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Uremic toxin and bone metabolism

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Abstract

Patients with end-stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known as renal osteodystrophy (ROD). Although the pathogenesis of ESRD may be similar in many patients, the response of the bone varies widely, ranging from high to low turnover. ROD is classified into several types, depending on the status of bone turnover, by histomorphometric analysis using bone biopsy samples [1,2]. In the mild type, bone metabolism is closest to that of persons with normal renal function. In osteitis fibrosa, bone turnover is abnormally activated. This is a condition of high-turnover bone. A portion of the calcified bone loses its lamellar structure and appears as woven bone. In the cortical bone also, bone resorption by osteoclasts is active, and a general picture of bone marrow tissue infiltration and the formation of cancellous bone can be observed. In osteomalacia, the bone surface is covered with uncalcified osteoid. This condition is induced by aluminum accumulation or vitamin D deficiency. The mixed type possesses characteristics of both osteitis fibrosa and osteomalacia. The bone turnover is so markedly accelerated that calcification of the osteoid cannot keep pace. In the adynamic bone type, bone resorption and bone formation are both lowered. While bone turnover is decreased, there is little osteoid. The existence of these various types probably accounts for the diversity in degree of renal impairment, serum parathyroid hormone (PTH) level, and serum vitamin D level in patients with ROD. However, all patients share a common factor, i.e., the presence of a uremic condition.

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References

  1. HH Malluche E Ritz HP Lange L Kutschera M Hodgson U Seiffert W Schoeppe (1976) ArticleTitleBone histology in incipient and advanced renal failure Kidney Int 9 355–362 Occurrence Handle1:STN:280:CSmB2c7ks1E%3D Occurrence Handle940274

    CAS  PubMed  Google Scholar 

  2. DJ Sherrard G Hercz Y Pei NA Maloney C Greenwood A Manuel C Saiphoo SS Fenton GV Segre (1993) ArticleTitleThe spectrum of bone disease in end-stage renal failure – an evolving disorder Kidney Int 43 436–442 Occurrence Handle1:STN:280:ByyC1c%2FjvVc%3D Occurrence Handle8441240

    CAS  PubMed  Google Scholar 

  3. R Vanholder RD Smet G Glorieux A Argiles U Baurmeister P Brunet W Clark G Cohen PP De Deyn R Deppisch B Descamps-Latscha T Henle A Jorres HD Lemke ZA Massy J Passlick-Deetjen M Rodriguez B Stegmayr P Stenvinkel C Tetta C Wanner W Zidek InstitutionalAuthorNameEuropean Uremic Toxin Work Group (EUTox) (2003) ArticleTitleReview on uremic toxins: classification, concentration, and interindividual variability Kidney Int 63 1934–1943 Occurrence Handle1:CAS:528:DC%2BD3sXjslygsbk%3D Occurrence Handle12675874

    CAS  PubMed  Google Scholar 

  4. R Vanholder G Glorieux RD Smet N Lameire InstitutionalAuthorNamefor the European Uremic Toxin Work Group (EUTox) (2003) ArticleTitleNew insights into uremic toxins Kidney Int 84 S6–S10 Occurrence Handle1:CAS:528:DC%2BD3sXjslCku78%3D

    CAS  Google Scholar 

  5. DL Andress GA Howard RS Birnbaum (1991) ArticleTitleIdentification of low molecular weight inhibitor of osteoblast mitogenesis in uremic plasma Kidney Int 39 942–945 Occurrence Handle1:STN:280:By6B1Mrkslc%3D Occurrence Handle2067211

    CAS  PubMed  Google Scholar 

  6. S Disthabanchong H Hassan CL McConkey KJ Martin EA Gonzalez (2004) ArticleTitleRegulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106–01 osteoblast-like cells Kidney Int 65 897–903 Occurrence Handle10.1111/j.1523-1755.2004.00472.x Occurrence Handle1:CAS:528:DC%2BD2cXitleksLs%3D Occurrence Handle14871409

