warfarin and Chronic-Kidney-Disease-Mineral-and-Bone-Disorder

The use of warfarin in patients undergoing hemodialysis is associated with decreased bone mineral density and an increased incidence of bone fracture. However, no studies to date have directly estimated bone quality with bone histomorphometry in patients with bone abnormalities who are taking warfarin and undergoing hemodialysis.. A 47-year-old female with Noonan syndrome presented with progressive bilateral lower extremity pain on walking, and skin sclerosis. She had been undergoing maintenance hemodialysis for 25 years following 2 years of peritoneal dialysis for chronic glomerulonephritis. She had been taking warfarin as an anticoagulant agent for 13 years after she underwent an aortic valve replacement.. Warfarin-induced impairment of bone material quality.. Histomorphometric analysis of the bone biopsy specimens showed impairment in bone calcification processes, a high turnover of bone remodeling, low bone volume, and mild fibrosis. The bone abnormality could not be categorized into any type of representative bone disease classification such as osteitis fibrosa, osteomalacia, adynamic bone disease, uremic osteodystrophy, or hyperparathyroidism, but was consistent with warfarin-induced impairment of bone material quality.. Warfarin can induce impairment of bone material quality in a patient undergoing hemodialysis.

Topics: Anticoagulants; Bone Density; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Middle Aged; Noonan Syndrome; Renal Dialysis; Warfarin

Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease. Metformin protected from development toward severe CKD. Metformin-treated rats did not develop hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification and inhibited the progression toward high bone turnover disease. Kidneys of the metformin group showed significantly less cellular infiltration, fibrosis and inflammation. To study a possible direct effect of metformin on the development of vascular calcification, independent of its effect on renal function, metformin (200 mg/kg/day) or vehicle was dosed for ten weeks to rats with warfarin-induced vascular calcification. The drug did not reduce aorta or small vessel calcification in this animal model. Thus, metformin protected against the development of severe CKD and preserved calcium phosphorus homeostasis. As a result of its beneficial impact on renal function, associated comorbidities such as vascular calcification and high bone turnover disease were also prevented.

Topics: Adenine; Animals; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Models, Animal; Humans; Hypoglycemic Agents; Male; Metformin; Rats; Rats, Wistar; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Vascular Calcification; Warfarin