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As such, FGF-23 plays a central adaptive role in phosphate and 1,25-dihydroxyvitamin D homeostasis in healthy individuals, but may equally be involved in the pathogenesis of CKD [31]. In patients with CKD, circulating concentrations of FGF-23 increase progressively with declining renal capacity for phosphate excretion [27, 31]. Findings from animal studies and genetic research see more suggest that elevated FGF-23 may reflect pathogenetic changes in bone and/or kidney health [32, 33]. Other studies have shown an independent association of FGF-23 with early pathogenetic mechanisms, such as increased left ventricular mass Amiloride [34�C36]. Taken together, these studies suggest that features such as left ventricular hypertrophy, which are commonly observed in patients with CKD, may be an adverse consequence of adaptive mechanisms that involve FGF-23, triggered in response to phosphate overload [6]. Fig.?2. FGF-23 regulatory systems in phosphate metabolism. Reprinted with permission from Macmillan Publishers Ltd [30]. Although FGF-23 may have the potential to provide a better understanding of long-term phosphate status compared with the assessment of serum phosphate alone, the solution may not be entirely simple. The mechanism which regulates FGF-23 secretion from bone remains unclear, http://www.selleckchem.com/products/INCB18424.html and the presence of modulators, or the down-regulation of co-factors such as klotho, may confound any signal from FGF-23 relating to underlying disease progression [33]. From a practical perspective, there is no validated standard assay for FGF-23 yet, and consequently, no reference range for interpretation of FGF-23 levels in clinical practice. Furthermore, in a recent study in a rat model of CKD, specific antagonism of FGF-23 increased mortality risk in the animals [37], calling into question the feasibility of developing therapies targeting FGF-23. In the meantime, assessment of FGF-23 may provide additional insights into the effect of different treatments on CKD progression to those provided by serum phosphate assessments. For example, an open-label randomized trial in 100 patients with stage 4 CKD showed that sevelamer was associated with a significant decrease in FGF-23 levels (P = 0.002) and increase in flow-mediated vasodilation (P