title: Phosphate binders, vitamin D and calcimimetics in the management of chronic kidney disease-mineral bone disorders (CKD-MBD) in children.
abstract: In order to minimize complications on the skeleton and to prevent extraskeletal calcifications, the specific aims of the management of chronic kidney disease mineral and bone disorder (CKD-MBD) are to maintain blood levels of serum calcium and phosphorus as close to the normal range as possible, thereby maintaining serum parathyroid hormone (PTH) at levels appropriate for CKD stage, preventing hyperplasia of the parathyroid glands, avoiding the development of extra-skeletal calcifications, and preventing or reversing the accumulation of toxic substances such as aluminum and β2-microglobulin. In order to limit cardiovascular calcification, daily intake of elemental calcium, including from dietary sources and from phosphate binders, should not exceed twice the daily recommended intake for age and should not exceed 2.5 g/day. Calcium-free phosphate binders, such as sevelamer hydrochloride and sevelamer carbonate, are safe and effective alternatives to calcium-based binders, and their use widens the margin of safety for active vitamin D sterol therapy. Vitamin D deficiency is highly prevalent across the spectrum of CKD, and replacement therapy is recommended in vitamin D-deficient and insufficient individuals. Therapy with active vitamin D sterols is recommended after correction of the vitamin D deficiency state and should be titrated based on target PTH levels across the spectrum of CKD. Although the use of calcimimetic drugs has been proven to effectively control the biochemical features of secondary hyperparathyroidism, there is very limited experience with the use of such agents in pediatric patients and especially during the first years of life. Studies are needed to further define the role of such agents in the treatment of pediatric CKD-MBD.
authors: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors: Katherine
authors: K
authors: Wesseling-Perry
authors: Isidro B
authors: IB
authors: Salusky
mesh_terms: D015415:Biomarkers / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood*; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D010710:Phosphates / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D016896:Treatment Outcome; D014807:Vitamin D / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy; D014815:Vitamins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D057966:Calcimimetic Agents; D002614:Chelating Agents; D010710:Phosphates; D014815:Vitamins; D014807:Vitamin D; D002118:Calcium
references: Kidney Int. 2006 Nov;70(10):1858-65
references: 17021609
references: Nephron Clin Pract. 2007;105(3):c132-8
references: 17228173
references: Ther Apher Dial. 2005 Aug;9(4):336-9
references: 16076378
references: Ann Clin Biochem. 2012 Nov;49(Pt 6):546-53
references: 22984195
references: Kidney Int. 1990 Nov;38(5):931-6
references: 2266678
references: Kidney Int. 2010 Dec;78(12):1295-304
references: 20811335
references: J Endocrinol. 2007 Oct;195(1):125-31
references: 17911404
references: Hemodial Int. 2007 Oct;11(4):417-23
references: 17922738
references: Pediatr Nephrol. 2006 Feb;21(2):151-9
references: 16247644
references: Clin J Am Soc Nephrol. 2012 Apr;7(4):624-31
references: 22300739
references: Nephrol Dial Transplant. 2011 Feb;26(2):584-91
references: 20631407
references: J Am Soc Nephrol. 2007 Sep;18(9):2600-8
references: 17656479
references: J Clin Endocrinol Metab. 2009 Feb;94(2):511-7
references: 19050056
references: Pediatr Nephrol. 2010 Dec;25(12):2483-8
references: 20872152
references: Kidney Int. 2010 Oct;78(8):818; author reply 818
references: 20877377
references: J Pediatr. 1982 May;100(5):815-20
references: 7069549
references: J Clin Invest. 2007 Dec;117(12):4003-8
references: 17992255
references: Miner Electrolyte Metab. 1998;24(4):290-5
references: 9554570
references: Nephron Clin Pract. 2006;102(2):c61-71
references: 16224198
references: Nephrol Dial Transplant. 2003 Jun;18 Suppl 3:iii13-7
references: 12771292
references: Kidney Int. 1998 Sep;54(3):907-14
references: 9734615
references: J Bone Miner Res. 2010 Feb;25(2):305-12
references: 19594303
references: Kidney Int. 2007 Oct;72(8):1004-13
references: 17687259
references: Nephrol Dial Transplant. 2006 Aug;21(8):2217-24
references: 16595583
references: Clin J Am Soc Nephrol. 2012 Mar;7(3):487-93
