Osteoporosis International

, Volume 18, Issue 3, pp 363–368 | Cite as

Failure of successful renal transplant to produce appropriate levels of 1,25-dihydroxyvitamin D

Original Article
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Abstract

Introduction

Bone metabolism disturbances following renal transplantation (RT) are complex and multifactorial in origin. Abnormalities in 1,25-dihydroxyvitamin D levels in RT patients under treatment at our Bone Center prompted this retrospective study.

Methods

Parameters of vitamin D metabolism were compared in RT patients and a cohort of patients with primary hyperparathyroidism (PHTP) who mimicked the hyperparathyroid state of the RT patients. Thirty-one RT recipients (from 300 reviewed) matched our inclusion criteria with a stable graft function for more than 1 year and a glomerular filtration rate (GFR) >50 mL/min per 1.73 m2 (Group A); these were compared with 42 consecutive patients with PHTP who had been referred to the same Bone Center for treatment for over 1 month (Group B). Statistical analysis included the chi-square or Fisher’s exact tests for categorical data and the Wilcoxon rank sum test for quantitative measures.

Results

The mean (±SD) 1,25-dihydroxyvitamin D level was significantly lower (p < 0.001) in Group A patients (29.8 ± 16.2) than in Group B patients (70.2 ± 25.9) despite non-significant differences in the levels of parathyroid hormone (PTH) (mean: 184.0 vs.101.1;p < 0.29), phosphorus (mean: 3.2 vs. 3.1; p < 0.3) and 1,25-vitamin D (mean: 19.5 vs. 25.2; p < 0.06). Group A patients had lower levels (p < 0.05) of mean serum calcium and calculated GFR (9.3 mg/dL, 65.7 mL/min) than Group B patients (10.6 mg/dL, 97.6 mL/min). 1,25-Dihydroxyvitamin D significantly correlated with calcium (p < 0.001), 25-vitamin D (p < 0.005) and GFR (p < 0.001) in both groups, but there was a notable lack of association between 1,25-dihydroxyvitamin D and PTH (p < 0.64) or phosphorus (p < 0.26) in Group A patients. In this group, 1,25-dihydroxyvitamin D was not influenced by the type of immunosuppresion regimen (p < 0.06), use of biphosphonates (p < 0.73), presence of diabetes (p < 0.59), menopause in women (p < 0.08), season (p < 0.43) or race (p < 0.31). Our data indicate that 1,25-dihydroxyvitamin D metabolism remains disturbed for a considerable time after successful RT, with the result that the level of 1,25-dihydroxyvitamin D in RT patients is lower despite physiological signals that should stimulate its production. Our analysis of many clinical variables was unable to elucidate the underlying mechanism(s) for this disturbance.

Conclusion

Successful RT may not produce appropriate levels of 1,25-dihydroxyvitamin D commensurate to the elevated levels of PTH. This abnormality along with sustained hyperparathyroidism may contribute to bone loss following transplantation.

Keywords

1,25 dihydroxyvitamin D Hyperparathyroidism Physiology Renal osteodystrophy Renal transplant 
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References

