Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods: CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results: Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P<0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P<0.01). Conclusions: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.
Abstract
Background: High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods: CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results: Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P<0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P<0.01). Conclusions: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.
참고문헌 (29)
- Denker M, "Chronic renal insufficiency cohort study (CRIC): overview and summary of selected findings", Clin J Am Soc Nephrol, 10, pp.2073~2083 (2015)[DOI]
- Weiner DE, "Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies", J Am Soc Nephrol, 15, pp.1307~1315 (2004)[DOI]
- Oliveira RB, "Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy?", Clin J Am Soc Nephrol, 5, pp.286~291 (2010)[DOI]
- Munoz Mendoza J, "Fibroblast growth factor 23 and Inflammation in CKD", Clin J Am Soc Nephrol, 7, pp.1155~1162 (2012)[DOI]
- Gutierrez OM, "Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis", N Engl J Med, 359, pp.584~592 (2008)[DOI]
- Wesseling-Perry K, "FGF23: is it ready for prime time?", Clin Chem, 57, pp.1476~1477 (2011)[DOI]
- Burnett SM, "Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women", J Bone Miner Res, 21, pp.1187~1196 (2006)[DOI]
- Munoz-Garcia B, "Fn14 is upregulated in cytokine-stimulated vascular smooth muscle cells and is expressed in human carotid atherosclerotic plaques: modulation by atorvastatin", Stroke, 37, pp.2044~2053 (2006)[DOI]
- Isakova T, "Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease", JAMA, 305, pp.2432~2439 (2011)[DOI]
- Gutierrez OM, "Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study", Clin J Am Soc Nephrol, 6, pp.2871~2878 (2011)[DOI]
- Cozzolino M, "The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats", J Am Soc Nephrol, 13, pp.2299~2308 (2002)[DOI]
- Ketteler M, "Phosphate and FGF23 in early CKD: on how to tackle an invisible foe", Nephrol Dial Transplant, 26, pp.2430~2432 (2011)[DOI]
- Ferrari SL, "Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men", J Clin Endocrinol Metab, 90, pp.1519~1524 (2005)[DOI]
- Antoniucci DM, "Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men", J Clin Endocrinol Metab, 91, pp.3144~3149 (2006)[DOI]
- Ito N, "Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in humans", J Bone Miner Metab, 25, pp.419~422 (2007)[DOI]
- Rodriguez-Osorio L, "Use of sevelamer in chronic kidney disease: beyond phosphorus control", Nefrologia, 35, pp.207~217 (2015)[DOI]
- Koiwa F, "Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients", Ther Apher Dial, 9, pp.336~339 (2005)[DOI]
- Nagano N, "Effects of intermittent treatment with sevelamer hydrochloride on parathyroid hyperplasia and vascular calcification in rats with chronic kidney disease", Clin Calcium, 15(Suppl 1), pp.35~39 (2005)
- Spaia S, "Phosphate binders: sevelamer in the prevention and treatment of hyperphosphataemia in chronic renal failure", Hippokratia, 15, pp.22~26 (2011)
- Tamagaki K, "Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia", Nephrol Dial Transplant, 21, pp.651~659 (2006)[DOI]
- Nagano N, "Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats", Kidney Int, 69, pp.531~537 (2006)[DOI]
- Nagano N, "Sevelamer hydrochloride, a phosphate binder, protects against deterioration of renal function in rats with progressive chronic renal insufficiency", Nephrol Dial Transplant, 18, pp.2014~2023 (2003)[DOI]
- Cancela AL, "Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate binder, calcitriol and calcium concentration in the dialysate", Nephron Clin Pract, 117, pp.c74~c82 (2011)[DOI]
- Bansal S, "New insights into regulation of FGF23 in chronic kidney disease and its role in cardiovascular disease", SM J Cardiolog and Cardiovasc Disord, 1, pp.1003~ (2015)
- Liu S, "Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D", J Am Soc Nephrol, 17, pp.1305~1315 (2006)[DOI]
- Spatz C, "Effect of a non-calcium-based phosphate binder on fibroblast growth factor 23 in chronic kidney disease", Nephron Clin Pract, 123, pp.61~66 (2013)[DOI]
- Yilmaz MI, "Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial", Am J Kidney Dis, 59, pp.177~185 (2012)[DOI]
- Ketteler M, "Use of phosphate binders in chronic kidney disease", Curr Opin Nephrol Hypertens, 22, pp.413~420 (2013)[DOI]
- Yokota H, "Model-based analysis of FGF23 regulation in chronic kidney disease", Gene Regul Syst Bio, 4, pp.53~60 (2010)