Laboratory Abnormalities in CKD-MBD: Markers, Predictors, or Mediators of Disease?

Seminars in Nephrology

Volumn 34, Issue 2, 2014, Pages 151-163

  Evenepoel, Pieter ^a   Rodriguez, Mariano ^b   Ketteler, Markus ^c  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b HOSPITAL UNIVERSITARIO REINA SOFÍA   (Spain)

^c KLINIKUM COBURG   (Germany)

Author keywords

Calcium; FGF23; Hyperphosphatemia; Klotho; PTH; Uremic toxins; Vitamin D

Indexed keywords

AMG 641; CALCIMIMETIC AGENT; CALCITRIOL; CALCIUM; CALCIUM ACETATE; CINACALCET; COLECALCIFEROL; DOXERCALCIFEROL; ERGOCALCIFEROL; FIBROBLAST GROWTH FACTOR 23; KLOTHO PROTEIN; LANTHANUM CARBONATE; PARATHYROID HORMONE; PARICALCITOL; PHOSPHATE; PHOSPHATE BINDING AGENT; PLACEBO; SEVELAMER CARBONATE; UNCLASSIFIED DRUG; UREMIC TOXIN; VITAMIN D; VITAMIN D DERIVATIVE; BIOLOGICAL MARKER; FIBROBLAST GROWTH FACTOR; TOXIN;

ABSENCE OF SIDE EFFECTS; ALBUMINURIA; BLOOD VESSEL CALCIFICATION; BONE DISEASE; CALCIUM BALANCE; CARDIOVASCULAR DISEASE; CHRONIC KIDNEY DISEASE; CHRONIC KIDNEY DISEASE MINERAL AND BONE DISORDER; DIET RESTRICTION; DISEASE COURSE; DISEASE MARKER; DISEASE SEVERITY; DOSE RESPONSE; DRUG EFFECT; DRUG MEGADOSE; DRUG TARGETING; HEART LEFT VENTRICLE HYPERTROPHY; HORMONE RESISTANCE; HUMAN; HYPERPHOSPHATEMIA; KIDNEY CALCIFICATION; LOW DRUG DOSE; MINERAL METABOLISM; NONHUMAN; PHOSPHATE BALANCE; PREDICTION; PRIORITY JOURNAL; RENAL REPLACEMENT THERAPY; REVIEW; SECONDARY HYPERPARATHYROIDISM; VITAMIN D DEFICIENCY; VITAMIN SUPPLEMENTATION; BLOOD; BONE DISEASES, METABOLIC; COMPLICATION; PHYSIOLOGY; RENAL INSUFFICIENCY, CHRONIC; UREMIA;

BIOLOGICAL MARKERS; BONE DISEASES, METABOLIC; CALCIUM; FIBROBLAST GROWTH FACTORS; HUMANS; PARATHYROID HORMONE; PHOSPHATES; RENAL INSUFFICIENCY, CHRONIC; TOXINS, BIOLOGICAL; UREMIA; VITAMIN D;

EID: 84899062133     PISSN: 02709295     EISSN: 15584488     Source Type: Journal    
DOI: 10.1016/j.semnephrol.2014.02.007     Document Type: Review

References (139)