  1. 1.
    Siddiqi N, McBride M, Hariharan S (2004) Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis. Kidney Int 65(5):1906–1913PubMedCrossRefGoogle Scholar
  2. 2.
    Lobo R, Cortez MS, Stevenson WC, Pruett TL (1995) Normocalcemic hyperparathyroidism associated with relatively low 1:25 vitamin D levels post-renal transplant can be successfully treated with oral calcitriol. Clin Transplant 9(4):277–281Google Scholar
  3. 3.
    Rubello D et al (2005) Secondary hyperparathyroidism is associated with vitamin D receptor polymorphism and bone density after renal transplantation. Biomed Pharmacother 59(7):402–407PubMedCrossRefGoogle Scholar
  4. 4.
    Messa P et al (1998) Persistent secondary hyperparathyroidism after renal transplantation. Kidney Int 54(5):1704–1713PubMedCrossRefGoogle Scholar
  5. 5.
    Mikuls T et al (2003) Bone mineral density changes within six months of renal transplantation. Transplantation 75(1):49–54PubMedCrossRefGoogle Scholar
  6. 6.
    de Sevaux R et al (2003) Abnormal vitamin D metabolism and loss of bone mass after renal transplantation. Nephron Physiol 93(1):C21–C28CrossRefGoogle Scholar
  7. 7.
    Kim H et al (1998) Bone mineral density after renal transplantation. Transplant Proc 30(7):3029–3030PubMedCrossRefGoogle Scholar
  8. 8.
    Abdallah K et al (2006) Improvement of adynamic bone disease after renal transplantation. Braz J Med Biol Res 39(1):31–41PubMedCrossRefGoogle Scholar
  9. 9.
    Julian et al (1991) Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 325(8):544–550PubMedCrossRefGoogle Scholar
  10. 10.
    Levey A et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470PubMedGoogle Scholar
  11. 11.
    Brandenburg V, Westenfeld R, Ketteler M (2004) The fate of bone after renal transplantation. J Nephrol 17(2):190–204PubMedGoogle Scholar
  12. 12.
    Silver J, Levi R (2005) Regulation of PTH synthesis and secretion relevant to the management of secondary hyperparathyroidism in chronic kidney disease. Kidney Int Suppl 95:S8–S12PubMedCrossRefGoogle Scholar
  13. 13.
    Levi R, Silver J (2005) Pathogenesis of parathyroid dysfunction in end-stage kidney disease. Pediatr Nephrol 20(3):342–345PubMedCrossRefGoogle Scholar
  14. 14.
    Gutierrez O et al (2005) Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16(7):2205–2215PubMedCrossRefGoogle Scholar
  15. 15.
    Reichel H et al (2003) Influence of PTH assay methodology on differential diagnosis of renal bone disease. Nephrol Dial Transplant 18(4):759–768PubMedCrossRefGoogle Scholar
  16. 16.
    Bonnin M et al (1990) 1,25-Dihydroxycholecalciferol as measured by a radioreceptor assay in normal subjects and patients after kidney transplantation. Clin Chem 36(2):389–390PubMedGoogle Scholar
  17. 17.
    Bonnin M et al (1992) Serum calcitriol concentrations in the early follow-up after renal transplantation. Transplant Proc 24(1):103–104PubMedGoogle Scholar
  18. 18.
    Querings K et al (2006) 25-hydroxyvitamin D deficiency in renal transplant recipients. J Clin Endocrinol Metab 91(2):526–529PubMedCrossRefGoogle Scholar
  19. 19.
    Reinhardt W et al (1998) Sequential changes of biochemical bone parameters after kidney transplantation. Nephrol Dial Transplant 13(2):436–442PubMedCrossRefGoogle Scholar
  20. 20.
    Riancho J et al (1988) Serum levels of 1,25-dihydroxyvitamin D after renal transplantation. Miner Electrolyte Metab 14(6):332–337PubMedGoogle Scholar
  21. 21.
    Stein B et al (1991) Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse. Endocrinology 128(3):1369–1373PubMedGoogle Scholar
  22. 22.
    Henry H (1981) 25(OH)D3 metabolism in kidney cell cultures: lack of a direct effect of estradiol. Am J Physiol 240(2):E119–E124PubMedGoogle Scholar
  23. 23.
    Gallagher J, B Riggs, DeLuca H (1980) Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab 51(6):1359–1364PubMedCrossRefGoogle Scholar
  24. 24.
    Heaf J et al (2003) Hyperparathyroidism and long-term bone loss after renal transplantation. Clin Transplant 17(3):268–274PubMedCrossRefGoogle Scholar
  25. 25.
    Palmer S, McGregor D, Strippoli G (2005) Interventions for preventing bone disease in kidney transplant recipients. Cochrane Database Syst Rev 2:CD005015PubMedGoogle Scholar
  26. 26.
    Stempfle H et al (1999) Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol. Transplantation (Baltimore) 68(4):523–530Google Scholar
  27. 27.
    Torres A et al (2004) Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation. Kidney Int 65(2):705–712PubMedCrossRefGoogle Scholar
  28. 28.
    Wissing K et al (2005) A controlled study of vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids. Transplantation (Baltimore) 79(1):108–115Google Scholar
  29. 29.
    Al-Gabri S et al (2005) Changes in bone mineral density and selected metabolic parameters over 24 months following renal transplantation. Transplant Proc 37(2):1014–1019PubMedCrossRefGoogle Scholar
  30. 30.
    Carling T et al (1997) Vitamin D receptor polymorphisms correlate to parathyroid cell function in primary hyperparathyroidism. J Clin Endocrinol Metab 82(6):1772–1775PubMedCrossRefGoogle Scholar
  31. 31.
    Giannini S et al (2002) The effects of vitamin D receptor polymorphism on secondary hyperparathyroidism and bone density after renal transplantation. J Bone Miner Res 17(10):1768–1773PubMedCrossRefGoogle Scholar
  32. 32.
    Toro J, Gentil MA, Garcia R, Perez-Valdivia MA et al (2005) Alendronate in kidney transplant patients: a single-center experience. Transplant Proc 37(3):1471–1472Google Scholar
  33. 33.
    Falkiewicz K, BidziDska B, Demissie M, BoratyDska M, Zmonarski SC, Tworowska K et al (2005) Influence of vitamin D receptor gene polymorphisms on secondary hyperparathyroidism and bone density after kidney transplantation. Transplant Proc 37(2):1023–1025Google Scholar
  34. 34.
    Bover J, Bosch R (1999) Vitamin D receptor polymorphisms as a determinant of bone mass and PTH secretion: from facts to controversies. Nephrol Dial Transplant 14(5):1066–1068PubMedCrossRefGoogle Scholar
  35. 35.
    Hullett D, Laeseke PF, Malin G, Nessel R et al (2005) Prevention of chronic allograft nephropathy with vitamin D. Transpl Int 18(10):1175–1186Google Scholar
  36. 36.
    Sezer S, Uyar M, Arat Z, Ozdemir FN et al (2005) Potential effects of 1,25-dihydroxyvitamin D3 in renal transplant recipients. Transplant Proc 37(7):3109–3111Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  1. 1.Department of Endocrinology, Diabetes and MetabolismCleveland ClinicClevelandUSA

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