references: 22241819
references: Arch Dis Child. 2008 Nov;93(11):959-62
references: 18463127
references: J Am Soc Nephrol. 2012 Aug;23(8):1407-15
references: 22822075
references: Pediatrics. 2009 Mar;123(3):791-6
references: 19255004
references: Pediatr Nephrol. 2011 Jun;26(6):945-51
references: 21359960
references: Bone. 2009 Dec;45(6):1161-8
references: 19679205
references: Arch Dis Child. 1977 Jun;52(6):473-81
references: 879833
references: Kidney Int. 2005 Dec;68(6):2809-13
references: 16316357
references: Lancet. 1986 Apr 19;1(8486):880-2
references: 2870354
references: Clin J Am Soc Nephrol. 2010 Oct;5(10):1860-6
references: 20634327
references: N Engl J Med. 2000 May 18;342(20):1478-83
references: 10816185
references: Kidney Int. 2011 Jan;79(1):112-9
references: 20861820
references: J Pediatr. 1986 May;108(5 Pt 1):767-70
references: 3701525
references: N Engl J Med. 2008 Aug 7;359(6):584-92
references: 18687639
references: Clin J Am Soc Nephrol. 2010 Feb;5(2):286-91
references: 19965540
references: J Am Soc Nephrol. 2007 Feb;18(2):613-20
references: 17202417
references: J Am Soc Nephrol. 2011 May;22(5):956-66
references: 21436289
references: Nephrol Dial Transplant. 1999 Dec;14(12):2907-14
references: 10570096
references: Clin J Am Soc Nephrol. 2012 Feb;7(2):216-23
references: 22266572
references: Nephrol Dial Transplant. 2008 Sep;23(9):2761-7
references: 18408076
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16810-5
references: 17942703
references: Proc Soc Exp Biol Med. 1985 Mar;178(3):432-6
references: 3871952
references: Nephron Physiol. 2007;107(2):p35-44
references: 17687191
references: J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):381-8
references: 17293108
references: Nephrol Dial Transplant. 2011 Apr;26(4):1327-39
references: 21148030
references: N Engl J Med. 2003 Jul 31;349(5):446-56
references: 12890843
references: Am J Kidney Dis. 2008 Jun;51(6):987-95
references: 18430500
references: Am J Kidney Dis. 2007 Jun;49(6):814-23
references: 17533024
references: J Clin Invest. 1997 Dec 15;100(12):2977-83
references: 9399943
references: Circulation. 2009 May 19;119(19):2545-52
references: 19414634
references: Kidney Int. 2005 Sep;68(3):1236-43
references: 16105056
references: Kidney Int. 2005 Dec;68(6):2823-8
references: 16316359
references: Kidney Int. 1998 Jun;53(6):1696-705
references: 9607202
references: Am J Kidney Dis. 2005 Jun;45(6):1026-33
references: 15957131
references: Kidney Int. 2012 Jun;81(11):1116-22
references: 22297674
references: Kidney Int Suppl. 2009 Aug;(113):S1-130
references: 19644521
references: J Am Soc Nephrol. 2004 Jul;15(7):1943-51
references: 15213285
references: Am J Kidney Dis. 1999 Apr;33(4):694-701
references: 10196011
references: Clin J Am Soc Nephrol. 2009 Jan;4(1):178-85
references: 19056618
references: Clin Nephrol. 1999 Jan;51(1):18-26
references: 9988142
references: Nephrol Dial Transplant. 2009 Aug;24(8):2595-8
references: 19420106
references: Clin Nephrol. 1986 Oct;26(4):185-91
references: 3536232
references: Nephrol Dial Transplant. 2011 Aug;26(8):2567-71
references: 21436379
references: J Clin Invest. 2011 Nov;121(11):4393-408
references: 21985788
references: Nephrol Dial Transplant. 1999 Apr;14(4):863-7
references: 10328460
references: Am J Kidney Dis. 2006 Feb;47(2):263-76
references: 16431255
references: Pediatr Nephrol. 2010 Jan;25(1):143-8
references: 19838738
references: Pediatr Nephrol. 2008 Oct;23(10):1831-6
references: 18575896
references: J Am Soc Nephrol. 2005 Apr;16(4):1115-25
references: 15728786
references: Kidney Int. 1994 Oct;46(4):1160-6
references: 7861712
references: Clin J Am Soc Nephrol. 2010 Jan;5(1):110-6
references: 19965548
references: Clin J Am Soc Nephrol. 2012 Jan;7(1):146-52
references: 22052943
references: Kidney Int. 2002 Jul;62(1):245-52
references: 12081584
references: Kidney Int. 1998 Jan;53(1):205-11
references: 9453020
references: Kidney Int. 2006 Jun;69(11):1945-53
references: 16641930
references: N Engl J Med. 2012 Dec 27;367(26):2482-94
references: 23121374
references: Pediatr Nephrol. 2012 Oct;27(10):1953-9
references: 22639045
references: J Am Soc Nephrol. 2010 Oct;21(10):1713-23
references: 20651168
references: Kidney Int. 2006 Aug;70(4):654-9
references: 16807549
references: Clin Nephrol. 2008 Apr;69(4):269-78
references: 18397701
references: J Am Coll Cardiol. 2002 Feb 20;39(4):695-701
references: 11849871