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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2017
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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 |
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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 |
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