Skip to main content

Advertisement

SpringerLink
Log in

The importance of kidney calcium handling in the homeostasis of extracellular fluid calcium

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Extracellular fluid calcium concentration must be maintained within a narrow range in order to sustain many biological functions, encompassing muscle contraction, blood coagulation, and bone and tooth mineralization. Blood calcium value is critically dependent on the ability of the renal tubule to reabsorb the adequate amount of filtered calcium. Tubular calcium reabsorption is carried out by various and complex mechanisms in 3 distinct segments: the proximal tubule, the cortical thick ascending limb of the loop of Henle, and the late distal convoluted/connecting tubule. In addition, calcium reabsorption is tightly controlled by many endocrine, paracrine, and autocrine factors, as well as by non-hormonal factors, in order to adapt the tubular handling of calcium to the metabolic requirements. The present review summarizes the current knowledge of the mechanisms and factors involved in calcium handling by the kidney and, ultimately, in extracellular calcium homeostasis. The review also highlights some of our gaps in understanding that need to be addressed in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. van Abel M, Hoenderop JG, van der Kemp AW, Friedlaender MM, van Leeuwen JP, Bindels RJ (2005) Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone. Kidney Int 68:1708–1721

    Article  PubMed  Google Scholar 

  2. Agus ZS, Chiu PJ, Goldberg M (1977) Regulation of urinary calcium excretion in the rat. Am J Physiol 232:F545-549. https://doi.org/10.1152/ajprenal.1977.232.6.F545

    Article  CAS  PubMed  Google Scholar 

  3. Agus ZS, Gardner LB, Beck LH, Goldberg M (1973) Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium, and phosphate. Am J Physiol 224:1143–1148

    Article  CAS  PubMed  Google Scholar 

  4. Alexander RT, Beggs MR, Zamani R, Marcussen N, Frische S, Dimke H (2015) Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia. Am J Physiol Renal Physiol 309:F604-616. https://doi.org/10.1152/ajprenal.00651.2014

    Article  CAS  PubMed  Google Scholar 

  5. Alexander RT, Woudenberg-Vrenken TE, Buurman J, Dijkman H, van der Eerden BC, van Leeuwen JP, Bindels RJ, Hoenderop JG (2009) Klotho prevents renal calcium loss. J Am Soc Nephrol 20:2371–2379. https://doi.org/10.1681/asn.2008121273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R, Shalhoub V, Mohammadi M, Pohl EE, Lanske B, Erben RG (2014) FGF23 promotes renal calcium reabsorption through the TRPV5 channel. Embo j 33:229–246. https://doi.org/10.1002/embj.201284188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bailly C, Imbert-Teboul M, Roinel N, Amiel C (1990) Isoproterenol increases Ca, Mg, and NaCl reabsorption in mouse thick ascending limb. Am J Physiol 258:F1224-1231

    CAS  PubMed  Google Scholar 

  8. Beggs MR, Young K, Pan W, O’Neill DD, Saurette M, Plain A, Rievaj J, Doschak MR, Cordat E, Dimke H, Alexander RT (2021) Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis. Proc Natl Acad Sci U S A 118. https://doi.org/10.1073/pnas.2111247118

  9. Belge H, Gailly P, Schwaller B, Loffing J, Debaix H, Riveira-Munoz E, Beauwens R, Devogelaer JP, Hoenderop JG, Bindels RJ, Devuyst O (2007) Renal expression of parvalbumin is critical for NaCl handling and response to diuretics. Proc Natl Acad Sci U S A 104:14849–14854. https://doi.org/10.1073/pnas.0702810104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bergsland KJ, Worcester EM, Coe FL (2013) Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria. Am J Physiol Renal Physiol 305:F592-599. https://doi.org/10.1152/ajprenal.00116.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bomsztyk K, George JP, Wright FS (1984) Effects of luminal fluid anions on calcium transport by proximal tubule. Am J Physiol 246:F600-608. https://doi.org/10.1152/ajprenal.1984.246.5.F600

    Article  CAS  PubMed  Google Scholar 

  12. Bonny O, Edwards A (2013) Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow. Am J Physiol Renal Physiol 304:F585-600. https://doi.org/10.1152/ajprenal.00493.2012

    Article  CAS  PubMed  Google Scholar 

  13. Bonny O, Rubin A, Huang CL, Frawley WH, Pak CY, Moe OW (2008) Mechanism of urinary calcium regulation by urinary magnesium and pH. J Am Soc Nephrol 19:1530–1537. https://doi.org/10.1681/asn.2007091038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bourdeau JE, Burg MB, Knepper MA (1979) Voltage dependence of calcium transport in the thick ascending limb of Henle’s loop. Am J Physiol 236:F357-364

    CAS  PubMed  Google Scholar 

  15. Bourdeau JE, Buss SL, Vurek GG (1982) Inhibition of calcium absorption in the cortical thick ascending limb of Henle’s loop by furosemide. J Pharmacol Exp Ther 221:815–819

    CAS  PubMed  Google Scholar 

  16. Breiderhoff T, Himmerkus N, Drewell H, Plain A, Günzel D, Mutig K, Willnow TE, Müller D, Bleich M (2018) Deletion of claudin-10 rescues claudin-16-deficient mice from hypomagnesemia and hypercalciuria. Kidney Int 93:580–588. https://doi.org/10.1016/j.kint.2017.08.029

    Article  CAS  PubMed  Google Scholar 

  17. Breiderhoff T, Himmerkus N, Meoli L, Fromm A, Sewerin S, Kriuchkova N, Nagel O, Ladilov Y, Krug SM, Quintanova C, Stumpp M, Garbe-Schönberg D, Westernströer U, Merkel C, Brinkhus MA, Altmüller J, Schweiger MR, Müller D, Mutig K, Morawski M, Halbritter J, Milatz S, Bleich M, Günzel D (2022) Claudin-10a Deficiency Shifts Proximal Tubular Cl(-) Permeability to Cation Selectivity via Claudin-2 Redistribution. J Am Soc Nephrol. https://doi.org/10.1681/asn.2021030286

