PMID- 28235038
OWN - NLM
STAT- MEDLINE
DCOM- 20170816
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 2
DP  - 2017
TI  - Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute 
      tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion 
      injury.
PG  - e0168981
LID - 10.1371/journal.pone.0168981 [doi]
LID - e0168981
AB  - Several lines of evidence have demonstrated the anti-inflammatory and 
      cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine 
      protease inhibitor. The aim of the present study was to investigate the effects 
      of human AAT (hAAT) monotherapy during the early and recovery phase of 
      ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) 
      injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery 
      and vein for 20 min. hAAT (80 mg/kg, Prolastin(R)) was administered daily 
      intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals 
      received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys 
      were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological 
      and biochemical analysis. hAAT partially preserved renal function and tubular 
      integrity after induction of bilateral kidney I/R injury, which was accompanied 
      with reduced renal influx of macrophages and a significant decrease of neutrophil 
      gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During 
      the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) 
      protein levels in urine but showed no significant effect on renal fibrosis. 
      Although the observed effect size of hAAT administration was limited and 
      therefore the clinical relevance of our findings should be evaluated carefully, 
      these data support the potential of this natural protein to ameliorate ischemic 
      and inflammatory conditions.
FAU - Maicas, Nuria
AU  - Maicas N
AD  - Department of Nephrology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - van der Vlag, Johan
AU  - van der Vlag J
AD  - Department of Nephrology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - Bublitz, Janin
AU  - Bublitz J
AD  - Department of Nephrology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - Florquin, Sandrine
AU  - Florquin S
AD  - Department of Pathology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - Bakker-van Bebber, Marinka
AU  - Bakker-van Bebber M
AD  - Department of Nephrology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - Dinarello, Charles A
AU  - Dinarello CA
AD  - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
AD  - Department of Medicine, University of Colorado Health Sciences Center Denver, 
      Colorado, United States of America.
FAU - Verweij, Vivienne
AU  - Verweij V
AD  - Department of Pharmacology and Toxicology, Radboud University Medical Center, 
      Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
FAU - Masereeuw, Roos
AU  - Masereeuw R
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, 
      the Netherlands.
FAU - Joosten, Leo A
AU  - Joosten LA
AD  - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
FAU - Hilbrands, Luuk B
AU  - Hilbrands LB
AUID- ORCID: 0000-0002-4935-9765
AD  - Department of Nephrology, Radboud University Medical Center, Nijmegen, the 
      Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20170224
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Havcr1 protein, mouse)
RN  - 0 (Hepatitis A Virus Cellular Receptor 1)
RN  - 0 (SERPINA1 protein, human)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Acute Kidney Injury/*drug therapy/pathology
MH  - Animals
MH  - Disease Models, Animal
MH  - Hepatitis A Virus Cellular Receptor 1/metabolism
MH  - Humans
MH  - Kidney/drug effects/pathology
MH  - Kidney Tubular Necrosis, Acute/*drug therapy/physiopathology
MH  - Mice
MH  - Reperfusion Injury/*drug therapy/physiopathology
MH  - alpha 1-Antitrypsin/*administration & dosage/metabolism
PMC - PMC5325207
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/02/25 06:00
MHDA- 2017/08/17 06:00
PMCR- 2017/02/24
CRDT- 2017/02/25 06:00
PHST- 2016/02/17 00:00 [received]
PHST- 2016/12/11 00:00 [accepted]
PHST- 2017/02/25 06:00 [entrez]
PHST- 2017/02/25 06:00 [pubmed]
PHST- 2017/08/17 06:00 [medline]
PHST- 2017/02/24 00:00 [pmc-release]
AID - PONE-D-16-06915 [pii]
AID - 10.1371/journal.pone.0168981 [doi]
PST - epublish
SO  - PLoS One. 2017 Feb 24;12(2):e0168981. doi: 10.1371/journal.pone.0168981. 
      eCollection 2017.