Abstract
The kidney plays a major role in bone and mineral homeostasis by regulating calcium, phosphorus, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23) and calcitriol (1,25 dihydroxyvitamin D3, 1,25(OH)2D3) metabolism. Disordered regulation of mineral metabolism occurs early in the course of chronic kidney disease (CKD) and results in alterations in bone modeling, remodeling, and growth. These alterations have been a focus of CKD management in children for decades. However, a growing awareness that cardiovascular calcifications accompany CKD, that cardiovascular disease is the leading cause of mortality in both adults and children with kidney disease, and that therapies designed to treat the skeletal consequences of CKD affect the progression of vascular pathology, has led to a reclassification of the mineral, skeletal, and vascular complications associated with progressive kidney disease. Together, these alterations are termed “CKD Mineral and Bone Disorder” (“CKD-MBD”) (1).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G. Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945–1953.
Groothoff JW, Offringa M, Van Eck-Smit BL, Gruppen MP, Van De Kar NJ, Wolff ED, Lilien MR, Davin JC, Heymans HS, Dekker FW. Severe bone disease and low bone mineral density after juvenile renal failure. Kidney Int 2003;63:266–275.
Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71:31–38.
Goldman R, Bassett SH. Phosphorus excretion in renal failure. J Clin Invest 1954;33:1623–1628.
Coburn JW, Popovtzer MM, Massry SG, Kleeman CR. The physicochemical state and renal handling of divalent ions in chronic renal failure. Arch Intern Med 1969;124:302–311.
Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: Regulation by phosphate? Bone 2004;35:1192–1199.
Yoshiko Y, Wang H, Minamizaki T, Ijuin C, Yamamoto R, Suemune S, Kozai K, Tanne K, Aubin JE, Maeda N. Mineralized tissue cells are a principal source of FGF23. Bone 2007;40(6):1564–1573.
Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006;444:770–774.
Portale AA, Booth BE, Halloran BP, Morris RC Jr. Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest 1984;73:1580–1589.
Antoniucci DM, Yamashita T, Portale AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab 2006;91:3144–3149.
Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson KB. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 2003;64:2272–2279.
Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004;19:429–435.
Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, Juppner H, Wolf M. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16:2205–2215.
Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro O, Mohammadi M, Sirkis R, Naveh-Many T, Silver J. The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007;117:4003–4008.
Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G, Larsson TE. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 2007;195:125–131.
Martinez I, Saracho R, Montenegro J, Llach F. A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism. Nephrol Dial Transplant 1996;11:Suppl 3:22–28.
Li YC, Pirro AE, Amling M, Delling G, Baron R, Bronson R, Demay MB. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci USA 1997;94:9831–9835.
Amling M, Priemel M, Holzmann T, Chapin K, Rueger JM, Baron R, Demay MB. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: Formal histomorphometric and biomechanical analyses. Endocrinology 1999;140:4982–4987.
Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, Goltzman D. Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem 2004;279:16754–16766.
Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen YS, Rigor DL, Stillman I, Tamez H, Kroeger PE, Wu-Wong RR, Karumanchi SA, Thadhani R, Kang PM. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci USA 2007;104:16810–16815.
Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int 2008;74:170–179.
Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 2005;16:1115–1125.
Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003;349:446–456.
Holick MF, Garabedian M. Vitamin D: Photobiology, metabolism, mechanism of action, and clinical applications. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn. Favus MJ (ed.). Washington, DC, American Society for Bone and Mineral Research, 2006, pp. 129–137.
DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004;80S:1689S–1696S.
Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006;116:2062–2072.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281.
Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 1999;96:507–515.
Leheste JR, Melsen F, Wellner M, Jansen P, Schlichting U, Renner-Muller I, Andreassen TT, Wolf E, Bachmann S, Nykjaer A, Willnow TE. Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defect. FASEB J 2003;17:247–249.
Zehnder D, Landray MJ, Wheeler DC, Fraser W, Blackwell L, Nuttall S, Hughes SV, Townend J, Ferro C, Baigent C, Hewison M. Cross-sectional analysis of abnormalities of mineral homeostasis, vitamin D and parathyroid hormone in a cohort of pre-dialysis patients. The chronic renal impairment in Birmingham (CRIB) study. Nephron Clin Pract 2007;107:c109–c116.
Lambert PW, Stern PH, Avioli RC, Brackett NC, Turner RT, Greene A, Fu IY, Bell NH. Evidence for extrarenal production of 1 alpha,25-dihydroxyvitamin D in man. J Clin Invest 1982;69:722–725.
Dusso A, Lopez-Hilker S, Rapp N, Slatopolsky E. Extra-renal production of calcitriol in chronic renal failure. Kidney Int 1988;34:368–375.
Dusso AS, Finch J, Brown A, Ritter C, Delmez J, Schreiner G, Slatopolsky E. Extrarenal production of calcitriol in normal and uremic humans. J Clin Endocrinol Metab 1991;72:157–164.
Khaw KT, Sneyd MJ, Compston J. Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. BMJ 1992;305:273–277.
LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999;281:1505–1511.
K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:S1–S201.
Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777–783.
Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med 2004;158:531–537.
Stavroulopoulos A, Porter CJ, Roe SD, Hosking DJ, Cassidy MJ. Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4. Nephrology (Carlton) 2008;13:63–67.