1. Renkema K.Y., Alexander R.T., Bindels R.J., Hoenderop J.G. Calcium and phosphate homeostasis: concerted interplay of new regulators. Ann Med 2008, 40:82-91.
2. Isakova T., Wahl P., Vargas G.S., Gutierrez O.M., Scialla J., Xie H., et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011, 79:1370-1378.
3. Evenepoel P., Meijers B., Viaene L., Bammens B., Claes K., Kuypers D., et al. Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. Clin J Am Soc Nephrol 2010, 5:1268-1276.
4. Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 2012, 82:737-747.
5. Silver J., Rodriguez M., Slatopolsky E. FGF23 and PTH--double agents at the heart of CKD. Nephrol Dial Transplant 2012, 27:1715-1720.
6. Pavik I., Jaeger P., Ebner L., Wagner C.A., Petzold K., Spichtig D., et al. Secreted Klotho and FGF23 in chronic kidney disease stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant 2013, 28:352-359.
7. Slatopolsky E., Caglar S., Gradowska L., Canterbury J., Reiss E., Bricker N.S. On the prevention of secondary hyperparathyroidism in experimental chronic renal disease using "proportional reduction" of dietary phosphorus intake. Kidney Int 1972, 2:147-151.
8. Moe S., Drueke T., Cunningham J., Goodman W., Martin K., Olgaard K., et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006, 69:1945-1953.
9. Hamdy N.A., Kanis J.A., Beneton M.N., Juttmann J.R., Jordans J.G., Josse S., et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. Br Med J. 1995, 310:358-363.
10. Coen G., Ballanti P., Bonucci E., Calabria S., Costantini S., Ferrannini M., et al. Renal osteodystrophy in predialysis and hemodialysis patients: comparison of histologic patterns and diagnostic predictivity of intact PTH. Nephron 2002, 91:103-111.
11. Malluche H.H., Mawad H.W., Monier-Faugere M.C. Renal osteodystrophy in the first decade of the new millennium: analysis of 630 bone biopsies in black and white patients. J Bone Miner Res 2011, 26:1368-1376.
12. Malluche H.H., Mawad H., Monier-Faugere M.C. The importance of bone health in end-stage renal disease: out of the frying pan, into the fire?. Nephrol Dial Transplant 2004, 19(Suppl 1):i9-13.
13. Budoff M.J., Rader D.J., Reilly M.P., Mohler E.R., Lash J., Yang W., et al. Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) study. Am J Kidney Dis 2011, 58:519-526.
14. Toussaint N.D., Lau K.K., Strauss B.J., Polkinghorne K.R., Kerr P.G. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 2008, 23:586-593.
15. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009, 113:S1-130. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group.
16. Hill K.M., Martin B.R., Wastney M.E., McCabe G.P., Moe S.M., Weaver C.M., et al. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 2013, 83:959-966.
17. Evenepoel P., Wolf M. A balanced view of calcium and phosphate homeostasis in chronic kidney disease. Kidney Int 2013, 83:789-791.
18. Block G., Hulbert-Shearon T., Levin N.W., Port F. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998, 31:607-617.
19. Block G.A., Klassen P.S., Lazarus J.M., Ofsthun N., Lowrie E.G., Chertow G.M. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004, 15:2208-2218.
20. Kalantar-Zadeh K., Kuwae N., Regidor D.L., Kovesdy C.P., Kilpatrick R.D., Shinaberger C.S., et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 2006, 70:771-780.
21. Jono S., McKee M.D., Murry C.E., Shioi A., Nishizawa Y., Mori K., et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000, 87:10e-117.
22. Giachelli C.M. The emerging role of phosphate in vascular calcification. Kidney Int 2009, 75:890-897.
23. Villa-Bellosta R., Sorribas V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler Thromb Vasc Biol 2009, 29:761-766.
24. Zhao M.M., Xu M.J., Cai Y., Zhao G., Guan Y., Kong W., et al. Mitochondrial reactive oxygen species promote p65 nuclear translocation mediating high-phosphate-induced vascular calcification in vitro and in vivo. Kidney Int 2011, 79:1071-1079.
