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. 2020 Nov 4;2(1):26-32.
doi: 10.34067/KID.0003552020. eCollection 2021 Jan 28.

Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients

Alexander H Flannery  1 , Katherine Bosler  2   3 , Victor M Ortiz-Soriano  4 , Fabiola Gianella  3 , Victor Prado  3 , Joshua Lambert  5 , Robert D Toto  6 , Orson W Moe  3   6 , Javier A Neyra  3   4
Affiliations

Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients

Alexander H Flannery et al. Kidney360. .

Abstract

Background: Several biomarkers of AKI have been examined for their ability to predict AKI before serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research.

Methods: Single-center prospective study collecting blood and urine samples from critically ill patients with AKI Kidney Disease Improving Global Outcomes stage 2 or above, and matched controls from a single, tertiary care intensive care unit (ICU). Samples were collected at 24-48 hours after AKI diagnosis (patients) or ICU admission (controls), 5-7 days later, and 4-6 weeks after discharge for patients with AKI. The primary outcome of interest was MAKE at hospital discharge (MAKE-DC), consisting of the composite end point of death, RRT dependence, or a decrease in estimated glomerular filtration to <75% of baseline.

Results: Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE-DC compared with those not experiencing MAKE-DC. Additionally, serum/urinary NGAL and serum cystatin C measurements at the first time point remained significantly associated with MAKE events at 3, 6, and 12 months. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a logistic regression clinical prediction model of MAKE-DC (AUROC 0.94 and 0.87 versus 0.83; P=0.001 and P=0.02, respectively). Patients without MAKE-DC experienced a greater decline in serum NGAL from first to second measurement than those patients experiencing MAKE-DC.

Conclusions: Early measures of kidney biomarkers in patients who are critically ill are associated with MAKE-DC. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE-DC.

Keywords: acute kidney injury; acute kidney injury and ICU nephrology; biomarker; critical care; critical illness; intensive care; major adverse kidney event; outcome.

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Conflict of interest statement

J. Lambert reports honoraria from SAS Institute, outside the submitted work. A.H. Flannery is supported by KidneyCure/American Society of Nephrology and the La Jolla Pharmaceutical company, outside the submitted work. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Kidney biomarker trends from time 1 (24–48 hours) to time 2 (5–7 days). DC, hospital discharge; MAKE, major adverse kidney event; NGAL, neutrophil gelatinase-associated lipocalin.
Figure 2.
Figure 2.
Receiver operating characteristic curves for MAKE-DC. AUC, area under the curve; 95% CI, 95% confidence interval.
See this image and copyright information in PMC

References

    1. Griffin BR, Gist KM, Faubel S: Current status of novel biomarkers for the diagnosis of acute kidney injury: A historical perspective. J Intensive Care Med 35: 415–424, 2020. 10.1177/0885066618824531 - DOI - PMC - PubMed
    1. Vijayan A, Faubel S, Askenazi DJ, Cerda J, Fissell WH, Heung M, Humphreys BD, Koyner JL, Liu KD, Mour G, Nolin TD, Bihorac A; American Society of Nephrology Acute Kidney Injury Advisory Group: Clinical use of the urine biomarker [TIMP-2] × [IGFBP7] for Acute kidney injury risk assessment. Am J Kidney Dis 68: 19–28, 2016. 10.1053/j.ajkd.2015.12.033 - DOI - PMC - PubMed
    1. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN, Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes-Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmelé T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA: Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17: R25, 2013. 10.1186/cc12503 - DOI - PMC - PubMed
    1. Parikh CR, Coca SG, Thiessen-Philbrook H, Shlipak MG, Koyner JL, Wang Z, Edelstein CL, Devarajan P, Patel UD, Zappitelli M, Krawczeski CD, Passik CS, Swaminathan M, Garg AX; TRIBE-AKI Consortium: Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol 22: 1748–1757, 2011. 10.1681/ASN.2010121302 - DOI - PMC - PubMed
    1. Billings FT 4th, Shaw AD: Clinical trial endpoints in acute kidney injury. Nephron Clin Pract 127: 89–93, 2014. 10.1159/000363725 - DOI - PMC - PubMed

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