Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery

Stafford‐Smith, Mark; Podgoreanu, Mihai V.; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P.; Hauser, Elizabeth R.; Winn, Michelle P.; Milano, Carmelo A.; Nielsen, Dahlia M.; Smith, Matthew F.; Morris, Richard L.; Newman, Mark F.; Schwinn, Debra A.

doi:10.1053/j.ajkd.2004.11.021

Cited by 107 publications

(110 citation statements)

References 62 publications

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“…A cute Kidney Injury (AKI) is a common complication after cardiac surgery, with reported incidence varying from 20% to 50% depending on the definition used (1)(2)(3)(4). Early detection of injury is desirable to facilitate early intervention aimed at limiting associated morbidity and mortality.…”

mentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery

McIlroy¹,

Wagener²,

Lee³

2010

Clinical Journal of the American Society of Nephrology

180

102

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Background and objectives: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules after injury, potentially allowing early identification of acute kidney injury (AKI) after cardiac surgery. However, the diagnostic performance of NGAL has varied widely in clinical studies, and it remains unknown what factors modify the relationship between NGAL and AKI. We hypothesized the relationship between urinary NGAL and AKI would vary with baseline renal function, allowing a stratified analysis to improve diagnostic performance of this novel biomarker.Design, setting, participants, & measurements: We performed a prospective observational study in 426 adult cardiac surgical patients. Urinary NGAL was serially determined, commencing preoperatively and continuing 24 hours postoperatively. AKI was defined as increase in serum creatinine from baseline by either >50% or >0.3 mg/dl within 48 hours postoperatively. Patients were stratified by baseline estimated GFR (eGFR). NGAL levels were compared between patients with and without AKI and diagnostic characteristics determined according to baseline eGFR.Results: In patients with baseline eGFR >60 ml/min, urinary NGAL was higher at all postoperative time points in patients who developed AKI compared with those who did not. In patients with baseline eGFR <60 ml/min, urinary NGAL did not differ at any time between those who did and those who did not develop AKI. Postoperative NGAL best identified AKI in patients with baseline eGFR 90 to 120 ml/min. Conclusions: The relationship between urinary NGAL and AKI after cardiac surgery varies with baseline renal function, with optimal discriminatory performance in patients with normal preoperative function.

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mentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery

McIlroy¹,

Wagener²,

Lee³

2010

Clinical Journal of the American Society of Nephrology

180

102

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“…Perioperative complications, including acute kidney injury [6], postoperative bleeding [7], myocardial injury [8], and stroke [9], have been correlated with a variety of proinflammatory genotypes. The fact that a number of these genes (and/or gene products) identified in these association studies, such as the inflammatory mediators IL-6 and CRP as well as the endothelial adhesion molecules E-selectin and ICAM, have been previously implicated in the natural history of chronic inflammatory diseases provides proof of principle that this model is robust and can be extrapolated beyond the perioperative context.…”

Section: How Do We Study Patients In the Perioperative Period?mentioning

confidence: 99%

Understanding the Transition to Acute Illness: The Promise of Perioperative Genomics

Turer

Schwinn

2008

J. of Cardiovasc. Trans. Res.

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Over the last decades, tremendous advances have been made in understanding the genomic basis of a large number of chronic human diseases. Such advances were made possible by studying large numbers of patients over relatively long periods of time. It is increasingly recognized that acute robust stress stimulates pathways activated in chronic disease, facilitating mechanistic studies in much shorter time frames. A new field of molecular medicine, called perioperative genomics, uses robust surgical stress as a perturbation designed to explore such mechanisms. This new field is described briefly below. KeywordsPerioperative Care; Genomics; Risk Assessment; Postoperative Complications; Acute Disease Importance of the Perioperative PeriodMore than 40 million patients undergo surgery in the United States each year, and that number is expected to rise by 25% by 2020 [1]. In terms of monetary costs, the numbers are staggering with current estimates of $450 billion spent annually in the perioperative period [2]. Adverse events such as perioperative myocardial injury, renal failure, cognitive dysfunction, and stroke are devastating. Cardiovascular complications can occur after procedures even in patients without known heart disease. This problem is increasing as the population ages and cardiac risk factors, such as hypertension and diabetes mellitus, become more prevalent.Outside of its overall economic impact, the perioperative period provides an ideal model of acute illness. Although a dynamic and complicated environment, the operating room offers unique advantages for studying patients. In this environment, physiologic changes from baseline with robust stress can be prospectively quantified (e.g., hemo-dynamic parameters or plasma biomarkers). Even perturbations such as drug administration and organ ischemic time can be studied. Exposure to extremes of physiology offers the advantage of revealing (uncovering) phenotypes which might otherwise be dormant or take years to be expressed. Indeed, for patients at risk for proinflammatory activation, the operating room may transition an otherwise healthy individual into one who is acutely ill and at risk for postoperative complications and organ dysfunction.Coronary thrombosis is one example of how perioperative genomics can aid our understanding of illness beyond the operating room. There are more than one million spontaneous myocardial infarctions annually in the United States, but despite this incidence, molecular events triggering

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“…Genetic variants have been found for adverse events such as myocardial ischemia [53], postoperative arrhythmias [54], vein graft restenosis [55], transplant rejection [56], renal compromise [57,58], neurocognitive dysfunction [59,60], stroke [61], and death [62], as well as more systemic outcomes such as bleeding [63], thrombosis [64], inflammatory responses and severe sepsis [65], and alterations in vascular reactivity [66] (see Podgoreanu [2]). Even more broadly, genetic variants affecting inflammatory responses have been identified.…”

Section: Genomic Variability and Complex Diseasementioning

confidence: 99%

“…These studies should ideally focus on mechanistic pathways with carefully defined clinical endpoints and include all appropriate clinical covariates in order to optimize reproducibility of the final results. End-points examined thus far include bleeding, renal injury, stroke, neurocognitive deficits, myocardial injury, sepsis, and arrhythmias [3,58,61,63,69,[79][80][81]; analysis typically includes creation of clinical models, genetic models, and combined clinical/genetic models for these adverse outcomes, with careful adjustment for multiple comparisons. A recent invited review [2] introduced the concept of perioperative genomics to the broader cardiovascular community.…”

Section: Genetics and Adverse Perioperative Outcomesmentioning

confidence: 99%

Pharmacogenomics and end-organ susceptibility to injury in the perioperative period

Schwinn

Podgoreanu

2008

Best Practice & Research Clinical Anaesthesiology

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Genomic medicine has provided new mechanistic understanding for many complex diseases over the last 5-10 years. More recently genomic approaches have been applied to the perioperative paradigm, facilitating identification of patients at high risk for adverse events, as well as those who will respond better/worse to specific pharmacologic therapies. The consistent biological theme emerging is that while inflammation is important in healing from surgical trauma, patients who are too robustly proinflammatory appear to be at higher risk for adverse perioperative events. Precise predictors of each adverse event are being elucidated so that corrective therapeutics can be instituted to improve outcomes in high-risk patients. While the field of perioperative genomics could be considered in its infancy, such approaches are the wave of the future.

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Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery

Cited by 107 publications

References 62 publications

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery

Understanding the Transition to Acute Illness: The Promise of Perioperative Genomics

Pharmacogenomics and end-organ susceptibility to injury in the perioperative period

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