Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review.

Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.

Vitamin K status and mortality after kidney transplantation: a cohort study.

BACKGROUND: Vitamin K modulates calcification by activating calcification inhibitors such as matrix Gla protein (MGP). In kidney transplant recipients, vitamin K insufficiency is common, but implications for long-term outcomes are unclear. STUDY DESIGN: Single-center observational study with a longitudinal design. SETTING & PARTICIPANTS: 518 stable kidney transplant recipients; 56% men; mean age, 51±12 (SD) years; and a median of 6 (IQR, 3-12) years after kidney transplantation. FACTOR: Plasma desphosphorylated-uncarboxylated MGP (dp-ucMGP) levels, reflecting vitamin K status. OUTCOMES: All-cause mortality and transplant failure. RESULTS: At inclusion, median dp-ucMGP level was 1,038 (IQR, 733-1,536) pmol/L, with 473 (91%) patients having vitamin K insufficiency (defined as dp-ucMGP>500pmol/L). During a median follow-up of 9.8 (IQR, 8.5-10.2) years, 152 (29%) patients died and 54 (10%) developed transplant failure. Patients in the highest quartile of dp-ucMGP were at considerably higher mortality risk compared with patients in the lowest quartile (HR, 3.10; 95% CI, 1.87-5.12; P for trend<0.001; P for quartile 1 [Q1] vs Q4<0.001). After adjustment for potential confounders, including kidney function and exclusion of patients treated with a vitamin K antagonist, this association remained significant. Patients in the highest quartile also were at higher risk of developing transplant failure (HR, 2.61; 95% CI, 1.22-5.57; P for trend=0.004; P for Q1 vs Q4=0.01), but this association was lost after adjustment for baseline kidney function (HR, 1.20; 95% CI, 0.52-2.75; P for trend=0.6; P for Q1 vs Q4=0.7). LIMITATIONS: Although MGP exists as various species, only dp-ucMGP was measured. No data were available for vascular calcification as an intermediate end point. CONCLUSIONS: Vitamin K insufficiency, that is, a high circulating level of dp-ucMGP, is highly prevalent in stable kidney transplant recipients and is associated independently with increased risk of mortality. Future studies should address whether vitamin K supplementation may lead to improved outcomes after kidney transplantation.

Coagulopathy caused by vitamin K deficiency in critically ill, hospitalized patients.

A coagulopathy due to vitamin K deficiency was discovered in 42 hospitalized patients, most of whom had been misdiagnosed as having disseminated intravascular coagulation. Factors contributing to vitamin deficiency included inadequate diet, malabsorption, failure of physicians to prescribe vitamin K supplements, antibiotic therapy, renal insufficiency, hepatic dysfunction, recent major surgery, and possibly pregnancy. Sixteen patients (34%) bled sufficiently to need red blood cell transfusions and ten patients (24%) ultimately died. Of 18 patients who also had thrombocytopenia, three did have disseminated intravascular coagulation. The deficiency, a contributor to morbidity and mortality, can be prevented by prophylactic administration of vitamin K to severely ill patients who are eating inadequately and receiving antibiotics.

Vitamin K prophylaxis in the neonate by the oral route and its significance in reducing infant mortality and morbidity.

PIP: Vitamin K in oral drops and intramuscular injection given at birth to Thai infants were compared to determine whether these routes and doses would influence prothrombin complex activity, mortality or morbidity at 0.5, 1 and 2 months of age. The infants were 321 normal fullterm babies born at Bangkok Adventist Hospital in 1983, exclusively breastfed during the study. Prothrombin complex (PC) was measured by the Owren capillary thrombotest method using a reagent from Nyegaard Co., Oslo. Vitamin K was given in single 1 or 2 mg oral doses, or 1 mg im, within 12 hours of delivery. Judging by the number of PC deficient children, the 1 mg im and 2 mg oral doses of vitamin K maintained clotting factors best at 2 months of age. All formulations were significantly better than no treatment at 1 month at age. No toxicity or side effects were seen. Vitamin K deficiency is a known cause of bleeding disorders, particularly fatal and handicapping intracranial hemorrhage in newborns, in developing countries where injections cannot be given by midwives. These inexpensive oral pediatric drops may provide a practical form of primary health care for routine vitamin K prophylaxis in newborns.^ieng

Avitaminosis K and the lack of heart lesions in poultry.

Poultry susceptibility to avitaminosis K-induced granulomatous endocardial lesions was studied in broiler and layer chicks. They were fed either a practical corn-soybean meal diet with and without added vitamin K (vit K), or a 61% raw sugar-isolated soybean protein diet (RS-IS) with no added vit K for 10 weeks. Heart lesions were not found in birds fed any of the experimental diets. Mortality, body weight gain, and prothrombin time did not differ significantly between birds fed the practical diet regardless of vit K supplementation. In contrast, the RS-IS diet significantly increased mortality, prothrombin time, and markedly decreased growth. Furthermore, more than a third of the birds fed the high sugar diet had subcutaneous edema, which resembled exudative diathesis. Compared with swine, poultry are apparently less susceptible to granulomatous endocardial lesions induced by a vit K deficiency.