D D D D (dose-depen- D (Vitamin D receptors) dent relationship) cal- (calcium-sensing receptors) citriol 0.5 mcg (phosphate transporters) PTH [3] (PTH gene transcription) (osteodystrophy) [1] ( 1) [4] 6407 (hypocalcemia) (hyperphosphatemia) 72 mg 2 /dl 2 34% 6.5 mg/dl 27% ( 2) calcitriol PTH ( 3) pre-pro-pth gene (transcription) [5] D [2] D ( s e c o n d a r y 3 hyperparathyroidism) D (calcitriol) 91 14 1 5
1α, 25(OH) 2 PTH 1, 25(OH) 2 1. [21] 2. 6 91 14 1
PTH PTH 3. [6] citrate ferric chloride (renal osteodystrophy) [12-13] Polyallylamine-hydrochloride (Sevelamer hydrochloride ) RenaGel PTH 200 pg/ml FDA (calcitriol) (pulse therapy) [7-9] RenaGel (calcimimetic agents) (calcium-sensing receptor CaR) [14-15] [10-11] (CaR) C-cell iron (III) oxide-hydroxide-modified dextran ferric ammonium CaR 91 14 1 7
PTH (analogs of vitamin ) CaR Vit. receptor ( VDR) PTH D PTH R- pre-pro-pth gene 568 CaR ( (analogs) ) [16-17] [18] R-568 (Serum binding protein, DBP) ( PTH [16-17] ) VDR ( VDR ) R-568 VDR ( PTH ) D ( 4) R-568 [20] D ( transcaltachia R- phenomenon) 568 [3] CaR [19] R-568 cal- citriol alfa-altacalcidol 4. D3 8 91 14 1
calcitriol [3] FDA RenaGel (lanthanum-base compound) ( 1) 1. Gokal R, Hutchison AJ, Ritz E, Slatopolsky E: Introduction. Kidney Int 1999; 56(suppl. 73): S1. 2. Okazaki T, Ando K, Igarashi T, et al: Conserved mechanism of negative gene regulation by extracellular calcium: Parathyroid hormone gene versus atrial natriuretic polypeptide gene. J Clin Invest 1992; 89: 1268-73. 3. William G, Goodman: Recent developments in the management of secondary hyperparathyroidism. Kidney Int 2001; 59: 1187-201. 4. 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(4): 607-17. 5. Llach F: Hyperphosphatemia in end-stage renal disease patients: pathophysiological consequences. Kidney Int 1999; 56: S31-7. 6. Amann K, Gross ML, London GM, Ritz E: Hyperphosphataemia--a silent killer of patients with renal failure? [editorial]. 1. D calcitriol calcitriol D 91 14 1 9
Nephrol Dial Transplant 1999; 14(9): 2085-7. 7. Chertow GM, Burke SK, Lazarus JM, et al: Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis 1997; 29(1): 66-71. 8. Slatopolsky EA, Burke SK, Dillon MA: RenaGel, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. The Rena- Gel Study Group. Kidney Int. 1999; 55(1): 299-307. 9. Bleyer AJ, Burke SK, Dillon M, et al: A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients [see comments]. Am J Kidney Dis 1999; 33(4): 694-701. 10. Chu HI, Hsu HC, Chao HC, Cheu SH: Calcium and phosphorus metabolism in osteomalacia. J Clin Invest 1941; 20: 255-71. 11. Chu HI: Studies of calcium and phosphorus metabolism with special reference to pathogenesis and effects of dihydrotachy-sterol and iron. Medicine 1943; 22: 103-61. 12. Hergesell O, Ritz E: Stabilized polynuclear iron hydroxide is an efficient oral phosphate binder in uraemic patients. Nephrol Dial Transplant 1999; 14(4): 863-7. 13. Chang JM, Hwang SJ, Tsai JC, Chen HC, Guh JY, Lai YH: Effect of ferric polymaltose complex as a phosphate binder in haemodialysis patients [letter]. Nephrol Dial Transplant 1999; 14(4): 1045-7. 14. Brown EM: Extracellular Ca 2+ sensing, regulation of parathyroid cell function, and role of Ca 2+ and other ions as extracellular (first) messengers. Physiol Rev 1991; 71(2): 371-411. 15. Brown EM, Gamba G, Riccardi D, et al: Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993; 366(6455): 575-80. 16. Silverberg SJ, Bone HG 3rd,Marriott TB, et al: Short-term inhibition of parathyroid hormone secretion by a calciumreceptor agonist in patients with primary hyperparathyroidism. N Engl J Med 1997; 337(21): 1506-10. 17. Antonsen JE, Sherrard DJ, Andress DL: A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication. Kidney Int 1998; 53(1): 223-7. 18. Collins MT, Skarulis MC, Bilezikian JP, Silverberg SJ, Spiegel AM, Marx SJ: Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent [see comments]. J Clin Endocrinol Metab 1998; 83(4): 1083-8. 19. Gogusev J, Duchambon P, Hory B, et al: Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997; 51(1): 328-36. 20. Brown AJ: Therapeutically active vitamin D analogs. Nephrol Exchange 1999, 8: 14-9. 21. Slatopolsky E, Brown A, Dusso A: Pathogenesis of secondary hyperparathyroidism. [Review] Kidney Int 1999; 56: S14-9. 10 91 14 1