Neutrophil Gelatinase Associated Lipocalin Is an Early and Accurate Biomarker of Graft Function and Tissue Regeneration in Kidney Transplantation from Extended Criteria Donors

PLoS One. 2015 Jun 30;10(6):e0129279. doi: 10.1371/journal.pone.0129279. eCollection 2015.

Abstract

Background: Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.

Methods: We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction.

Results: Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio).

Conclusions: NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Aged
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Cell Hypoxia
  • Cells, Cultured
  • Cohort Studies
  • Delayed Graft Function / blood
  • Delayed Graft Function / etiology
  • Donor Selection
  • Female
  • Gene Expression
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney / drug effects
  • Kidney / physiopathology
  • Kidney Transplantation* / adverse effects
  • Kidney Tubules / drug effects
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Lipocalin-2
  • Lipocalins / blood*
  • Lipocalins / genetics
  • Male
  • Middle Aged
  • Prospective Studies
  • Proto-Oncogene Proteins / blood*
  • Proto-Oncogene Proteins / genetics
  • Regeneration
  • Tacrolimus / adverse effects
  • Tissue Donors*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Immunosuppressive Agents
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Tacrolimus

Grant support

This work was supported by Italian Government MIUR PRIN project (G.C.), ‘Regione Piemonte, Piattaforme Biotecnologiche PiSTEM project (G.C.) and Ricerca Finalizzata and Local University Grants (“ex-60%”) (V.C., G.C., L.B.). Co-author C.T. is employed by EMEALA Medical Board, Fresenius Medical Care. EMEALA Medical Board, Fresenius Medical Care provided support in the form of salary for author C.T., but it did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.