Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Mar 27;9(3):e93460.
doi: 10.1371/journal.pone.0093460. eCollection 2014.

Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery

Melanie Meersch  1 , Christoph Schmidt  1 , Hugo Van Aken  1 , Sven Martens  2 , Jan Rossaint  1 , Kai Singbartl  3 , Dennis Görlich  4 , John A Kellum  5 , Alexander Zarbock  1
Affiliations
Clinical Trial

Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery

Melanie Meersch et al. PLoS One. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and the following conflicts exist: JAK has received grant support and consulting fees from Astute Medical and Alere. This does not alter their adherence to PLOS One policies on sharing data and materials. Alexander Zarbock is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. The remaining authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1. CONSORT 2010 Flow Diagram.
Figure 2
Figure 2. Analysis of urine [TIMP-2]*[IGFBP7].
(A) Graph shows mean urine [TIMP-2]*[IGFBP7] concentrations at various time points before and after cardiopulmonary bypass. (B) Graph shows urine [TIMP-2]*[IGFBP7] corrected for urine creatinine excretion. (C) Graph shows mean urine NGAL concentrations at various time points before and after cardiopulmonary bypass. Error bars are SE. Asterisks (*) denote significant differences (p≤0.05) between groups (AKI, non-AKI) at the respective time point.
Figure 3
Figure 3. ROC curves for the maximum early composite and the 4
(A) This figure displays the receiver operating characteristic (ROC) curve for the maximum early composite (maximum value from the first 24 postoperative hours) for [TIMP-2]*[IGFBP7]. (B) This figure displays the receiver operating characteristic (ROC) curves for the 4 h values of [TIMP-2]*[IGFBP7] (black solid line) and NGAL (gray dashed line).
Figure 4
Figure 4. ROC curve for recovery from AKI after cardiac surgery.
This figure displays the area under the curve (AUC) for predicting renal recovery. [TIMP-2]*[IGFBP7] (black solid line) and urine neutrophil gelatinase-associated lipocalin (NGAL, gray dashed line).
See this image and copyright information in PMC

References

    1. Wijeysundera DN, Karkouti K, Dupuis JY, Rao V, Chan CT, et al. (2007) Derivation and validation of a simplified predictive index for renal replacement therapy after cardiac surgery. JAMA 297: 1801–1809. - PubMed
    1. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J (1998) Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104: 343–348. - PubMed
    1. Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, et al. (1998) Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med 128: 194–203. - PubMed
    1. Zanardo G, Michielon P, Paccagnella A, Rosi P, Calo M, et al. (1994) Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg 107: 1489–1495. - PubMed
    1. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, et al. (2004) Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 15: 1597–1605. - PubMed

Publication types

MeSH terms

Substances