Reichel H, Deibert B, Schmidt-Gayk H, Ritz E. Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism. Nephrol Dial Transplant 1991;6:162–169.
Saab G, Young DO, Gincherman Y, Giles K, Norwood K, Coyne DW. Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients. Nephron Clin Pract 2007;105:c132–c138.
Mucsi I, Almasi C, Deak G, Marton A, Ambrus C, Berta K, Lakatos P, Szabo A, Horvath C. Serum 25(OH)-vitamin D levels and bone metabolism in patients on maintenance hemodialysis. Clin Nephrol 2005;64:288–294.
Coburn JW, Koppel MH, Brickman AS, Massry SG. Study of intestinal absorption of calcium in patients with renal failure. Kidney Int 1973;3:264–272.
Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997;7:439–443.
Holick MF. Vitamin D and the kidney. Kidney Int 1987;32:912–929.
Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet 1982;1:74–76.
Koenig KG, Lindberg JS, Zerwekh JE, Padalino PK, Cushner HM, Copley JB. Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease. Kidney Int 1992;41:161–165.
Saha H. Calcium and vitamin D homeostasis in patients with heavy proteinuria. Clin Nephrol 1994;41:290–296.
Zisman AL, Hristova M, Ho LT, Sprague SM. Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid hormone concentrations in chronic kidney disease. Am J Nephrol 2007;27:36–43.
Chandra P, Binongo JN, Ziegler TR, Schlanger LE, Wang W, Someren JT, Tangpricha V. Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. Endocr Pract 2008;14:10–17.
Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int 2006;70:654–659.
Saggese G, Federico G, Cinquanta L. In vitro effects of growth hormone and other hormones on chondrocytes and osteoblast-like cells. Acta Paediatr Suppl 1993;82:Suppl 391:54–59.
Scharla SH, Strong DD, Mohan S, Baylink DJ, Linkhart TA. 1,25-Dihydroxyvitamin D3 differentially regulates the production of insulin-like growth factor I (IGF-I) and IGF-binding protein-4 in mouse osteoblasts. Endocrinology 1991;129:3139–3146.
Akiyama H, Hiraki Y, Shigeno C, Kohno H, Shukunami C, Tsuboyama T, Kasai R, Suzuki F, Konishi J, Nakamura T. 1 alpha,25-dihydroxyvitamin D3 inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5. J Bone Miner Res 1996;11:22–28.
Silver J, Russell J, Sherwood LM. Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells. Proc Natl Acad Sci USA 1985;82:4270–4273.
Silver J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat. J Clin Invest 1986;78:1296–1301.
Kifor O, Moore FD, Jr., Wang P, Goldstein M, Vassilev P, Kifor I, Hebert SC, Brown EM. Reduced immunostaining for the extracellular Ca2 + -sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 1996;81:1598–1606.
Brown AJ, Zhong M, Finch J, Ritter C, McCracken R, Morrissey J, Slatopolsky E. Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am J Physiol 1996;270:F454–F460.
Slatopolsky E, Caglar S, Pennell JP, Taggart DD, Canterbury JM, Reiss E, Bricker NS. On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog. J Clin Invest 1971;50:492–499.
Llach F, Massry SG. On the mechanism of secondary hyperparathyroidism in moderate renal insufficiency. J Clin Endocrinol Metab 1985;61:601–606.
Almaden Y, Canalejo A, Ballesteros E, Anon G, Canadillas S, Rodriguez M. Regulation of arachidonic acid production by intracellular calcium in parathyroid cells: effect of extracellular phosphate. J Am Soc Nephrol 2002;13:693–698.
Silver J, Kilav R, Sela-Brown A, Naveh-Many T. Molecular mechanisms of secondary hyperparathyroidism. Pediatr Nephrol 2000;14:626–628.
Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993;366:575–580.
John MR, Goodman WG, Gao P, Cantor TL, Salusky IB, Juppner H. A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: Implications for PTH measurements in renal failure. J Clin Endocrinol Metab 1999;84:4287–4290.
Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F. Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 1996;137:3842–3848.
Kirkwood JR, Ozonoff MB, Steinbach HL. Epiphyseal displacement after metaphyseal fracture in renal osteodystrophy. Am J Roentgenol Radium Ther Nucl Med 1972;115:547–554.
Martin-Salvago M, Villar-Rodriguez JL, Palma-Alvarez A, Beato-Moreno A, Galera-Davidson H. Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure. Endocr Pathol 2003;14:61–70.
Brown AJ, Zhong M, Ritter C, Brown EM, Slatopolsky E. Loss of calcium responsiveness in cultured bovine parathyroid cells is associated with decreased calcium receptor expression. Biochem Biophys Res Commun 1995;212:861–867.
Wada M, Furuya Y, Sakiyama J, Kobayashi N, Miyata S, Ishii H, Nagano N. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor. J Clin Invest 1997;100:2977–2983.
Canaff L, Hendy GN. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem 2002;277:30337–30350.
Goodman WG, Veldhuis JD, Belin TR, Van Herle AJ, Juppner H, Salusky IB. Calcium-sensing by parathyroid glands in secondary hyperparathyroidism. J Clin Endocrinol Metab 1998;83:2765–2772.