25. Reynolds J.L., Joannides A.J., Skepper J.N., McNair R., Schurgers L.J., Proudfoot D., et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 2004, 15:2857-2867.
26. Ewence A.E., Bootman M., Roderick H.L., Skepper J.N., McCarthy G., Epple M., et al. Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 2008, 103:e28-e34.
27. Sage A.P., Lu J., Tintut Y., Demer L.L. Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int 2011, 79:414-422.
28. Lau W.L., Pai A., Moe S.M., Giachelli C.M. Direct effects of phosphate on vascular cell function. Adv Chronic Kidney Dis 2011, 18:105-112.
29. Di Marco G.S., Konig M., Stock C., Wiesinger A., Hillebrand U., Reiermann S., et al. High phosphate directly affects endothelial function by downregulating annexin II. Kidney Int 2013, 83:213-222.
30. Kuro O. Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol 2013, 9:650-660.
31. Zoccali C., Ruggenenti P., Perna A., Leonardis D., Tripepi R., Tripepi G., et al. Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition. J Am Soc Nephrol 2011, 22:1923-1930.
32. Bellasi A., Mandreoli M., Baldrati L., Corradini M., Di N.P., Malmusi G., et al. Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 2011, 6:883-891.
33. Chue C.D., Edwards N.C., Davis L.J., Steeds R.P., Townend J.N., Ferro C.J. Serum phosphate but not pulse wave velocity predicts decline in renal function in patients with early chronic kidney disease. Nephrol Dial Transplant 2011, 26:2576-2582.
34. Scialla J.J., Astor B.C., Isakova T., Xie H., Appel L.J., Wolf M. Mineral metabolites and CKD progression in African Americans. J Am Soc Nephrol 2013, 24:125-135.
35. Lezaic V., Tirmenstajn-Jankovic B., Bukvic D., Vujisic B., Perovic M., Novakovic N., et al. Efficacy of hyperphosphatemia control in the progression of chronic renal failure and the prevalence of cardiovascular calcification. Clin Nephrol 2009, 71:21-29.
36. Schwarz S., Trivedi B.K., Kalantar-Zadeh K., Kovesdy C.P. Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 2006, 1:825-831.
37. Fliser D., Kollerits B., Neyer U., Ankerst D.P., Lhotta K., Lingenhel A., 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, 18:2601-2608.
38. Lau K. Phosphate excess and progressive renal failure: the precipitation-calcification hypothesis. Kidney Int 1989, 36:918-937.
39. Sayer J.A., Carr G., Simmons N.L. Nephrocalcinosis: molecular insights into calcium precipitation within the kidney. Clin Sci 2004, 106:549-561.
40. Brown S.A., Crowell W.A., Barsanti J.A., White J.V., Finco D.R. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. J Am Soc Nephrol 1991, 1:1169-1179.
41. Lumlertgul D., Burke T.J., Gillum D.M., Alfrey A.C., Harris D.C., Hammond W.S., et al. Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Kidney Int 1986, 29:658-666.
42. Cozzolino M., Dusso A.S., Liapis H., Finch J., Lu Y., Burke S.K., et al. The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats. J Am Soc Nephrol 2002, 13:2299-2308.
43. Cozzolino M., Staniforth M.E., Liapis H., Finch J., Burke S.K., Dusso A.S., et al. Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia. Kidney Int 2003, 64:1653-1661.
44. Haut L.L., Alfrey A.C., Guggenheim S., Buddington B., Schrier N. Renal toxicity of phosphate in rats. Kidney Int 1980, 17:722-731.
45. Kalantar-Zadeh K., Gutekunst L., Mehrotra R., Kovesdy C.P., Bross R., Shinaberger C.S., et al. Understanding sources of dietary phosphorus in the treatment of patients with chronic kidney disease. Clin J Am Soc Nephrol 2010, 5:519-530.
46. Uribarri J. Phosphorus additives in food and their effect in dialysis patients. Clin J Am Soc Nephrol 2009, 4:1290-1292.
47. Sullivan C., Sayre S.S., Leon J.B., Machekano R., Love T.E., Porter D., et al. Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial. JAMA 2009, 301:629-635.