    Article  CAS  PubMed  Google Scholar 

  7. SJ Steddon CW Mcintyre NJ Schrieder JM Burrin J Cunningham (2004) ArticleTitleImpaired release of interleukin-6 from human osteoblastic cells in the uraemic milieu Nephrol Dial Transplant 19 3078–3083 Occurrence Handle1:CAS:528:DC%2BD2cXhtVCrsrnF Occurrence Handle15494357

    CAS  PubMed  Google Scholar 

  8. MS Wangner S Stracke PM Jehle F Keller D Zellner DJ Baylink S Mohan (2000) ArticleTitleEvaluation of IGF system component levels and mitogenic activity of uremic serum on normal human osteoblasts Nephron 84 158–166

    Google Scholar 

  9. G Hercz Y Pei C Greenwood A Manuel C Saiphoo WG Goodman GV Segre S Fenton DJ Sherrard (1993) ArticleTitleAplastic osteodystrophy without aluminum: the role of “suppressed” parathyroid function Kidney Int 44 860–866 Occurrence Handle1:STN:280:ByuD1c7msVQ%3D Occurrence Handle8258962

    CAS  PubMed  Google Scholar 

  10. Y Iwasaki-Ishizuka H Yamato T Nii-Kohno K Kurokawa M Fukagawa (2005) ArticleTitleDown-regulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low-turnover bone Nephrol Dial Transplant 20 1904–1911 Occurrence Handle1:CAS:528:DC%2BD2MXovVKqtbs%3D Occurrence Handle15985520

    CAS  PubMed  Google Scholar 

  11. T Niwa N Takeda A Tatematsu K Maeda (1998) ArticleTitleAccumulation of indoxyl sulfate, an inhibitor of drug-binding, in uremic serum as demonstrated by internal-surface reversed-phase liquid chromatography Clin Chem 34 2264–2267

    Google Scholar 

  12. T Niwa T Nomura M Sugano T Kodama Y Uehara K Maeda (1991) ArticleTitleInhibitory effect of oral sorbent on accumulation of albumin-bound indoxyl sulfate in serum of experimental uremic rats Nephron 57 84–88 Occurrence Handle1:CAS:528:DyaK3MXhtFGjtr4%3D Occurrence Handle1904558

    CAS  PubMed  Google Scholar 

  13. T Niwa (2000) Uremic toxicity. Indoxyl sulfate SG Massry RJ Glassock (Eds) Textbook of Nephrology EditionNumber4th edn. Williams and Wilkins, Baltimore Lippincott 1269–1272

    Google Scholar 

  14. T Niwa I Aoyama F Takayama S Tsukushi T Miyazaki A Owada T Shigai (1999) ArticleTitleUrinary indoxyl sulfate is a clinical factor that affects the progression of renal failure Miner Electrolyte Metab 25 118–122 Occurrence Handle10.1159/000057433 Occurrence Handle1:CAS:528:DyaK1MXislOkur0%3D Occurrence Handle10207273

    Article  CAS  PubMed  Google Scholar 

  15. Y Iwasaki-Ishizuka H Yamato T Nii-Kono K Kurokawa M Fukagawa (2003) ArticleTitleSkeletal resistance to PTH is induced by indoxyl sulfate, one of the uremic toxins, leading to adynamic bone J Am Soc Nephrol 14 469

    Google Scholar 

  16. Y Iwasaki H Yamato T Takahashi K Ikeda T Kurosawa K Kurokawa M Fukagawa (2002) ArticleTitleRenal dysfunction causes suppression of bone turnover in the absence of secondary hyperparathyroidism, leading to adynamic bone disease J Am Soc Nephrol 13 578

    Google Scholar 

  17. M Motojima A Hosokawa H Yamato T Muraki T Yoshioka (2002) ArticleTitleUremic toxins proximal tubular injury via organic anion transporter-1-mediated uptake Br J Pharmacol 135 555–563 Occurrence Handle10.1038/sj.bjp.0704482 Occurrence Handle1:CAS:528:DC%2BD38Xht1Krt74%3D Occurrence Handle11815391

