TY - CHAP
T1 - Klotho and chronic kidney disease
AU - Hu, Ming C
AU - Kuro-o, Makoto
AU - Moe, Orson W
N1 - Funding Information:
The authors appreciate Dr. Orson Moe for helpful interactions in the editing of this chapter. The research work in MC Hu's research laboratory is in part supported by the NIH (R01-DK091392, R01-DK092461), the George M. O’Brien Kidney Research Center (P30-DK-07938), the Charles and Jane Pak Foundation, and the Pak Center Innovative Research Support. J.A.N. is in part supported by the Ben J. Lipps Research Fellowship Program of American Society of Nephrology Foundation for Kidney Research and the Truelson Fellowship Fund at the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research.
PY - 2013
Y1 - 2013
N2 - Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain could be shed from the cell surface by secretases and released into the circulation to act as endocrine factor. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23) to modulate FGF23 signal transduction, soluble Klotho is a multifunction protein present in the biological fluids including blood, urine and cerebrospinal fluid and plays important roles in antiaging, energy metabolism, inhibition of Wnt signaling, antioxidation, modulation of ion transport, control of parathyroid hormone and 1,25(OH)2VD3 production, and antagonism of renin-angiotensin-aldosterone system. Emerging evidence from clinical and basic studies reveal that chronic kidney disease is a state of endocrine and renal Klotho deficiency, which may serve as an early biomarker and a pathogenic contributor to chronic progression and complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. Supplementation of exogenous Klotho and/or upregulation of endogenous Klotho production by using rennin angiotensin system inhibitors, HMG CoA reductase inhibitors, vitamin D analogues, peroxisome proliferator-activated receptors-gamma agonists, or anti-oxidants may confer renoprotection from oxidation and suppression of renal fibrosis, and also on prevention or alleviation of complications in chronic kidney disease. Therefore, Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease.
AB - Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain could be shed from the cell surface by secretases and released into the circulation to act as endocrine factor. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23) to modulate FGF23 signal transduction, soluble Klotho is a multifunction protein present in the biological fluids including blood, urine and cerebrospinal fluid and plays important roles in antiaging, energy metabolism, inhibition of Wnt signaling, antioxidation, modulation of ion transport, control of parathyroid hormone and 1,25(OH)2VD3 production, and antagonism of renin-angiotensin-aldosterone system. Emerging evidence from clinical and basic studies reveal that chronic kidney disease is a state of endocrine and renal Klotho deficiency, which may serve as an early biomarker and a pathogenic contributor to chronic progression and complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. Supplementation of exogenous Klotho and/or upregulation of endogenous Klotho production by using rennin angiotensin system inhibitors, HMG CoA reductase inhibitors, vitamin D analogues, peroxisome proliferator-activated receptors-gamma agonists, or anti-oxidants may confer renoprotection from oxidation and suppression of renal fibrosis, and also on prevention or alleviation of complications in chronic kidney disease. Therefore, Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease.
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U2 - 10.1159/000346778
DO - 10.1159/000346778
M3 - Chapter
C2 - 23652549
AN - SCOPUS:84925735151
SN - 9783318023510
T3 - Contributions to Nephrology
SP - 47
EP - 63
BT - Phosphate and Vitamin D in Chronic Kidney Disease
A2 - Razzaque, Mohammed S.
ER -