Información de la revista
Vol. 33. Núm. 5.septiembre 2013
Páginas 623-868
Vol. 33. Núm. 5.septiembre 2013
Páginas 623-868
Acceso a texto completo
Paricalcitol oral como agente antiproteinúrico en la enfermedad renal crónica
Oral paricalcitol as antiproteinuric agent in chronic kidney disease
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12743
Alberto de Lorenzoa, Alberto de Lorenzob, Laura Salanovaa, Laura Salanovab, Andrew S. Bombackc, Andrew S. Bombackd, María Moyaa, Maria Moyab, Francisco Coronele, Carmen Bernisa, Carmen Bernisb, José A. Sánchez-Tomeroa, José Antonio Sánchez-Tomerob, Vicente Álvareza, Vicente Álvarezb
a Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, Spain,
b Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, Madrid, España,
c Division of Nephrology, Columbia University College of Physicians and Surgeons, Presbyterian Hospital, New York, USA,
d Division of Nephrology, Columbia University College of Physicians and Surgeons, Presbyterian Hospital, New York, New York, USA,
e Servicio de Nefrología, Hospital Clinico Universitario San Carlos, Madrid, Madrid, España,
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Introducción: La vitamina D posee un efecto regulatorio del eje renina-angiotensina-aldosterona, jugando, por lo tanto, un papel importante en cuanto a proteinuria se refiere. Presentamos nuestra experiencia en el uso de paricalcitol como antiproteinúrico. Métodos: Incluimos 36 pacientes con un eGFR of 30-90 ml/min/1,73 m2 y proteinuria > 400 mg/d con dosis estables de inhibidores del SRAA durante 3 meses. Se le admistró durante 12 meses 1 µg/día de paricalcitol. Como objetivo primario estudiamos el descenso de proteinuria; como secundarios cambios en Cr, eFG, calcio, fósforo, iPTH, 25(OH)vitD, PCR y tension arterial. Resultados: La proteinuria media fue 2806 mg/d cayendo  hasta 2199 mg/d en el mes 6 (p < 0,0001) y 1931,5 mg/d a los 12 meses (p < 0,0001). Aquellos con una proteinuria basal  > 3000 mg/d (n=12) sufrieron una menor disminución (5956,9 ± 2492,6 mg/d a 4220,4 ± 2613 mg/d en mes 12) respecto a aquellos con una proteinuria < 3000 mg/d (1371 ± 627,5 mg/d a 821,3 ± 491,5 mg/d en mes 12). No se objetivaron cambios en tension arterial, eGFR y PCR. Los cambios en calcio, fósforo, iPTH y vitamina D 25(OH) fueron estadísticamente significativos. Conclusión: Nuestro estudio demuestra una reducción importante de proteinuria con dosis bajas de paricalcitol en pacientes con IRC, que es de particular importancia en aquellos con porteinuria basal entre 1-3 g/d.

Palabras clave:
Proteinuria
Palabras clave:
Sistema renina-angiotensina-aldosterona
Palabras clave:
Paricalcitol
Palabras clave:
Enfermedad renal crónica
Palabras clave:
Vitamina D

Background: Vitamin D has an important regulatory effect on the renin-angiotensin-aldosterone system, playing a central role in the regulation of proteinuria. We therefore studied the antiproteinuric effect of paricalcitol. Methods: 36 patients with an estimated GFR of 30-90mL/min/1.73m2 and proteinuria >400mg/d with a stable dose of ACE inhibitor or ARB for at least 3 months were recruited. Patients received oral paricalcitol 1µg/day for 12 months. Primary endpoint was decrease in proteinuria from baseline. Secondary endpoints were changes in creatinine, eGFR, serum levels of calcium, phosphorus, iPTH, 25(OH)vitD, C-Reactive Protein and blood presure. Results: Mean proteinuria was 2806mg/d and fell to 2199mg/d at month 6 (p<.0001) and 1931.5mg/d at month 12 (p<.0001). Patients with >3000mg/d baseline proteinuria (n=12) saw smaller relative reductions in proteinuria (5956.9±2492.6mg/d to 4220.4±2613mg/d at 12 months) than patients with <3000mg/d baseline proteinuria (1371±627.5 mg/d to 821.3±491.5mg/d at 12 months). There were no changes in BP, eGFR and CRP. We observed significant changes in serum levels of calcium, phosphorus, iPTH, 25(OH) vitamin D. Conclusion: Our study shows an important reduction in proteinuria with a low dose of oral paricalcitol in CKD, that is particularly robust with baseline proteinuria between 1-3g/d.

Keywords:
Proteinuria
Keywords:
Renin-angiotensin system
Keywords:
Paricalcitol
Keywords:
Chronic kidney disease
Keywords:
Vitamin D
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Bibliografía
[1]
Keane Wf, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): A position paper of the National Kidney Foundation. Am J Kidney Dis 1999;33:1004-10. [Pubmed]
[2]
de Zeeuw D. Targeting proteinuria as a valid surrogate for individualized kidney protective therapy. Am J Kidney Dis 2008;51:713-6. [Pubmed]
[3]
Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, et al. 1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter. J Biol Chem 2007;282(41):29821-30.
[4]
Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen YS, et al. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci U S A 2007;104:16810-5. [Pubmed]
[5]
Levin A, Li YC. Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease? Kidney Int 2005;68:1973-81. [Pubmed]
[6]
Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004;141:929-37. [Pubmed]
[7]
Wu-Wong JR, Nakane M, Ma J, Ruan X, Kroeger PE. Effects of Vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis 2006;186:20-8. [Pubmed]
[8]
Szeto C, Chow KM, Kwan BC, Chung KY, Leung CB, Li PK. Oral Calcitriol for the Treatment of Persistent Proteinuria in Immunoglobulin A Nephropathy: An Uncontrolled Trial. Am J Kidney Dis 2008;51(5):724-31. [Pubmed]
[9]
Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 2005;68:2823-8. [Pubmed]
[10]
Fishbane S, Chittineni H, Packman M, Dutka P, Ali N, Durie N. Oral Paricalcitol in the Treatment of Patients With CKD and Proteinuria: A Randomized Trial. Am J Kidney Dis 2009;54(4):647-52. [Pubmed]
[11]
Alborzi P, Patel NA, Peterson C, Bills JE, Bekele DM, Bunaye Z, et al. Paricalcitol Reduces Albuminuria and Inflammation in Chronic Kidney Disease: A Randomized Double-Blind Pilot Trial. Hypertension 2008;52:249-55.
[12]
Aperis G, Paliouras C, Zervos A, Arvanitis A, Alivanis P. The role of paricalcitol on proteinuria. J Ren Care 2011;37(2):80-4. [Pubmed]
[13]
de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010;376(9752):1543-51. [Pubmed]
[14]
De Nicola L, Conte G, Russo D, Gorini A, Minutolo R. Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study. BMC Nephrol 2012;13:150. [Pubmed]
[15]
Blanco-García R, Bravo-López JJ, Moreiras-Plaza M, Nájera-de la Garza W, Cossio-Annibar C, Beato-Coo L, et al. Microalbuminuria, another use for paricalcitol? Our experience in advanced chronic kidney disease. Nefrologia 2012;32(3):401-2.
[16]
Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25¿Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229-38.
[17]
Freundlich M, Quiroz Y, Zhang Z, Zhang Y, Bravo Y, Weisinger JR, et al. Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. Kidney Int 2008;74:1394-402. [Pubmed]
[18]
Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet 2007;369:1208-19. [Pubmed]
[19]
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. RENAAL Study Investigators: effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9. [Pubmed]
[20]
The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-63. [Pubmed]
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