Urinary Biomarkers in the Clinical Prognosis and Early Detection of Acute Kidney Injury

Koyner, Jay L.; Vaidya, Vishal S.; Bennett, Michael; Ma, Qing; Worcester, Elaine M.; Akhter, Shahab A.; Raman, Jai; Jeevanandam, Valluvan; O'Connor, Micheal F.; Devarajan, Prasad; Bonventre, Joseph V.; Murray, Patrick

doi:10.2215/cjn.00740110

Cited by 314 publications

(266 citation statements)

References 47 publications

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“…Koyner et al (29) found that urine NGAL soon after arrival into the ICU after cardiac surgery accurately predicted the development of stage 3 AKI and that preoperative urine KIM-1 levels were moderately predictive. Parikh et al (30) For risk classification, predicted primary outcome occurrence (increased AKI stage from enrollment to peak creatinine, need for dialysis or in-hospital death) of Ͻ20%, 20 to 40%, and Ͼ40% was considered low, intermediate, and high risk, respectively.…”

Section: Discussionmentioning

confidence: 99%

Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis

Hall

Coca

Perazella³

et al. 2011

Clinical Journal of the American Society of Nephrology

105

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SummaryBackground and objectives Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone.Design, setting, participants, & measurements This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.Results In 249 recipients, 57% were Ն65 years old, 48% were from intensive care, and mean baseline GFR was 69 Ϯ 30 ml/min per 1.73 m 2 . AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and "other" in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values Ͻ0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful. ConclusionsOn the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.

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Section: Discussionmentioning

confidence: 99%

Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis

Hall

Coca

Perazella³

et al. 2011

Clinical Journal of the American Society of Nephrology

105

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“…In patients with ADHF, fluid retention, low protein intake, and decreased creatinine production secondary to muscle atrophy may dissociate creatinine levels from reflecting the true severity of renal dysfunction. Diagnostic mainstays such as the fractional excretion of sodium and urea have been shown to be suboptimal in a variety of clinical settings (13)(14)(15)(16)(17). Assessment of biomarkers for renal tubular injury (e.g., neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1] and IL-18) at the time of creatinine-based diagnosis of AKI offers prognostic information in multiple clinical settings such as cardiac surgery, ICU, transplantation, and cirrhosis (18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

Chen¹,

Yang

Lei

et al. 2016

CJASN

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Background and objectives A major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS.Design, settings, participants, & measurements In this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients).Results After multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P,0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation.Conclusions uAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.

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“…As described above, baseline renal function has been shown to impact a biomarker's ability to detect AKI in a variety of clinical settings (35,46). However, for several biomarkers, some clinical variables, outside of renal function, have been shown to impact biomarker concentrations and affect their ability to detect clinical end points.…”

Section: Biomarkers In the Setting Of Critical Illness And Sepsismentioning

confidence: 99%

“…Each individual type of AKI has its own distinct pathophysiologic (and biomarker) fingerprint; for example, the biomarkers that diagnose and prognosticate ischemia-reperfusion AKI may be different from those biomarkers that detect sepsis-associated AKI or those biomarkers that forecast radio contrastassociated AKI. Similarly, every biomarker has its own distinctive kinetics, and accordingly, certain individual biomarkers may excel in detecting early AKI, whereas others may help prognosticate outcomes at the time of creatinine elevation (46). To date, several individual biomarkers have excelled at detecting multiple aspects of AKI in the setting of both cardiac surgery and critical illness.…”

Section: Summationmentioning

confidence: 99%

Clinical Utility of Biomarkers of AKI in Cardiac Surgery and Critical Illness

Koyner

Parikh

2013

Clinical Journal of the American Society of Nephrology

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SummaryAKI is a common and serious complication that is associated with several adverse outcomes in hospitalized patients. The past several years have seen a large number of multicenter investigations of biomarkers of AKI in the setting of cardiac surgery and critical illness. This review summarizes these biomarker results to identify applications for clinical use. The Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study showed that blood and urine biomarkers measured preoperatively, immediately postoperatively, and at the time of the clinical increase in serum creatinine in the setting of cardiac surgery all had the ability to improve patient risk stratification for a variety of important clinical end points. Analyses of biomarkers concentrations from the Acute Respiratory Distress Syndrome Network, EARLY ARF, and other studies of critically ill subjects have similarly shown that biomarkers measured early in the clinical course can forecast the development of AKI and need for renal replacement therapy as well as inpatient mortality. Although biomarkers have informed the diagnosis, prognosis, and treatment of AKI and are inching closer to clinical application, large multicenter interventional clinical trials to prevent AKI using biomarkers should continue to be an active area of clinical investigation.

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Urinary Biomarkers in the Clinical Prognosis and Early Detection of Acute Kidney Injury

Cited by 314 publications

References 47 publications

Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis

Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

Clinical Utility of Biomarkers of AKI in Cardiac Surgery and Critical Illness

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