    Article  PubMed  Google Scholar 

  18. Breiderhoff T, Himmerkus N, Stuiver M, Mutig K, Will C, Meij IC, Bachmann S, Bleich M, Willnow TE, Muller D (2012) Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis. Proc Natl Acad Sci U S A 109:14241–14246. https://doi.org/10.1073/pnas.1203834109

    Article  PubMed  PubMed Central  Google Scholar 

  19. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC (1993) Cloning and characterization of an extracellular Ca2+ sensing receptor from bovine parathyroid. Nature 366:575–580

    Article  CAS  PubMed  Google Scholar 

  20. Chabardès D, Gagnan-Brunette M, Imbert-Teboul M, Gontcharevskaia O, Montégut M, Clique A, Morel F (1980) Adenylate cyclase responsiveness to hormones in various portions of the human nephron. J Clin Invest 65:439–448. https://doi.org/10.1172/jci109687

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG (2005) The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science 310:490–493

    Article  CAS  PubMed  Google Scholar 

  22. Chen L, Chou CL, Knepper MA (2021) A comprehensive map of mRNAs and their isoforms across all 14 renal tubule segments of mouse. J Am Soc Nephrol 32:897–912. https://doi.org/10.1681/asn.2020101406

    Article  CAS  PubMed Central  Google Scholar 

  23. Chou KJ, Hsu CY, Huang CW, Chen HJ, Ou SH, Chen CL, Lee PT, Fang HC (2022) A new missense mutation of calcium sensing receptor with isoleucine replaced by serine at codon 857 leading to type V Bartter syndrome. Exp Cell Res 414:113080. https://doi.org/10.1016/j.yexcr.2022.113080

    Article  CAS  PubMed  Google Scholar 

  24. Claverie-Martín F, García-Nieto V, Loris C, Ariceta G, Nadal I, Espinosa L, Fernández-Maseda Á, Antón-Gamero M, Avila A, Madrid Á, González-Acosta H, Córdoba-Lanus E, Santos F, Gil-Calvo M, Espino M, García-Martinez E, Sanchez A, Muley R (2013) Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. PLoS ONE 8:e53151. https://doi.org/10.1371/journal.pone.0053151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Costanzo LS, Sheehe PR, Weiner IM (1974) Renal actions of vitamin D in D-deficient rats. Am J Physiol 226:1490–1495. https://doi.org/10.1152/ajplegacy.1974.226.6.1490

    Article  CAS  PubMed  Google Scholar 

  26. Costanzo LS, Windhager EE (1978) Calcium and sodium transport by the distal convoluted tubule of the rat. Am J Physiol 235:F492–F506

    CAS  PubMed  Google Scholar 

  27. Crisi GM, Rockwell GF, Braden GL, Campfield TJ (2013) Immunolocalization of the calcium sensing receptor in developing human kidney. Pediatr Res pr201372. https://doi.org/10.1038/pr.2013.72

  28. Curry JN, Saurette M, Askari M, Pei L, Filla MB, Beggs MR, Rowe PS, Fields T, Sommer AJ, Tanikawa C, Kamatani Y, Evan AP, Totonchi M, Alexander RT, Matsuda K, Yu AS (2020) Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease. J Clin Invest 130:1948–1960. https://doi.org/10.1172/jci127750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Desfleurs E, Wittner M, Simeone S, Pajaud S, Moine G, Rajerison R, Di Stefano A, Mandon B, Roinel N, de Rouffignac C (1998) Calcium-sensing receptor: regulation of electrolyte transport in the thick ascending limb of Henle’s loop. Kidney Blood Press Res 21:401–412

    Article  CAS  PubMed  Google Scholar 

  30. Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT (2013) Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol 304:F761-769. https://doi.org/10.1152/ajprenal.00263.2012

    Article  CAS  PubMed  Google Scholar 

  31. Ding H, Zhang L, Yang Q, Zhang X, Li X (2021) Epigenetics in kidney diseases. Adv Clin Chem 104:233–297. https://doi.org/10.1016/bs.acc.2020.09.005

    Article  CAS  PubMed  Google Scholar 

  32. Edwards BR, Baer PG, Sutton RA, Dirks JH (1973) Micropuncture study of diuretic effects on sodium and calcium reabsorption in the dog nephron. J Clin Invest 52:2418–2427. https://doi.org/10.1172/jci107432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463. https://doi.org/10.1038/nature02625

    Article  CAS  PubMed  Google Scholar 

  34. Feher JJ (1983) Facilitated calcium diffusion by intestinal calcium-binding protein. Am J Physiol 244:C303-307. https://doi.org/10.1152/ajpcell.1983.244.3.C303

    Article  CAS  PubMed  Google Scholar 

  35. Friedman PA (1988) Basal and hormone-activated calcium absorption in mouse renal thick ascending limbs. Am J Physiol 254:F62-70

    CAS  PubMed  Google Scholar 

  36. Gauci C, Moranne O, Fouqueray B, de la Faille R, Maruani G, Haymann JP, Jacquot C, Boffa JJ, Flamant M, Rossert J, Urena P, Stengel B, Souberbielle JC, Froissart M, Houillier P, Group NS (2008) Pitfalls of measuring total blood calcium in patients with CKD. J Am Soc Nephrol 19:1592–1598

