Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure

• Published in: Nephrology, dialysis, transplantation Vol. 27; no. 11; pp. 4166 - 4172
• Main Authors: LEE, Iris J, HILLIARD, Brendan, COHEN, Philip L, SWAMI, Abhishek, MADARA, John C, RAO, Swati, PATEL, Tapan, GAUGHAN, John P, LEE, Jean, GADEGBEKU, Crystal A, CHOI, Eric T
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2012
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers - blood; Clinical Science; Emergency and intensive care: renal failure. Dialysis management; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intensive care medicine; Intercellular Signaling Peptides and Proteins - blood; Kidney Failure, Chronic - blood; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Protein Precursors - blood; Protein S - analysis; Prothrombin; Renal Dialysis; Renal failure; Human; Kidney disease; chronic kidney disease; Urinary system disease; Hemodialysis; Mortality; Cardiovascular disease; Inflammation; Vascular disease; Extrarenal dialysis; Renal failure; Dialysis; Gas6
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfs337

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. 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. 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). 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.