Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this ...

P ATIENTS \VITH UREMIA frequently have both prolonged bleeding times,11#{176} suggesting poor platelet plug formation, and impaired prothrombin consumption,1’2’46’#{176}14 ascribed to defective platelet factor 3 activalion. Considerable evidence points to the presence of a qualitative platelet defect in uremia, since such abnormalities cannot be attributed to the mild thrombocytopenia occasiona...

Cardiovascular disease is the leading cause of mortality in uremic patients. In large cross-sectional studies of dialysis patients, traditional cardiovascular risk factors such as hypertension and hypercholesterolemia have been found to have low predictive power, while markers of inflammation and malnutrition are highly correlated with cardiovascular mortality. However, the pathophysiology of t...

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D(3) C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contrib...

UNLABELLED We have studied the mechanism(s) of hyperlipidemia and liver insulin sensitivity in a rat model of severe chronic uremia (U). Basal lipid synthesis was decreased in freshly isolated hepatocytes from U when compared with sham-operated ad lib.-fed controls (alfC). Basal lipid synthesis in pair-fed controls (pfC) was in between U and alfC. Similarly, the activity of liver acetyl CoA car...

Serum FGF23 is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. FGF23 expression is increased by activation of the FGF receptor 1 (FGFR1) in rats with normal renal function and in vitro in bone-derived osteoblast-like cells. We studied the regulation of FGF23 by FGFR1 in vivo in acute and chronic uremia in mice and rats. Folic acid-induced acute ...

Uremia impairs the atheroprotective properties of HDL, but the mechanisms underlying why this occurs are unknown. Here, we observed that HDL isolated from healthy individuals inhibited the production of inflammatory cytokines by peripheral monocytes stimulated with a Toll-like receptor 2 agonist. In contrast, HDL isolated from the majority of patients with ESRD did not show this anti-inflammato...

Vascular dysfunction induced by uremia has 4 main aspects. (1) Atherosclerosis is increased. Intima-media thickness is increased, and animal studies have established that uremia accelerates atherosclerosis. Uremic toxins are involved in several steps of atherosclerosis. Leukocyte activation is stimulated by guanidines, advanced glycation end products (AGE), p-cresyl sulfate, platelet diadenosin...