menaquinone-6 and Renal-Insufficiency

Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC.. We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies.. The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress.. In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Topics: Animals; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Male; Models, Animal; Phosphates; Rats; Renal Dialysis; Renal Insufficiency; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; X-Ray Microtomography

Renal insufficiency induces cortical bone loss in rats. The present study examined the influence of vitamin K(2) on renal function, cortical bone mass, and bone strength in rats with renal insufficiency. Thirty male Sprague-Dawley rats (8 weeks old) were randomized by the stratified weight method to the following three groups of 10 animals each: sham operation (control), 5/6 nephrectomy, and 5/6 nephrectomy + oral vitamin K(2) (menaquinone-4, menatetrenone, 30 mg/kg, 5 days/week). Treatment was initiated 10 days after surgery. After 6 weeks of treatment, samples of serum, urine, and bone (femur and tibia) were obtained. Renal function was evaluated, bone histomorphometric analysis was performed on the tibial diaphysis, and the bone mineral density (BMD) and mechanical strength of the femoral diaphysis were determined by peripheral quantitative computed tomography and a three-point bending test, respectively. Nephrectomy induced renal dysfunction, as indicated by increased levels of serum creatinine and urea nitrogen along with a decrease of creatinine clearance; and it also decreased BMD without significantly affecting bone strength at the femoral diaphysis. Vitamin K(2) improved renal function parameters but did not significantly influence BMD at the femoral diaphysis. However, vitamin K(2) decreased the bone marrow area of the tibial diaphysis and increased the stiffness of the femoral diaphysis. These findings suggest that administration of vitamin K(2) improves renal function and increases cortical bone strength without altering BMD in rats with renal insufficiency.

Topics: Animals; Biomechanical Phenomena; Bone Density; Bone Density Conservation Agents; Femur; Male; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Tibia; Vitamin K 2