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

Vincenzo Cantaluppi; Sergio Dellepiane; Michela Tamagnone; Davide Medica; Federico Figliolini; Maria Messina; Ana Maria Manzione; Massimo Gai; Giuliana Tognarelli; Andrea Ranghino; Caterina Dolla; Silvia Ferrario; Ciro Tetta; Giuseppe Paolo Segoloni; Giovanni Camussi; Luigi Biancone

doi:10.1371/journal.pone.0129279

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.

Authors

Vincenzo Cantaluppi¹, Sergio Dellepiane¹, Michela Tamagnone¹, Davide Medica¹, Federico Figliolini¹, Maria Messina¹, Ana Maria Manzione¹, Massimo Gai¹, Giuliana Tognarelli¹, Andrea Ranghino¹, Caterina Dolla¹, Silvia Ferrario¹, Ciro Tetta², Giuseppe Paolo Segoloni¹, Giovanni Camussi¹, Luigi Biancone¹

Affiliations

¹ "A. Vercellone" Kidney Transplantation Center, Department of Medical Sciences, University of Torino, Azienda Ospedaliera "Città della Salute e della Scienza- Molinette", Torino, Italy.
² EMEALA Medical Board, Fresenius Medical Care, Bad Homburg, Germany.

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

Grants and funding

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.