Renal Phosphate Transport
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  • 1 Institute of Physiology, University of Zurich, Zurich, Switzerland and National Center of Competence in Research, Kidney.CH – Kidney Control of Homeostasis, Switzerland
  • 1.

    Mohammad J, Scanni R, Bestmann L, Hulter HN, Krapf R: A controlled increase in dietary phosphate elevates BP in healthy human subjects. J Am Soc Nephrol 29: 20892098, 2018 10.1681/ASN.2017121254

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  • 2.

    Scanni R, vonRotz M, Jehle S, Hulter HN, Krapf R: The human response to acute enteral and parenteral phosphate loads. J Am Soc Nephrol 25: 27302739, 2014 10.1681/ASN.2013101076

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  • 3.

    Bourgeois S, Capuano P, Stange G, Mühlemann R, Murer H, Biber J, et al. .: The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels. Pflugers Arch 465: 15571572, 2013 10.1007/s00424-013-1298-9 PubMed

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  • 4.

    Giral H, Caldas Y, Sutherland E, Wilson P, Breusegem S, Barry N, et al. .: Regulation of rat intestinal Na-dependent phosphate transporters by dietary phosphate. Am J Physiol Renal Physiol 297: F1466F1475, 2009 10.1152/ajprenal.00279.2009

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  • 5.

    Hernando N, Wagner CA: Mechanisms and regulation of intestinal phosphate absorption. Compr Physiol 8: 10651090, 2018 10.1002/cphy.c170024 PubMed

  • 6.

    Pastor-Arroyo EM, Knöpfel T, Imenez Silva PH, Schnitzbauer U, Poncet N, Biber J, et al. .: Intestinal epithelial ablation of Pit-2/Slc20a2 in mice leads to sustained elevation of vitamin D3 upon dietary restriction of phosphate. Acta Physiol (Oxf) 230: e13526, 2020 10.1111/apha.13526 PubMed

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  • 7.

    Ichida Y, Ohtomo S, Yamamoto T, Murao N, Tsuboi Y, Kawabe Y, et al. .: Evidence of an intestinal phosphate transporter alternative to type IIb sodium-dependent phosphate transporter in rats with chronic kidney disease [published online ahead of print September 3, 2020]. Nephrol Dial Transplant 10.1093/ndt/gfaa156 PubMed

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  • 8.

    King AJ, Siegel M, He Y, Nie B, Wang J, Koo-McCoy S, et al. .: Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med 10: eaam6474, 2018 10.1126/scitranslmed.aam6474

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  • 9.

    Cozzolino M, Ketteler M, Wagner CA: An expert update on novel therapeutic targets for hyperphosphatemia in chronic kidney disease: preclinical and clinical innovations. Expert Opin Ther Targets 24: 477488, 2020 10.1080/14728222.2020.1743680 PubMed

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  • 10.

    Wagner CA: Coming out of the PiTs-novel strategies for controlling intestinal phosphate absorption in patients with CKD. Kidney Int 98: 273275, 2020 10.1016/j.kint.2020.04.010 PubMed

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  • 11.

    Motta SE, Imenez Silva PH, Daryadel A, Haykir B, Pastor-Arroyo EM, Bettoni C, et al. .: Expression of NaPi-IIb in rodent and human kidney and upregulation in a model of chronic kidney disease. Pflugers Arch 472: 449460, 2020 10.1007/s00424-020-02370-9 PubMed

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  • 12.

    Levi M, Gratton E, Forster IC, Hernando N, Wagner CA, Biber J, et al. .: Mechanisms of phosphate transport. Nat Rev Nephrol 15: 482500, 2019 10.1038/s41581-019-0159-y PubMed

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  • 13.

    Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JR, et al. .: Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet 47: 579581, 2015 10.1038/ng.3289

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  • 14.

    Anheim M, Lopez-Sanchez U, Giovannini D, Richard AC, Touhami J, N'Guyen L, et al. .: XPR1 mutations are a rare cause of primary familial brain calcification. J Neurol 263: 15591564, 2016 10.1007/s00415-016-8166-4 10.1007/s00415-016-8166-4

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  • 15.

    Ansermet C, Moor MB, Centeno G, Auberson M, Hu DZ, Baron R, et al. .: Renal fanconi syndrome and hypophosphatemic rickets in the absence of xenotropic and polytropic retroviral receptor in the nephron. J Am Soc Nephrol 28: 10731078, 2017 10.1681/ASN.2016070726

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  • 16.

    Picard N, Capuano P, Stange G, Mihailova M, Kaissling B, Murer H, et al. .: Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters. Pflugers Arch 460: 677687, 2010 10.1007/s00424-010-0841-1 PubMed

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  • 17.

    Bacic D, Lehir M, Biber J, Kaissling B, Murer H, Wagner CA: The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone. Kidney Int 69: 495503, 2006 10.1038/sj.ki.5000148

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  • 18.

    Nishida Y, Taketani Y, Yamanaka-Okumura H, Imamura F, Taniguchi A, Sato T, et al. .: Acute effect of oral phosphate loading on serum fibroblast growth factor 23 levels in healthy men. Kidney Int 70: 21412147, 2006 10.1038/sj.ki.5002000

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  • 19.

