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

Cantaluppi V, Dellepiane S, Tamagnone M, Medica D, Figliolini F, Messina M, Manzione AM, Gai M, Tognarelli G, Ranghino A, Dolla C, Ferrario S, Tetta C, Segoloni GP, Camussi G, Biancone L - PLoS ONE (2015)

Bottom Line: Plasma levels of NGAL at day 1 were significantly higher in DGF group.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).

View Article: PubMed Central - PubMed

Affiliation: "A. Vercellone" Kidney Transplantation Center, Department of Medical Sciences, University of Torino, Azienda Ospedaliera "Città della Salute e della Scienza- Molinette", Torino, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Percentage of DGF risk estimated by the prediction algorithm proposed by Irish et al. (DGF calculator).No significant differences between DGF and non-DGF KT patients were observed (p = 0.19, n = 50). DGF: delayed graft function.
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pone.0129279.g002: Percentage of DGF risk estimated by the prediction algorithm proposed by Irish et al. (DGF calculator).No significant differences between DGF and non-DGF KT patients were observed (p = 0.19, n = 50). DGF: delayed graft function.

Mentions: On the basis of a retrospective study on 1180 KT performed in our centre between 2002 and 2012, we observed a significant overall higher incidence of DGF in KT recipients from ECD (ECD 29.7% vs. non ECD 15.6%; p<0.001) (Fig 1A and 1B). We previously analysed plasma NGAL levels in a first cohort of 25 kidney transplanted patients from ECD, observing that values >400 ng/ml were associated with DGF [21]. Therefore, we designed a prospective study in a second cohort of KT from ECD performed in 2013–2014: the incidence of DGF in this study group was 28% (14/50). The non-DGF group (n = 36) included 19 cases of SGF (53%) and 17 cases of IGF (47%); two patients developed acute rejection before hospital discharge, one patient of the DGF group and one of the IGF group. Comparison of donor-, recipient- and KT-associated variables between the studied group (n = 50) and all other KT from ECD performed between 2013 and 2014 (n = 93) did not show any significant differences. For this reason, we considered our study group as a representative sample of the whole KT population from ECD in our center (Table 1). We did not observe any significant difference in DGF vs. non-DGF group regarding donor and recipient age and co-morbidities, CIT, HLA-mismatches and donor pre-transplant Karpinski biopsy score (Table 2). We also applied the risk prediction model for DGF proposed by Irish et al. Values obtained by using the individual risk calculator were not significantly different between the DGF and the non-DGF group (DGF 0.23±0.06 vs. non-DGF 0.27±0.10; p = 0.2) (Fig 2).


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

Cantaluppi V, Dellepiane S, Tamagnone M, Medica D, Figliolini F, Messina M, Manzione AM, Gai M, Tognarelli G, Ranghino A, Dolla C, Ferrario S, Tetta C, Segoloni GP, Camussi G, Biancone L - PLoS ONE (2015)

Percentage of DGF risk estimated by the prediction algorithm proposed by Irish et al. (DGF calculator).No significant differences between DGF and non-DGF KT patients were observed (p = 0.19, n = 50). DGF: delayed graft function.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488380&req=5

pone.0129279.g002: Percentage of DGF risk estimated by the prediction algorithm proposed by Irish et al. (DGF calculator).No significant differences between DGF and non-DGF KT patients were observed (p = 0.19, n = 50). DGF: delayed graft function.
Mentions: On the basis of a retrospective study on 1180 KT performed in our centre between 2002 and 2012, we observed a significant overall higher incidence of DGF in KT recipients from ECD (ECD 29.7% vs. non ECD 15.6%; p<0.001) (Fig 1A and 1B). We previously analysed plasma NGAL levels in a first cohort of 25 kidney transplanted patients from ECD, observing that values >400 ng/ml were associated with DGF [21]. Therefore, we designed a prospective study in a second cohort of KT from ECD performed in 2013–2014: the incidence of DGF in this study group was 28% (14/50). The non-DGF group (n = 36) included 19 cases of SGF (53%) and 17 cases of IGF (47%); two patients developed acute rejection before hospital discharge, one patient of the DGF group and one of the IGF group. Comparison of donor-, recipient- and KT-associated variables between the studied group (n = 50) and all other KT from ECD performed between 2013 and 2014 (n = 93) did not show any significant differences. For this reason, we considered our study group as a representative sample of the whole KT population from ECD in our center (Table 1). We did not observe any significant difference in DGF vs. non-DGF group regarding donor and recipient age and co-morbidities, CIT, HLA-mismatches and donor pre-transplant Karpinski biopsy score (Table 2). We also applied the risk prediction model for DGF proposed by Irish et al. Values obtained by using the individual risk calculator were not significantly different between the DGF and the non-DGF group (DGF 0.23±0.06 vs. non-DGF 0.27±0.10; p = 0.2) (Fig 2).

Bottom Line: Plasma levels of NGAL at day 1 were significantly higher in DGF group.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).

View Article: PubMed Central - PubMed

Affiliation: "A. Vercellone" Kidney Transplantation Center, Department of Medical Sciences, University of Torino, Azienda Ospedaliera "Città della Salute e della Scienza- Molinette", Torino, Italy.

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.

No MeSH data available.


Related in: MedlinePlus