  37. Gkika D, Topala CN, Chang Q, Picard N, Thebault S, Houillier P, Hoenderop JG, Bindels RJ (2006) Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5. Embo J 25:4707–4716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Godron A, Harambat J, Boccio V, Mensire A, May A, Rigothier C, Couzi L, Barrou B, Godin M, Chauveau D, Faguer S, Vallet M, Cochat P, Eckart P, Guest G, Guigonis V, Houillier P, Blanchard A, Jeunemaitre X, Vargas-Poussou R (2012) Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations. Clin J Am Soc Nephrol 7:801–809. https://doi.org/10.2215/cjn.12841211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gong Y, Hou J (2014) Claudin-14 underlies Ca(+)(+)-sensing receptor-mediated Ca(+)(+) metabolism via NFAT-microRNA-based mechanisms. J Am Soc Nephrol 25:745–760. https://doi.org/10.1681/ASN.2013050553

    Article  CAS  PubMed  Google Scholar 

  40. Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J (2012) Claudin-14 regulates renal Ca(+)(+) transport in response to CaSR signalling via a novel microRNA pathway. EMBO J 31:1999–2012. https://doi.org/10.1038/emboj.2012.49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gong Y, Renigunta V, Zhou Y, Sunq A, Wang J, Yang J, Renigunta A, Baker LA, Hou J (2015) Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization. Mol Biol Cell 26:4333–4346. https://doi.org/10.1091/mbc.E15-06-0422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gorvin CM, Frost M, Malinauskas T, Cranston T, Boon H, Siebold C, Jones EY, Hannan FM, Thakker RV (2018) Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias. Hum Mol Genet 27:3720–3733. https://doi.org/10.1093/hmg/ddy263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Graca JA, Schepelmann M, Brennan SC, Reens J, Chang W, Yan P, Toka H, Riccardi D, Price SA (2016) Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney. Am J Physiol Renal Physiol 310:F518-533. https://doi.org/10.1152/ajprenal.00208.2015

    Article  CAS  PubMed  Google Scholar 

  44. Le Grimellec C (1975) Micropuncture study along the proximal convoluted tubule. Electrolyte reabsorption in first convolutions. Pflugers Arch 354:133–150. https://doi.org/10.1007/bf00579944

    Article  PubMed  Google Scholar 

  45. Le Grimellec C, Poujeol P, Rouffignac Cd (1975) 3H-inulin and electrolyte concentrations in Bowman’s capsule in rat kidney. Comparison with artificial ultrafiltration. Pflugers Arch 354:117–131

    Article  CAS  PubMed  Google Scholar 

  46. de Groot T, Kovalevskaya NV, Verkaart S, Schilderink N, Felici M, van der Hagen EA, Bindels RJ, Vuister GW, Hoenderop JG (2011) Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone. Mol Cell Biol 31:2845–2853. https://doi.org/10.1128/mcb.01319-10

    Article  PubMed  PubMed Central  Google Scholar 

  47. de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels RJ, Hoenderop JG (2009) Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation. J Am Soc Nephrol 20:1693–1704. https://doi.org/10.1681/asn.2008080873

    Article  PubMed  PubMed Central  Google Scholar 

  48. Günzel D, Amasheh S, Pfaffenbach S, Richter JF, Kausalya PJ, Hunziker W, Fromm M (2009) Claudin-16 affects transcellular Cl- secretion in MDCK cells. J Physiol 587:3777–3793. https://doi.org/10.1113/jphysiol.2009.173401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Günzel D, Stuiver M, Kausalya PJ, Haisch L, Krug SM, Rosenthal R, Meij IC, Hunziker W, Fromm M, Müller D (2009) Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function. J Cell Sci 122:1507–1517. https://doi.org/10.1242/jcs.040113

    Article  CAS  PubMed  Google Scholar 

  50. Hall AK, Norman AW (1990) Regulation of calbindin-D28K gene expression by 1,25-dihydroxyvitamin D3 in chick kidney. J Bone Miner Res 5:325–330. https://doi.org/10.1002/jbmr.5650050404

    Article  CAS  PubMed  Google Scholar 

  51. Harris CA, Baer PG, Chirito E, Dirks JH (1974) Composition of mammalian glomerular filtrate. Am J Physiol 227:972–976. https://doi.org/10.1152/ajplegacy.1974.227.4.972

    Article  CAS  PubMed  Google Scholar 

  52. Himmerkus N, Shan Q, Goerke B, Hou J, Goodenough DA, Bleich M (2008) Salt and acid-base metabolism in claudin-16 knockdown mice: impact for the pathophysiology of FHHNC patients. Am J Physiol Renal Physiol 295:F1641-1647. https://doi.org/10.1152/ajprenal.90388.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ho C, Conner DA, Pollak MR, Ladd DJ, Kifor O, Warren HB, Brown EM, Seidman JG, Seidman CE (1995) A mouse model for familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nature Genet 11:389–394

    Article  CAS  PubMed  Google Scholar 

  54. Hoenderop JG, Hartog A, Stuiver M, Doucet A, Willems PH, Bindels RJ (2000) Localization of the epithelial Ca(2+) channel in rabbit kidney and intestine. J Am Soc Nephrol 11:1171–1178

    Article  CAS  PubMed  Google Scholar 

  55. Hoenderop JG, van der Kemp AW, Hartog A, van de Graaf SF, van Os CH, Willems PH, Bindels RJ (1999) Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem 274:8375–8378

    Article  CAS  PubMed  Google Scholar 

  56. Hoenderop JG, van der Kemp AW, Hartog A, van Os CH, Willems PH, Bindels RJ (1999) The epithelial calcium channel, ECaC, is activated by hyperpolarization and regulated by cytosolic calcium. Biochem Biophys Res Commun 261:488–492

