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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 4/2015

01-08-2015 | Review Article

Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities

Authors: Takashi Hirukawa, Takatoshi Kakuta, Michio Nakamura, Masafumi Fukagawa

Published in: Clinical and Experimental Nephrology | Issue 4/2015

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Abstract

Given the advances in medical technologies related to kidney transplantation, the post-transplant graft survival rate and quality of life have improved dramatically. Nevertheless, post-transplant mortality rate still remains high as compared to the general population due to the development of cardiovascular events. It has recently been widely recognized that chronic kidney disease-mineral and bone disorders (CKD-MBD) significantly contribute to such poor prognosis at least in part. In the majority of kidney recipients, abnormal serum parameters for mineral and bone disorder (MBD), such as phosphorus, calcium, 1,25-dihydroxyvitamin D, parathyroid hormone and fibroblast growth factor 23, gradually return toward acceptable levels following the re-establishment of kidney function after transplantation; however, some irreversible abnormalities, developed as the result of long-term dialysis, persist, require treatment, or even progress after kidney transplantation. Thus, better management of CKD-MBD during pre-dialysis and dialysis period as well as after kidney transplantation is highly appreciated.
Literature
1.
KDIGO Clinical Practice Guideline for the Diagnosis. Evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2009;76(Suppl. 113):S1–130.
2.
Fukagwa M, Yokoyama K, Koiwa F, et al. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorders. Ther Apher Dial. 2013;17:247–88.CrossRef
3.
Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117:4003–8.PubMedCentralPubMed
4.
Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79:1370–8.PubMedCentralCrossRefPubMed
5.
Ryan ZC, Ketha H, McNulty MS, et al. Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium. Proc Natl Acad Sci USA. 2013;110:6199–204.PubMedCentralCrossRefPubMed
6.
7.
Li X, Warmington KS, Niu QT, et al. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. J Bone Miner Res. 2010;25:2647–56.CrossRefPubMed
8.
Padhi D, Jang G, Stouch B, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26:19–26.CrossRefPubMed
9.
Tominaga Y, Tanaka Y, Sato K, et al. Histopathology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism. Semin Surg Oncol. 1997;13:78–86.CrossRefPubMed
10.
Sprague SM, Belozeroff V, Danese MD, et al. Abnormal bone and mineral metabolism in kidney transplant patients—a review. Am J Nephrol. 2008;28:246–53.CrossRefPubMed
11.
Copley JB, Wuthrich RP. Therapeutic management of post kidney transplant hyperparathyroidism. Clin Transplant. 2011;25:24–39.CrossRefPubMed
12.
Saha HH, Salmela KT, Ahonen PJ, et al. Sequential changes in vitamin D and calcium metabolism after successful renal transplantation. Scand J Urol Nephrol. 1994;28:21–7.CrossRefPubMed
13.
Casez JP, Lippuner K, Horber FF, et al. Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone. Nephrol Dial Transplant. 2002;17:1318–26.CrossRefPubMed
14.
Amanzadeh J, Reilly RF Jr. Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Clin Protect Nephrol. 2006;2:136–48.CrossRef
15.
Torres A, Lorenzo V, Salido E. Calcium metabolism and skeletal problems after transplantation. J Am Soc Nephrol. 2002;13:551–8.PubMed
16.
Bhan I, Shah A, Holmes J, et al. Post-transplant hypophosphatemia: tertiary ‘hyper-phosphatonism’? Kidney Int. 2006;70:1486–96.CrossRefPubMed
17.
Kawarazaki Hiroo, Shibagaki Yugo, Fukumoto Seiji, et al. Natural history of mineral and bone disorders after living-donor kidney transplantation: a one-year prospective observational study. Ther Apher Dial. 2011;15:481–7.CrossRefPubMed
18.