    Article  CAS  PubMed  Google Scholar 

  18. A Enomoto M Takeda A Tojo T Sekine SO Cha S Khamdang F Takayama I Aoyama S Nakamura H Endou T Niwa (2002) ArticleTitleRole of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicity J Am Soc Nephrol 13 1711–1720 Occurrence Handle10.1097/01.ASN.0000022017.96399.B2 Occurrence Handle1:CAS:528:DC%2BD38XlvVSqsbk%3D Occurrence Handle12089366

    Article  CAS  PubMed  Google Scholar 

  19. M Motojima A Hosokawa H Yamato T Muraki T Yoshioka (2003) ArticleTitleUremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-kB and free radicals in proximal tubular cells Kidney Int 63 1671–1680 Occurrence Handle10.1046/j.1523-1755.2003.00906.x Occurrence Handle1:CAS:528:DC%2BD3sXjslygs7k%3D Occurrence Handle12675842

    Article  CAS  PubMed  Google Scholar 

  20. T Deguchi H Kusuhara A Takedate H Endou M Otagiri Y Sugiyama (2004) ArticleTitleCharacterization of uremic toxin transport by organic anion transporters in kidney Kidney Int 65 162–174 Occurrence Handle10.1111/j.1523-1755.2004.00354.x Occurrence Handle1:CAS:528:DC%2BD2cXmt1Wjug%3D%3D Occurrence Handle14675047

    Article  CAS  PubMed  Google Scholar 

  21. XC Bai D Lu J Bai H Zheng ZY Ke Li Xm SQ Luo (2004) ArticleTitleOxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappa B Biochem Biophys Res Commun 314 197–207 Occurrence Handle10.1016/j.bbrc.2003.12.073 Occurrence Handle1:CAS:528:DC%2BD2cXjtVeisA%3D%3D Occurrence Handle14715266

    Article  CAS  PubMed  Google Scholar 

  22. N Mody F Parhami TA Sarafian LL Demer (2001) ArticleTitleOxidative stress modulates osteoblastic differentiation of vascular and bone cells Free Radic Biol Med 31 509–519 Occurrence Handle10.1016/S0891-5849(01)00610-4 Occurrence Handle1:CAS:528:DC%2BD3MXlslGnur4%3D Occurrence Handle11498284

    Article  CAS  PubMed  Google Scholar 

  23. H Suzuki M Hayakawa K Kobayashi H Takiguchi Y Abiko (1997) ArticleTitleH2O2-derived free radical-treated fibronectin substratum reduces the bone nodule formation of rat calvarial osteoblasts Mech Ageing Dev 98 113–125 Occurrence Handle10.1016/S0047-6374(97)00077-8 Occurrence Handle1:CAS:528:DyaK2sXmt1Sjt7s%3D Occurrence Handle9379708

    Article  CAS  PubMed  Google Scholar 

  24. JS Sun YH Tsuang WC Huang LT Chen YS Hang FJ Lu (1997) ArticleTitleMenadione-induced cytotoxicity to rat osteoblasts Cell Mol Life Sci 53 967–976 Occurrence Handle10.1007/s000180050118 Occurrence Handle1:CAS:528:DyaK1cXhsVWltw%3D%3D Occurrence Handle9447250

    Article  CAS  PubMed  Google Scholar 

  25. H Yasuda N Shima N Nakagawa S Mochizuki K Yano N Fujise Y Sato M Goto K Yamaguchi M Kuriyama T Kanno A Murakami E Tsuda T Morinaga K Higashio (1998) ArticleTitleIdentification of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin: a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro Endocrinology 139 1329–1337 Occurrence Handle10.1210/en.139.3.1329 Occurrence Handle9492069