48. Tonelli M., Pannu N., Manns B. Oral phosphate binders in patients with kidney failure. N Engl J Med 2010, 362:1312-1324.
49. Isakova T., Gutierrez O.M., Chang Y., Shah A., Tamez H., Smith K., et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 2009, 20:388-396.
50. Block G.A., Wheeler D.C., Persky M.S., Kestenbaum B., Ketteler M., Spiegel D.M., et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 2012, 23:1407-1415.
51. Seifert M.E., de Las F.L., Rothstein M., Dietzen D.J., Bierhals A.J., Cheng S.C., et al. Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease. Am J Nephrol 2013, 38:158-167.
52. Houillier P., Froissart M., Maruani G., Blanchard A. What serum calcium can tell us and what it can't. Nephrol Dial Transplant 2006, 21:29-32.
53. Spiegel D.M., Brady K. Calcium balance in normal individuals and in patients with chronic kidney disease on low- and high-calcium diets. Kidney Int 2012, 81:1116-1122.
54. Evenepoel P., Viaene L., Meijers B. Calcium balance in chronic kidney disease: walking the tightrope. Kidney Int 2012, 81:1057-1059.
55. Floege J., Kim J., Ireland E., Chazot C., Drueke T., de Francisco A., et al. Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol Dial Transplant 2011, 26:1948-1955.
56. Goodman W.G., Goldin J., Kuizon B.D., Yoon C., Gales B., Sider D., et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000, 342:1478-1483.
57. Shroff R.C., McNair R., Skepper J.N., Figg N., Schurgers L.J., Deanfield J., et al. Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol 2010, 21:103-112.
58. Jamal S.A., Vandermeer B., Raggi P., Mendelssohn D.C., Chatterley T., Dorgan M., et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet 2013, 382:1268-1277.
59. Cannata-Andia J.B., Fernandez-Martin J.L., Locatelli F., London G., Gorriz J.L., Floege J., et al. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int 2013, 84:998-1008.
60. Koh N., Fujimori T., Nishiguchi S., Tamori A., Shiomi S., Nakatani T., et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 2001, 280:1015-1020.
61. Hu M.C., Shi M., Zhang J., Quiñones H., Griffith C., Kuro-o M., et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 2011, 22:124-136.
62. Komaba H., Goto S., Fujii H., Hamada Y., Kobayashi A., Shibuya K., et al. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int 2010, 77:232-238.
63. Kuro-o M. Klotho in health and disease. Curr Opin Nephrol Hypertens 2012, 21:362-368.
64. Shimizu H., Bolati D., Adijiang A., Adelibieke Y., Muteliefu G., Enomoto A., et al. Indoxyl sulfate downregulates renal expression of Klotho through production of ROS and activation of nuclear factor-kB. Am J Nephrol 2011, 33:319-324.
65. Sun C.Y., Chang S.C., Wu M.S. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int 2012, 81:640-650.
66. Sirich T.L., Meyer T.W., Gondouin G., Brunet P., Niwa T. Protein-bound molecules: a large family with a bad character. Semin Nephrol 2014, 34:106-117.
67. Goetz R., Nakada Y., Hu M.C., Kurosu H., Wang L., Nakatani T., et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A 2010, 107:407-412.
68. Smith E.R., Cai M.M., McMahon L.P., Holt S.G. Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab 2012, 97:3357-3365.
69. Shimada T., Urakawa I., Isakova T., Yamazaki Y., Epstein M., Wesseling-Perry K., et al. Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab 2010, 95:578-585.
70. Wolf M., Molnar M.Z., Amaral A.P., Czira M.E., Rudas A., Ujszaszi A., et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 2011, 22:956-966.
71. Isakova T., Xie H., Yang W., Xie D., Anderson A.H., Scialla J., et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011, 305:2432-2439.
72. Gutierrez O.M., Mannstadt M., Isakova T., Rauh-Hain J.A., Tamez H., Shah A., et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008, 359:584-592.