Ramirez JA, Goodman WG, Gornbein J, Menezes C, Moulton L, Segre GV, Salusky IB. Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism. J Clin Endocrinol Metab 1993;76:1489–1494.
K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 2005;46:S1–S121.
Norris KC, Goodman WG, Howard N, Nugent ME, Coburn JW. Iliac crest bone biopsy for diagnosis of aluminum toxicity and a guide to the use of deferoxamine. Semin Nephrol 1986;6:27–34.
Salusky IB, Coburn JW, Brill J, Foley J, Slatopolsky E, Fine RN, Goodman WG. Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD. Kidney Int 1988;33:975–982.
Atkins D, Peacock M. A comparison of the effects of the calcitonins, steroid hormones and thyroid hormones on the response of bone to parathyroid hormone in tissue culture. J Endocrinol 1975;64:573–583.
Lee K, Deeds JD, Bond AT, Juppner H, bou-Samra AB, Segre GV. In situ localization of PTH/pthrp receptor mrna in the bone of fetal and young rats. Bone 1993;14:341–345.
Sherrard DJ. Renal osteodystrophy. Semin Nephrol 1986;6:56–67.
Malluche HH, Ritz E, Lange HP, Schoeppe W. Changes of bone histology during maintenance hemodialysis at various levels of dialyzate Ca concentration. Clin Nephrol 1976;6:440–447.
Hamdy NA, Kanis JA, Beneton MN, Brown CB, Juttmann JR, Jordans JG, Josse S, Meyrier A, Lins RL, Fairey IT. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995;310:358–363.
Norman ME, Mazur AT, Borden S, Gruskin A, Anast C, Baron R, Rasmussen H. Early diagnosis of juvenile renal osteodystrophy. J Pediatr 1980;97:226–232.
Malluche H, Faugere MC. Renal bone disease 1990: An unmet challenge for the nephrologist. Kidney Int 1990;38:193–211.
Cohen-Solal ME, Sebert JL, Boudailliez B, Westeel PF, Moriniere PH, Marie A, Garabedian M, Fournier A. Non-aluminic adynamic bone disease in non-dialyzed uremic patients: A new type of osteopathy due to overtreatment? Bone 1992;13:1–5.
Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB. Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 1994;46:1160–1166.
Salusky IB, Coburn JW, Foley J, Nelson P, Fine RN. Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis. J Pediatr 1986;108:767–770.
Ott SM, Maloney NA, Klein GL, Alfrey AC, Ament ME, Coburn JW, Sherrard DJ. Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition. Ann Intern Med 1983;98:910–914.
London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, de Vernejoul MC. Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol 2004;15:1943–1951.
Kuizon BD, Salusky IB. Intermittent calcitriol therapy and growth in children with chronic renal failure. Miner Electrolyte Metab 1998;24:290–295.
Kuizon BD, Goodman WG, Juppner H, Boechat I, Nelson P, Gales B, Salusky IB. Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int 1998;53:205–211.
Massry SG, Friedler RM, Coburn JW. Excretion of phosphate and calcium. Physiology of their renal handling and relation to clinical medicine. Arch Intern Med 1973;131:828–859.
Galceran T, Martin KJ, Morrissey JJ, Slatopolsky E. Role of 1,25-dihydroxyvitamin D on the skeletal resistance to parathyroid hormone. Kidney Int 1987;32:801–807.
Mathias R, Salusky I, Harman W, Paredes A, Emans J, Segre G, Goodman W. Renal bone disease in pediatric and young adult patients on hemodialysis in a children’s hospital. J Am Soc Nephrol 1993;3:1938–1946.
Salusky IB, Ramirez JA, Oppenheim W, Gales B, Segre GV, Goodman WG. Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int 1994;45:253–258.
Urena P, Ferreira A, Morieux C, Drueke T, de Vernejoul MC. PTH/pthrp receptor mrna is down-regulated in epiphyseal cartilage growth plate of uraemic rats. Nephrol Dial Transplant 1996;11:2008–2016.
Sanchez CP, Salusky IB, Kuizon BD, Abdella P, Juppner H, Goodman WG. Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol. Kidney Int 1998;54:1879–1887.
Massry SG, Stein R, Garty J, Arieff AI, Coburn JW, Norman AW, Friedler RM. Skeletal resistance to the calcemic action of parathyroid hormone in uremia: Role of 1,25 (OH)2 D3. Kidney Int 1976;9:467–474.
Sherrard DJ, Baylink DJ, Wergedal JE, Maloney NA. Quantitative histological studies on the pathogenesis of uremic bone disease. J Clin Endocrinol Metab 1974;39:119–135.
NIDDK. USRDS 1994 Annual Report. 2008.
De Beur SM, Finnegan RB, Vassiliadis J, Cook B, Barberio D, Estes S, Manavalan P, Petroziello J, Madden SL, Cho JY, Kumar R, Levine MA, Schiavi SC. Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res 2002;17:1102–1110.
Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 2003;348:1656–1663.
Nelson AE, Bligh RC, Mirams M, Gill A, Au A, Clarkson A, Juppner H, Ruff S, Stalley P, Scolyer RA, Robinson BG, Mason RS, Bligh PC. Clinical case seminar: Fibroblast growth factor 23: a new clinical marker for oncogenic osteomalacia. J Clin Endocrinol Metab 2003;88:4088–4094.
Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004;113:561–568.
Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, Juppner H, Lanske B. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 2004;23:421–432.
Salusky IB, Goodman WG, Kuizon BD, Lavigne JR, Zahranik RJ, Gales B, Wang HJ, Elashoff RM, Juppner H. Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis. Kidney Int 2003;63:1801–1808.
Salusky IB, Goodman WG, Sahney S, Gales B, Perilloux A, Wang HJ, Elashoff RM, Juppner H. Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J Am Soc Nephrol 2005;16:2501–2508.
Ho AY, Kung AW. Determinants of peak bone mineral density and bone area in young women. J Bone Miner Metab 2005;23:470–475.
Tonshoff B, Schaefer F, Mehls O. Disturbance of growth hormone – insulin-like growth factor axis in uraemia. Implications for recombinant human growth hormone treatment. Pediatr Nephrol 1990;4:654–662.
North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2006 Annual Report. 2006.
Nash MA, Torrado AD, Greifer I, Spitzer A, Edelmann CM Jr. Renal tubular acidosis in infants and children. Clinical course, response to treatment, and prognosis. J Pediatr 1972;80:738–748.
Challa A, Chan W, Krieg RJ Jr, Thabet MA, Liu F, Hintz RL, Chan JC. Effect of metabolic acidosis on the expression of insulin-like growth factor and growth hormone receptor. Kidney Int 1993;44:1224–1227.
Maniar S, Kleinknecht C, Zhou X, Motel V, Yvert JP, Dechaux M. Growth hormone action is blunted by acidosis in experimental uremia or acid load. Clin Nephrol 1996;46:72–76.
Challa A, Krieg RJ Jr, Thabet MA, Veldhuis JD, Chan JC. Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol 1993;265:E547–E553.
Green J, Maor G. Effect of metabolic acidosis on the growth hormone/IGF-I endocrine axis in skeletal growth centers. Kidney Int 2000;57:2258–2267.
Lefebvre A, de Vernejoul MC, Gueris J, Goldfarb B, Graulet AM, Morieux C. Optimal correction of acidosis changes progression of dialysis osteodystrophy. Kidney Int 1989;36:1112–1118.
Goodman WG, Salusky IB. Evolution of secondary hyperparathyroidism during oral calcitriol therapy in pediatric renal osteodystrophy. Contrib Nephrol 1991;90:189–195.
Waller SC, Ridout D, Cantor T, Rees L. Parathyroid hormone and growth in children with chronic renal failure. Kidney Int 2005;67:2338–2345.
Schmitt CP, Ardissino G, Testa S, Claris-Appiani A, Mehls O. Growth in children with chronic renal failure on intermittent versus daily calcitriol. Pediatr Nephrol 2003;18:440–444.
Martin KJ, Ballal HS, Domoto DT, Blalock S, Weindel M. Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations. Am J Kidney Dis 1992;19:540–545.
Nickerson T, Huynh H. Vitamin D analogue EB1089-induced prostate regression is associated with increased gene expression of insulin-like growth factor binding proteins. J Endocrinol 1999;160:223–229.
Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest 2001;107:73–81.
Richman C, Baylink DJ, Lang K, Dony C, Mohan S. Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo. Endocrinology 1999;140:4699–4705.
Longobardi L, Torello M, Buckway C, O’Rear L, Horton WA, Hwa V, Roberts CT Jr, Chiarelli F, Rosenfeld RG, Spagnoli A. A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis. Endocrinology 2003;144:1695–1702.
Collard TJ, Guy M, Butt AJ, Perks CM, Holly JM, Paraskeva C, Williams AC. Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells. Carcinogenesis 2003;24:393–401.
Samaan NA, Freeman RM. Growth hormone levels in severe renal failure. Metabolism 1970;19:102–113.
Tonshoff B, Veldhuis JD, Heinrich U, Mehls O. Deconvolution analysis of spontaneous nocturnal growth hormone secretion in prepubertal children with preterminal chronic renal failure and with end-stage renal disease. Pediatr Res 1995;37:86–93.
Tonshoff B, Sammet A, Sanden I, Mehls O, Waldherr R, Scharer K. Outcome and prognostic determinants in the hemolytic uremic syndrome of children. Nephron 1994;68:63–70.
Schaefer F, Chen Y, Tsao T, Nouri P, Rabkin R. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. J Clin Invest 2001;108:467–475.
Tonshoff B, Cronin MJ, Reichert M, Haffner D, Wingen AM, Blum WF, Mehls O. Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. J Clin Endocrinol Metab 1997;82:1007–1013.
Powell DR. Effects of renal failure on the growth hormone-insulin-like growth factor axis. J Pediatr 1997;131:S13–S16.
Powell DR, Liu F, Baker BK, Hintz RL, Lee PD, Durham SK, Brewer ED, Frane JW, Watkins SL, Hogg RJ. Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group. Kidney Int 1997;51:1970–1979.
Mehls O, Ritz E, Krempien B, Gilli G, Link K, Willich E, Scharer K. Slipped epiphyses in renal osteodystrophy. Arch Dis Child 1975;50:545–554.
Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet 1976;1:626–629.
Smith R, Stern G. Myopathy, osteomalacia and hyperparathyroidism. Brain 1967;90:593–602.
