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10.1093/ndt/gfu291

http://scihub22266oqcxt.onion/10.1093/ndt/gfu291
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25324355!4309192!25324355
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suck abstract from ncbi


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pmid25324355      Nephrol+Dial+Transplant 2015 ; 30 (2): 223-33
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  • The demonstration of alphaKlotho deficiency in human chronic kidney disease with a novel synthetic antibody #MMPMID25324355
  • Barker SL; Pastor J; Carranza D; Quinones H; Griffith C; Goetz R; Mohammadi M; Ye J; Zhang J; Hu MC; Kuro-o M; Moe OW; Sidhu SS
  • Nephrol Dial Transplant 2015[Feb]; 30 (2): 223-33 PMID25324355show ga
  • BACKGROUND: alphaKlotho is the prototypic member of the Klotho family and is most highly expressed in the kidney. alphaKlotho has pleiotropic biologic effects, and in the kidney, its actions include regulation of ion transport, cytoprotection, anti-oxidation and anti-fibrosis. In rodent models of chronic kidney disease (CKD), alphaKlotho deficiency has been shown to be an early biomarker as well as a pathogenic factor. The database for alphaKlotho in human CKD remains controversial even after years of study. METHODS: We used a synthetic antibody library to identify a high-affinity human antigen-binding fragment that recognizes human, rat and mouse alphaKlotho primarily in its native, rather than denatured, form. RESULTS: Using an immunoprecipitation-immunoblot (IP-IB) assay, we measured both serum and urinary levels of full-length soluble alphaKlotho in humans and established that human CKD is associated with alphaKlotho deficiency in serum and urine. alphaKlotho levels were detectably lower in early CKD preceding disturbances in other parameters of mineral metabolism and progressively declined with CKD stages. We also found that exogenously added alphaKlotho is inherently unstable in the CKD milieu suggesting that decreased production may not be the sole reason for alphaKlotho deficiency. CONCLUSION: Synthetic antibody libraries harbor tremendous potential for a variety of biomedical and clinical applications. Using such a reagent, we furnish data in support of alphaKlotho deficiency in human CKD, and we set the foundation for the development of diagnostic and therapeutic applications of anti-alphaKlotho antibodies.
  • |Animals[MESH]
  • |Antibodies/*blood[MESH]
  • |Biomarkers/blood[MESH]
  • |Case-Control Studies[MESH]
  • |Enzyme-Linked Immunosorbent Assay[MESH]
  • |Fibroblast Growth Factors/blood[MESH]
  • |Glucuronidase/*deficiency/immunology[MESH]
  • |Healthy Volunteers[MESH]
  • |Humans[MESH]
  • |Immunoblotting[MESH]
  • |Immunoglobulin Fab Fragments/blood[MESH]
  • |Immunoprecipitation[MESH]
  • |Klotho Proteins[MESH]
  • |Mice[MESH]
  • |Peptide Library[MESH]
  • |Rats[MESH]


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