Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism?
ABSTRACT Recent studies describe a novel role of fibroblast growth factor-23 (Fgf23)-klotho activity in the systemic regulation of calcium and phosphate homeostasis. Both Fgf23 and klotho ablated mice develop extensive vascular and soft tissue calcification. Inability to clear the required amount of phosphate by the kidney, due to the absence of Fgf23-klotho activity, leads to increased accumulation of serum phosphate in these genetically modified mice, causing extensive calcification. Serum calcium and 1,25 hydroxyvitamin D levels are also elevated in both Fgf23 and klotho ablated mice. Moreover, increased sodium phosphate co-transporter activity in both Fgf23 and klotho ablated mice increases renal phosphate reabsorption which in turn can facilitate calcification. Collectively, these observations bring new insights into our understanding of the roles of the Fgf23-klotho axis in the development of vascular and soft tissue calcification.
SourceAvailable from: Priscilla Gross[Show abstract] [Hide abstract]
ABSTRACT: Chronic kidney disease (CKD) is characterized by high cardiovascular morbidity/mortality, which is linked in part to vascular calcification (VC) and endothelial dysfunction (ED). Hyperphosphatemia, a feature of CKD, is a well-known inducer of VC in preclinical models and is associated with poor outcomes in epidemiological studies. However, it remains to be seen whether lowering phosphate levels in CKD patients reduces VC and the morbidity/mortality rate. Furthermore, it is now clear from preclinical and clinical studies that phosphate is involved in ED. The present article reviews the direct and indirect mechanisms (eg, via fibroblast growth factor 23 and/or parathyroid hormone) by which hyperphosphatemia influence the onset of VC and ED in CKD.Circulation Journal 07/2014; 78(10). DOI:10.1253/circj.CJ-14-0735 · 3.69 Impact Factor
Article: Pathophysiology of CKD-MBD[Show abstract] [Hide abstract]
ABSTRACT: To maintain calcium and phosphate balance despite declining kidney function, adaptations must begin in the earliest stages of chronic kidney disease (CKD). These are generally successful in maintaining calcium and phosphate levels within the normal range through CKD stages 1–4. Although routine biochemistry is not informative about net gain of these minerals, newer markers such as Klotho and fibroblast growth factor 23 may provide clues to these early adjustments and be of prognostic value. Bone cells play a central role in modulating responses to CKD. This review describes that role and highlights the dynamic communication between bone and the kidneys.Clinical Reviews in Bone and Mineral Metabolism 09/2011; 10(3). DOI:10.1007/s12018-011-9120-8
Article: Role of Vitamin D in AtherosclerosisCirculation 12/2013; 128(23):2517-31. DOI:10.1161/CIRCULATIONAHA.113.002654 · 14.95 Impact Factor