Mallette LE, Patten BM, Engel WK. Neuromuscular disease in secondary hyperparathyroidism. Ann Intern Med 1975;82:474–483.
Henderson RG, Russell RG, Ledingham JG, Smith R, Oliver DO, Walton RJ, Small DG, Preston C, Warner GT. Effects of 1,25-dihydroxycholecalciferol on calcium absorption, muscle weakness, and bone disease in chronic renal failure. Lancet 1974;1:379–384.
Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int 1990;38:931–936.
Conger JD, Hammond WS, Alfrey AC, Contiguglia SR, Stanford RE, Huffer WE. Pulmonary calcification in chronic dialysis patients. Clinical and pathologic studies. Ann Intern Med 1975;83:330–336.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478–1483.
Chavers BM, Li S, Collins AJ, Herzog CA. Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int 2002;62:648–653.
Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 2002;106:100–105.
Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. J Am Soc Nephrol 2005;16:2796–2803.
Shroff RC, Donald AE, Hiorns MP, Watson A, Feather S, Milford D, Ellins EA, Storry C, Ridout D, Deanfield J, Rees L. Mineral metabolism and vascular damage in children on dialysis. J Am Soc Nephrol 2007;18:2996–3003.
Russo D, Palmiero G, De Blasio AP, Balletta MM, Andreucci VE. Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 2004;44:1024–1030.
Moe SM, Duan D, Doehle BP, O’Neill KD, Chen NX. Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 2003;63:1003–1011.
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997;89:747–754.
Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000;87:E10–E17.
Ahmed S, O’Neill KD, Hood AF, Evan AP, Moe SM. Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis 2001;37:1267–1276.
Bostrom K. Insights into the mechanism of vascular calcification. Am J Cardiol 2001;88:20E–22E.
Moe SM, O’Neill KD, Duan D, Ahmed S, Chen NX, Leapman SB, Fineberg N, Kopecky K. Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 2002;61:638–647.
Chen NX, O’Neill KD, Duan D, Moe SM. Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int 2002;62:1724–1731.
Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003;112:357–366.
Schinke T, Amendt C, Trindl A, Poschke O, Muller-Esterl W, Jahnen-Dechent W. The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 1996;271:20789–20796.
Sweatt A, Sane DC, Hutson SM, Wallin R. Matrix Gla protein (MGP) and bone morphogenetic protein-2 in aortic calcified lesions of aging rats. J Thromb Haemost 2003;1:178–185.
Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T, Sugimura K, Kishimoto T, Kinoshita S, Kuroki T, Nabeshima Y. Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 2001;280:1015–1020.
Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, Miura M, Miyauchi A, Kobayashi K, Miki T, Shoji T, Ishimura E, Nishizawa Y. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 2004;65:1943–1946.
Miyamoto K, Ito M, Segawa H, Kuwahata M. Molecular targets of hyperphosphataemia in chronic renal failure. Nephrol Dial Transplant 2003;18:Suppl 3:iii79–iii80.
Tonelli M, Keech A, Shepherd J, Sacks F, Tonkin A, Packard C, Pfeffer M, Simes J, Isles C, Furberg C, West M, Craven T, Curhan G. Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol 2005;16:3748–3754.
Holdaas H, Fellstrom B, Cole E, Nyberg G, Olsson AG, Pedersen TR, Madsen S, Gronhagen-Riska C, Neumayer HH, Maes B, Ambuhl P, Hartmann A, Staffler B, Jardine AG. Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant 2005;5:2929–2936.
Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, Ritz E. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–248.
Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005;68:1815–1824.
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007;71:438–441.
Brown EM, Wilson RE, Eastman RC, Pallotta J, Marynick SP. Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. J Clin Endocrinol Metab 1982;54:172–179.
Salusky IB, Fine RN, Kangarloo H, Gold R, Paunier L, Goodman WG, Brill JE, Gilli G, Slatopolsky E, Coburn JW. “High-dose” calcitriol for control of renal osteodystrophy in children on CAPD. Kidney Int 1987;32:89–95.
Kurz P, Monier-Faugere MC, Bognar B, Werner E, Roth P, Vlachojannis J, Malluche HH. Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int 1994;46:855–861.
Sherrard DJ, Hercz G, Pei Y, Maloney NA, Greenwood C, Manuel A, Saiphoo C, Fenton SS, Segre GV. The spectrum of bone disease in end-stage renal failure–evolving disorder. Kidney Int 1993;43:436–442.
Cohen-Solal ME, Shih MS, Lundy MW, Parfitt AM. A new method for measuring cancellous bone erosion depth: Application to the cellular mechanisms of bone loss in postmenopausal osteoporosis. J Bone Miner Res 1991;6:1331–1338.
Quarles LD, Lobaugh B, Murphy G. Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 1992;75:145–150.
Malluche HH, Monier-Faugere MC. The role of bone biopsy in the management of patients with renal osteodystrophy. J Am Soc Nephrol 1994;4:1631–1642.
Andress DL, Endres DB, Maloney NA, Kopp JB, Coburn JW, Sherrard DJ. Comparison of parathyroid hormone assays with bone histomorphometry in renal osteodystrophy. J Clin Endocrinol Metab 1986;63:1163–1169.
Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, Keutmann HT, Wang CA, Potts JT Jr, Segre GV. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 1987;33:1364–1367.
