Experiencia inicial con cinacalcet en Argentina
Resumen
Introducción: El hiperparatiroidismo secundario es una complicación frecuente de la enfermedad renal crónica. Cinacalcet, un moduladoralostérico del receptor sensor del calcio incrementa su sensibilidad a la activación por parte del calcio iónico extracelular, demostró ser efectivo en reducir los niveles de PTH. Objetivo: Evaluar la eficacia de cinacalcet en pacientes en hemodiálisis con HPTS. Material y métodos: Se realizó un estudio retrospectivo, multicéntrico, observacional, en 76 pacientes que recibieron al menos 3 meses de cinacalcet como tratamiento del HPTS. Resultados: La edad media fue 51±16 años, 61% eran varones. La mediana del tiempo en HD previo al inicio de cinacalcet fue 67 meses (43-109). El 40.8% completó el año de tratamiento. La mediana de PTH basal fue 1110 pg/ml (887-1477). Los niveles de PTH disminuyeron significativamente desde el primer mes de tratamiento 874(p<0.0001) al tercero 729 p<0.0001 y al sexto mes 602 p<0.0001. A partir del 9 mes permanecieron estables, logrando niveles objetivos de PTH en el 49% de los pacientes. La FAL bajó en forma significativa entre el 3 y 6 mes manteniéndose luego sin modificaciones. Descenso significativo en la calcemia (9.4mg/dl basal a 9 y 8.7 p< 0.0001) y fosfatemia (5.9 mg/dl basal a 5.5 y 5.3, p< 0.0001) al 1º y 3º mes de tratamiento. Conclusión: La dosis inicial de cinacalcet de 30 mg se aumentó significativamente al 3º y 6º mes (dosis media 50mg/día) pero sin modificaciones en el mes 9 y 12.Citas
Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011; 6:913–21.
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, et al. Association of elevated serum PO 4, CaPO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12:2131–8.
Young EW, Albert JM, Satayathum S, Goodkin DA, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005; 67:1179–87.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD). Kidney Int Suppl 2009; 113:S1-130.
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis2003; 42: S1–S201.
Goodman WG, Quarles LD. Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics. Kidney Int 2008; 74:276–88.
Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J Kidney Dis 2000; 35:1226–37.
Slatopolsky E, Brown A, Dusso A. Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl 1999; 73:S14–S19.
Cooper K, Quarles D, Kubo Y, Tomlin H, et al. Relationship between Reductions in Parathyroid Hormone and Serum Phosphorus during the Management of Secondary Hyperparathyroidism with Calcimimetics in Hemodialysis Patients. Nephron Clin Pract. 2012; 121:c124-30.
Brown EM, Mac Leod RJ. Extracellular Calcium Sensing and Extracellular Calcium Signaling. Physiol Rev 2001; 81:239-97.
Ne meth EF, Steffey ME, Hammerland LG, Hung BC, et al. Calcimimetics with potent and selective activity on the Parathyroid calcium receptor. Proc Natl Acad Sci USA 1998; 95:4040-5.
Block GA, Martin KJ, de Francisco AL, Turner SA, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med2004; 350:1516-25.
Yano S, Suzuki K, Sumi M, Tokumoto A, et al. Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism. J Bone Miner Metab 2010; 28: 49-54.
Bover J, Pérez R, Molina M, Benavides B, et al. Cinacalcet treatment for secondary hyperparathyroidism in dialysis patients: an observational study in routine clinical practice. Nephron Clin Pract 2011; 118:c109-21.
Komaba H, Nakanishi S, Fujimori A, et al. Cinacalcet effectively reduces parathyroid hormone secretion and gland volume regardless of pretreatment gland size in patients with secondary hyperparathyroidism. Clin J Am Soc Nephrol 2010; 5:2305-14.
Ureña-Torres P, Floege J, Hawley C, Pedagogos E, et al. Protocol adherence and the progression of cardiovascular calcification in the ADVANCE study. Nephrol Dial Transplant. 2013; 28:146-52.
Ureña P, Jacobson SH, Zitt E, Vervloet M, et al. Cinacalcet and achievement of the NKF/KDOQI recommended target values for bone and mineral metabolism in real-world clinical practice the ECHO observational study. Nephrol Dial Transplant 2009; 24:2852–9.
Moe SM, Chertow GM, Coburn JW, Quarles LD, et al. Achieving NKF-K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int 2005; 67:760–71.
Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012; 367:2482–94.
Fishbane S, Shapiro WB, Corry DB, Vicks SL, et al. Cinacalcet HCl and concurrent low dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results. Clin J Am Soc Nephrol 2008; 3:1718–25.
Messa P, Macario F, Yaqoob M, Bouman K, et al. The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol 2008; 3:36-45.
Ureña-Torres P, Bridges I, Christiano C, Cournoyer SH, et al. Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrol Dial Transplant 2013; 28:1241-54.
Raggi P, Chertow GM, Torres PU, Csiky B, et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 2001; 26:1327–39.
Malluche HH, Monier-Faugere MC, Wang G, et al. Cinacalcet HCl reduces bone turnover and bone marrow fibrosis in hemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant 2004: M016.
Serra AL, Savoca R, Huber AR, Hepp U, et al. Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Nephrol Dial Transplant 2007; 22:577–83.
Behets GJ, Spasovski G, Sterling LR, Goodman WG, et al. Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism. Kidney Int 2015; 87:846.56.
Fouque D, Roth H, Pelletier S, London GM, et al. Control of mineral metabolism and bone disease in haemodialysis. Nephrol Dial Transplant 2013; 28:360–7.
Fukagawa M, Kitaoka M, Yi H, Fukuda N, et al. Serial evaluation of parathyroid size by ultrasonography is another useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients. Nephron 1994; 68:221-8.
Indridason OS, Heath III H, Khosla S, Yohay DA, et al. Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism. Kidney Int 1996; 50:1663–71.
Drueke TB. Cell biology of parathyroid gland hyperplasia in chronic renal failure. J Am Soc Nephrol 2000; 11:1141–52.
Fukagawa M, Kitaoka M, Kurokawa K. Ultrasonographic intervention of parathyroid hyperplasia in chronic dialysis patients: a theoretical approach. Nephrol Dial Transplant 1996; 11 (Suppl 3):125-9.
Sumida E, Nakamura M, Ubara Y, et al. Cinacalcet Upregulates Calcium-Sensing Receptors of Parathyroid Glands in Hemodialysis Patients. Am J Nephrol 2013; 37:405–12.
Ritter CS, Finch JL, Slatopolsky EA, et al. Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor. Kidney Int 2001;60:1737-44.
Mizobuchi M, Hatamura I, Ogata H, Saji F, et al. Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency. J Am Soc Nephrol. 2004; 15:2579-87.
Mathias RS, Nguyen HT, Zhang MY, et al. Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency. J Am Soc Nephrol 1998; 9:2067-74.
Molostvov G, James S, Fletcher S, Bennett J, et al. Extracellular calcium-sensing receptor is functionally expressed in human artery. Am J Physiol Renal Physiol 2007; 293: F946-55.
