Subclinical and clinical contrast-induced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO), a prospective study

Akrawinthawong, Krittapoom; Ricci, Jason; Cannon, Louis; Dixon, Simon; Küpfer, K.; Stivers, David; Alexander, Patrick; David, Shukri; McCullough, Peter A.

doi:10.3109/0886022x.2014.991994

Cited by 22 publications

(32 citation statements)

References 47 publications

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“…Biomarkers of AKI, such as NGAL, KIM‐1, and IL‐18, may be potentially beneficial for early detection, diagnosis, and prognosis of AKI after cardiac surgery 35, 36. However, in our study and others, these markers are commonly elevated at baseline, and thus a relatively large change from baseline (doubling or tripling) would be needed to detect AKI in this setting 37, 38, 39. In our study, the results in functional and novel injury markers were concordant in demonstrating no benefit of ABT‐719 treatment.…”

Section: Discussionmentioning

confidence: 68%

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

McCullough

Bennett‐Guerrero

Chawla³

et al. 2016

JAHA

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BackgroundPatients undergoing cardiac surgeries with cardiopulmonary bypass (on‐pump) have a high risk for acute kidney injury (AKI). We tested ABT‐719, a novel α‐melanocyte‐stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.Methods and ResultsThis phase 2b randomized, double‐blind, placebo‐controlled trial included adult patients with stable renal function undergoing high‐risk on‐pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT‐719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72‐hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800‐, 1600‐, and 2100‐μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair‐wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.Conclusions ABT‐719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90‐day outcomes in patients after cardiac surgery.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

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Section: Discussionmentioning

confidence: 68%

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

McCullough

Bennett‐Guerrero

Chawla³

et al. 2016

JAHA

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“…Haase et al (28) analyzed data from 191 patients in 3 studies and found that when urinary NGAL is measured within 6 hours after contrast medium administration, it has better sensitivity than serum creatinine alone for acute kidney injury detection. Moreover, recent studies and a meta-analysis have demonstrated the role of serum and urinary NGAL in the prediction of CIN (15,16,(29)(30)(31)(32)(33)(34)(35)(36) and, although this biomarker has also been reported to have a low sensitivity in predicting CIN in specific settings, such as ACS (37), a previous study also suggested that it can also predict the severity of CIN (38).…”

Section: Discussionmentioning

confidence: 99%

Cystatin C, but not urinary or serum NGAL, may be associated with contrast induced nephropathy after

Cecchi

Avveduto

DʼAlfonso

et al. 2017

AMA

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“…In contrast, in humans with CI-AKI, 4 of 8 studies showed an excellent value (0.93-1.0) [39][40][41][42] , 2 of 8 studies showed a good value of NGAL (0.83-0.84) [43,44], and 2 of 8 studies showed a poor value of NGAL (0.63-0.68) [29,45] . In CKD patients undergoing elective coronary angiography with contrast, postprocedural NGAL increases from baseline in each stage of CKD [46] . In patients undergoing open heart surgery with AKI, urine catalytic iron levels are highly correlated with urine NGAL levels [47] .…”

Section: Similar Pathogenesis Of Ed and Asymmetric Dimethylarginine Imentioning

confidence: 99%

“…Mild contrast exposure in SHRs results in kidney injury but not total loss of renal function. Therefore, SHRs with mild contrast exposure can serve as a model for subclinical CI-AKI [46] . On the other hand, moderate or heavy contrast exposure in SHRs results in complete loss of renal function.…”

Section: The Concept Of a Renal Functional Reserve: Insights From Thementioning

confidence: 99%

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Zhang

Fallahzadeh

McCullough³

2016

Cardiorenal Med

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Background:Although there are some animal models for biomarkers of contrast-induced acute kidney injury (CI-AKI), for cardiorenal syndrome (CRS) and for acute renal failure, the interplay between CI-AKI and CRS has yet to be evaluated. Insight into the pathogenesis of CRS is urgently needed from animal models in order to foster the discovery and implementation of novel biomarkers for this disease. Specially designed animal models for type 1 and 3 CRS, particularly CI-AKI, have not yet emerged. Summary: We hypothesize that the aging male spontaneously hypertensive rat (SHR) is likely to be a suitable model. The SHR model is able to mimic risk factors for preclinical CRS that appears in the clinical setting, specifically hypertension, age, preexisting damage and dysfunction of the heart and kidney, endothelial dysfunction, increased level of reactive oxygen species, decreased level and bioavailability of nitric oxide (NO), impairment of the L -arginine-NO pathway, and insulin resistance. In the SHR, CI-AKI results in a different profile of AKI biomarkers than is seen with preexisting chronic kidney injury. Key Messages: The SHR model can be used to evaluate the interaction between CI-AKI and CRS type 1 and 3 and to verify neutrophil gelatinase-associated lipocalin (NGAL) as a reliable CI-AKI biomarker for clinical application. Further research is warranted with a large number of aging male SHRs to prove NGAL as a sensitive, specific, highly predictive, early biomarker for CI-AKI.

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Subclinical and clinical contrast-induced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO), a prospective study

Cited by 22 publications

References 47 publications

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

Cystatin C, but not urinary or serum NGAL, may be associated with contrast induced nephropathy after

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

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