Brossard JH, Cloutier M, Roy L, Lepage R, Gascon-Barre M, D’Amour P. Accumulation of a non-(1–84) molecular form of parathyroid hormone (PTH) detected by intact PTH assay in renal failure: Importance in the interpretation of PTH values. J Clin Endocrinol Metab 1996;81:3923–3929.
Lepage R, Roy L, Brossard JH, Rousseau L, Dorais C, Lazure C, D’Amour P. A non-(1–84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples. Clin Chem 1998;44:805–809.
Brossard JH, Yamamoto LN, D’Amour P. Parathyroid hormone metabolites in renal failure: bioactivity and clinical implications. Semin Dial 2002;15:196–201.
Slatopolsky E, Finch J, Clay P, Martin D, Sicard G, Singer G, Gao P, Cantor T, Dusso A. A novel mechanism for skeletal resistance in uremia. Kidney Int 2000;58:753–761.
Nguyen-Yamamoto L, Rousseau L, Brossard JH, 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.
Monier-Faugere MC, Geng Z, Mawad H, Friedler RM, Gao P, Cantor TL, Malluche HH. Improved assessment of bone turnover by the PTH-(1–84)/large C-PTH fragments ratio in ESRD patients. Kidney Int 2001;60:1460–1468.
Coen G, Bonucci E, Ballanti P, Balducci A, Calabria S, Nicolai GA, Fischer MS, Lifrieri F, Manni M, Morosetti M, Moscaritolo E, Sardella D. PTH 1–84 and PTH “7–84” in the noninvasive diagnosis of renal bone disease. Am J Kidney Dis 2002;40:348–354.
Alfrey AC. Aluminum metabolism. Kidney Int Suppl 1986;18:S8–S11.
Dent CE, Hodson CJ. Radiological changes associated with certain metabolic bone diseases. Br J Radiol 1954;27:605–618.
Meema HE, Rabinovich S, Meema S, Lloyd GJ, Oreopoulos DG. Improved radiological diagnosis of azotemic osteodystrophy. Radiology 1972;102:1–10.
Mehls O, Krempien B, Ritz E, Scharer K, Schuler HW. Renal osteodystrophy in children on maintenance haemodialysis. Proc Eur Dial Transplant Assoc 1973;10:197–201.
Olgaard K, Heerfordt J, Madsen S. Scintigraphic skeletal changes in uremic patients on regular hemodialysis. Nephron 1976;17:325–334.
Institute of medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, National Academy Press, 1997.
Blumenkrantz MJ, Kopple JD, Moran JK, Coburn JW. Metabolic balance studies and dietary protein requirements in patients undergoing continuous ambulatory peritoneal dialysis. Kidney Int 1982;21:849–861.
Pierratos A. Daily hemodialysis: Why the renewed interest? Am J Kidney Dis 1998;32:S76–S82.
Fischbach M, Terzic J, Menouer S, Dheu C, Soskin S, Helmstetter A, Burger MC. Intensified and daily hemodialysis in children might improve statural growth. Pediatr Nephrol 2006;21:1746–1752.
Mucsi I, Hercz G, Uldall R, Ouwendyk M, Francoeur R, Pierratos A. Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis. Kidney Int 1998;53:1399–1404.
Brickman AS, Coburn JW, Massry SG, Norman AW. 1,25 Dihydroxy-vitamin D3 in normal man and patients with renal failure. Ann Intern Med 1974;80:161–168.
Roodhooft AM, Van Hoeck KJ, Van Acker KJ. Hypophosphatemia in infants on continuous ambulatory peritoneal dialysis. Clin Nephrol 1990;34:131–135.
Tejeda A, Saffarian N, Uday K, Dave M. Hypophosphatemia in end stage renal disease. Nephron 1996;73:674–678.
Coburn JW, Mischel MG, Goodman WG, Salusky IB. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis 1991;17:708–711.
Alon U, Davidai G, Bentur L, Berant M, Better OS. Oral calcium carbonate as phosphate-binder in infants and children with chronic renal failure. Miner Electrolyte Metab 1986;12:320–325.
Tsukamoto Y, Moriya R, Nagaba Y, Morishita T, Izumida I, Okubo M. Effect of administering calcium carbonate to treat secondary hyperparathyroidism in nondialyzed patients with chronic renal failure. Am J Kidney Dis 1995;25:879–886.
Indridason OS, Quarles LD. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group. Kidney Int 2000;57:282–292.
Tamanaha K, Mak RH, Rigden SP, Turner C, Start KM, Haycock GB, Chantler C. Long-term suppression of hyperparathyroidism by phosphate binders in uremic children. Pediatr Nephrol 1987;1:145–149.
Slatopolsky E, Weerts C, Lopez-Hilker S, Norwood K, Zink M, Windus D, Delmez J. Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 1986;315:157–161.
Fournier A, Moriniere P, Sebert JL, Dkhissi H, Atik A, Leflon P, Renaud H, Gueris J, Gregoire I, Idrissi A. Calcium carbonate, an aluminum-free agent for control of hyperphosphatemia, hypocalcemia, and hyperparathyroidism in uremia. Kidney Int Suppl 1986;18:S114–S119.
