Abstract
The efficacy and acceptability of cinacalcet for treatment of secondary hyperparathyroidism (SHPT) was assessed in seven pediatric patients suffering from end-stage renal disease (ESRD) presenting with inadequately controlled SHPT despite conventional management. Patients received daily treatment with cinacalcet (dosage 0.25 mg/kg body weight) for a total of 4 weeks. Within 4 h after application of the first dose, median levels of serum parathyroid hormone (PTH) had decreased from 932 pg/ml (range 511–1,938 pg/ml) to 584 pg/ml (88–937 pg/ml), and final pre-dose values after 4 weeks were 199 pg/ml (121–940 pg/ml; each P < 0.05 versus baseline). Median concentrations of serum calcium (Ca) decreased within 4 h of the first administration, from 2.56 mmol/l to 2.38 mmol/l, returning to 2.58 mmol/l at 24 h, and they remained slightly decreased compared to baseline values thereafter (each P < 0.05 versus baseline). Both the median levels of serum phosphorus (P) and the Ca × P ion product decreased significantly during the 4-week period. Cinacalcet was well tolerated and without drug-related adverse effects. Thus, even with approximately half of the dose usually given to adult dialysis patients, PTH and the Ca × P ion product were markedly reduced in pediatric ESRD patients presenting with inadequately controlled SHPT. Therefore, our results support the initiation of a randomized, controlled, long-term trial in children.
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Abbreviations
- Alk. Ptases:
-
alkaline phosphatase
- ARPKD:
-
autosomal-recessive polycystic kidney disease
- Ca:
-
calcium
- Ca × P:
-
calcium-phosphorus ion product
- CaSR:
-
Ca sensing receptor
- CKD:
-
chronic kidney disease
- P:
-
phosphorus
- PTH:
-
parathyroid hormone
- SHPT:
-
secondary hyperparathyroidism
References
Chesney RW, Moorthy AV, Eisman JA, Jax DK, Mazess RB, DeLuca HF (1978) Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy. N Engl J Med 298:238–242
Mehls O, Wuhl E, Haffner D, Schaefer F, Tonshoff B (1996) Growth hormone treatment of short children with chronic renal failure before and after renal transplantation: rationale and recent results. Nephrol Dial Transplant 11:1747–1750
Parfitt AM (1997) The hyperparathyroidism of chronic renal failure: a disorder of growth. Kidney Int 52:3–9
Slatopolsky E, Delmez JA (1994) Pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 23:229–236
Wuhl E, Haffner D, Nissel R, Schaefer F, Mehls O (1996) Short dialyzed children respond less to growth hormone than patients prior to dialysis. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Pediatr Nephrol 10:294–298
Pieper AK, Haffner D, Hoppe B, Dittrich K, Offner G, Bonzel KE, John U, Frund S, Klaus G, Stubinger A, Duker G, Querfeld U (2006) A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD. Am J Kidney Dis 47:625–635
Briese S, Wiesner S, Will JC, Lembcke A, Opgen-Rhein B, Nissel R, Wernecke KD, Andreae J, Haffner D, Querfeld U (2006) Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease—impact of calcium and vitamin D therapy. Nephrol Dial Transplant 21:1906–1914
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483
Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105
Kuizon BD, Goodman WG, Juppner H, Boechat I, Nelson P, Gales B, Salusky IB (1998) Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int 53:205–211
Nemeth EF, Steffey ME, Hammerland LG, Hung BC, Van Wagenen BC, DelMar EG, Balandrin MF (1998) Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci U S A 95:4040–4045
Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, Hercz G, Cunningham J, Abu-Alfa AK, Messa P, Coyne DW, Locatelli F, Cohen RM, Evenepoel P, Moe SM, Fournier A, Braun J, McCary LC, Zani VJ, Olson KA, Drueke TB, Goodman WG (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350:1516–1525
