P BALI 1, I RUDERMAN 1, N TOUSSAINT 1,2, E SMITH 1,2
1The Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine, University of Melbourne, Parkville, Australia
Aim: To investigate the association between vitamin K-dependent carboxylation of growth arrest-specific protein 6 (cGas6) and the risk of developing calciphylaxis in haemodialysis patients.
Background: Calciphylaxis affects patients with CKD, especially those on dialysis, and is characterised by painful progressive cutaneous calcification, necrosis and infection. Growth arrest-specific protein 6 (Gas6) is a homeostatic factor which may play an important role in protection against vascular injury and calcification. Biological activity requires vitamin K-dependent gamma-carboxylation, which is inhibited by warfarin.
Methods: We conducted a case-control study including 13 patients receiving haemodialysis with calciphylaxis (cases) and 13 patients receiving haemodialysis without calciphylaxis (controls) matched for age, sex, race and warfarin use. Plasma cGas6 concentrations were determined using a dual immunoprecipitation-ELISA method developed in-house. Functional vitamin K deficiency was defined according to PIVKA-II levels (protein induced by vitamin K absence-II, ≥2 ng/mL).
Results: Mean age of the total cohort was 59±14 years, 54% were female and 46% were taking warfarin. Median BMI was 36.3 and 29.3 kg/m2 and median dialysis vintage was 49 and 51 months for controls and cases, respectively. Cases were more likely to be vitamin K-deficient compared to controls (PIVKA-II ≥2 ng/mL, 85% vs 54%) and had lower levels of cGas6 (9±5 vs 19±10 pg/mL; P=0.0038). In patients not taking warfarin (7 cases, 7 controls), cGas6 levels remained lower in cases than controls (11±5 vs. 26±6 vs. pg/mL; P=0.0004) and a greater disparity in vitamin K deficiency was observed (71% vs 14%).
Conclusion: Vitamin K deficiency is associated with lower levels of cGas6 and may influence the risk of calciphylaxis. Whether vitamin K supplementation has an effect on cGas6 levels requires further study.
Parul has completed her Nephrology training at The Royal Melbourne hospital and is currently completing her dual training in general medicine.