Evenepoel P, Claes K, Kuypers D, et al. Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study. Nephrol Dial Transplant. 2004;19:1281–7.CrossRefPubMed
19.
Cundy T, Kanis JA, Heynen G, et al. Calcium metabolism and hyperparathyroidism after renal transplantation. Q J Med. 1983;52:67.PubMed
20.
Roe SD, Porter CJ, Godber IM, et al. Reduced bone mineral density in male renal transplant recipients: evidence for persisting hyperparathyroidism. Osteoporos Int. 2005;16:142.CrossRefPubMed
21.
Iwasaki Y, Yamato H, Nii-Kono T, et al. Insufficiency of PTH action of bone in uremia. Kidney Int. 2006;70:S34.CrossRef
22.
Evenepoel P, Naesens M, Claes K, et al. Tertiary ‘hyperphosphatoninism’ accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant. 2007;7:1193–2000.CrossRefPubMed
23.
de Sevaux RG, Hoitsma AJ, van Hoof HJ, et al. Abnormal vitamin D metabolism and loss of bone mass after renal transplantation. Nephron Clin Pract. 2003;93:C21–8.CrossRefPubMed
24.
Bagni B, Gilli P, Cavallini A, et al. Continuing loss of vertebral mineral density in renal transplant recipients. Eur J Nucl Med. 1994;21:108–12.CrossRefPubMed
25.
Taniguchi M, Tokumoto M, Matsuo D, et al. Persistent hyperparathyroidism in renal allograft recipients:vitamin D receptor, calcium-sensing receptor, and apoptosis. Kidney Int. 2006;70:363–70.CrossRefPubMed
26.
Komaba H, Koizumi M, Fukagawa M. Parathyroid resistance to FGF23 in kidney transplant recipients: back to the past or ahead to the future? Kidney Int. 2010;78:953–5.CrossRefPubMed
27.
Nakamura M, Tanaka K, Marui Y, et al. Clinicopathological analysis of persistent hypercalcemia and hyperparathyroidism after kidney transplantation in long-term dialysis patients. Ther Apher Dial. 2013;17:551–6.PubMed
28.
Evenepoel P. Recovery versus persistence of disordered mineral metabolism in kidney transplant recipients. Semin Nephrol. 2013;33:191–203.CrossRefPubMed
29.
Takayanagi H, Kim S, Koga T, et al. Induction and activation of the transcription factor NFATc1(NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002;2:889–901.CrossRef
30.
Yeo H, Beck LH, McDonald JM, et al. Cyclosporin a elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. Bone. 2007;40:1502–16.PubMedCentralCrossRefPubMed
31.
Aroldi A, Tarantino A, Montagnino G, et al. Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study. Transplant. 1997;63:380–6.CrossRef
32.
Singha UK, Jiang Y, Yu S, et al. Rapamycin inhibits osteoblast proliferation and differentiation in MC3T3-E1 cells and primary mouse bone marrow stromal cells. J Cell Biochem. 2008;103:434–46.CrossRefPubMed
33.
Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci. 2002;966:73–81.CrossRefPubMed
34.
Kunzendorf U, Kramer BK, Arns W, et al. Bone disease after renal transplantation. Nephrol Dial Transplant. 2008;23:450–8.CrossRefPubMed
35.
Hahn TJ, Halstead LR, Baran DT, et al. Effects off short term glucocorticoid administration on interstitial calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab. 1981;52:111–5.CrossRefPubMed
36.
Nikkel EL, Mohan S, Zhang A, et al. Reduced fracture risk with early corticosteroid withdrawal after kidney transplant. Am J Transplant. 2012;12:649–59.PubMedCentralCrossRefPubMed
37.
Lehman G, Ott U, Stein G, et al. Renal osteodystrophy after successful renal transplantation: a histomorphometric analysis in 57 patients. Transplant Proc. 2007;39:3153–8.CrossRef
38.
Monier-Faugere MC, Mawad H, Qi Q, et al. High prevalence of low bone turnover and occurrence of osteomalacia after kidney transplantation. J Am Soc Nephrol. 2000;11:1093–9.PubMed
39.
Weisinger JR, Carlini RG, Rojas E, et al. Bone disease after renal transplantation. Clin J Am Nephrol. 2006;6:1300–13.CrossRef
40.
Zhang R, Chouhan KK, et al. Metabolic bone diseases in kidney transplant recipients. World J Nephrol. 2012;6:127–33.CrossRef
41.
Brandenburg VM, Politt D, Ketteler M, et al. Early rapid loss followed by long-term consolidation characterizes the development of lumbar bone mineral density after kidney transplantation. Transplant. 2004;77:1566–71.CrossRef
