P-NGAL Day 1 predicts early but not one year graft function following deceased donor kidney transplantation - The CONTEXT study

PLoS One. 2019 Feb 28;14(2):e0212676. doi: 10.1371/journal.pone.0212676. eCollection 2019.

Abstract

Background: Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months.

Methods: 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR).

Results: All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months.

Conclusion: High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function.

Trial registration: ClinicalTrials.gov NCT01395719.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Allografts / physiopathology
  • Biomarkers / blood
  • Biomarkers / urine
  • Creatinine / blood
  • Delayed Graft Function / diagnosis*
  • Delayed Graft Function / physiopathology
  • Female
  • Glomerular Filtration Rate
  • Graft Survival
  • Humans
  • Kidney / physiopathology
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy*
  • Kidney Failure, Chronic / urine
  • Kidney Transplantation / adverse effects*
  • Lipocalin-2 / blood*
  • Lipocalin-2 / urine
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Renal Dialysis / statistics & numerical data
  • Time Factors

Substances

  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT01395719

Grants and funding

The Danish Council for Independent Research, the Danish Society of Nephrology, Grosserer L.F. Foghts Fond, the Lundbeck Foundation, the Novo Nordic Foundation, Nyreforeningen (the Danish Kidney Patient Association), Swedish Society of Medicine, A.P. Møller og hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal, Aarhus University, and Aarhus University Hospital funded this study. The 18 ELISA kits for L-FABP measurements were kindly donated by ®CMIC HOLDINDS Co., Tokyo, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Marie Bodilsen Nielsen received a research scholarship from The Danish Council for Independent Research.