Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients

Alexander H. Flannery, Katherine Bosler, Victor M. Ortiz-Soriano, Fabiola Gianella, Victor Prado, Joshua Lambert, Robert D. Toto, Orson W. Moe, Javier A. Neyra

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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; P0.001 and P0.02, 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.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
Issue number1
StatePublished - Jan 1 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.


  • acute kidney injury
  • acute kidney injury and ICU nephrology
  • biomarker
  • critical care
  • critical illness
  • intensive care
  • major adverse kidney event
  • outcome

ASJC Scopus subject areas

  • Nephrology
  • Medicine (miscellaneous)
  • General Medicine


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