    Article  PubMed  Google Scholar 

  26. WS Simonet DL Lacey CR Dunstan M Kelley MS Chang R Luthy HQ Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero HL Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg TM Hughes D Hill W Pattison P Campbell S Sander G Van J Tarpley P Derby R Lee WJ Boyle (1997) ArticleTitleOsteoprotegerin: a novel secreted protein involved in the regulation of bone density Cell 89 309–319 Occurrence Handle10.1016/S0092-8674(00)80209-3 Occurrence Handle1:CAS:528:DyaK2sXislCgtLc%3D Occurrence Handle9108485

    Article  CAS  PubMed  Google Scholar 

  27. H Yasuda N Shima N Nakagawa K Yamaguchi M Kinosaki S Mochizuki A Tomoyasu K Yano M Goto A Murakami E Tsuda T Morinaga K Higashio N Udagawa N Takahashi T Suda (1998) ArticleTitleOsteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis inhibitory factor and is identical to TRANCE/RANKL Proc Natl Acad Sci USA 95 3597–3602 Occurrence Handle10.1073/pnas.95.7.3597 Occurrence Handle1:CAS:528:DyaK1cXitlKjsLY%3D Occurrence Handle9520411

    Article  CAS  PubMed  Google Scholar 

  28. DL Lacey E Timms HL Tan MJ Kelley CR Dunstan T Burgess R Elliott A Colombero G Elliott S Scully H Hsu J Sullivan N Hawkins E Davy C Capparelli A Eli YX Qian S Kaufman I Sarosi V Shalhoub G Senaldi J Guo J Delaney WJ Boyle (1998) ArticleTitleOsteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation Cell 93 165–176 Occurrence Handle10.1016/S0092-8674(00)81569-X Occurrence Handle1:CAS:528:DyaK1cXivVyhtrg%3D Occurrence Handle9568710

    Article  CAS  PubMed  Google Scholar 

  29. JJ Kazama T Shigematsu K Yano E Tsuda M Miura Y Iwasaki Y Kawaguchi F Gejyo K Kurokawa M Fukagawa (2002) ArticleTitleIncreased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure Am J Kidney Dis 39 525–532 Occurrence Handle1:CAS:528:DC%2BD38Xit1eitb8%3D Occurrence Handle11877571

    CAS  PubMed  Google Scholar 

  30. G Coen P Ballanti A Balducci S Calabria F Stephanie L Jankovic M Manni M Moroseti E Moscaritolo D Sardella E Bonucci (2002) ArticleTitleSerum osteoprotegerin and renal osteodystrophy Nephrol Dial Transplant 17 233–238 Occurrence Handle1:CAS:528:DC%2BD38XitVSnsrw%3D Occurrence Handle11812872

    CAS  PubMed  Google Scholar 

  31. M Satoh H Hayashi M Watanabe K Ueda H Yamato T Yohioka M Motojima (2003) ArticleTitleUremic toxins overload accelerates renal damage in a rat model of chronic renal failure Nephron Exp Nephrol 95 e111–118 Occurrence Handle10.1159/000074327 Occurrence Handle1:CAS:528:DC%2BD3sXpsVKrtbk%3D Occurrence Handle14646363

    Article  CAS  PubMed  Google Scholar 

  32. T Niwa T Nomura S Sugiyama T Miyazaki S Tsukushi S Tsutsui (1997) ArticleTitleThe protein metabolite hypothesis: a model for the progression of renal failure. An oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients Kidney Int 52 IssueIDSuppl 62 S23–28

    Google Scholar 

  33. T Niwa M Ise (1994) ArticleTitleIndoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis J Lab Clin Med 124 96–104 Occurrence Handle1:CAS:528:DyaK2cXlslKrs7k%3D Occurrence Handle8035108

    CAS  PubMed  Google Scholar 

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Iwasaki, Y., Yamato, H., Nii-Kono, T. et al. Uremic toxin and bone metabolism. J Bone Miner Metab 24, 172–175 (2006). https://doi.org/10.1007/s00774-005-0667-7

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