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. 2015 Jun 8;10(6):e0129619.
doi: 10.1371/journal.pone.0129619. eCollection 2015.

Association of Perioperative Plasma Neutrophil Gelatinase-Associated Lipocalin Levels with 3-Year Mortality after Cardiac Surgery: A Prospective Observational Cohort Study

Dennis G Moledina  1 , Chirag R Parikh  1 , Amit X Garg  2 , Heather Thiessen-Philbrook  3 , Jay L Koyner  4 , Uptal D Patel  5 , Prasad Devarajan  6 , Michael G Shlipak  7 , Steven G Coca  1 ; TRIBE-AKI Consortium
Collaborators, Affiliations

Association of Perioperative Plasma Neutrophil Gelatinase-Associated Lipocalin Levels with 3-Year Mortality after Cardiac Surgery: A Prospective Observational Cohort Study

Dennis G Moledina et al. PLoS One. .

Abstract

Background: Higher levels of plasma neutrophil gelatinase-associated lipocalin (pNGAL) are an early marker of acute kidney injury and are associated with increased risk of short-term adverse outcomes. The independent association between pNGAL and long-term mortality is unknown.

Methods: In this prospective observational cohort study, we studied 1191 adults who underwent cardiac surgery between 2007 and 2009 at 6 centers in the TRIBE-AKI cohort. We measured the pNGAL on the pre-operative and first 3 post-operative days and assessed the relationship of peri-operative pNGAL concentrations with all-cause mortality.

Results: During a median follow-up of 3.0 years, 139 participants died (50/1000 person-years). Pre-operative levels of pNGAL were associated with 3-year mortality (unadjusted HR 1.96, 95% CI 1.34,2.85) and the association persisted after adjustment for pre-operative variables including estimated glomerular filtration rate (adjusted HR 1.48, 95% CI 1.04-2.12). After adjustment for pre- and intra-operative variables, including pre-operative NGAL levels, the highest tertiles of first post-operative and peak post-operative pNGAL were also independently associated with 3-year mortality risk (adjusted HR 1.31, 95% CI 1.0-1.7 and adjusted HR 1.78, 95% CI 1.2-2.7, respectively). However, after adjustment for peri-operative changes in serum creatinine, there was no longer an independent association between the first post-operative and peak post-operative pNGAL and long-term mortality (adjusted HR 0.98,95% CI 0.79-1.2 for first pNGAL and adjusted HR 1.19, 95% CI 0.87-1.61 for peak pNGAL).

Conclusions: Pre-operative pNGAL levels were independently associated with 3-year mortality after cardiac surgery. While post-operative pNGAL levels were also associated with 3-year mortality, this relationship was not independent of changes in serum creatinine. These findings suggest that while pre-operative pNGAL adds prognostic value for mortality beyond routinely available serum creatinine, post-operative pNGAL measurements may not be as useful for this purpose.

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Conflict of interest statement

Competing Interests: 1. Details of IL-18 patent: Methods for detection of IL-18 as an early marker for diagnosis of acute renal failure and predictor of mortality, United States Patent number 7141382 issued on November 28, 2006. Inventors: Chirag R. Parikh and Charles L. Edelstein, Family ID: 37449883, Appl. No.: 10/964,201. 2. NGAL patents: Dr. Prasad Devarjan is named co-inventor on the NGAL patents. United States Patent Names (numbers): NGAL for reduction and amelioration of ischemic and nephrotoxic injuries (7776824), NGAL for reduction and amelioration of ischemic and nephrotoxic injuries (8247376), and High molecular weight NGAL as a biomarker for chronic kidney disease (8592170). 3. The plasma NGAL assays were donated by Biosite, Inc. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Biomarker levels and the risk of death.
*Mortality Rate per 1000 patient-years adjusted for site.
See this image and copyright information in PMC

References

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