73. Jean G., Terrat J.C., Vanel T., Hurot J.M., Lorriaux C., Mayor B., et al. High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant 2009, 24:2792-2796.
74. Parker B.D., Schurgers L.J., Brandenburg V.M., Christenson R.H., Vermeer C., Ketteler M., et al. The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 2010, 152:640-648.
75. Lim K., Lu T.S., Molostvov G., Lee C., Lam F., Zehnder D., et al. Vascular klotho deficiency potentiates the development of human artery calcification and mediates resistance to FGF-23. Circulation 2012, 125:2243-2255.
76. Semba R.D., Cappola A.R., Sun K., Bandinelli S., Dalal M., Crasto C., et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci 2011, 66:794-800.
77. Seiler S., Wen M., Roth H.J., Fehrenz M., Flugge F., Herath E., et al. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney Int 2013, 83:121-128.
78. Gutierrez O.M., Januzzi J.L., Isakova T., Laliberte K., Smith K., Collerone G., et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009, 119:2545-2552.
79. Faul C., Amaral A.P., Oskouei B., Hu M.C., Sloan A., Isakova T., et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011, 121:4393-4408.
80. Seiler S., Cremers B., Rebling N.M., Hornof F., Jeken J., Kersting S., et al. The phosphatonin fibroblast growth factor 23 links calcium-phosphate metabolism with left-ventricular dysfunction and atrial fibrillation. Eur Heart J 2011, 32:2688-2696.
81. Shalhoub V., Shatzen E.M., Ward S.C., Davis J., Stevens J., Bi V., et al. FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. J Clin Invest 2012, 122:2543-2553.
82. Santamaria R., Almaden Y., Felsenfeld A., Martin-Malo A., Gao P., Cantor T., et al. Dynamics of PTH secretion in hemodialysis patients as determined by the intact and whole PTH assays. Kidney Int 2003, 64:1867-1873.
83. D'Amour P., Lazure C. Metabolism of radioiodinated carboxy-terminal fragments of bovine parathyroid hormone in normal and anephric rats. Endocrinology 1985, 117:127-134.
84. Mannstadt M., Juppner H., Gardella T.J. Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol 1999, 277:F665-F675.
85. Berdud I., Martin-Malo A., Almaden Y., Tallon S., Concepcion M.T., Torres A., et al. Abnormal calcaemic response to PTH in the uraemic rat without secondary hyperparathyroidism. Nephrol Dial Transplant 1996, 11:1292-1298.
86. Wesseling-Perry K., Harkins G.C., Wang H.J., Elashoff R., Gales B., Horwitz M.J., et al. The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). J Clin Endocrinol Metab 2010, 95:2772-2780.
87. Massry S.G., Coburn J.W., Lee D.B., Jowsey J., Kleeman C.R. Skeletal resistance to parathyroid hormone in renal failure. Studies in 105 human subjects. Ann Intern Med 1973, 78:357-364.
88. Iwasaki Y., Yamato H., Nii-Kono T., Fujieda A., Uchida M., Hosokawa A., et al. Insufficiency of PTH action on bone in uremia. Kidney Int Suppl 2006, 102:S34-S36.
89. Urena P., Mannstadt M., Hruby M., Ferreira A., Schmitt F., Silve C., et al. Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats. Kidney Int 1995, 47:1797-1805.
90. Picton M.L., Moore P.R., Mawer E.B., Houghton D., Freemont A.J., Hutchison A.J., et al. Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure. Kidney Int 2000, 58:1440-1449.
91. Iwasaki-Ishizuka Y., Yamato H., Nii-Kono T., Kurokawa K., Fukagawa M. Downregulation 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 2005, 20:1904-1911.
92. Langub M.C., Monier-Faugere M.C., Qi Q., Geng Z., Koszewski N.J., Malluche H.H. Parathyroid hormone/parathyroid hormone-related peptide type 1 receptor in human bone. J Bone Miner Res 2001, 16:448-456.
93. Disthabanchong S., Hassan H., McConkey C.L., Martin K.J., Gonzalez E.A. Regulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106-01 osteoblast-like cells. Kidney Int 2004, 65:897-903.
94. Nii-Kono T., Iwasaki Y., Uchida M., Fujieda A., Hosokawa A., Motojima M., et al. Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. Kidney Int 2007, 71:738-743.