    Article  CAS  PubMed  Google Scholar 

  57. Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Merillat AM, Waarsing JH, Rossier BC, Vallon V, Hummler E, Bindels RJ (2003) Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest 112:1906–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hoenderop JGJ, Müller D, AWCM VDK, Hartog A, Suzuki M, Ishibashi K, Imai M, Sweep F, Willems P, Os CHV, Bindels RJM (2001) Calcitriol controls the epithelial calcium channel in kidney. J Am Soc Nephrol 12:1342–1349. https://doi.org/10.1681/asn.v1271342

  59. Hou J, Paul DL, Goodenough DA (2005) Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci 118:5109–5118. https://doi.org/10.1242/jcs.02631

    Article  CAS  PubMed  Google Scholar 

  60. Hou J, Renigunta A, Konrad M, Gomes AS, Schneeberger EE, Paul DL, Waldegger S, Goodenough DA (2008) Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest 118:619–628. https://doi.org/10.1172/JCI33970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hou J, Shan Q, Wang T, Gomes AS, Yan Q, Paul DL, Bleich M, Goodenough DA (2007) Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. J Biol Chem 282:17114–17122. https://doi.org/10.1074/jbc.M700632200

    Article  CAS  PubMed  Google Scholar 

  62. Hough TA, Bogani D, Cheeseman MT, Favor J, Nesbit MA, Thakker RV, Lyon MF (2004) Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification. Proc Natl Acad Sci U S A 101:13566–13571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Houillier P, Normand M, Froissart M, Blanchard A, Jungers P, Paillard M (1996) Calciuric response to an acute acid load in healthy subjects and hypercalciuric calcium stone formers. Kidney Int 50:987–997

    Article  CAS  PubMed  Google Scholar 

  64. Ikari A, Hirai N, Shiroma M, Harada H, Sakai H, Hayashi H, Suzuki Y, Degawa M, Takagi K (2004) Association of paracellin-1 with ZO-1 augments the reabsorption of divalent cations in renal epithelial cells. J Biol Chem 279:54826–54832. https://doi.org/10.1074/jbc.M406331200

    Article  CAS  PubMed  Google Scholar 

  65. Ikari A, Matsumoto S, Harada H, Takagi K, Hayashi H, Suzuki Y, Degawa M, Miwa M (2006) Phosphorylation of paracellin-1 at Ser217 by protein kinase A is essential for localization in tight junctions. J Cell Sci 119:1781–1789. https://doi.org/10.1242/jcs.02901

    Article  CAS  PubMed  Google Scholar 

  66. Imai M (1981) Effects of parathyroid hormone and N6, O2’-dibutyryl cyclic AMP on Ca2+ transport across the rabbit distal nephron segments perfused in vitro. Pflugers Arch 390:145–151. https://doi.org/10.1007/bf00590197

    Article  CAS  PubMed  Google Scholar 

  67. Imenez Silva PH, Katamesh-Benabbas C, Chan K, Pastor Arroyo EM, Knöpfel T, Bettoni C, Ludwig MG, Gasser JA, Brandao-Burch A, Arnett TR, Bonny O, Seuwen K, Wagner CA (2020) The proton-activated ovarian cancer G protein-coupled receptor 1 (OGR1) is responsible for renal calcium loss during acidosis. Kidney Int 97:920–933. https://doi.org/10.1016/j.kint.2019.12.006

    Article  CAS  PubMed  Google Scholar 

  68. Van Itallie CM, Rogan S, Yu A, Vidal LS, Holmes J, Anderson JM (2006) Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities. Am J Physiol Renal Physiol 291:F1288-1299. https://doi.org/10.1152/ajprenal.00138.2006

    Article  CAS  PubMed  Google Scholar 

  69. de Jesus Ferreira MC, Helies-Toussaint C, Imbert-Teboul M, Bailly C, Verbavatz JM, Bellanger AC, Chabardes D (1998) Co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing receptor in the cortical thick ascending limb cell of the rat kidney. Inhibition of hormone-dependent cAMP accumulation by extracellular Ca2+. J Biol Chem 273:15192–15202

    Article  PubMed  Google Scholar 

  70. Kausalya PJ, Amasheh S, Gunzel D, Wurps H, Muller D, Fromm M, Hunziker W (2006) Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. J Clin Invest 116:878–891. https://doi.org/10.1172/JCI26323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Konrad M, Hou J, Weber S, Dötsch J, Kari JA, Seeman T, Kuwertz-Bröking E, Peco-Antic A, Tasic V, Dittrich K, Alshaya HO, von Vigier RO, Gallati S, Goodenough DA, Schaller A (2008) CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 19:171–181. https://doi.org/10.1681/asn.2007060709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kos CH, Karaplis AC, Peng JB, Hediger MA, Goltzman D, Mohammad KS, Guise TA, Pollak MR (2003) The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone. J Clin Invest 111:1021–1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kurokawa K (1994) The kidney and calcium homeostasis. Kidney Int Suppl 44:S97-105

    CAS  PubMed  Google Scholar 

  74. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51. https://doi.org/10.1038/36285

    Article  CAS  PubMed  Google Scholar 

  75. Lassiter WE, Gottschalk CW, Mylle M (1963) Micropuncture study of renal tubular reabsorption of calcium in normal rodents. Am J Physiol 204:771–775

    Article  CAS  Google Scholar 

  76. Lee JJ, Alzamil J, Rehman S, Pan W, Dimke H, Alexander RT (2021) Activation of the calcium sensing receptor increases claudin-14 expression via a PLC -p38-Sp1 pathway. FASEB J 35:e21982. https://doi.org/10.1096/fj.202002137RRR

