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Regulation of parathyroid function in chronic renal failure

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Abstract

This review summarizes the factors involved in the development of hyperparathyroidism secondary (2nd-HPTH) to chronic kidney disease (CKD). Calcium and calcitriol act on their respective specific parathyroid cell receptors to inhibit parathyroid function. As well as the well-known effect of calcium and calcitriol on parathyroid cell function, there is experimental work that demonstrates that phosphate, changes in pH, PTHrP, estrogens, and some cytokines also have an effect on PTH secretion. These factors are relevant in patients with chronic kidney disease. However, low calcium, vitamin D deficiency, and an accumulation of phosphate due to the decrease in renal function are the main pathogenic factors involved in the pathogenesis of 2nd-HPTH in CKD patients.

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References

  1. EM Brown G Gamba D Riccardi et al. (1993) ArticleTitleCloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid Nature 366 575–580 Occurrence Handle1:CAS:528:DyaK2cXhvVGmtLs%3D Occurrence Handle8255296

    CAS  PubMed  Google Scholar 

  2. AJ Felsenfeld F Llach (1993) ArticleTitleParathyroid gland function in renal failure Kidney Int 43 771–789 Occurrence Handle1:STN:280:ByyB2c%2FnsVI%3D Occurrence Handle8479113

    CAS  PubMed  Google Scholar 

  3. R Kilav J Silver T Naveh-Many (2001) ArticleTitleA conserved cis-acting element in the parathyroid hormone 3′-untranslated region is sufficient for regulation of RNA stability by calcium and phosphate J Biol Chem 276 8727–8733 Occurrence Handle10.1074/jbc.M005471200 Occurrence Handle1:CAS:528:DC%2BD3MXisVCnsbc%3D Occurrence Handle11118432

    Article  CAS  PubMed  Google Scholar 

  4. T Naveh-Many R Rahamimov N Livni J Silver (1995) ArticleTitleParathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D J Clin Invest 96 1786–1793 Occurrence Handle1:CAS:528:DyaK2MXosFyhtr4%3D Occurrence Handle7560070

    CAS  PubMed  Google Scholar 

  5. B Garfia S Canadillas A Canalejo et al. (2002) ArticleTitleRegulation of parathyroid vitamin D receptor expression by extracellular calcium J Am Soc Nephrol 13 2945–2952 Occurrence Handle10.1097/01.ASN.0000037676.54018.CB Occurrence Handle1:CAS:528:DC%2BD38XoslSntL8%3D Occurrence Handle12444213

    Article  CAS  PubMed  Google Scholar 

  6. S Tallon I Berdud A Hernandez MT Concepcion Y Almaden A Torres A Marti-Malo AJ Felsenfeld P Aljama M Rodriguez (1996) ArticleTitleThe relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats Kidney Int 49 1441–1446 Occurrence Handle1:CAS:528:DyaK28Xkslagtro%3D Occurrence Handle8731112

    CAS  PubMed  Google Scholar 

  7. M Rodriguez E Nemeth D Martín (2005) ArticleTitleThe calcium sensing receptor: a key factor in the patogenesis of secondary hyperparathyroidism Am J Physiol Renal Physiol 288 F253–F264 Occurrence Handle1:CAS:528:DC%2BD2MXhsFeltrY%3D Occurrence Handle15507543

    CAS  PubMed  Google Scholar 

  8. GA Block KJ Martin AL de Francisco et al. (2004) ArticleTitleCinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis N Engl J Med 350 1516–1525 Occurrence Handle1:CAS:528:DC%2BD2cXjtVeqtLY%3D Occurrence Handle15071126

    CAS  PubMed  Google Scholar 

  9. O Kifor FD Moore P Wang et al. (1996) ArticleTitleReduced immunostaining for the extracellular Ca2+ – sensing receptor in primary and uremic secondary hyperparathyroidism J Clin Endocrinol Metab 81 1598–1606 Occurrence Handle10.1210/jc.81.4.1598 Occurrence Handle1:CAS:528:DyaK28Xit1Ont74%3D Occurrence Handle8636374

    Article  CAS  PubMed  Google Scholar 

  10. J Gogusev P Duchambon B Hory M Giovannini E Sarfati TB Drüeke (1997) ArticleTitleDepressed expression of calcium receptor in parathyroid gland tissue of patients with primary or secondary uremic hyperparathyroidism Kidney Int 51 328–336 Occurrence Handle1:STN:280:ByiC2cfpt1I%3D Occurrence Handle8995751