95. Sneddon W.B., Magyar C.E., Willick G.E., Syme C.A., Galbiati F., Bisello A., et al. Ligand-selective dissociation of activation and internalization of the parathyroid hormone (PTH) receptor: conditional efficacy of PTH peptide fragments. Endocrinology 2004, 145:2815-2823.
96. Divieti P., John M.R., Juppner H., Bringhurst F.R. Human PTH-(7-84) inhibits bone resorption in vitro via actions independent of the type 1 PTH/PTHrP receptor. Endocrinology 2002, 143:171-176.
97. Slatopolsky E., Finch J., Clay P., Martin D., Sicard G., Singer G., et al. A novel mechanism for skeletal resistance in uremia. Kidney Int 2000, 58:753-761.
98. Nguyen-Yamamoto L., Rousseau L., Brossard J.H., Lepage R., D'Amour P. Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor. Endocrinology 2001, 142:1386-1392.
99. Liu B.Y., Guo J., Lanske B., Divieti P., Kronenberg H.M., Bringhurst F.R. Conditionally immortalized murine bone marrow stromal cells mediate parathyroid hormone-dependent osteoclastogenesis in vitro. Endocrinology 1998, 139:1952-1964.
100. Himmelfarb J. Uremic toxicity, oxidative stress, and hemodialysis as renal replacement therapy. Semin Dial 2009, 22:636-643.
101. Hocher B., Armbruster F.P., Stoeva S., Reichetzeder C., Gron H.J., Lieker I., et al. Measuring parathyroid hormone (PTH) in patients with oxidative stress--do we need a fourth generation parathyroid hormone assay?. PLoS One 2012, 7:e40242.
102. Lund R.J., Davies M.R., Brown A.J., Hruska K.A. Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model. J Am Soc Nephrol 2004, 15:359-369.
103. Klahr S., Slatopolsky E. Toxicity of parathyroid hormone in uremia. Annu Rev Med 1986, 37:71-78.
104. Slatopolsky E., Martin K., Hruska K. Parathyroid hormone metabolism and its potential as a uremic toxin. Am J Physiol 1980, 239:F1-12.
105. Massry S.G., Smogorzewski M. The mechanisms responsible for the PTH-induced rise in cytosolic calcium in various cells are not uniform. Miner Electrolyte Metab 1995, 21:13-28.
106. Bogin E., Levi J., Harary I., Massry S.G. Effects of parathyroid hormone on oxidative phosphorylation of heart mitochondria. Miner Electrolyte Metab 1982, 7:151-156.
107. Baczynski R., Massry S.G., Kohan R., Magott M., Saglikes Y., Brautbar N. Effect of parathyroid hormone on myocardial energy metabolism in the rat. Kidney Int 1985, 27:718-725.
108. Drueke T., Fauchet M., Fleury J., Lesourd P., Toure Y., Le P.C., et al. Effect of parathyroidectomy on left-ventricular function in haemodialysis patients. Lancet 1980, 1:112-114.
109. London G.M., de Vernejoul M.C., Fabiani F., Marchais S.J., Guerin A.P., Metivier F., et al. Secondary hyperparathyroidism and cardiac hypertrophy in hemodialysis patients. Kidney Int 1987, 32:900-907.
110. Amann K., Ritz E., Wiest G., Klaus G., Mall G. A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol 1994, 4:1814-1819.
111. Neves K.R., Graciolli F.G., dos Reis L.M., Graciolli R.G., Neves C.L., Magalhaes A.O., et al. Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int 2007, 71:1262-1270.
112. Shao J.S., Cheng S.L., Pingsterhaus J.M., Charlton-Kachigian N., Loewy A.P., Towler D.A. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest 2005, 115:1210-1220.
113. Sherrard D.J., Hercz G., Pei Y., Maloney N.A., Greenwood C., Manuel A., et al. The spectrum of bone disease in end-stage renal failure--an evolving disorder. Kidney Int 1993, 43:436-442.
114. Raggi P., Chertow G.M., Torres P.U., Csiky B., Naso A., Nossuli K., et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 2011, 26:1327-1339.
115. Chertow G.M., Block G.A., Correa-Rotter R., Drueke T.B., Floege J., Goodman W.G., et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012, 367:2482-2494.
116. Liabeuf S., Neirynck N., Drueke T., Vanholder R., Massy Z. Clinical studies and chronic kidney disease: what did we learn recently?. Sem Nephrol 2014.