    Article  CAS  PubMed  Google Scholar 

  77. Lee JW, Chou CL, Knepper MA (2015) Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J Am Soc Nephrol 26:2669–2677. https://doi.org/10.1681/asn.2014111067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lee CT, Huynh VM, Lai LW, Lien YH (2002) Cyclosporine A-induced hypercalciuria in calbindin-D28k knockout and wild-type mice. Kidney Int 62:2055–2061. https://doi.org/10.1046/j.1523-1755.2002.00670.x

    Article  CAS  PubMed  Google Scholar 

  79. Lee CT, Ng HY, Lee YT, Lai LW, Lien YH (2016) The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics. Am J Physiol Renal Physiol 310:F230-236. https://doi.org/10.1152/ajprenal.00057.2015

    Article  CAS  PubMed  Google Scholar 

  80. Lemann J, Litzow JE, Lennon EJ (1966) The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest 45:1608–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lemann J, Litzow JR, Lennon EJ (1967) Studies of the mechanism by which chronic metabolic acidosis augments urinary calcium excretion in man. J Clin Invest 46:1318–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Levi M, Molitoris BA, Burke TJ, Schrier RW, Simon FR (1987) Effects of vitamin D-induced chronic hypercalcemia on rat renal cortical plasma membranes and mitochondria. Am J Physiol 252:F267-275

    Article  CAS  PubMed  Google Scholar 

  83. Limbutara K, Chou CL, Knepper MA (2020) Quantitative proteomics of all 14 renal tubule segments in rat. J Am Soc Nephrol 31:1255–1266. https://doi.org/10.1681/asn.2020010071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Loupy A, Ramakrishnan SK, Wootla B, Chambrey R, de la Faille R, Bourgeois S, Bruneval P, Mandet C, Christensen EI, Faure H, Cheval L, Laghmani K, Collet C, Eladari D, Dodd RH, Ruat M, Houillier P (2012) PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor. J Clin Invest 122:3355–3367. https://doi.org/10.1172/JCI57407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lupp A, Klenk C, Röcken C, Evert M, Mawrin C, Schulz S (2010) Immunohistochemical identification of the PTHR1 parathyroid hormone receptor in normal and neoplastic human tissues. Eur J Endocrinol 162:979–986. https://doi.org/10.1530/eje-09-0821

    Article  CAS  PubMed  Google Scholar 

  86. Maiti A, Beckman MJ (2007) Extracellular calcium is a direct effecter of VDR levels in proximal tubule epithelial cells that counter-balances effects of PTH on renal vitamin D metabolism. J Steroid Biochem Mol Biol 103:504–508. https://doi.org/10.1016/j.jsbmb.2006.11.012

    Article  CAS  PubMed  Google Scholar 

  87. Maiti A, Hait NC, Beckman MJ (2008) Extracellular calcium-sensing receptor activation induces vitamin D receptor levels in proximal kidney HK-2G cells by a mechanism that requires phosphorylation of p38alpha MAPK. J Biol Chem 283:175–183. https://doi.org/10.1074/jbc.M707269200

    Article  CAS  PubMed  Google Scholar 

  88. Mandon B, Siga E, Roinel N, de Rouffignac C, Knepper MA (1993) Ca2+, Mg2+ and K+ transport in the cortical and medullary thick ascending limb of the rat nephron: influence of transepithelial voltage. Pflugers Arch 424:558–560

    Article  CAS  PubMed  Google Scholar 

  89. Marshall DH, Nordin BE, Speed R (1976) Calcium, phosphorus and magnesium requirement. Proc Nutr Soc 35:163–173

    Article  CAS  Google Scholar 

  90. Maruani G, Hertig A, Paillard M, Houillier P (2003) Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to parathyroid hormone. J Clin Endocrinol Metab 88:4641–4648

    Article  CAS  PubMed  Google Scholar 

  91. Marunaka K, Fujii N, Kimura T, Furuta T, Hasegawa H, Matsunaga T, Endo S, Ikari A (2019) Rescue of tight junctional localization of a claudin-16 mutant D97S by antimalarial medicine primaquine in Madin-Darby canine kidney cells. Sci Rep 9:9647. https://doi.org/10.1038/s41598-019-46250-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. McCarron DA, Rankin LI, Bennett WM, Krutzik S, McClung MR, Luft FC (1981) Urinary calcium excretion at extremes of sodium intake in normal man. Am J Nephrol 1:84–90. https://doi.org/10.1159/000166496

    Article  CAS  PubMed  Google Scholar 

  93. Merlin JPJ, Li X (2021) Role of nanotechnology and their perspectives in the treatment of kidney diseases. Front Genet 12:817974. https://doi.org/10.3389/fgene.2021.817974

    Article  CAS  PubMed  Google Scholar 

  94. Milatz S, Himmerkus N, Wulfmeyer VC, Drewell H, Mutig K, Hou J, Breiderhoff T, Müller D, Fromm M, Bleich M, Günzel D (2017) Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport. Proc Natl Acad Sci U S A 114:E219-e227. https://doi.org/10.1073/pnas.1611684114

    Article  CAS  PubMed  Google Scholar 

  95. Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T, Nakayama K, Okamura Y, Sasaki H, Miyachi Y, Furuse M, Tsukita S (2005) Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice. J Cell Biol 169:527–538. https://doi.org/10.1083/jcb.200501154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Morel F, Imbert-Teboul M, Chabardès D (1981) Distribution of hormone-dependent adenylate cyclase in the nephron and its physiological significance. Annu Rev Physiol 43:569–581. https://doi.org/10.1146/annurev.ph.43.030181.003033

    Article  CAS  PubMed  Google Scholar 

  97. Motoyama HI, Friedman PA (2002) Calcium-sensing receptor regulation of PTH-dependent calcium absorption by mouse cortical ascending limbs. Am J Physiol Renal Physiol 283:F399-406

