Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation

Abstract Background Acute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric)....

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Autores principales:	Arie Passov, Minna Ilmakunnas, Marjut Pihlajoki, Kethe Hermunen, Marko Lempinen, Ilkka Helanterä, Villemikko Kailari, Markku Heikinheimo, Sture Andersson, Eero Pesonen
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	Neutrophil-gelatinase associated lipocalin Acute Kidney Injury Kidney transplantation Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
Acceso en línea:	https://doaj.org/article/e5e5f653dbca4be2b56bbea2ac24517c
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spelling	oai:doaj.org-article:e5e5f653dbca4be2b56bbea2ac24517c2021-11-28T12:23:48ZNeutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation10.1186/s40635-021-00422-72197-425Xhttps://doaj.org/article/e5e5f653dbca4be2b56bbea2ac24517c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40635-021-00422-7https://doaj.org/toc/2197-425XAbstract Background Acute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules. Methods Kidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage. Results Significant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood. Conclusions Ischaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.Arie PassovMinna IlmakunnasMarjut PihlajokiKethe HermunenMarko LempinenIlkka HelanteräVillemikko KailariMarkku HeikinheimoSture AnderssonEero PesonenSpringerOpenarticleNeutrophil-gelatinase associated lipocalinAcute Kidney InjuryKidney transplantationMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENIntensive Care Medicine Experimental, Vol 9, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neutrophil-gelatinase associated lipocalin Acute Kidney Injury Kidney transplantation Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
spellingShingle	Neutrophil-gelatinase associated lipocalin Acute Kidney Injury Kidney transplantation Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Arie Passov Minna Ilmakunnas Marjut Pihlajoki Kethe Hermunen Marko Lempinen Ilkka Helanterä Villemikko Kailari Markku Heikinheimo Sture Andersson Eero Pesonen Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
description	Abstract Background Acute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules. Methods Kidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage. Results Significant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood. Conclusions Ischaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.
format	article
author	Arie Passov Minna Ilmakunnas Marjut Pihlajoki Kethe Hermunen Marko Lempinen Ilkka Helanterä Villemikko Kailari Markku Heikinheimo Sture Andersson Eero Pesonen
author_facet	Arie Passov Minna Ilmakunnas Marjut Pihlajoki Kethe Hermunen Marko Lempinen Ilkka Helanterä Villemikko Kailari Markku Heikinheimo Sture Andersson Eero Pesonen
author_sort	Arie Passov
title	Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
title_short	Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
title_full	Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
title_fullStr	Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
title_full_unstemmed	Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
title_sort	neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/e5e5f653dbca4be2b56bbea2ac24517c
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Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation

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