    CAS  PubMed  Google Scholar 

  11. Y Almadén A Hernandez V Torregrosa et al. (1998) ArticleTitleHigh phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro J Am Soc Nephrol 9 1845–1852 Occurrence Handle9773785

    PubMed  Google Scholar 

  12. M Rodriguez F Caravaca E Fernandez et al. (1997) ArticleTitleEvidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism J Bone Miner Res 12 347–355 Occurrence Handle1:STN:280:ByiB3s7hvVY%3D Occurrence Handle9076577

    CAS  PubMed  Google Scholar 

  13. S Canadillas A Canalejo R Santamaria ME Rodriguez JC Estepa A Martin-Malo J Bravo B Ramos E Aguilera-Tejero M Rodriguez Y Almaden (2005) ArticleTitleCalcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans J Am Soc Nephrol 16 2190–2197 Occurrence Handle10.1681/ASN.2004080657 Occurrence Handle1:CAS:528:DC%2BD2MXms1egsL0%3D Occurrence Handle15888568

    Article  CAS  PubMed  Google Scholar 

  14. M Denda J Finch E Slatopolsky (1996) ArticleTitlePhosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure Am J Kidney Dis 28 596–602 Occurrence Handle1:CAS:528:DyaK28XmtlKgtr0%3D Occurrence Handle8840952

    CAS  PubMed  Google Scholar 

  15. E Lewin B Garfia F Luque Recio M Rodriguez K Olgaard (2002) ArticleTitlePersistent down-regulation of the calcium sensing receptor mRNA in rat parathyroid glands when severe secondary hyperparathyroidism is reversed by an experimental isogenic kidney transplantation J Am Soc Nephrol 13 2110–2116 Occurrence Handle10.1097/01.ASN.0000024439.38838.03 Occurrence Handle1:CAS:528:DC%2BD38Xmt1Ogsbc%3D Occurrence Handle12138143

    Article  CAS  PubMed  Google Scholar 

  16. CS Ritter JL Finch EA Slatopolsky AJ Brown (2001) ArticleTitleParathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor Kidney Int 60 1737–1744 Occurrence Handle10.1046/j.1523-1755.2001.00027.x Occurrence Handle1:CAS:528:DC%2BD3MXotlGnsbo%3D Occurrence Handle11703591

    Article  CAS  PubMed  Google Scholar 

  17. L Canaff GN Hendy (2002) ArticleTitleHuman calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D J Biol Chem 277 30337–30350 Occurrence Handle10.1074/jbc.M201804200 Occurrence Handle1:CAS:528:DC%2BD38XmsVKht7w%3D Occurrence Handle12036954

    Article  CAS  PubMed  Google Scholar 

  18. AJ Felsenfeld M Rodriguez (1999) ArticleTitlePhosphorus, calcium regulation and secondary hyperparathyroidism: an attempt to integrate a historical and modern perspective J Am Soc Nephrol 10 878–890 Occurrence Handle1:CAS:528:DyaK1MXitl2kur0%3D Occurrence Handle10203374

    CAS  PubMed  Google Scholar 

  19. Y Almaden A Canalejo A Hernandez et al. (1996) ArticleTitleDirect effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro J Bone Miner Res 11 970–976 Occurrence Handle1:CAS:528:DyaK28XkslKhurk%3D Occurrence Handle8797118

    CAS  PubMed  Google Scholar 

  20. E Slatopolsky J Finch M Denda et al. (1996) ArticleTitlePhosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro J Clin Invest 97 2534–2540 Occurrence Handle1:CAS:528:DyaK28XjsFKjsL4%3D Occurrence Handle8647946

    CAS  PubMed  Google Scholar 

  21. PK Nielsen U Feldt-Rasmussen K Olgaard (1996) ArticleTitleA direct effect of in vitro phosphate on PTH release from bovine parathyroid tissue slices but not from dispersed parathyroid cells Nephrol Dial Transplant 11 1762–1768 Occurrence Handle1:CAS:528:DyaK28Xmtlygtrs%3D Occurrence Handle8918619

