Joint association of vitamins D and K status with long-term outcomes in stable kidney transplant recipients

Background: Kidney transplant recipients (KTRs) experience substantial survival benefit compared with dialysis patients. However, their mortality and graft failure risk remain high. KTRs are often low in micronutrient status, including vitamins D and K. We investigated the association of both vitamins D and K status, and vitamin D treatment with all-cause mortality and death-censored graft failure. Methods: We studied 461 KTRs from a single-centre study at median 6.1 years after transplantation. At baseline, vitamins D and K concentrations were measured by 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP) and patients were categorized into: 25(OH)D <50/≥50 nmol/L and median dp-ucMGP <1057/≥1057 pmol/L. Results: Mean age was 52 ± 12 years, and 122 KTRs (26%) had low vitamins D and K status. During median 9.8 years follow-up, 128 patients (28%) died and 48 (10%) developed death-censored graft failure. Low vitamins D and K status was associated with 2.33 (1.26-4.30) [hazard ratio (95% confidence interval)] increased mortality risk and 3.25 (1.17-9.08) increased graft failure risk compared with KTR with 25(OH)D ≥50 nmol/L and dp-ucMGP <1057 pmol/L. Dp-ucMGP was strongly associated with mortality (per 500 pmol/L increase): 1.41 (1.08-1.41) for vitamin D treatment versus no treatment 1.07 (0.97-1.18), and graft failure 1.71 (1.17-2.49) for vitamin D treatment versus 1.19 (1.05-1.36) no treatment, P-interaction <0.07 for vitamin D treatment (n = 44). Conclusions: Combined vitamins D and K deficiency are highly prevalent and are associated with increased mortality and graft failure risk compared with high vitamins D and K status. Low vitamin K status was strongly associated with an increased risk of premature mortality and graft failure for patients treated with vitamin D versus no vitamin D treatment.