The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment

BACKGROUND: Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Facto...

Descripción completa

Detalles Bibliográficos
Autores principales: Knafl, Daniela, Müller, Markus, Pajenda, Sahra, Genc, Zeynep, Hecking, Manfred, Wagner, Ludwig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690422/
https://www.ncbi.nlm.nih.gov/pubmed/29145491
http://dx.doi.org/10.1371/journal.pone.0188316
_version_ 1783279605277261824
author Knafl, Daniela
Müller, Markus
Pajenda, Sahra
Genc, Zeynep
Hecking, Manfred
Wagner, Ludwig
author_facet Knafl, Daniela
Müller, Markus
Pajenda, Sahra
Genc, Zeynep
Hecking, Manfred
Wagner, Ludwig
author_sort Knafl, Daniela
collection PubMed
description BACKGROUND: Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment. METHOD: We collected urine samples of 33 kidney transplant recipients and 14 non-transplanted patients who all had AKI (stages 1–3 according to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck(®) Astute1 40 (™) meter. Concomitantly, we analyzed IGFBP7 and TIMP-2 mRNA expression by quantitative polymerase chain reaction (qPCR) from urinary sediment of the same patients, and correlated the results with [IGFBP7]x[TIMP-2] (protein), by linear regression analysis. We also determined the association between [IGFBP7]x[TIMP-2] and estimated glomerular filtration rate (eGFR), and between IGFBP7 and TIMP-2 mRNA expression and markers of inflammation. Light microscopy and confocal immunofluorescence served to illustrate changes in the urinary sediment over the time course of renal function improvement. RESULTS: Of the 47 analyzed AKI patients, 14 presented with ascending urinary tract infection. Serum creatinine (sCr), blood urea nitrogen (BUN) and eGFR in all patients were 3.9±2.28 mg/dL, 47.59±23.1 mg/dL and 22.88±16.0 mL/min/1.73m(2), respectively, on average ±standard deviation. [IGFBP7]x[TIMP-2] was 2.33±9.95 (ng/ml)(2)/1000, and did not associate with IGFBP7 and TIMP-2 gene expression (r = -0.0220, p = 0.4216; respectively r = 0.0972, p = 0.1909). [IGFBP7]x[TIMP-2] did not associate with eGFR; IGFBP7 and TIMP-2 mRNA expression. Improvement of renal function went along with disappearance of casts, decrease in aquaporin1 positive renal epithelial cells and leukocytes from the urinary sediment. CONCLUSION: The gene expression pattern of IGFBP7 and TIMP-2 from urinary sediment, which contains desquamated renal tubular epithelial cells, did not correlate with [IGFBP7]x[TIMP-2] protein, indicating that IGFBP7 and TIMP-2 measured in the NephroCheck(®) test originated predominantly from intact but stressed cells of the kidney itself.
format Online
Article
Text
id pubmed-5690422
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-56904222017-11-30 The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment Knafl, Daniela Müller, Markus Pajenda, Sahra Genc, Zeynep Hecking, Manfred Wagner, Ludwig PLoS One Research Article BACKGROUND: Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment. METHOD: We collected urine samples of 33 kidney transplant recipients and 14 non-transplanted patients who all had AKI (stages 1–3 according to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck(®) Astute1 40 (™) meter. Concomitantly, we analyzed IGFBP7 and TIMP-2 mRNA expression by quantitative polymerase chain reaction (qPCR) from urinary sediment of the same patients, and correlated the results with [IGFBP7]x[TIMP-2] (protein), by linear regression analysis. We also determined the association between [IGFBP7]x[TIMP-2] and estimated glomerular filtration rate (eGFR), and between IGFBP7 and TIMP-2 mRNA expression and markers of inflammation. Light microscopy and confocal immunofluorescence served to illustrate changes in the urinary sediment over the time course of renal function improvement. RESULTS: Of the 47 analyzed AKI patients, 14 presented with ascending urinary tract infection. Serum creatinine (sCr), blood urea nitrogen (BUN) and eGFR in all patients were 3.9±2.28 mg/dL, 47.59±23.1 mg/dL and 22.88±16.0 mL/min/1.73m(2), respectively, on average ±standard deviation. [IGFBP7]x[TIMP-2] was 2.33±9.95 (ng/ml)(2)/1000, and did not associate with IGFBP7 and TIMP-2 gene expression (r = -0.0220, p = 0.4216; respectively r = 0.0972, p = 0.1909). [IGFBP7]x[TIMP-2] did not associate with eGFR; IGFBP7 and TIMP-2 mRNA expression. Improvement of renal function went along with disappearance of casts, decrease in aquaporin1 positive renal epithelial cells and leukocytes from the urinary sediment. CONCLUSION: The gene expression pattern of IGFBP7 and TIMP-2 from urinary sediment, which contains desquamated renal tubular epithelial cells, did not correlate with [IGFBP7]x[TIMP-2] protein, indicating that IGFBP7 and TIMP-2 measured in the NephroCheck(®) test originated predominantly from intact but stressed cells of the kidney itself. Public Library of Science 2017-11-16 /pmc/articles/PMC5690422/ /pubmed/29145491 http://dx.doi.org/10.1371/journal.pone.0188316 Text en © 2017 Knafl et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Knafl, Daniela
Müller, Markus
Pajenda, Sahra
Genc, Zeynep
Hecking, Manfred
Wagner, Ludwig
The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title_full The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title_fullStr The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title_full_unstemmed The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title_short The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck(®) parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
title_sort urine biomarker panel [igfbp7]x[timp-2] (nephrocheck(®) parameter) does not correlate with igfbp7 and timp-2 gene expression in urinary sediment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690422/
https://www.ncbi.nlm.nih.gov/pubmed/29145491
http://dx.doi.org/10.1371/journal.pone.0188316
work_keys_str_mv AT knafldaniela theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT mullermarkus theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT pajendasahra theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT genczeynep theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT heckingmanfred theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT wagnerludwig theurinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT knafldaniela urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT mullermarkus urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT pajendasahra urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT genczeynep urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT heckingmanfred urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment
AT wagnerludwig urinebiomarkerpaneligfbp7xtimp2nephrocheckparameterdoesnotcorrelatewithigfbp7andtimp2geneexpressioninurinarysediment