    CAS  PubMed  Google Scholar 

  22. A Hernandez MT Concepcion M Rodriguez E Salido A Torres (1996) ArticleTitleHigh phosphorus diet increases preproPTH mRNA independent of calcium and calcitriol in normal rats Kidney Int 50 1872–1878 Occurrence Handle1:CAS:528:DyaK2sXjs1Giuw%3D%3D Occurrence Handle8943469

    CAS  PubMed  Google Scholar 

  23. R Kilav J Silver T Naveh-Many (1995) ArticleTitleParathyroid hormone gene expression in hypophosphatemic rats J Clin Invest 96 327–333 Occurrence Handle1:CAS:528:DyaK2MXmslyqs7g%3D Occurrence Handle7615802

    CAS  PubMed  Google Scholar 

  24. Y Almaden A Canalejo E Ballesteros G Anon M Rodriguez (2000) ArticleTitleEffect of high extracellular phosphate concentration on arachidonic acid production by parathyroid tissue in vitro J Am Soc Nephrol 11 1712–1718 Occurrence Handle1:CAS:528:DC%2BD3cXntFKru7g%3D Occurrence Handle10966496

    CAS  PubMed  Google Scholar 

  25. Y Almaden A Canalejo E Ballesteros G Anon S Canadillas M Rodriguez (2002) ArticleTitleRegulation of arachidonic acid production by intracellular calcium in parathyroid cells: effect of extracellular phosphate J Am Soc Nephrol 13 693–698 Occurrence Handle1:CAS:528:DC%2BD38Xit1Wrt7k%3D Occurrence Handle11856773

    CAS  PubMed  Google Scholar 

  26. E Moallem R Kilav J Silver T Naveh-Many (1998) ArticleTitleRNA–protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate J Biol Chem 273 5253–5259 Occurrence Handle10.1074/jbc.273.9.5253 Occurrence Handle1:CAS:528:DyaK1cXhs1Cnsrk%3D Occurrence Handle9478982

    Article  CAS  PubMed  Google Scholar 

  27. AS Dusso T Pavlopoulos L Naumovich et al. (2001) ArticleTitlep21 (WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth Kidney Int 59 855–865 Occurrence Handle10.1046/j.1523-1755.2001.059003855.x Occurrence Handle1:CAS:528:DC%2BD3MXitlOms7c%3D Occurrence Handle11231340

    Article  CAS  PubMed  Google Scholar 

  28. Y Almaden AJ Felsenfeld M Rodriguez et al. (2003) ArticleTitleProliferation in hyperplastic human and normal rat parathyroid glands: role of phosphate, calcitriol, and gender Kidney Int 64 2311–2317 Occurrence Handle10.1046/j.1523-1755.2003.00331.x Occurrence Handle1:CAS:528:DC%2BD3sXpvFOqtLY%3D Occurrence Handle14633156

    Article  CAS  PubMed  Google Scholar 

  29. J Silver J Russell LM Sherwood (1985) ArticleTitleRegulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells Proc Natl Acad Sci USA 82 4270–4273 Occurrence Handle1:CAS:528:DyaL2MXksVymu7k%3D Occurrence Handle3858880

    CAS  PubMed  Google Scholar 

  30. R Kremer I Bolivar D Goltzman GN Hendy (1989) ArticleTitleInfluence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells Endocrinology 125 935–941 Occurrence Handle1:STN:280:BiaA38rhvFU%3D Occurrence Handle2502380

    CAS  PubMed  Google Scholar 

  31. X Li W Zheng Y Chun Li (2003) ArticleTitleAltered gene expression profile in the kidney of vitamin D receptor knockout mice J Cell Biochem 89 709–719 Occurrence Handle10.1002/jcb.10547 Occurrence Handle1:CAS:528:DC%2BD3sXlt1Wqur4%3D Occurrence Handle12858337

    Article  CAS  PubMed  Google Scholar 

  32. F Llach SG Massry (1985) ArticleTitleOn the mechanism of secondary hyperparathyroidism in moderate renal insufficiency J Clin Endocrinol Metab 61 601–606 Occurrence Handle1:STN:280:BiqB1cbnsFQ%3D Occurrence Handle2993340

    CAS  PubMed  Google Scholar 

  33. E Slatopolsky C Weerts J Thielan R Horst H Harter KJ Martin (1984) ArticleTitleMarked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients J Clin Invest 74 2136–2143 Occurrence Handle1:STN:280:BiqD1c%2FlsVU%3D Occurrence Handle6549016