    Article  CAS  PubMed  Google Scholar 

  98. Nicolet-Barousse L, Blanchard A, Roux C, Pietri L, Bloch-Faure M, Kolta S, Chappard C, Geoffroy V, Morieux C, Jeunemaitre X, Shull G, Meneton P, Paillard M, Houillier P, and De Vernejoul M (2005) Inactivation of Na-Cl cotransporter (NCC) gene is associated with high bone density through both renal and bone machanisms: analysis of patients with Gitelman syndrome and Ncc null mice. J Bone Miner Res In press

  99. Nijenhuis T, Renkema KY, Hoenderop JG, Bindels RJ (2006) Acid-base status determines the renal expression of Ca2+ and Mg2+ transport proteins. J Am Soc Nephrol 17:617–626

    Article  CAS  PubMed  Google Scholar 

  100. Nijenhuis T, Vallon V, van der Kemp AW, Loffing J, Hoenderop JG, Bindels RJ (2005) Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest 115:1651–1658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Nordin BEC (1976) Calcium, phosphate and magnesium metabolism: Clinical Physiology and Diagnostic Procedures. Edinburgh: Churchill Livingstone

  102. Parfitt A (1976) The action of parathyroid hormone on bone. Relation to bone remodelling and turnover, calcium homeostasis and metabolic bone disease. Part III. Metabolism 25:1033–1069

    Article  CAS  PubMed  Google Scholar 

  103. Pearce SHS, Williamson C, Kifor O, Bai M, Coulthard MG, Davies M, Lewis-Barned N, McCredie D, Powel H, Kendall-Taylor P, Brown EM, Thakker RV (1996) A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med 335:1115–1122

    Article  CAS  PubMed  Google Scholar 

  104. Pei L, Solis G, Nguyen MT, Kamat N, Magenheimer L, Zhuo M, Li J, Curry J, McDonough AA, Fields TA, Welch WJ, Yu AS (2016) Paracellular epithelial sodium transport maximizes energy efficiency in the kidney. J Clin Invest 126:2509–2518. https://doi.org/10.1172/jci83942

    Article  PubMed  PubMed Central  Google Scholar 

  105. Peng JB, Chen XZ, Berger UV, Vassilev PM, Brown EM, Hediger MA (2000) A rat kidney-specific calcium transporter in the distal nephron. J Biol Chem 275:28186–28194. https://doi.org/10.1074/jbc.M909686199

    Article  CAS  PubMed  Google Scholar 

  106. Peterson LN (1990) Vitamin D-induced chronic hypercalcemia inhibits thick ascending limb NaCl reabsorption in vivo. Am J Physiol 259:F122-129

    Article  CAS  PubMed  Google Scholar 

  107. Picard N, Van Abel M, Campone C, Seiler M, Bloch-Faure M, Hoenderop JG, Loffing J, Meneton P, Bindels RJ, Paillard M, Alhenc-Gelas F, Houillier P (2005) Tissue kallikrein-deficient mice display a defect in renal tubular calcium absorption. J Am Soc Nephrol 16:3602–3610

    Article  CAS  PubMed  Google Scholar 

  108. Plain A, Pan W, O’Neill D, Ure M, Beggs MR, Farhan M, Dimke H, Cordat E, Alexander RT (2020) Claudin-12 knockout mice demonstrate reduced proximal tubule calcium permeability. Int J Mol Sci 21. https://doi.org/10.3390/ijms21062074

  109. Poujeol P, Chabardes D, Roinel N, De Rouffignac C (1976) Influence of extracellular fluid volume expansion on magnesium, calcium and phosphate handling along the rat nephron. Pflugers Arch 365:203–211

    Article  CAS  PubMed  Google Scholar 

  110. Prot-Bertoye C, Griveau C, Skjødt K, Cheval L, Brideau G, Lievre L, Ferriere E, Arbaretaz F, Garbin K, Zamani R, Marcussen N, Figueres L, Breiderhoff T, Muller D, Bruneval P, Houillier P, Dimke H (2021) Differential localization patterns of claudin 10, 16, and 19 in human, mouse, and rat renal tubular epithelia. Am J Physiol Renal Physiol 321:F207-f224. https://doi.org/10.1152/ajprenal.00579.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Prot-Bertoye C, Houillier P (2020) Claudins in renal physiology and pathology. Genes 11. https://doi.org/10.3390/genes11030290

  112. Puschett JB, Beck WS Jr, Jelonek A, Fernandez PC (1974) Study of the renal tubular interactions of thyrocalcitonin, cyclic adenosine 3’,5’-monophosphate, 25-hydroxycholecalciferol, and calcium ion. J Clin Invest 53:756–767. https://doi.org/10.1172/jci107614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Puschett JB, Moranz J, Kurnick WS (1972) Evidence for a direct action of cholecalciferol and 25-hydroxycholecalciferol on the renal transport of phosphate, sodium, and calcium. J Clin Invest 51:373–385. https://doi.org/10.1172/jci106823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Quamme GA (1982) Effect of hypercalcemia on renal tubular handling of calcium and magnesium. Can J Physiol Pharmacol 60:1275–1280

    Article  CAS  PubMed  Google Scholar 

  115. Quamme GA, Dirks JH (1980) Intraluminal and contraluminal magnesium on magnesium and calcium transfer in the rat nephron. Am J Physiol 238:F187-198

    CAS  PubMed  Google Scholar 

  116. Rector FC Jr (1983) Sodium, bicarbonate, and chloride absorption by the proximal tubule. Am J Physiol 244:F461-471. https://doi.org/10.1152/ajprenal.1983.244.5.F461

    Article  PubMed  Google Scholar 

  117. Riccardi D, Brown EM (2010) Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 298:F485-499. https://doi.org/10.1152/ajprenal.00608.2009

