., . : ( 2 ) R. Owen 1862 . 1880 . I. Sandstrom, Uppsala ( ( ) ) F. Mandle 1925 . »( ) 1883 . R. Lucas 1 3 XX « », 1943 . S. Liu C. Su « » , , , 4 F. Albright 1937 . , 45 , H. Ellis (1997), , , D. Sherrard 1993 . , 20 , 5 ) 2 5 . , , , , KDIGO (Kidney Diseases Improving Global Outcomes) 2006 . CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder) – ( , ), 6 D 3 7 1. ( ) Na+ = H+ 2. ) 3. 4. Na+ 5. ; ( ) , 6. 8 1. 2. 4 D3 9 1. 2. - 3. D : 7DBP CH2 HO D3 OH D3 : ) ) CH2 HO 25(OH) : D2 D3 , 25D) OH ) 24- CH2 OH HO ,25(OH)2 , , 1,25D) D3 24-hydroxylase 24,25(OH)2D3 ,24,25(OH)2D3 5 1 1 2+ 1,25(OH)2D3 VD R R R R 2+ VD 1,25(OH)2D3 : • • • 1,25(OH)2D3 23 (FGF 23) FGF-23 – 32 , , 257 30-60 . FGF-23 , (FGFR) FGF-23 , NaPi1 1,25( 25( )D3 , FGF-23 )2D3 24,25( )2D3 6 FGF 23 (2) FGF 23 , , FGF 23 FGFR FGF 23 FGF 23 . , 1,25( )2D3 FGF 23 (3) FGF 23 FGF 23 , Pi, , , FGF 23 7 Klotho (1) Klotho, , 1997 . ( 13 , ) 1014 ( ) NH2 ADAM17 980 ADAM10 Klotho, , , FGF 23, Klotho plexus , , choroidal Klotho , , , , ), Klotho Klotho (2) Klotho FGF 23 , Klotho FGF 23 FGF 23 (TRPV5) (ROMK) , (TRPC6) , Klotho , Klotho , Klotho 8 D. Sherrard (1993) • : ( ) ( • • ) : , 9 1 9 (CaR) (VDR) 25( 1,25(OH)2D3 )D3 , FGF-23 (L.Quarles, 2012) FGF-23, , 1,25( 1,25( )2D3 )2D3, , , , , , 20 10 , 3 4 7 6 5 4 3 2 1 0 110-199 < 60 /1,73 200-299 300-399 400-499 461 2 500+ 90 Johnson et al. National Kidney Foundation Spring Clinical Meeting,Chicago, IL April, 2006 21 VDR : 3 4 CaSR 5 Tokumoto et al., Kidney Int., 2002 22 11 ) : ) - D , , ) : 23 2 4 • 1,25( • )2D3 (OH)D3 • 22 -1,25( , one alfa )2D3 (OH)D2 19- -1,25( )2D2 24 12 ) ,% 1- 84,% ( Marianne Rix et al, Nephrol Dial Transplant (2004) 19: 870–876 D n = 67,399 100 90 (%) 90 (%) n = 16,483 100 80 80 70 70 60 60 50 50 40 40 30 3- 30 : 59% 20 51% p<0.001 10 2- 20 : 73% p=0.04 10 0 64% 0 0 5 10 15 20 25 30 35 0 40 ( 5 10 15 20 25 30 35 40 ) Teng M et al., N Engl J Med 2003;349:446–56. 26 13 2) ( , 24 48 Am Heart J 2012; 164: 902-909.e2. 27 II ( 40 100 20 0 VDR (-/-) 60 200 VDR (+/+) 80 300 VDR (-/-) .) 400 100 * * 120 . 500 II, 140 * VDR (+/+) 600 0 VDR(+/+) VDR(-/-) Kong et al., ASN Meeting, 2005 28 14 , CaSR CaSR 2 9 , CaSR ( Ca2+. )I II CaSR, Ca2+, III , , ( ) CaSR II , , , , CaSR 29 3 [ 100 ) 300 - 499 1000 500 - 800 >800 80 ( 1200 ] 800 60 600 40 –65%* –31%* 20 400 ( –49%* 200 ) = : 150-300 0 0 -6 300 - 499 500 - 800 > 800 . .3 .6 n = 275 n = 435 n = 606 n = 328 n = 483 n = 660 Ureña et al, Nephrol Dial Transplant 2009;24:2852-9. . 12 . 12 30 15 100 90 80 70 60 %50 40 30 20 10 0 2,24 2704 74% 74% , 0,58 Glen T. Schumock et al., Nephron Clin Pract 2011;117:c151–c159 3 2 INTIMA MEDIA 90% Mönckeberg) 60% 30% : 20% : ) , , , , , . 32 16 ( ) 33 5 ) 1 0 1 0.75 2 0.5 3 0.25 4 p<0.0001 N = 110 0 0 20 40 60 ( 80 ) Blacher et al., Hypertension, 2001 34 17 3 5 Al Ca Mg ( , ) (Fosrenol) ( 435 235 + ) 35 3 6 18 3 7 Ca x 3,5 ) 7 , 6,5 RenaGel 6 5,5 2,5 Ca x 5 2 Ca x P ( 3 4,5 0 1 Pi 2 3 4 5 6 7 8 9 10 11 12 , Ca x P E. Slatopolsky et al., Kidney Int, 1999; v.55, p 299 3 8 80 75 70 60 50 40 141 52 37 30 20 10 0 0 0 1 Chertow GM et al., Kidney International 2002; 62:245-252 19 , : « » , 20