Skip to main content
SpringerLink
Log in

Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Hyperphosphatemia is associated with cardiovascular disease in patients with chronic kidney disease. To examine the effects of correction of hyperphosphatemia, we investigated the association between phosphate metabolism and cardiac remodeling in uremic rats.

Methods

Four groups were studied for 8 weeks: (1) control (sham), (2) 5/6 nephrectomized (Nx) rats fed a normal phosphate regular diet (Nx + NP), (3) Nx rats fed a high phosphate (1.2 %) diet (Nx + HP), and (4) Nx rats fed a high phosphate diet containing 2 % lanthanum carbonate (Nx + HP + La). The relationship between phosphate metabolism and cardiac remodeling was analyzed.

Results

Nx + HP rats showed a significant increase in serum phosphate and PTH compared with Nx + NP rats, while Nx + HP + La rats showed slight decreases in these levels. Both Nx + HP and Nx + HP + La rats showed a significant increase in fibroblast growth factor-23 (FGF23) compared with Nx + NP rats. Urinary phosphate excretion showed a similar trend to that of FGF23. Nx + HP rats showed a significant increase in LV weight and matrix deposition compared with Nx + NP rats, and this increase was also significantly suppressed in Nx + HP + La rats. Serum phosphate levels and PTH were significantly correlated with LV weight and matrix deposition, but FGF23 levels did not show the correlation. FGF23 had a high correlation with urinary phosphate excretion.

Conclusions

These results suggest that correction of hyperphosphatemia by lanthanum carbonate could suppress cardiac remodeling independently of changes in FGF23.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15(8):2208–18.

    Article  CAS  PubMed  Google Scholar 

  2. Kestenbaum B, Sampson JN, Rudser KD, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005;16(2):520–8.

    Article  CAS  PubMed  Google Scholar 

  3. Menon V, Greene T, Pereira AA, et al. Relationship of phosphorus and calcium-phosphorus product with mortality in CKD. Am J Kidney Dis. 2005;46(3):455–63.

    Article  CAS  PubMed  Google Scholar 

  4. Voormolen N, Noordzij M, Grootendorst DC, et al. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant. 2007;22(10):2909–16.

    Article  CAS  PubMed  Google Scholar 

  5. Isakova T, Gutierrez OM, Chang Y, et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol. 2009;20(2):388–96.

    Article  CAS  PubMed  Google Scholar 

  6. Galetta F, Cupisti A, Franzoni F, et al. Changes in heart rate variability in chronic uremic patients during ultrafiltration and hemodialysis. Blood Purif. 2001;19(4):395–400.

    Article  CAS  PubMed  Google Scholar 

  7. Strozecki P, Adamowicz A, Nartowicz E, et al. Parathormon, calcium, phosphorus, and left ventricular structure and function in normotensive hemodialysis patients. Ren Fail. 2001;23(1):115–26.

    Article  CAS  PubMed  Google Scholar 

  8. Ayus JC, Mizani MR, Achinger SG, et al. Effects of short daily versus conventional hemodialysis on left ventricular hypertrophy and inflammatory markers: a prospective, controlled study. J Am Soc Nephrol. 2005;16(9):2778–88.

    Article  CAS  PubMed  Google Scholar 

  9. Culleton BF, Walsh M, Klarenbach SW, et al. Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial. JAMA. 2007;298(11):1291–9.

    Article  CAS  PubMed  Google Scholar 

  10. Amann K, Tornig J, Kugel B, et al. Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia. Kidney Int. 2003;63(4):1296–301.

    Article  PubMed  Google Scholar 

  11. Neves KR, Graciolli FG, dos Reis LM, et al. Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure. Kidney Int. 2004;66(6):2237–44.

    Article  CAS  PubMed  Google Scholar 

  12. Hutchison AJ. Oral phosphate binders. Kidney Int. 2009;75(9):906–14.

    Article  CAS  PubMed  Google Scholar 

  13. Neven E, Dams G, Postnov A, et al. Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats. Nephrol Dial Transplant. 2009;24(6):1790–9.