    Article  CAS  PubMed  Google Scholar 

  118. Riccardi D, Hall AE, Chattopadhyay N, Xu JZ, Brown EM, Hebert SC (1998) Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney. Am J Physiol 274:F611-622

    CAS  PubMed  Google Scholar 

  119. Riccardi D, Lee WS, Lee K, Segre GV, Brown EM, Hebert SC (1996) Localization of the extracellular Ca2+-sensing receptor and PTH/PTHrP receptor in rat kidney. Am J Physiol 271:F611-622

    Google Scholar 

  120. Rocha AS, Magaldi JB, Kokko JP (1977) Calcium and phosphate transport in isolated segments of rabbit Henle’s loop. J Clin Invest 59:975–983. https://doi.org/10.1172/jci108720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sands JM, Naruse M, Baum M, Jo I, Hebert SC, Brown EM, Harris HW (1997) Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest 99:1399–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Sato T, Courbebaisse M, Ide N, Fan Y, Hanai JI, Kaludjerovic J, Densmore MJ, Yuan Q, Toka HR, Pollak MR, Hou J, Lanske B (2017) Parathyroid hormone controls paracellular Ca(2+) transport in the thick ascending limb by regulating the tight-junction protein Claudin14. Proc Natl Acad Sci U S A 114:E3344-e3353. https://doi.org/10.1073/pnas.1616733114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Bröking E, Fehrenbach H, Wingen AM, Güran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365:410–421. https://doi.org/10.1056/NEJMoa1103864

    Article  CAS  PubMed  Google Scholar 

  124. Shareghi GR, Agus ZS (1982) Magnesium transport in the cortical thick ascending limb of Henle’s loop of the rabbit. J Clin Invest 69:759–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Shareghi GR, Stoner LC (1978) Calcium transport across segments of the rabbit distal nephron in vitro. Am J Physiol 235:F367-375

    CAS  PubMed  Google Scholar 

  126. Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285:103–106

    Article  CAS  PubMed  Google Scholar 

  127. Sooy K, Schermerhorn T, Noda M, Surana M, Rhoten WB, Meyer M, Fleischer N, Sharp GW, Christakos S (1999) Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem 274:34343–34349. https://doi.org/10.1074/jbc.274.48.34343

    Article  CAS  PubMed  Google Scholar 

  128. Di Stefano A, Wittner M, Nitschke R, Braitsch R, Greger R, Bailly C, Amiel C, Elalouf JM, Roinel N, de Rouffignac C (1989) Effects of glucagon on Na+, Cl-, K+, Mg2+ and Ca2+ transports in cortical and medullary thick ascending limbs of mouse kidney. Pflugers Arch 414:640–646

    Article  PubMed  Google Scholar 

  129. Di Stefano A, Wittner M, Nitschke R, Braitsch R, Greger R, Bailly C, Amiel C, Roinel N, de Rouffignac C (1990) Effects of parathyroid hormone and calcitonin on Na+, Cl-, K+, Mg2+ and Ca2+ transport in cortical and medullary thick ascending limbs of mouse kidney. Pflugers Arch 417:161–167

    Article  PubMed  Google Scholar 

  130. Suki WN, Rouse D (1981) Hormonal regulation of calcium transport in thick ascending limb renal tubules. Am J Physiol 241:F171-174

    CAS  PubMed  Google Scholar 

  131. Suki WN, Rouse D, Ng RC, Kokko JP (1980) Calcium transport in the thick ascending limb of Henle. Heterogeneity of function in the medullary and cortical segments. J Clin Invest 66:1004–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sutton RA, Wong NL, Dirks JH (1976) Effects of parathyroid hormone on sodium and calcium transport in the dog nephron. Clin Sci Mol Med 51:345–351. https://doi.org/10.1042/cs0510345

    Article  CAS  PubMed  Google Scholar 

  133. Toka HR, Al-Romaih K, Koshy JM, DiBartolo S 3rd, Kos CH, Quinn SJ, Curhan GC, Mount DB, Brown EM, Pollak MR (2012) Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria. J Am Soc Nephrol 23:1879–1890. https://doi.org/10.1681/ASN.2012030323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Tu Q, Pi M, Karsenty G, Simpson L, Liu S, Quarles LD (2003) Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest 111:1029–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Ullrich KJ, Rumrich G, Klöss S (1976) Active Ca2+ reabsorption in the proximal tubule of the rat kidney. Dependence on sodium- and buffer transport. Pflugers Arch 364:223–228. https://doi.org/10.1007/bf00581759

    Article  CAS  PubMed  Google Scholar 

  136. Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C, Treard C, Baudouin V, Beltran S, Broux F, Camard O, Cloarec S, Cormier C, Debussche X, Dubosclard E, Eid C, Haymann JP, Kiando SR, Kuhn JM, Lefort G, Linglart A, Lucas-Pouliquen B, Macher MA, Maruani G, Ouzounian S, Polak M, Requeda E, Robier D, Silve C, Souberbielle JC, Tack I, Vezzosi D, Jeunemaitre X, Houillier P (2016) Familial hypocalciuric hypercalcemia types 1 and 3 and primary hyperparathyroidism: similarities and differences. J Clin Endocrinol Metab 101:2185–2195. https://doi.org/10.1210/jc.2015-3442

    Article  CAS  PubMed  Google Scholar 

  137. Walser M (1961) Calcium clearance as a function of sodium clearance in the dog. Am J Physiol 200:1099–1104. https://doi.org/10.1152/ajplegacy.1961.200.5.1099

    Article  CAS  PubMed  Google Scholar 

  138. Wang W, Lu M, Balazy M, Hebert SC (1997) Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL. Am J Physiol 273:F421-429