Caglar K, Yilmaz MI, Saglam M, Cakir E, Acikel C, Eyileten T, Yenicesu M, Oguz Y, Vural A, Carrero JJ, Axelsson J, Lindholm B, Stenvinkel P. Short-term treatment with sevelamer increases serum fetuin-a concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients. Clin J Am Soc Nephrol 2008;3:61–68.
Slatopolsky EA, Burke SK, Dillon MA. Renagel, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. The renagel Study Group. Kidney Int 1999;55:299–307.
Bleyer AJ, Burke SK, Dillon M, Garrett B, Kant KS, Lynch D, Rahman SN, Schoenfeld P, Teitelbaum I, Zeig S, Slatopolsky E. A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am J Kidney Dis 1999;33:694–701.
Mahdavi H, Kuizon BD, Gales B, Wang HJ, Elashoff RM, Salusky IB. Sevelamer hydrochloride: an effective phosphate binder in dialyzed children. Pediatr Nephrol 2003;18:1260–1264.
Chertow GM, Dillon M, Burke SK, Steg M, Bleyer AJ, Garrett BN, Domoto DT, Wilkes BM, Wombolt DG, Slatopolsky E. A randomized trial of sevelamer hydrochloride (renagel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients. Clin Nephrol 1999;51:18–26.
Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245–252.
Delmez J, Block G, Robertson J, Chasan-Taber S, Blair A, Dillon M, Bleyer AJ. A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis. Clin Nephrol 2007;68:386–391.
Hergesell O, Ritz E. Stabilized polynuclear iron hydroxide is an efficient oral phosphate binder in uraemic patients. Nephrol Dial Transplant 1999;14:863–867.
Hutchison AJ, Maes B, Vanwalleghem J, Asmus G, Mohamed E, Schmieder R, Backs W, Jamar R, Vosskuhler A. Long-term efficacy and tolerability of lanthanum carbonate: results from a 3-year study. Nephron Clin Pract 2006;102:c61–c71.
Slatopolsky E, Liapis H, Finch J. Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int 2005;68:2809–2813.
Spasovski GB, Sikole A, Gelev S, Masin-Spasovska J, Freemont T, Webster I, Gill M, Jones C, De Broe ME, D’Haese PC. Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant 2006;21:2217–2224.
Sedman AB, Miller NL, Warady BA, Lum GM, Alfrey AC. Aluminum loading in children with chronic renal failure. Kidney Int 1984;26:201–204.
Winney RJ, Cowie JF, Robson JS. Role of plasma aluminum in the detection and prevention of aluminum toxicity. Kidney Int Suppl 1986;18:S91–S95.
Salusky IB, Foley J, Nelson P, Goodman WG. Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 1991;324:527–531.
Greenbaum LA, Grenda R, Qiu P, Restaino I, Wojtak A, Paredes A, Benador N, Melnick JZ, Williams LA, Salusky IB. Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis. Pediatr Nephrol 2005;20:622–630.
Greenbaum LA, Benador N, Goldstein SL, Paredes A, Melnick JZ, Mattingly S, Amdahl M, Williams LA, Salusky IB. Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis. Am J Kidney Dis 2007;49:814–823.
Brown AJ, Finch J, Slatopolsky E. Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport. J Lab Clin Med 2002;139:279–284.
Coburn JW, Maung HM, Elangovan L, Germain MJ, Lindberg JS, Sprague SM, Williams ME, Bishop CW. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Am J Kidney Dis 2004;43:877–890.
Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, Steele D, Chang Y, Camargo CA Jr, Tonelli M, Thadhani R. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2007;72:1004–1013.
Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, Johnson HK, Zager PG. Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 2006;70:1858–1865.
Adorini L. Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cell Immunol 2005;233:115–124.
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006;311:1770–1773.
Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353–373.
Greer RM, Rogers MA, Bowling FG, Buntain HM, Harris M, Leong GM, Cotterill AM. Australian children and adolescents with type 1 diabetes have low vitamin D levels. Med J Aust 2007;187:59–60.
Brekke HK, Ludvigsson J. Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study. Pediatr Diabetes 2007;8:11–14.
Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 1998;7:391–395.
Schwarz U, Amann K, Orth SR, Simonaviciene A, Wessels S, Ritz E. Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats. Kidney Int 1998;53:1696–1705.
Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, Williams L, Batlle D. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 2005;68:2823–2828.
Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229–238.
Nakane M, Ma J, Ruan X, Kroeger PE, Wu-Wong R. Mechanistic analysis of VDR-mediated renin suppression. Nephron Physiol 2007;107:35–44.
Al-Aly Z, Qazi RA, Gonzalez EA, Zeringue A, Martin KJ. Changes in serum 25-hydroxyvitamin D and plasma intact PTH levels following treatment with ergocalciferol in patients with CKD. Am J Kidney Dis 2007;50:59–68.
Wada M, Nagano N. Control of parathyroid cell growth by calcimimetics. Nephrol Dial Transplant 2003;18:Suppl 3:iii13–iii17.
Lopez I, guilera-Tejero E, Mendoza FJ, Almaden Y, Perez J, Martin D, Rodriguez M. Calcimimetic R-568 decreases extraosseous calcifications in uremic rats treated with calcitriol. J Am Soc Nephrol 2006;17:795–804.
