Urine matrix metalloproteinases and their extracellular inducer EMMPRIN in children with chronic kidney disease

Musiał, Kinga; Bargenda, Agnieszka; Zwołińska, Danuta

doi:10.3109/0886022x.2015.1040715

Cited by 19 publications

(19 citation statements)

References 26 publications

(37 reference statements)

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“…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]. Moreover, in a study of patients with type 2 diabetes, urinary MMP-9 was significantly increased in both non-and albuminuric patients in comparison to normal controls.…”

Section: Clusterin (Clu)contrasting

confidence: 64%

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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Section: Clusterin (Clu)contrasting

confidence: 64%

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

Ntrinias

Papasotiriou

Balta

et al. 2019

Prilozi

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“…Some comorbid conditions other than diabetes mellitus such as renal scars, nephrotic syndrome, focal segmental glomerulosclerosis, pancreatic cancer and chronic kidney failure may also affect urine MMP2 and MMP9, TIMP1 and TIMP2 and TGF-β1 concentrations (28,29,30,31,32,33). However, our diabetic patients did not have any known comorbid disorders.…”

Section: Discussionmentioning

confidence: 99%

Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus

Yıldırım

Yılmaz

Pehlivanoğlu

et al. 2019

Jcrpe

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Objective: Histopathological changes in the kidney in type 1 diabetes mellitus (T1DM) begin before detection of microalbuminuria. Therefore, there is interest in finding a better biomarker for the early detection of diabetic kidney injury. The aim of this present study was to determine whether urinary indicators of fibrosis are detectable early in the development of T1DM in children and if they may predict progressive renal injury. Methods: Urinary matrix metalloproteinase 2 and 9 (MMP2 and MMP9), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2) and transforming growth factor-β1 (TGF-β1) were assessed in 33 patients with T1DM with normal renal functions and in 24 healthy controls. Microalbuminuria was not present in the patient group with the exception of three patients. The results were adjusted to urine creatinine (Cr) and the differences between patients and controls were evaluated. These measurements were repeated after one year and the results were compared with the first year results. Results: Urine MMP2/Cr, MMP9/Cr, TIMP1/Cr, TIMP2/Cr, TGF-β1/Cr were not different between the patient and control groups (p>0.05). There were also no significant differences between the first and second year results for these biomarkers (p>0.05). None of these parameters were correlated with hemoglobin A1c, body mass index and duration of T1DM. Interestingly, all parameters were negatively correlated to age of onset of T1DM (p<0.05). Conclusion: Our findings suggest that urinary biomarkers of fibrosis do not show an increase in diabetic children without microalbuminuria. The results also indicate that the risk of early fibrosis may increase as age of onset of T1DM decreases.

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“…Moreover, elevated urinary levels of MMP-7 have been reported in patients with various kidney diseases compared to healthy controls and correlated well with renal fibrosis scores. Therefore, MMP-7 has been proposed as a putative urinary biomarker of kidney fibrosis in CKD and possible mediator of fibrotic events 41 , 42 . Along these lines, peptides that we detected and presumably originated from MMP-7 activity belong to cleaved alpha-1-antitrypsin (inhibitor of the following proteases: trypsin, chymotrypsin, and plasminogen activator) and fibrinogen alpha chain (monomers of which form the fibrotic tissue) 41 .…”

Section: Discussionmentioning

confidence: 99%

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Krochmal

Kontostathi

Magalhães

et al. 2017

Sci Rep

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Mechanisms underlying the onset and progression of nephropathy in diabetic patients are not fully elucidated. Deregulation of proteolytic systems is a known path leading to disease manifestation, therefore we hypothesized that proteases aberrantly expressed in diabetic nephropathy (DN) may be involved in the generation of DN-associated peptides in urine. We compared urinary peptide profiles of DN patients (macroalbuminuric, n = 121) to diabetic patients with no evidence of DN (normoalbuminuric, n = 118). 302 sequenced, differentially expressed peptides (adjusted p-value < 0.05) were analysed with the Proteasix tool predicting proteases potentially involved in their generation. Activity change was estimated based on the change in abundance of the investigated peptides. Predictions were correlated with transcriptomics (Nephroseq) and relevant protein expression data from the literature. This analysis yielded seventeen proteases, including multiple forms of MMPs, cathepsin D and K, kallikrein 4 and proprotein convertases. The activity of MMP-2 and MMP-9, predicted to be decreased in DN, was investigated using zymography in a DN mouse model confirming the predictions. Collectively, this proof-of-concept study links urine peptidomics to molecular changes at the tissue level, building hypotheses for further investigation in DN and providing a workflow with potential applications to other diseases.

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Urine matrix metalloproteinases and their extracellular inducer EMMPRIN in children with chronic kidney disease

Cited by 19 publications

References 26 publications

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

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

Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus

Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

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