117. Wang Y., Zhu J., DeLuca H.F. Where is the vitamin D receptor?. Arch Biochem Biophys 2012, 523:123-133.
118. Dusso A.S., Rodriguez M. Enhanced induction of Cyp24a1 by FGF23 but low serum 24,25-dihydroxyvitamin D in CKD: implications for therapy. Kidney Int 2012, 82:1046-1049.
119. Helvig C.F., Cuerrier D., Hosfield C.M., Ireland B., Kharebov A.Z., Kim J.W., et al. Dysregulation of renal vitamin D metabolism in the uremic rat. Kidney Int 2010, 78:463-472.
120. Dai B., David V., Alshayeb H.M., Showkat A., Gyamlani G., Horst R.L., et al. Assessment of 24,25(OH)2D levels does not support FGF23-mediated catabolism of vitamin D metabolites. Kidney Int 2012, 82:1061-1070.
121. Bosworth C.R., Levin G., Robinson-Cohen C., Hoofnagle A.N., Ruzinski J., Young B., et al. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int 2012, 82:693-700.
122. Gallieni M., Kamimura S., Ahmed A., Bravo E., Delmez J., Slatopolsky E., et al. Kinetics of monocyte 1 alpha-hydroxylase in renal failure. Am J Physiol Renal Physiol 1995, 268:F746-F753.
123. Bacchetta J., Sea J.L., Chun R.F., Lisse T.S., Wesseling-Perry K., Gales B., et al. Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes. J Bone Miner Res 2013, 28:46-55.
124. Viaene L., Evenepoel P., Meijers B., Vanderschueren D., Overbergh L., Mathieu C. Uremia suppresses immune signal-induced CYP27B1 expression in human monocytes. Am J Nephrol 2012, 36:497-508.
125. Patel S.R., Ke H.-Q., Vanholder R., Koenig R.J., Hsu C.H. Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins. J Clin Invest 1995, 96:50-59.
126. Vanholder R., Glorieux G. Molecular mechanisms of vitamin D hyporesponsiveness in renal failure. Nephrol Dial Transplant 1999, 14:16-19.
127. Sawaya B.P., Koszewski N.J., Qi Q., Langub M.C., Monier-Faugere M.C., Malluche H.H. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. J Am Soc Nephrol 1997, 8:271-278.
128. Cremer B., Lubbers E., Klooker P., Schmidt-Gayk H., Ritz E. Calciuric response to 1,25-(OH)2D3 in early renal failure. Miner Electrolyte Metab 1985, 11:182-185.
129. Viaene L., Meijers B.K., Vanrenterghem Y., Evenepoel P. Evidence in favor of a severely impaired net intestinal calcium absorption in patients with (early-stage) chronic kidney disease. Am J Nephrol 2012, 35:434-441.
130. Mehrotra R., Kermah D., Budoff M., Salusky I.B., Mao S.S., Gao Y.L., et al. Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol 2008, 3:1144-1151.
131. Ravani P., Malberti F., Tripepi G., Pecchini P., Cutrupi S., Pizzini P., et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 2009, 75:88-95.
132. Drechsler C., Verduijn M., Pilz S., Dekker F.W., Krediet R.T., Ritz E., et al. Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant 2011, 26:1024-1032.
133. Wolf M., Shah A., Gutierrez O., Ankers E., Monroy M., Tamez H., et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2007, 72:1004-1013.
134. Teng M., Wolf M., Ofsthun M.N., Lazarus J.M., Hernan M.A., Camargo C.A., et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 2005, 16:1115-1125.
135. Tamez H., Zoccali C., Packham D., Wenger J., Bhan I., Appelbaum E., et al. Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am Heart J 2012, 164:902-909.
136. de Zeeuw D., Agarwal R., Amdahl M., Audhya P., Coyne D., Garimella T., et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010, 376:1543-1551.
137. Mizobuchi M., Finch J.L., Martin D.R., Slatopolsky E. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int 2007, 72:709-715.
138. Lopez I., Mendoza F.J., Guilera-Tejero E., Perez J., Guerrero F., Martin D., et al. The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats. Kidney Int 2007, 73:300-307.
139. Mathew S., Lund R.J., Chaudhary L.R., Geurs T., Hruska K.A. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol 2008, 19:1509-1519.