    Thomas L, Bettoni C, Knopfel T, Hernando N, Biber J, Wagner CA: Acute adaption to oral or intravenous phosphate requires parathyroid hormone. J Am Soc Nephrol 28: 903914, 2017 10.1681/ASN.2016010082

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  • 20.

    Michigami T, Kawai M, Yamazaki M, Ozono K: Phosphate as a signaling molecule and its sensing mechanism. Physiol Rev 98: 23172348, 2018 10.1152/physrev.00022.2017 PubMed

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  • 21.

    Chande S, Bergwitz C: Role of phosphate sensing in bone and mineral metabolism. Nat Rev Endocrinol 14: 637655, 2018 10.1038/s41574-018-0076-3 PubMed

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  • 22.

    Lederer E, Wagner CA: Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: Mutations and disease associations. Pflugers Arch 471: 137148, 2019 10.1007/s00424-018-2246-5 PubMed

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  • 23.

    Magen D, Berger L, Coady MJ, Ilivitzki A, Militianu D, Tieder M, et al. .: A loss-of-function mutation in NaPi-IIa and renal Fanconi’s syndrome. N Engl J Med 362: 11021109, 2010 10.1056/NEJMoa0905647

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  • 24.

    Schlingmann KP, Ruminska J, Kaufmann M, Dursun I, Patti M, Kranz B, et al. .: Autosomal-recessive mutations in SLC34A1 encoding sodium-phosphate cotransporter 2A cause idiopathic infantile hypercalcemia. J Am Soc Nephrol 27: 604614, 2016 10.1681/ASN.2014101025

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  • 25.

    Dasgupta D, Wee MJ, Reyes M, Li Y, Simm PJ, Sharma A, et al. .: Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol 25: 23662375, 2014 10.1681/ASN.2013101085

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  • 26.

    Haito-Sugino S, Ito M, Ohi A, Shiozaki Y, Kangawa N, Nishiyama T, et al. .: Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria. Am J Physiol Cell Physiol 302: C1316C1330, 2012 10.1152/ajpcell.00314.2011

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  • 27.

    Kottgen A, Pattaro C, Boger CA, Fuchsberger C, Olden M, Glazer NL, et al. .: New loci associated with kidney function and chronic kidney disease. Nat Genet 42: 376384, 2010 10.1038/ng.568

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  • 28.

    Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, et al. .: Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun 7: 10023, 2016 10.1038/ncomms10023

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  • 29.

    Kottgen A, Glazer NL, Dehghan A, Hwang SJ, Katz R, Li M, et al. .: Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41: 712717, 2009 10.1038/ng.377

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  • 30.

    Oddsson A, Sulem P, Helgason H, Edvardsson VO, Thorleifsson G, Sveinbjornsson G, et al. .: Common and rare variants associated with kidney stones and biochemical traits. Nat Commun 6: 7975, 2015 10.1038/ncomms8975

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  • 31.

    Hernando N: NaPi-IIa interacting partners and their (un)known functional roles. Pflugers Arch 471: 6782, 2019 10.1007/s00424-018-2176-2 PubMed

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  • 32.

    Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, et al. .: NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 359: 11281135, 2008 10.1056/NEJMoa0802836

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  • 33.

    Cebeci AN, Zou M, BinEssa HA, Alzahrani AS, Al-Rijjal RA, Al-Enezi AF, et al. .: Mutation of SGK3, a novel regulator of renal phosphate transport, causes autosomal dominant hypophosphatemic rickets. J Clin Endocrinol Metab 105: dgz260, 2020 10.1210/clinem/dgz260 PubMed

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  • 34.

    Bhandaru M, Kempe DS, Rotte A, Capuano P, Pathare G, Sopjani M, et al. .: Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3. Kidney Int 80: 6167, 2011 10.1038/ki.2011.67

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  • 35.

    Marcucci G, Brandi ML: Congenital conditions of hypophosphatemia expressed in adults [published online ahead of print May 14, 2020]. Calcif Tissue Int 10.1007/s00223-020-00695-2 PubMed

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  • 36.

    Klootwijk ED, Reichold M, Unwin RJ, Kleta R, Warth R, Bockenhauer D: Renal Fanconi syndrome: Taking a proximal look at the nephron. Nephrol Dial Transplant 30: 14561460, 2015 10.1093/ndt/gfu377 PubMed

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  • 37.

    Hall AM, Bass P, Unwin RJ: Drug-induced renal Fanconi syndrome. QJM 107: 261269, 2014 10.1093/qjmed/hct258 PubMed

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    Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT: Tumor-induced osteomalacia [published online ahead of print June 5, 2020]. Calcif Tissue Int 10.1007/s00223-020-00691-6 PubMed

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  • 39.

    Baia LC, Heilberg IP, Navis G, de Borst MH; NIGRAM investigators: Phosphate and FGF-23 homeostasis after kidney transplantation. Nat Rev Nephrol 11: 656666, 2015 10.1038/nrneph.2015.153 PubMed

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  • 40.

