(PTH) X 56% Salusky 50% (renal osteodystrophy) (osteoclast) (osteoid) (ESRD) (woven) (osteitis fibrosa) 1. 25 30% (high turnover rate disease) (low turnover rate disease) (mixed (ionized calcium) osteodystrophy) Lopez-Hilker [2] ( 1) [1] Vit D PTH 1. 204 91 14 4
1α-hydroxylase calcitriol (1,25 (OH) 2 ) Portale [3] ipth receptor-adenylate cyclase system 1,25(OH) 2 2. (desensitization) calcitriol Vit D (osteomalacia) (adynamic bone disease) PTH mrna 3.Calcitriol hydroxyapatite 1α-hy- ipth droxylase 25(OH) calcitriol intact PTH (ipth) Vit D 22% calcitriol ipth 50% calcitriol pre-pro-parathyroid hormone calcitriol (intermittent) calcitriol calcitriol (hypocellular) (CCr 80 ml/min) calcitriol 4.iPTH Vit (calciphylaxis) (calcium-sensing receptor) (cytokine) mrna (set-point of calcium) ipth (osteoblast) [4] functional parathyroid mass [5] PTH PTH T B PTH C-terminal TNF-α IL-1 ipth IL-6 TNF-α IL-1 5. ipth (skeletal resistance) IL-6 [6].TGF-β ipth(transforming growth factor) (interfero-ns) [7] 91 14 4 205
gait) calcitriol syndrome Monckebergis arteriosclerosis (slipped epiphyses) 30 50% X-ray (subperiosteal resorption) IGF-1 (insulin-like growth factor) (intracortical) (endosteal) ( m i ddl e phalanges) [1] IGF-1 (metaphysis) (diaphysis) Vit D metaphysis [8] (radiolucent zone) VitD (rachitic rosary) Harrison's sulcus (frontal bossing) (periosteal neostosis) (craneotabes) (genu (osteosclerosis) valgum) X-ray (salt and calcitriol 25 30% pepper) (metaphysis) X-ray : looser 11.4 4.4 zones (radiolucent band) 3.9 4.3 (proximal myopathy) (wadding (extraskeletal calcification) 70 red eye 25 30% 400 800 mg/day 206 91 14 4
Ritz [15] calcitriol 4.8 7.2 mg/dl (creatinine 3 mg/dl) cre- 1 2 4.5 5.8 mg/dl 4 5.5 atinine 3 mg/dl PTH mg/dl [9] calcitirol calcitirol ( ) 30 mg/kg/day 2 3 (intermittent) (daily) ( calcium citrate sodium citrate Alka Seltzer) 3 5 µg/week tight junction ipth [17] [10-11] [20-21] 5.1 2.5 g/day ipth calcitriol ( sevelamer hydrochloride) [17] ipth [16-19] calcitriol calcitriol Ardissiono [20] 6.5 mg/dl 72 calcitriol [12-13] PTH Salusky [22] ipth PTH 33% 5.5 6 mg/dl 9.5 10.5 mg/dl Vit D calcitriol 0.25 µg alfacalcidol 0.5 µg [23] Vit D calcitriol ipth Vit D Salusky [24] 10 mg/dl ipth PTH 200 pg/ml (remoldeling) 10 mg/dl i PTH 150 pg/ml [14] ipth 150 91 14 4 207
200 pg/ml Vit D 1α-(OH) 1-hydroxylation 25-hydroxylation calcitriol calcifediol (25(OH) D) Kidney Int 1991; 39: 954-60. ipth 22-oxacalcitriol ipth Vit D ipth Vit D 10 ng/l (1) (2) (3) (4) (5) 1. Kuizon BD, Salusky IB: Diagnosis and treatment of renal bone diseases in children undergoing CAPD/CCPD. In CAPD/ CCPD in Children 2nd ed, Fine RN, Alexander SR, Warady BA eds. Kluwer Academic Publishers, USA 1998; pp.119-217. 2. Lopez-Hilker S, Dusso A, Rapp N, Mrtin KJ, Salatopolsky E: Phosphorus restriction reverses hyperparathyroidism in uremia independent of changes in calcium and calcitriol. Am J Physiol 1990; 259: F432-7. 3. Portale AA, Booth BE, Halloran BP, Morris RC: Effect of dietary phosphorus on circulating concentration of 1,25-dehydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest 1984; 73: 1580-9. 