42.
Zisman AL, Sprague SM, et al. Bone disease after kidney transplantation. Adv Chronic Kidney Dis. 2006;13:35–46.CrossRefPubMed
43.
Stenman-Bareen CO, Sherrard DJ, Alem AM, et al. Risk factors for hip fracture among patients with end-stage renal disease. Kidney Int. 2000;58:2200–5.CrossRef
44.
Abbott KC, Oglesby RJ, Hypolite IO, et al. Hospitalizations for fractures after renal transplantation in the United States. Ann Epidemiol. 2001;11:450–7.CrossRefPubMed
45.
Ball AM, Gillen DL, Sherrard D, et al. Risk of hip fracture among dialysis and renal transplant recipients. Jam. 2002;18:3014–8.CrossRef
46.
Malyszko J, Malyszko JS, Pawlak K, et al. Tartrate-resistant acid phosphatase 5b and its correlations with other markers of bone metabolism in kidney transplant recipients and dialyzed patients. Adv Med Sci. 2006;51:69–72.PubMed
47.
Gupta AK, Huang M, Prasad GV. Determinants of bone mineral density in stable kidney transplant recipients. J Nephrol. 2012;25:373–83.CrossRefPubMed
48.
Malyszko J, Wlczynski S, Malyszko JS, et al. Correlations of new markers of bone formation and resorption in kidney transplant recipients. Transplant Proc. 2003;35:1351–4.CrossRefPubMed
49.
Bozkaya G, Nart A, Uslu A, et al. Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients. Transplant Proc. 2008;40:151–5.CrossRefPubMed
50.
Cruz DN, Wysolmerski JJ, Brickel HM, et al. Parameters of high bone-turnover predict bone loss in renal transplant patients: a longitudinal study. Transplant. 2001;15:83–8.CrossRef
51.
Kanaan N, Claes K, Devogelaer JP, et al. Fibroblast growth factor-23 and parathyroid hormone are associated with post-transplant bone mineral density loss. Clin J Am Soc Nephrol. 2010;5:1887–92.PubMedCentralCrossRefPubMed
52.
Cianciolo G, Capelli I, Angelini ML, et al. Importance of vascular calcification in kidney transplant recipients. Am J Nephrol. 2014;39:418–26.CrossRefPubMed
53.
Hernandez D, Rufino M, Bartolomei S, et al. Clinical impact of preexisting vascular calcifications on mortality after renal transplantation. Kidney Int. 2005;67:2015–20.CrossRefPubMed
54.
Nguyen PT, Henrard S, Cohoe E, et al. Coronary artery calcification: a strong predictor of cardiovascular events in renal transplant recipients. Nephrol Dial Transplant. 2010;25:3773–8.CrossRefPubMed
55.
Egbuna O, Taylor J, Buchinsky D, et al. Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure. Clin Transplant. 2007;21:558–66.CrossRefPubMed
56.
Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD. J Am Soc Nephrol. 2013;24:179–89.CrossRefPubMed
57.
Moe SM, O’Neill KD, Resleravasa M, et al. Natural history of vascular calcification in dialysis and transplantation patients. Nephrol Dial Transplant. 2004;19:2387–793.CrossRefPubMed
58.
Mazzaferro S, Pasquali M, Taggi F, et al. Progression of coronary artery calcification in renal transplantation and the role of secondary hyperparathyroidism and inflammation. Clin J Am Soc Nephrol. 2009;4:685–90.PubMedCentralCrossRefPubMed
59.
DeLoach SS, Joffe MM, Mai X, et al. Aortic calcification predicts cardiovascular events and all-cause mortality in renal transplantation. Nephrol Dial Transplant. 2009;24:1314–9.PubMedCentralCrossRefPubMed
60.
Marechal C, Coche E, Goffin E, et al. Progression of coronary artery calcification and thoracic aorta calcification in kidney transplant recipients. Am J Kidney Dis. 2012;59:258–69.CrossRefPubMed
61.
Wolf M, Molnar MZ, Amaral AP, et al. Elevated fibroblast growth factor 23 is risk factor for kidney transplant loss and mortality. J Am Soc Nephrol. 2011;22:956–66.PubMedCentralCrossRefPubMed
62.
63.
Andrukhova O, Slavic S, Smorodchenko A, et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med. 2014;6:744–59.PubMedCentralPubMed
64.
Bellows CG, Reimers SM, Heersche JN, et al. Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1,25 dihydroxyvitamin D3. Cell Tissue Res. 1999;297:249–59.CrossRefPubMed
