Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
University Medical Center Groningen Transplant Center, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Nutrients. 2021 Aug 31;13(9):3069. doi: 10.3390/nu13093069.
High circulating dephosphorylated (dp) uncarboxylated (uc) matrix Gla protein (MGP) and uc osteocalcin (OC) concentrations are regarded as markers of vitamin K-deficiency. However, because MGP and OC are small molecules, they may potentially pass the glomerulus, and their blood concentrations may strongly depend on kidney function. However, many studies with vitamin K-status parameters do not structurally adjust for baseline kidney function, and detailed studies on kidney function-dependence of vitamin K-status markers are lacking. We therefore measured plasma dp-ucMGP using a chemiluminescent assay in 578 kidney transplant recipients (41% females, age 56 ± 13y, 7.5 (3.2 to 13.7)y after transplantation, eGFR 49 ± 17 mL/min/1.73 m) participating in the prospective TransplantLines Cohort Studies. Additionally, dp-carboxylated MGP, ucOC and carboxylated OC were measured using ELISA in plasma of a subgroup of 60 participants. Finally, dp-ucMGP was measured in a separate cohort of 124 kidney transplant recipients before and three months after kidney transplantation. Dp-ucMGP positively correlated with creatinine, cystatin C, and negatively with eGFR (Spearman's ρ 0.54, 0.60, and -0.54, respectively, < 0.001 for all), and each 10 mL/min/1.73 m increase in eGFR was associated with a 14.0% lower dp-ucMGP. Additionally, dp-ucMGP strongly declined after kidney transplantation (pretransplantation: 1252 (868 to 1744) pmol/L to posttransplantation: 609 (451 to 914) pmol/L, < 0.001). Proportions of dp-ucMGP over total MGP and ucOC over total OC were not associated with eGFR. This study highlights that dp-ucMGP is strongly associated with kidney function, and that levels strongly decrease after kidney transplantation. We therefore propose adequate adjustment for kidney function, or the use of kidney function-independent parameters such as proportion of uncarboxylated MGP or OC in the assessment of vitamin K-status in clinical practice and research.
高循环去磷酸化（dp）未羧化（uc）基质 Gla 蛋白（MGP）和 uc 骨钙素（OC）浓度被认为是维生素 K 缺乏的标志物。然而，由于 MGP 和 OC 是小分子，它们可能会潜在地通过肾小球，并且它们的血液浓度可能强烈依赖于肾功能。然而，许多具有维生素 K 状态参数的研究没有对基线肾功能进行结构性调整，并且缺乏关于维生素 K 状态标志物对肾功能依赖性的详细研究。因此，我们使用化学发光测定法在 578 名接受肾移植的患者（41%为女性，年龄 56±13 岁，移植后 7.5（3.2 至 13.7）年，eGFR 49±17 mL/min/1.73 m）中测量了血浆 dp-ucMGP。此外，在一个由 60 名参与者组成的亚组的血浆中使用 ELISA 测量了 dp-羧化 MGP、ucOC 和羧化 OC。最后，在 124 名肾移植患者中分别在肾移植前和 3 个月后测量了 dp-ucMGP。dp-ucMGP 与肌酐、胱抑素 C 呈正相关，与 eGFR 呈负相关（Spearman's ρ 分别为 0.54、0.60 和-0.54，均<0.001），每增加 10 mL/min/1.73 m 的 eGFR 与 dp-ucMGP 降低 14.0%相关。此外，肾移植后 dp-ucMGP 明显下降（移植前：1252（868 至 1744）pmol/L 至移植后：609（451 至 914）pmol/L，<0.001）。dp-ucMGP 占总 MGP 的比例和 ucOC 占总 OC 的比例与 eGFR 无关。本研究强调 dp-ucMGP 与肾功能密切相关，肾移植后水平明显下降。因此，我们建议在临床实践和研究中，在评估维生素 K 状态时，应充分调整肾功能，或使用与肾功能无关的参数，如未羧化 MGP 或 OC 的比例。