    CAS  PubMed  Google Scholar 

  139. Wang WH, Lu M, Hebert SC (1996) Cytochrome P-450 metabolites mediate extracellular Ca(2+)-induced inhibition of apical K+ channels in the TAL. Am J Physiol 271:C103-111

    Article  CAS  PubMed  Google Scholar 

  140. Watanabe H, Sutton RA, Wittner M, Mandon B, Roinel N, de Rouffignac C, Di Stefano A (1983) Renal calcium handling in familial hypocalciuric hypercalcemia. Kidney Int 24:353–357

    Article  CAS  PubMed  Google Scholar 

  141. Weber S, Schneider L, Peters M, Misselwitz J, Rönnefarth G, Böswald M, Bonzel KE, Seeman T, Suláková T, Kuwertz-Bröking E, Gregoric A, Palcoux JB, Tasic V, Manz F, Schärer K, Seyberth HW, Konrad M (2001) Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 12:1872–1881. https://doi.org/10.1681/asn.v1291872

    Article  CAS  PubMed  Google Scholar 

  142. Will C, Breiderhoff T, Thumfart J, Stuiver M, Kopplin K, Sommer K, Gunzel D, Querfeld U, Meij IC, Shan Q, Bleich M, Willnow TE, Muller D (2010) Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting. Am J Physiol Renal Physiol 00499:2009. https://doi.org/10.1152/ajprenal.00499.2009

    Article  CAS  Google Scholar 

  143. Winaver J, Sylk DB, Robertson JS, Chen TC, Puschett JB (1980) Micropuncture study of the acute renal tubular transport effect of 25-hydroxyvitamin D3 in the dog. Mineral Electrolyte Metab 4:178–188

    CAS  Google Scholar 

  144. Wittner M, Di Stefano A (1990) Effects of antidiuretic hormone, parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle’s loop of the mouse nephron. Pflugers Arch 415:707–712. https://doi.org/10.1007/bf02584009

    Article  CAS  PubMed  Google Scholar 

  145. Wittner M, Di Stefano A, Mandon B, Roinel N, de Rouffignac C (1991) Stimulation of NaCl reabsorption by antidiuretic hormone in the cortical thick ascending limb of Henle’s loop of the mouse. Pflugers Arch 419:212–214

    Article  CAS  PubMed  Google Scholar 

  146. Wittner M, di Stefano A, Wangemann P, Nitschke R, Greger R, Bailly C, Amiel C, Roinel N, de Rouffignac C (1988) Differential effects of ADH on sodium, chloride, potassium, calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron. Pflugers Arch 412:516–523

    Article  CAS  PubMed  Google Scholar 

  147. Wright FS (1971) Increasing magnitude of electrical potential along the renal distal tubule. Am J Physiol 220:624–638. https://doi.org/10.1152/ajplegacy.1971.220.3.624

    Article  CAS  PubMed  Google Scholar 

  148. Yamamoto M, Akatsu T, Nagase T, Ogata E (2000) Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders? J Clin Endocrinol Metab 85:4583–4591

    Article  CAS  PubMed  Google Scholar 

  149. Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E (1984) Vitamin D deficiency and calcium transport in the rat. J Clin Invest 74:507–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Yang T, Hassan S, Huang YG, Smart AM, Briggs JP, Schnermann JB (1997) Expression of PTHrP. PTH/PTHrP receptor and Ca2+-sensing receptor mRNAs along the rat nephron. Am J Physiol 272:F751–F758

    Article  CAS  PubMed  Google Scholar 

  151. Yatabe MS, Yatabe J, Takano K, Murakami Y, Sakuta R, Abe S, Sanada H, Kimura J, Watanabe T (2012) Effects of a high-sodium diet on renal tubule Ca2+ transporter and claudin expression in Wistar-Kyoto rats. BMC Nephrol 13:160. https://doi.org/10.1186/1471-2369-13-160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Yoon J, Liu Z, Lee E, Liu L, Ferre S, Pastor J, Zhang J, Moe OW, Chang AN, Miller RT (2021) Physiologic regulation of systemic klotho levels by renal CaSR signaling in response to CaSR ligands and pH(o). J Am Soc Nephrol 32:3051–3065. https://doi.org/10.1681/asn.2021020276

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Agence Nationale de la Recherche (ANR-12-BSV1-0031-01 and ANR-17-CE14-0032 awarded to PH).

Author information

Authors and Affiliations

  1. Centre de Recherche Des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, 75006, Paris, France

    Caroline Prot-Bertoye, Loïc Lievre & Pascal Houillier

  2. CNRS ERL 8228 - Laboratoire de Physiologie Rénale Et Tubulopathies, 75006, Paris, France

    Caroline Prot-Bertoye, Loïc Lievre & Pascal Houillier

  3. Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie, 20 rue Leblanc, 75015, Paris, France

    Caroline Prot-Bertoye & Pascal Houillier

  4. Centre de Référence Des Maladies Rénales Héréditaires de L’Enfant Et de L’Adulte (MARHEA), 75015, Paris, France

    Caroline Prot-Bertoye & Pascal Houillier

  5. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, 75015, Paris, France

    Caroline Prot-Bertoye & Pascal Houillier

Authors
  1. Caroline Prot-Bertoye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loïc Lievre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pascal Houillier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pascal Houillier.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the special issue on Kidney Control of Homeostasis in Pflügers Archiv—European Journal of Physiology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prot-Bertoye, C., Lievre, L. & Houillier, P. The importance of kidney calcium handling in the homeostasis of extracellular fluid calcium. Pflugers Arch - Eur J Physiol 474, 885–900 (2022). https://doi.org/10.1007/s00424-022-02725-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-022-02725-4

Keywords

Search

Navigation