMP-9 concentration and lower median serum MMP-9/TIMP-1, -2 ratios in comparison with those without this condition. Patients with nonglomerular proteinuria had a significantly higher median serum TIMP-1 concentration, a higher median urinary TIMP-2/Cr ratio, and a lower serum MMP-9/TIMP-1 ratio compared to those without this symptom. The relationship between the measured biomarkers and the relative function of the obstructed kidney showed no correlations. The ROC curve analysis showed a promising diagnostic profile for the detection of ON for serum MMP-9 and the serum MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios. In conclusion, the results of this study suggest that patients with HN, particularly with grades 3 and 4, are at higher risk of renal tubulointerstitial fibrosis. The noninvasive markers of this condition considered are urinary MMP-2/Cr and MMP-9/Cr, serum MMP-9, serum and urinary MMP-2, MMP-9/TIMP-1, -2. Additionally, serum MMP-9 and MMP-9/TIMP-1, -2 may become promising markers of ON.

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“…Indeed, MMP9, MMP9/Cr, MMP9/TIMP1, and MMP9/TIMP1/Cr ratios were higher in patients with VUR than in those without VUR. Based on these results, the authors discussed the use of screening tests for the presence of VUR in neonates with hydronephrosis to reduce their exposure to radiation, as in VCUG 40) . Other studies suggests that MMP9 and TIMP1 could be used as biomarkers to predict renal scars in children with UTIs 41,42) .…”

Section: Wwwchikdorgmentioning

confidence: 99%

Predictive Markers for Screening Renal Damage in Children with Urinary Tract infections and Vesicoureteral Reflux

et al. 2020

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Purpose: Urinary tract infections (UTIs) are the most common and serious bacterial infections in children. Therefore, early diagnosis of vesicoureteral reflux (VUR) for treatment planning and the identification of noninvasive markers that can predict renal injury are important in patients with UTIs. We analyzed the clinical features of pediatric UTIs commonly encountered by general practitioners and reinterpreted the blood tests and imaging findings to identify the important clinical predictive markers of VUR in order to selectively perform VCUG. Methods: This retrospective study was performed among 183 children diagnosed with a UTI or acute pyelonephritis. Results: The most significant predictor of high grade and bilateral VUR identified using area under the curve analyses was hydronephrosis on kidney ultrasound images with renal cortical defects on dimercaptosuccinic acid (DMSA) kidney scan simultaneously, followed by hydronephrosis only on kidney ultrasound. Conclusion: The presence of hydronephrosis on kidney ultrasound images or cortical defects or asymmetric kidneys on the DMSA kidney scans can be predictive markers of VUR, reducing the need for VCUG. Our study can thus help minimize the exposure to radiation among patients through selective VCUG.

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The role of urinary TIMP1 and MMP9 levels in predicting vesicoureteral reflux in neonates with antenatal hydronephrosis

Abstract: Evaluation of urinary levels of MMP9, or the MMP9/Cr, MMP9/TIMP1, or MMP9/TIMP1/Cr ratios may help us to differentiate the newborns with hydronephrosis and VUR from those without reflux.

Cited by 8 publications

References 34 publications

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, andN-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, andN-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis

Predictive Markers for Screening Renal Damage in Children with Urinary Tract infections and Vesicoureteral Reflux

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