    Article  CAS  PubMed  Google Scholar 

  14. Toussaint ND, Lau KK, Polkinghorne KR, et al. Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis: a pilot randomized controlled trial. Nephrology (Carlton). 2011;16(3):290–8.

    Article  CAS  Google Scholar 

  15. Shigematsu T, Kazama JJ, Yamashita T, et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44(2):250–6.

    Article  CAS  PubMed  Google Scholar 

  16. Gutierrez OM, Januzzi JL, Isakova T, et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009;119(19):2545–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Hsu HJ, Wu MS. Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci. 2009;337(2):116–22.

    Article  PubMed  Google Scholar 

  18. Mirza MA, Hansen T, Johansson L, et al. Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant. 2009;24(10):3125–31.

    Article  CAS  PubMed  Google Scholar 

  19. Yilmaz MI, Sonmez A, Saglam M, et al. FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int. 2010;78(7):679–85.

    Article  CAS  PubMed  Google Scholar 

  20. Middleton RJ, Parfrey PS, Foley RN. Left ventricular hypertrophy in the renal patient. J Am Soc Nephrol. 2001;12(5):1079–84.

    CAS  PubMed  Google Scholar 

  21. Henry RM, Kostense PJ, Bos G, et al. Mild renal insufficiency is associated with increased cardiovascular mortality: the Hoorn study. Kidney Int. 2002;62(4):1402–7.

    Article  PubMed  Google Scholar 

  22. Gross ML, Ritz E. Hypertrophy and fibrosis in the cardiomyopathy of uremia—beyond coronary heart disease. Semin Dial. 2008;21(4):308–18.

    Article  PubMed  Google Scholar 

  23. Harnett JD, Parfrey PS. Cardiac disease in uremia. Semin Nephrol. 1994;14(3):245–52.

    CAS  PubMed  Google Scholar 

  24. London GM, Parfrey PS. Cardiac disease in chronic uremia: pathogenesis. Adv Ren Replace Ther. 1997;4(3):194–211.

    CAS  PubMed  Google Scholar 

  25. Himmelfarb J, McMenamin E, McMonagle E. Plasma aminothiol oxidation in chronic hemodialysis patients. Kidney Int. 2002;61(2):705–16.

    Article  CAS  PubMed  Google Scholar 

  26. Hostetter TH, Olson JL, Rennke HG, et al. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241(1):F85–93.

    CAS  PubMed  Google Scholar 

  27. Fliser D, Kollerits B, Neyer U, et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007;18(9):2600–8.

    Article  CAS  PubMed  Google Scholar 

  28. Gutierrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359(6):584–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393–408.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Bernheim J, Benchetrit S. The potential roles of FGF23 and Klotho in the prognosis of renal and cardiovascular diseases. Nephrol Dial Transplant. 2011;26(8):2433–8.

    Article  CAS  PubMed  Google Scholar 

  31. Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004;113(4):561–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Wolf M. Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens. 2009;18(6):463–8.

    Article  CAS  PubMed  Google Scholar 

  33. Scialla JJ, Lau WL, Reilly MP, et al. Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int. 2013. doi:10.1038/ki.2013.3.

Download references

Acknowledgments

Lanthanum carbonate was kindly provided by Bayer Health Care, Osaka, Japan.

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Ai Yamazaki-Nakazawa, Masahide Mizobuchi, Chiaki Kumata, Fumiko Kondo, Naoko Ono & Tadao Akizawa

  2. Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan

    Hiroaki Ogata & Eriko Kinugasa

  3. Division of Nephrology, Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan

    Fumihiko Koiwa

  4. Division of Nephrology, Kanto Rosai Hospital, Kawasaki, Japan

    Susumu Uda

Authors
  1. Ai Yamazaki-Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahide Mizobuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroaki Ogata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chiaki Kumata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fumiko Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naoko Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fumihiko Koiwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susumu Uda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eriko Kinugasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tadao Akizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahide Mizobuchi.

About this article

Cite this article

Yamazaki-Nakazawa, A., Mizobuchi, M., Ogata, H. et al. Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats. Clin Exp Nephrol 18, 56–64 (2014). https://doi.org/10.1007/s10157-013-0816-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-013-0816-6

Keywords

Search

Navigation