Fukuda N, Tanaka H, Tominaga Y, Fukagawa M, Kurokawa K, Seino Y. Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest 1993;92:1436–1443.
Arnold A, Brown MF, Urena P, Gaz RD, Sarfati E, Drueke TB. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest 1995;95:2047–2053.
Mawad HW, Sawaya BP, Sarin R, Malluche HH. Calcific uremic arteriolopathy in association with low turnover uremic bone disease. Clin Nephrol 1999;52:160–166.
Offner G, Aschendorff C, Brodehl J. Growth after renal transplantation: an update. Pediatr Nephrol 1991;5:472–476.
Potter DE, Genant HK, Salvatierra O. Avascular necrosis of bone after renal transplantation. Am J Dis Child 1978;132:1125–1129.
Feber J, Cochat P, Braillon P, Castelo F, Martin X, Glastre C, Chapuis F, David L, Meunier PJ. Bone mineral density after renal transplantation in children. J Pediatr 1994;125:870–875.
Chesney RW, Rose PG, Mazess RB. Persistence of diminished bone mineral content following renal transplantation in childhood. Pediatrics 1984;73:459–466.
Grotz WH, Mundinger FA, Gugel B, Exner VM, Kirste G, Schollmeyer PJ. Bone mineral density after kidney transplantation. A cross-sectional study in 190 graft recipients up to 20 years after transplantation. Transplantation 1995;59:982–986.
Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 1991;325:544–550.
Velasquez-Forero F, Mondragon A, Herrero B, Pena JC. Adynamic bone lesion in renal transplant recipients with normal renal function. Nephrol Dial Transplant 1996;11:Suppl 3:58–64.
Sanchez CP, Salusky IB, Kuizon BD, Ramirez JA, Gales B, Ettenger RB, Goodman WG. Bone disease in children and adolescents undergoing successful renal transplantation. Kidney Int 1998;53:1358–1364.
Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB, Roger SD, Husserl FE, Klassen PS, Guo MD, Albizem MB, Coburn JW. Cinacalcet hcl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: A randomized, double-blind, multicenter study. J Am Soc Nephrol 2005;16:800–807.
Allen DB, Goldberg BD. Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children. Pediatrics 1992;89:416–421.
Root AW, Bongiovanni AM, Eberlein WR. Studies of the secretion and metabolic effects of human growth hormone in children with glucocorticoid-induced growth retardation. J Pediatr 1969;75:826–832.
Ortoft G, Oxlund H. Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid. Bone 1996;18:581–590.
Wehrenberg WB, Bergman PJ, Stagg L, Ndon J, Giustina A. Glucocorticoid inhibition of growth in rats: Partial reversal with somatostatin antibodies. Endocrinology 1990;127:2705–2708.
Aubia J, Serrano S, Marinoso L, Hojman L, Diez A, Lloveras J, Masramon J. Osteodystrophy of diabetics in chronic dialysis: A histomorphometric study. Calcif Tissue Int 1988;42:297–301.
Movsowitz C, Epstein S, Fallon M, Ismail F, Thomas S. Cyclosporin-A in vivo produces severe osteopenia in the rat: Effect of dose and duration of administration. Endocrinology 1988;123:2571–2577.
Bryer HP, Isserow JA, Armstrong EC, Mann GN, Rucinski B, Buchinsky FJ, Romero DF, Epstein S. Azathioprine alone is bone sparing and does not alter cyclosporin A-induced osteopenia in the rat. J Bone Miner Res 1995;10:132–138.
Evenepoel P, Naesens M, Claes K, Kuypers D, Vanrenterghem Y. Tertiary ‘hyperphosphatoninism’ accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant 2007;7:1193–1200.
Hokken-Koelega AC, van Zaal MA, van BW, de Ridder MA, Stijnen T, Wolff ED, de Jong RC, Donckerwolcke RA, de Muinck Keizer-Schrama SM, Drop SL. Final height and its predictive factors after renal transplantation in childhood. Pediatr Res 1994;36:323–328.
Sarwal MM, Yorgin PD, Alexander S, Millan MT, Belson A, Belanger N, Granucci L, Major C, Costaglio C, Sanchez J, Orlandi P, Salvatierra O, Jr. Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation. Transplantation 2001;72:13–21.
Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O, Jr. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extened daclizumab induction in pediatric renal transplantation. Transplantation 2003;76:1331–1339.
Fine RN, Yadin O, Nelson PA, Pyke-Grimm K, Boechat MI, Lippe BH, Sherman BM, Ettenger RB, Kamil E. Recombinant human growth hormone treatment of children following renal transplantation. Pediatr Nephrol 1991;5:147–151.
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation. Circulation 2004;110:97–101.
Ishitani MB, Milliner DS, Kim DY, Bohorquez HE, Heimbach JK, Sheedy PF, Morgenstern BZ, Gloor JM, Murphy JG, McBane RD, Bielak LF, Peyser PA, Stegall MD. Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients. Am J Transplant 2005;5:1689–1693.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Wesseling-Perry, K., Salusky, I.B. (2009). Chronic Kidney Disease Mineral and Bone Disorder. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76341-3_71
Download citation
DOI: https://doi.org/10.1007/978-3-540-76341-3_71
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-76327-7
Online ISBN: 978-3-540-76341-3
eBook Packages: MedicineReference Module Medicine