    Payne RB: Renal tubular reabsorption of phosphate (TmP/GFR): Indications and interpretation. Ann Clin Biochem 35: 201206, 1998 10.1177/000456329803500203 PubMed

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  • 41.

    Vervloet MG, Sezer S, Massy ZA, Johansson L, Cozzolino M, Fouque D; ERA–EDTA Working Group on Chronic Kidney Disease–Mineral and Bone Disorders and the European Renal Nutrition Working Group: The role of phosphate in kidney disease. Nat Rev Nephrol 13: 2738, 2017 10.1038/nrneph.2016.164 PubMed

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  • 42.

    Yoo KD, Kang S, Choi Y, Yang SH, Heo NJ, Chin HJ, et al. .: Sex, age, and the association of serum phosphorus with all-cause mortality in adults with normal kidney function. Am J Kidney Dis 67: 7988, 2016 10.1053/j.ajkd.2015.06.027

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  • 43.

    Tonelli M, Curhan G, Pfeffer M, Sacks F, Thadhani R, Melamed ML, et al. .: Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. Circulation 120: 17841792, 2009 10.1161/CIRCULATIONAHA.109.851873

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  • 44.

    Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G; Cholesterol and Recurrent Events Trial Investigators: Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112: 26272633, 2005 10.1161/CIRCULATIONAHA.105.553198 PubMed

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  • 45.

    Dhingra R, Gona P, Benjamin EJ, Wang TJ, Aragam J, D'Agostino RB, Sr., et al. .: Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community. Eur J Heart Fail 12: 812818, 2010 10.1093/eurjhf/hfq106

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  • 46.

    Sim JJ, Bhandari SK, Smith N, Chung J, Liu IL, Jacobsen SJ, et al. .: Phosphorus and risk of renal failure in subjects with normal renal function. Am J Med 126: 311318, 2013 10.1016/j.amjmed.2012.08.018 PubMed

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  • 47.

    Chang AR, Lazo M, Appel LJ, Gutierrez OM, Grams ME: High dietary phosphorus intake is associated with all-cause mortality: Results from NHANES III. Am J Clin Nutr 99: 320327, 2014 10.3945/ajcn.113.073148

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  • 48.

    Pavik I, Jaeger P, Ebner L, Wagner CA, Petzold K, Spichtig D, et al. .: Secreted Klotho and FGF23 in chronic kidney disease stage 1 to 5: A sequence suggested from a cross-sectional study. Nephrol Dial Transplant 28: 352359, 2013 10.1093/ndt/gfs460

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  • 49.

    Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, et al. .: Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79: 13701378, 2011 10.1038/ki.2011.47

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    Hu MC, Shiizaki K, Kuro-o M, Moe OW: Fibroblast growth factor 23 and Klotho: Physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 75: 503533, 2013 10.1146/annurev-physiol-030212-183727 PubMed

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    Dhayat NA, Ackermann D, Pruijm M, Ponte B, Ehret G, Guessous I, et al. .: Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function. Kidney Int 90: 648657, 2016 10.1016/j.kint.2016.04.024

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    Egli-Spichtig D, Imenez Silva PH, Glaudemans B, Gehring N, Bettoni C, Zhang MYH, et al. .: Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation. Kidney Int 96: 890905, 2019 10.1016/j.kint.2019.04.009 PubMed

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    Durlacher-Betzer K, Hassan A, Levi R, Axelrod J, Silver J, Naveh-Many T: Interleukin-6 contributes to the increase in fibroblast growth factor 23 expression in acute and chronic kidney disease. Kidney Int 94: 315325, 2018 10.1016/j.kint.2018.02.026 PubMed

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    Shalhoub V, Shatzen EM, Ward SC, Davis J, Stevens J, Bi V, et al. .: FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. J Clin Invest 122: 25432553, 2012 10.1172/JCI61405

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    Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. .: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359: 584–592, 2008 10.1056/NEJMoa0706130

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    Marthi A, Donovan K, Haynes R, Wheeler DC, Baigent C, Rooney CM, et al. .: Fibroblast growth factor-23 and risks of cardiovascular and noncardiovascular diseases: A meta-analysis. J Am Soc Nephrol 29: 20152027, 2018 10.1681/ASN.2017121334

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    Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al. .: FGF23 induces left ventricular hypertrophy. J Clin Invest 121: 43934408, 2011 10.1172/JCI46122

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    Wagner CA, Rubio-Aliaga I, Egli-Spichtig D: Fibroblast growth factor 23 in chronic kidney disease: What is its role in cardiovascular disease? Nephrol Dial Transplant 34: 19861990, 2019 10.1093/ndt/gfz044 PubMed

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  • 59.

    Pastor-Arroyo EM, Gehring N, Krudewig C, Costantino S, Bettoni C, Knöpfel T, et al. .: The elevation of circulating fibroblast growth factor 23 without kidney disease does not increase cardiovascular disease risk. Kidney Int 94: 4959, 2018 10.1016/j.kint.2018.02.017 PubMed

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