4. Ramirez JA, Goodman WG, Belin T, et al: Calcitriol therapy and calcium-regulated PTH secretion in patients with secondry hyperparathyroidism. Am J Physiol 1994; 267: E961-7. 5. Lefebvre A, De Vernejoul DC, Gueris J, et al: Optimal correction of acidosis changes progression of renal osteodystrophy. Kidney Int 1989; 36: 1112-8. 6. Descamps-Latscha B, Herbelin A, Nguyen AT, et al: Balance between IL-1β, TNF and their specific inhibitors in chronic renal failure and maintenance dialysis. J Immunol 1995; 154: 882-92. 7. Brockhaus M, Bar-Khayim Y, Gurwicz S, et al: Plasma tumor necrosis factor soluble receptors in chronic renal failure. 8. Brook CG.D, Hindmarch PC: Clinical Pediatric Endocrinology. 4th ed, Blackwell Scinece Ltd, London 2000; pp.393. 9. Potale A: Calcium and Phosphate. In Pediatric Nephrology, Holliday MA, Barratt TM, Avner ED, eds. Williams & Wilkins, Baltimore 1994; pp.247. 10. Cobum JW, Mischel MG, Goodman WG, Salusky IB: Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis 1991; 17: 708-11. 11. Bakir AA, Hryhorczuk DO, Berman E, et al: Acute fatal hyperaluminemic encephalophthy in undialyzed and recently dialyzed uremic patients. Trans Am Soc Artif Intern Organs 1986; 32: 171-6. 12. Block GA, Hulbert-Shearon TE, Levin NW, Port FK: 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: 607-17. 13. Goodmen WG, Goldin J, Kuizon B, et al: Coronary artery calcification in young adult with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478-83. 14. Dabbagh S:Renal osteodystrophy. Curr Opin Pediatr 1998; 10: 190-6. 15. Ritz E, Kuster S, Schmidt-Gayk H, et al: Low-dose clacitriol prevents the rise in 1,84 ipth without affecting serum calcium and phosphate in patients with moderate renal failure. Nephrol Dial Transplant 1995; 10: 2228-34. 16. Saltopolsky E, Weerts C, Thielan J, et al: Marked suppression of secondary hyperparathroidism by intravenous administration of 1,25-dihydroxycholecalci-ferol in uremic patients. J Clin Invest. 1984; 74: 2136-43. 17. 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: 1160-6. 18. Cano F, Delucchi A, Wolff E, Rodriguez, Fuentes A: Calcitriol oral pulse therapy in children with renal osteodystrophy. Pediatr Nephrol 1995; 9: 606-8. 19. Watanabe Y, Inaguma D, Fukuzawa Y, et al: Oral vitamin D3 pulse therapy for overt secondary hyperparathyroidism at predialysis stage. Nephrol Dial Transplant 1996; 11: 910-1. 20. Ardissiono G, Schmitt CP, Testa S, et al: Calcitriol pulse therapy is not more effective than daily calcitriol therapy in controlling secondary hyperparathyroidism in children with chronic renal failure. Pediatr Nephrol 2000; 14: 664-8. 21. Moe SM, Kraus MA, Gassensmith CM, Fineberg NS, Gannon FH, Peacock M: Safety and efficacy of pulse and daily calcitriol in patients on CAPD: A randomized trial. Nephrol Dial Transplant 1998 ; 13: 1234-41. 22. Salusky IB, Goodman WG, Kuizon BD: Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism. Pediat Nephrol 2000; 14: 641-5. 23. Cheryl P. Sanchez: Prevention and treatment of renal osteodystrophy in children with chronic renal insufficiency and endstage renal disease. Semin Nephrol 2001; 21: 441-50. 24. Salusky IB, Ramirez JA, Openheim W, et al: Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int 1994; 45: 253-8. 208 91 14 4