Document Detail

Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure.
MedLine Citation:
PMID:  22907951     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The TAM receptors (tyro3, axl and mer) and their ligands (vitamin K-dependent proteins-Gas6 and Protein S) are crucial modulators of inflammation, which may be relevant in chronic kidney disease (CKD). Gas6 and axl have multiple roles in mediating vascular atherosclerosis and injury, thrombosis and inflammation, yet nothing is known about the Gas6-axl pathway in humans with CKD. Given the prevalence of chronic inflammation and vascular disease in this population, we measured TAM ligands in patients with various levels of renal function.
METHODS: Gas6 and protein S were quantified in the plasma by ELISA in three patient groups: end-stage renal disease on chronic hemodialysis (HD), CKD and normal controls.
RESULTS: Significantly increased levels of Gas6 and protein S were found in CKD patients compared with normal controls (P < 0.01 and <0.001, respectively). In HD patients, Gas6 levels were elevated compared with controls (P < 0.001) and positively associated with low albumin (r = 0.33; P = 0.01), dialysis vintage (r = 0.36; P = 0.008) and IV iron administration (r = 0.33; P = 0.01). The levels of Gas6 rose with CKD stage and were inversely associated with estimated GFR (P < 0.0001).
CONCLUSIONS: Dysregulation of circulating Gas6 is associated with renal disease and inversely proportional to renal function. Low albumin and higher IV iron administration were associated with higher Gas6 levels, suggesting a possible connection between inflammation and oxidative stress mediated by iron. Protein S levels were also elevated in CKD patients, but the relevance of this finding needs to be further investigated.
Iris J Lee; Brendan Hilliard; Abhishek Swami; John C Madara; Swati Rao; Tapan Patel; John P Gaughan; Jean Lee; Crystal A Gadegbeku; Eric T Choi; Philip L Cohen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-20
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  27     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-06-27     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  4166-72     Citation Subset:  IM    
Section of Nephrology, Hypertension and Kidney Transplantation, Temple University, Philadelphia, PA, USA.
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MeSH Terms
Aged, 80 and over
Biological Markers / blood
Enzyme-Linked Immunosorbent Assay
Intercellular Signaling Peptides and Proteins / blood*
Kidney Failure, Chronic / blood*
Middle Aged
Protein Precursors / blood
Protein S / analysis
Renal Dialysis
Grant Support
1U19A1082726//PHS HHS
Reg. No./Substance:
0/Biological Markers; 0/Intercellular Signaling Peptides and Proteins; 0/Protein Precursors; 0/Protein S; 0/growth arrest-specific protein 6; 53230-14-1/acarboxyprothrombin; 9001-26-7/Prothrombin

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