Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure.
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.
Section of Nephrology, Hypertension and Kidney Transplantation, Temple University, Philadelphia, PA, USA. iris.lee@tuhs.temple.edu
Iris J
IJ
Lee
Brendan
B
Hilliard
Abhishek
A
Swami
John C
JC
Madara
Swati
S
Rao
Tapan
T
Patel
John P
JP
Gaughan
Jean
J
Lee
Crystal A
CA
Gadegbeku
Eric T
ET
Choi
Philip L
PL
Cohen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood; D017293:Protein S / Q000032:analysis; D011516:Prothrombin; D006435:Renal Dialysis; D000099255:Growth Arrest-Specific Protein 6
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D011498:Protein Precursors; D017293:Protein S; D011516:Prothrombin; D000099255:Growth Arrest-Specific Protein 6; C008208:acarboxyprothrombin