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Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery

BACKGROUND: Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tiss...

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Autores principales: Meersch, Melanie, Schmidt, Christoph, Van Aken, Hugo, Martens, Sven, Rossaint, Jan, Singbartl, Kai, Görlich, Dennis, Kellum, John A., Zarbock, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968141/
https://www.ncbi.nlm.nih.gov/pubmed/24675717
http://dx.doi.org/10.1371/journal.pone.0093460
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author Meersch, Melanie
Schmidt, Christoph
Van Aken, Hugo
Martens, Sven
Rossaint, Jan
Singbartl, Kai
Görlich, Dennis
Kellum, John A.
Zarbock, Alexander
author_facet Meersch, Melanie
Schmidt, Christoph
Van Aken, Hugo
Martens, Sven
Rossaint, Jan
Singbartl, Kai
Görlich, Dennis
Kellum, John A.
Zarbock, Alexander
author_sort Meersch, Melanie
collection PubMed
description BACKGROUND: Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients. METHODS: We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge. RESULTS: 26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1–3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery. CONCLUSIONS: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery. CLINICAL TRIAL REGISTRATION INFORMATION: www.germanctr.de/, DRKS-ID: DRKS00005062
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spelling pubmed-39681412014-04-01 Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery Meersch, Melanie Schmidt, Christoph Van Aken, Hugo Martens, Sven Rossaint, Jan Singbartl, Kai Görlich, Dennis Kellum, John A. Zarbock, Alexander PLoS One Research Article BACKGROUND: Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients. METHODS: We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge. RESULTS: 26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1–3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery. CONCLUSIONS: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery. CLINICAL TRIAL REGISTRATION INFORMATION: www.germanctr.de/, DRKS-ID: DRKS00005062 Public Library of Science 2014-03-27 /pmc/articles/PMC3968141/ /pubmed/24675717 http://dx.doi.org/10.1371/journal.pone.0093460 Text en © 2014 Meersch 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Meersch, Melanie
Schmidt, Christoph
Van Aken, Hugo
Martens, Sven
Rossaint, Jan
Singbartl, Kai
Görlich, Dennis
Kellum, John A.
Zarbock, Alexander
Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title_full Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title_fullStr Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title_full_unstemmed Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title_short Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
title_sort urinary timp-2 and igfbp7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968141/
https://www.ncbi.nlm.nih.gov/pubmed/24675717
http://dx.doi.org/10.1371/journal.pone.0093460
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