Potential of Serum and Urinary Matrix Metalloproteinase-9 Levels for the Early Detection of Renal Involvement in Children With Henoch-Schönlein Purpura

Erol, Meltem; Yiğit, Özgül; Taşdemir, Mehmet; Gayret, Özlem Bostan; Büke, Övgü; Gunes, Ayşegül; Hamilçıkan, Şahin; Kasapçopur, Özgür

doi:10.5812/ijp.6129

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…[ 48 ] Other authors reported higher urinary MMP-9 activity in patients with CKD [ 38 – 40 ] and HSP with renal involvement. [ 49 ] Our study showed increased urinary MMP-9 excretions and decreased urinary MMP-9/TIMP-1 ratio. These results may suggest activation of ECM remodeling processes in children with SDNS and SRNS.…”

Section: Discussionmentioning

confidence: 59%

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Bieniaś¹,

Sikora²

2018

Medicine

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In chronic glomerulopathies, renal fibrosis (RF) results from extracellular matrix remodeling processes regulated by matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). We assessed urinary (u-) and serum (s-) MMP-1, -2, -9, TIMP-1, -2 concentrations and MMP-1, -2, -9/TIMP-1, -2 ratios in children with nephrotic syndrome. Steroid-dependent and steroid-resistant nephrotic patients (SDNS-Ps and SRNS-Ps, respectively) were compared with respect to measured parameters. The correlations of measured parameters with magnitude of proteinuria and histopathological diagnosis were determined.The study comprised of 39 children with nephrotic syndrome and 20 healthy controls. Twenty-three patients had SDNS and 16 ones—SRNS. The concentrations MMPs and TIMPs were measured using enzyme-linked immunosorbent assay.In nephrotic patients, higher u-MMP-1, -2, -9/creatinine ratios and u-TIMP-1, -2/creatinine ratios were observed as compared with controls. Nephrotic children were also characterized by lower MMP-1, -2, -9/TIMP-1 ratios. In SRNS-Ps, u-MMP-2/creatinine ratio and u-TIMP-1/creatinine ratio were higher as compared with SDNS-Ps. Magnitude of proteinuria correlated positively with u-MMP-2/creatinine ratio and negatively with u-MMP-2/TIMP-1. In minimal change disease (MCD) patients as compared with those with other glomerulopathies, there was higher u-MMP-2/TIMP-1 ratio. No significant differences in s-MMPs, s-TIMPs, and s-MMPs/TIMPs ratios between nephrotic patients and controls were observed.Children with nephrotic syndrome are characterized by increased u-fibrotic biomarkers excretions. U-MMP-1, -2, -9 excretions and u-MMP-2/TIMP-1 ratio may become potential early biomarkers for RF. SRNS-Ps, those with heavier proteinuria and other than MCD glomerulopathies, seem to be more susceptible to early RF.

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Section: Discussionmentioning

confidence: 59%

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Bieniaś¹,

Sikora²

2018

Medicine

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“…In addition, MMP-9 is co-localized in scattered neutrophils within diseased glomeruli in acute post-streptococcal glomerulonephritis [59]. In children with HSN, urinary MMP-9 levels are found significantly higher in comparison to controls and patients with just Henoch-Schönlein purpura [67]. In another study in children with CKD, urinary MMP-9 levels were significantly higher in comparison to controls, though, despite that, this study was not able to prospectively show a correlation of this finding with progressive CKD [68].…”

Section: Clusterin (Clu)mentioning

confidence: 99%

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Ntrinias

Papasotiriou

Balta

et al. 2019

Prilozi

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The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient’s individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

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“…Some experimental studies found higher expression of TIMPs, particularly TIMP-1, in the renal tissue in the course of various kidney diseases [32,50]. This was confirmed in patients with CKD of different aetiology [23,51].…”

mentioning

confidence: 74%

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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Potential of Serum and Urinary Matrix Metalloproteinase-9 Levels for the Early Detection of Renal Involvement in Children With Henoch-Schönlein Purpura

Cited by 5 publications

References 19 publications

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

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

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