Chertow GM, Blumenthal S, Turner S, Roppolo M, Stern L, Chi EM, Reed J (2006) Cinacalcet hydrochloride (Sensipar) in hemodialysis patients on active vitamin D derivatives with controlled PTH and elevated calcium × phosphate. Clin J Am Soc Nephrol 1:305–312
El-Amm JM, Doshi MD, Singh A, Migdal S, Morawski K, Sternbauer D, Cincotta E, West MS, Losanoff JE, Gruber SA (2007) Preliminary experience with cinacalcet use in persistent secondary hyperparathyroidism after kidney transplantation. Transplantation 83:546–549
Goodman WG, Hladik GA, Turner SA, Blaisdell PW, Goodkin DA, Liu W, Barri YM, Cohen RM, Coburn JW (2002) The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 13:1017–1024
Lindberg JS, Moe SM, Goodman WG, Coburn JW, Sprague SM, Liu W, Blaisdell PW, Brenner RM, Turner SA, Martin KJ (2003) The calcimimetic AMG 073 reduces parathyroid hormone and calcium × phosphorus in secondary hyperparathyroidism. Kidney Int 63:248–254
Martin KJ, Juppner H, Sherrard DJ, Goodman WG, Kaplan MR, Nassar G, Campbell P, Curzi M, Charytan C, McCary LC, Guo MD, Turner SA, Bushinsky DA (2005) First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl. Kidney Int 68:1236–1243
Moe SM, Cunningham J, Bommer J, Adler S, Rosansky SJ, Urena-Torres P, Albizem MB, Guo MD, Zani VJ, Goodman WG, Sprague SM (2005) Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Nephrol Dial Transplant 20:2186–2193
Quarles LD, Sherrard DJ, Adler S, Rosansky SJ, McCary LC, Liu W, Turner SA, Bushinsky DA (2003) The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 14:575–583
Serra AL, Savoca R, Huber AR, Hepp U, Delsignore A, Hersberger M, Wuthrich RP (2007) Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Nephrol Dial Transplant 22:577–583
Szwarc I, Argiles A, Garrigue V, Delmas S, Chong G, Deleuze S, Mourad G (2006) Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism. Transplantation 82:675–680
Goodman WG (2003) Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials. Pediatr Nephrol 18:1206–1210
Payne RB, Carver ME, Morgan DB (1979) Interpretation of serum total calcium: effects of adjustment for albumin concentration on frequency of abnormal values and on detection of change in the individual. J Clin Pathol 32:56–60
Langman CB, Salusky IB, Greenbaum L, Jueppner H, Leonard M, Nelson P, Portale A, Warady BA (2005) K/DOQI Clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 46:1–121
Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S, Yamaguchi A (1997) Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 99:2961–2970
Schmitt CP, Hessing S, Oh J, Weber L, Ochlich P, Mehls O (2000) Intermittent administration of parathyroid hormone (1–37) improves growth and bone mineral density in uremic rats. Kidney Int 57:1484–1492
Wada M, Furuya Y, Kobayashi N, Kobayashi N, Miyata S, Ishii H, Nagano N (2003) The calcimimetic compound AMG 073 (cinacalcet HCl) ameliorates osteitis fibrosa in rats with chronic renal insufficiency. J Am Soc Nephrol 14:48A
Daschner M, Philippin B, Nguyen T, Wiesner RJ, Walz C, Oh J, Sandow J, Mehls O, Schaefer F (2002) Circulating inhibitor of gonadotropin releasing hormone secretion by hypothalamic neurons in uremia. Kidney Int 62:1582–1590
Haffner D, Schaefer F, Nissel R, Wuhl E, Tonshoff B, Mehls O (2000) Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. N Engl J Med 343:923–930
Schaefer F, Seidel C, Binding A, Gasser T, Largo RH, Prader A, Scharer K (1990) Pubertal growth in chronic renal failure. Pediatr Res 28:5–10
Nakagawa K, Geldyyev A, Oh J, Gross ML, Santos F, Schaefer F, Schmitt CP (2006) Calcimimetics do not alter epiphyseal growth in healthy and uremic rats. J Am Soc Nephrol 17:132A
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Muscheites, J., Wigger, M., Drueckler, E. et al. Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol 23, 1823–1829 (2008). https://doi.org/10.1007/s00467-008-0810-5
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DOI: https://doi.org/10.1007/s00467-008-0810-5