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Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine provides early risk stratification for adverse outcomes after cardiac surgery: a prospective observational study.

ABSTRACT: OBJECTIVES:Novel biomarkers of renal injury appear inconsistent in identifying a creatinine-based diagnosis of acute kidney injury. To be clinically useful, novel acute kidney injury biomarkers should identify patients at increased risk for adverse outcomes that are a consequence of acute kidney injury earlier and with greater utility than conventional creatinine-based metrics. We sought to determine the prognostic utility of both urinary neutrophil gelatinase-associated lipocalin and varying creatinine-based metrics of renal injury at multiple time points associated with cardiac surgery. DESIGN:Prospective observational study. SETTING:Academic medical center. PATIENTS:Six hundred three adults undergoing cardiac surgery. INTERVENTIONS:Nil. MEASUREMENTS AND MAIN RESULTS:Urinary neutrophil gelatinase-associated lipocalin was measured at baseline and again less than 1 hour, 3 hours, and 18-24 hours after separation from cardiopulmonary bypass. Creatinine-based metrics included a Kidney Disease: Improving Global Outcomes definition of acute kidney injury through 7 days postoperatively as well as ?SCr-initial, defined as the incremental change in SCr from baseline to first postoperative measure. Multivariable regression determined the prognostic utility of neutrophil gelatinase-associated lipocalin and creatinine, alone and in combination, for the primary composite outcome of hospital mortality or renal replacement therapy. The primary outcome occurred in 25 patients. Adjusted for covariates ?SCr-initial greater than or equal to 0.0 mg/dL provided early prognostic utility for the primary outcome (odds ratio, 8.9; 95% CI, 3.0-26.6), the odds ratio comparable to a creatinine-based Kidney Disease: Improving Global Outcomes definition of acute kidney injury applied over 7 days postoperatively. The upper quartile of urinary neutrophil gelatinase-associated lipocalin best predicted the primary outcome when measured 18-24 hours post-cardiopulmonary bypass (odds ratio, 18.6; 95% CI, 5.1-68.4; p = 0.001) with earlier post-cardiopulmonary bypass measures of uncertain utility. Combining both ?SCr-initial and neutrophil gelatinase-associated lipocalin measured 3 hours after cardiopulmonary bypass provided excellent early risk stratification for the primary outcome (odds ratio, 18.3; 95% CI, 4.5-75.0). CONCLUSIONS:Combining urinary neutrophil gelatinase-associated lipocalin with a novel creatinine-based metric, both available soon after completion of surgery, may provide previously unavailable early and effective risk stratification for serious adverse outcomes after cardiac surgery.

SUBMITTER: McIlroy DR

PROVIDER: S-EPMC7485262 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine provides early risk stratification for adverse outcomes after cardiac surgery: a prospective observational study.

McIlroy David R DR Farkas David D Matto Matthew M Lee H Thomas HT

Critical care medicine 20150501 5

<h4>Objectives</h4>Novel biomarkers of renal injury appear inconsistent in identifying a creatinine-based diagnosis of acute kidney injury. To be clinically useful, novel acute kidney injury biomarkers should identify patients at increased risk for adverse outcomes that are a consequence of acute kidney injury earlier and with greater utility than conventional creatinine-based metrics. We sought to determine the prognostic utility of both urinary neutrophil gelatinase-associated lipocalin and va ...[more]

PMID: 25768681

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Project description:BackgroundAccumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders. We aimed to analyse sex-related differences of NGAL in AS and its role in the inflammatory and fibrocalcific progression of AS.Methods and results220 (60.45% men) patients with severe AS elective for surgical aortic valve (AV) replacement were recruited. Immunohistochemistry revealed higher expression of NGAL in calcific areas of AVs and that was validated by qPCR in in 65 (60% men) donors. Valve interstitial cells (VICs) were a source of NGAL in these samples. Proteome profiler analyses evidenced higher expression of NGAL in men compared to women, and that was further validated by ELISA. NGAL expression in the AV was correlated with inflammation, oxidative stress, and osteogenic markers, as well as calcium score. The expression of NGAL, both intracellular and secreted (sNGAL), was significantly deregulated only in calcifying male-derived VICs. Depletion of intracellular NGAL in calcifying male-derived VICs was associated with pro-inflammatory profiles, dysbalanced matrix remodelling and pro-osteogenic profiles. Conversely, exogenous NGAL mediated inflammatory and dysbalanced matrix remodelling in calcifying VICs, and all that was prevented by the pharmacological blockade of NGAL.ConclusionsOwing to the over-expression of NGAL, the AV from men may be endowed with higher expression of inflammatory, oxidative stress, matrix remodelling and osteogenic markers supporting the progression of calcific AS phenotypes. The expression of NGAL in the VIC emerges as a potential therapeutic checkpoint, with its effects being potentially reverted by the pharmacological blockade of extracellular NGAL.

Dataset Information

Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine provides early risk stratification for adverse outcomes after cardiac surgery: a prospective observational study.

Publications

Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine provides early risk stratification for adverse outcomes after cardiac surgery: a prospective observational study.

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