65.
Cunningham J, Danese M, Olson K, et al. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005;68:1793–800.CrossRefPubMed
66.
Bergua C, Torregrosa JV, Gutierrez-Dalmau A, et al. Effect of cinacalcet on hypercalcemia and bone mineral density in renal transplanted patients with secondary hyperparathyroidism. Transplant. 2008;86:413–7.CrossRef
67.
Fleseriu M, Licata AA. Failure of successful renal transplant to produce appropriate levels of 1,25-dihydroxyvitamin D. Osteoporos Int. 2007;18:363–8.CrossRefPubMed
68.
Torres A, Garcia S, Gonzalez A, et al. Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation. Kidney Int. 2004;65:705–12.CrossRefPubMed
69.
El-Agroudy AE, El-Husseini AA, El-Sayed M, et al. Preventing bone loss in renal transplant recipients with vitamin D. J Am Soc Nephrol. 2003;14:2975–9.CrossRefPubMed
70.
Chadban S, Chan M, Fry K, et al. The CARI guidelines. Nutritional management of hypophosphataemia in adult kidney transplant recipients. Nephrology (Carlton). 2010;15:S48–51.CrossRef
71.
Ambuhl PM, Meier D, Wolf B, et al. Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis. Am J Kidney Dis. 1999;34:875–83.CrossRefPubMed
72.
Riella LV, Rennke HG, Grafals M, et al. Hypophosphatemia in kidney transplant recipients: report of acute phosphate nephropathy as a complication of therapy. Am J Kidney Dis. 2011;57:641–5.CrossRefPubMed
73.
Caravaca F, Fernandez MA, Ruiz-Calero R, et al. Effects of oral phosphorus supplementation on mineral metabolism of renal transplant recipients. Nephrol Dial Transplant. 1998;13:2605–11.CrossRefPubMed
74.
Balal M, Paydas S, Seyrek N, et al. Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients. Clin Nephrol. 2005;63:87–91.CrossRefPubMed
75.
Felsenfeld AJ, Levine BS. Approach to treatment of hypophosphatemia. Am J Kidney Dis. 2012;60:655–61.CrossRefPubMed
76.
Carpenter TO, Imel EA, Ruppe MD, et al. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014;124:1587–97.PubMedCentralCrossRefPubMed
77.
Kruse AE, Eisenberger U, Frey FJ, et al. Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2007;22:2362–5.CrossRefPubMed
78.
Kruse AE, Eisenberger U, Frey FJ, et al. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20:1311–4.CrossRefPubMed
79.
Serra AL, Savoca R, Huber AR, et al. Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Nephrol Dial Transplant. 2007;22:577–83.CrossRefPubMed
80.
Serra AL, Schwarz AA, Wick FH, et al. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20:1315–9.CrossRefPubMed
81.
Srinivas TR, Schold JD, Wormer KL, et al. Improvement in hypercalcemia with cinacalcet after kidney transplantation. Clin J Am Soc Nephrol. 2006;1:323–6.CrossRefPubMed
82.
Leca N, Laftavi M, Gundroo A, et al. Early and severe hyperparathyroidism associated with hypercalcemia after renal transplant treated with cinacalcet. Am J Transplant. 2006;6:2391–5.CrossRefPubMed
83.
Schwarz A, Rustien G, Merkel S, et al. Decreased renal transplant function after parathyroidectomy. Nephrol Dial Transplant. 2007;22:584–91.CrossRefPubMed
84.
Kandil E, Florman S, Alabbas H, et al. Exploring the effect of parathyroidectomy for tertiary hyperparathyroidism after kidney transplantation. Am J Med Sci. 2010;339:420–4.PubMedCentralPubMed
85.
Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Eng J Med. 2003;349:1207–15.CrossRef
86.
Cejka D, Benesch T, Krestan C, et al. Effect of teriparatide on early bone loss after kidney transplantation. Am J Transplant. 2008;8:1864–70.CrossRefPubMed
87.
Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.CrossRefPubMed
Metadata
Title
Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities
Authors
Takashi Hirukawa
Takatoshi Kakuta
Michio Nakamura
Masafumi Fukagawa
Publication date
01-08-2015
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 4/2015
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-015-1117-z

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