    CAS  PubMed  Google Scholar 

  34. N Fukuda H Tanaka Y Tominaga M Fukagawa K Kurokawa Y Seino (1993) ArticleTitleDecreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients J Clin Invest 92 1436–1443 Occurrence Handle1:STN:280:ByyA1cfosl0%3D Occurrence Handle8397225

    CAS  PubMed  Google Scholar 

  35. M Tokumoto K Tsuruya K Fukuda H Kanai S Kuroki H Hirakata (2002) ArticleTitleReduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients with advanced secondary hyperparathyroidism Kidney Int 62 1196–1207 Occurrence Handle10.1111/j.1523-1755.2002.kid585.x Occurrence Handle1:CAS:528:DC%2BD38XotVSntbw%3D Occurrence Handle12234290

    Article  CAS  PubMed  Google Scholar 

  36. SR Patel HQ Ke R Vanholder RJ Koenig CH Hsu (1995) ArticleTitleInhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins J Clin Invest 96 50–59 Occurrence Handle1:CAS:528:DyaK2MXmslyruro%3D Occurrence Handle7615822

    CAS  PubMed  Google Scholar 

  37. I Lopez E Aguilera-Tejero A Felsenfeld JC Estepa M Rodriguez (2002) ArticleTitleDirect effect of acute metabolic and respiratory acidosis on parathyroid hormone secretion in dog J Bone Min Res 17 1691–1700 Occurrence Handle1:CAS:528:DC%2BD38XntlSrsLY%3D

    CAS  Google Scholar 

  38. I Lopez M Rodriguez AJ Felsenfeld JC Estepa E Aguilera-Tejero (2003) ArticleTitleDirect suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog J Bone Min Res 18 1478–1485 Occurrence Handle1:CAS:528:DC%2BD3sXmslSnsro%3D

    CAS  Google Scholar 

  39. I Lopez E Aguilera-Tejero JC Estepa M Rodriguez AJ Felsenfeld (2004) ArticleTitleRole of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog Am J Physiol Endocrinol Metab 286 E780–E785 Occurrence Handle10.1152/ajpendo.00473.2003 Occurrence Handle1:CAS:528:DC%2BD2cXkt1emurg%3D Occurrence Handle14722029

    Article  CAS  PubMed  Google Scholar 

  40. Quinn et al. (2004) ArticleTitlepH sensing by the calcium-sensing receptor J Biol Chem 279 37241–37249 Occurrence Handle10.1074/jbc.M404520200 Occurrence Handle1:CAS:528:DC%2BD2cXntFSgtLk%3D Occurrence Handle15201280

    Article  CAS  PubMed  Google Scholar 

  41. E Lewin Y Almaden M Rodriguez K Olgaard (2000) ArticleTitlePTHrP enhances the secretory response of PTH to a hypocalcemic stimulus in rat parathyroid glands Kidney Int 58 71–81 Occurrence Handle10.1046/j.1523-1755.2000.00142.x Occurrence Handle1:CAS:528:DC%2BD3cXltVyjt7g%3D Occurrence Handle10886551

    Article  CAS  PubMed  Google Scholar 

  42. E Lewin B Garfia Y Almaden M Rodriguez K Olgaard (2003) ArticleTitleAutoregulation in the parathyroid glands by PTH/PTHrP receptor ligands in normal and uremic rats Kidney Int 64 63–70 Occurrence Handle10.1046/j.1523-1755.2003.00056.x Occurrence Handle1:CAS:528:DC%2BD3sXlsFelu7w%3D Occurrence Handle12787396

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Nephrology Service, Research Unit, Hospital Reina Sofia, Department of Medicine, Veterinary School, University of Cordoba, Cordoba, Spain

    Mariano Rodriguez, Sagrario Cañadillas, Ignacio Lopez, Escolástico Aguilera-Tejero & Yolanda Almaden

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  1. Mariano Rodriguez
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  2. Sagrario Cañadillas
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  3. Ignacio Lopez
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  4. Escolástico Aguilera-Tejero
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  5. Yolanda Almaden
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Correspondence to Mariano Rodriguez.

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Rodriguez, M., Cañadillas, S., Lopez, I. et al. Regulation of parathyroid function in chronic renal failure. J Bone Miner Metab 24, 164–168 (2006). https://doi.org/10.1007/s00774-005-0665-9

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  • DOI: https://doi.org/10.1007/s00774-005-0665-9

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