Información de la revista
Vol. 35. Núm. 1.Enero 2015
Páginas 1-124
Vol. 35. Núm. 1.Enero 2015
Páginas 1-124
Acceso a texto completo
Endurecimiento arterial en el trasplante renal: estudio caso-control en un único centro para la comparación de un tratamiento inmunosupresor con belatacept frente a uno con inhibidores de la calcineurina
Arterial stiffness in kidney transplantation: a single center case-control study comparing belatacept versus calcineurin inhibitor immunosuppressive based regimen
Visitas
9359
Edoardo Melillia, Oriol Bestard-Matamorosb, Anna Manonelles-Monterob, Neus Sala-Bassab, Richard Mastb, Josep M. Grinyó-Boirab, Josep M. Cruzadob
a Departamento de Nefrología y Trasplante Renal, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona,
b Departamento de Nefrología y Trasplante Renal, Hospital Universitari de Bellvitge L'Hospitalet de Llobregat, Barcelona,
Este artículo ha recibido
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas

Actualmente, el endurecimiento arterial se considera un buen indicador de mortalidad cardiovascular tanto en la población general como en receptores de trasplantes de renales. Para cuantificarlo, el método más empleado es la medición de la velocidad de onda del pulso carótido-femoral (VOPcf). El objetivo de este estudio es analizar si un tratamiento inmunosupresor con belatacept, sin inhibidores de la calcineurina (ICN), se asocia a una VOPcf (como marcador alternativo del endurecimiento arterial) menor que la asociada a un tratamiento con ICN. Se trata de un estudio retrospectivo caso-control, en el que incluimos todos los casos que recibieron un tratamiento inmunosupresor de mantenimiento con belatacept en nuestro centro (n=20). Para estos, seleccionamos un grupo de controles adecuado (n=20), que había recibido un tratamiento con ICN y con idénticos factores clave asociados al endurecimiento arterial. Tras el seguimiento llevado a cabo durante los 5 años posteriores al trasplante, la prevalencia de pacientes con una VOPcf superior a 8,1 m/s se había reducido en el grupo al que se le administró belatacept (50% en el grupo BLC frente al 25% en el grupo ICN, p = 0,08). El análisis de regresión logística multivariante reveló que el riesgo de presentar una VOPcf alta se encontraba correlacionado con la edad (OR: 1,24; p < 0,03) y el índice de resistencia renal (OR: 1,25; p < 0,05). El tratamiento con belatacept se asoció a una reducción significativa del riesgo de aumentar la VOPcf (OR: 0,008; p = 0,045). La inmunosupresión de mantenimiento con belatacept podría favorecer la tasa de supervivencia de receptores de trasplantes renales gracias a la disminución de los eventos cardiovasculares relacionados con el endurecimiento arterial.

Palabras clave:
Trasplante renal
Palabras clave:
Inhibidores de la calcineurina
Palabras clave:
Endurecimiento arterial
Palabras clave:
Belatacept
Palabras clave:
Velocidad de onda del pulso

Arterial stiffness is nowadays a well-accepted predictor of cardiovascular mortality in general population; as well as in kidney transplant recipient population. The femoral-carotid pulse wave velocity (cf-PWV) is the widest used method to assess the arterial stiffness. The aim of this study was to test whether CNI-free immunosuppression based on belatacept was associated with lower cf-PWV, as a surrogate marker of arterial stiffness, than CNI. This was a retrospective case-control study. We included all the cases treated with belatacept as a maintenance immunosuppression in our center (n=20). An appropriate control group of patients (n=20) treated with CNI was selected to achieve match for key factors associated with arterial stiffness. After a follow-up of 5 years after transplantation, the Belatacept group had a reduced prevalence of patients with a cf-PWV higher than 8.1m/s (50% in BLC vs. 25% in CNI, p=0.08). At multivariate logistic regression analysis, the risk of high cf-PWV was correlated with age (OR 1.24; p<0.03) and renal resistive index (OR 1.25; p<0.05). Belatacept treatment was associated with a significant reduction in risk of cf-PWV (OR 0.008; P=0.045). Belatacept-based maintenance immunosuppression could improve kidney transplant recipient’s survival by reducing cardiovascular events related to stiffness.

Keywords:
Renal transplantation
Keywords:
Calcineurin inhibitors
Keywords:
Arterial stiffness
Keywords:
Belatacept
Keywords:
Pulse wave velocity
El Texto completo está disponible en PDF
Bibliografía
[1]
Pilmore H, Dent H, Chang S, McDonald SP, Chadban SJ. Reduction in cardiovascular death after kidney transplantation. Transplantation 2010;89:851-7. [Pubmed]
[2]
Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int 2012;82:388-400. [Pubmed]
[3]
Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal disease. Circulation 2001;103:987-92. [Pubmed]
[4]
Verbeke F, Maréchal C, Van Laecke S, Van Biesen W, Devuyst O, Van Bortel LM, et al. Aortic stiffness and central wave reflections predict outcome in renal transplant recipients. Hypertension 2011;58:833-8. [Pubmed]
[5]
Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236-41. [Pubmed]
[6]
Kusche-Vihrog K, Urbanova K, Blanqué A, Wilhelmi M, Schillers H, Kliche K, et al. C-reactive protein makes human endothelium stiff and tight. Hypertension 2011;57(2):231-7. [Pubmed]
[7]
Barnes JN, Nualnim N, Sugawara J, Sommerlad SM, Renzi CP, Tanaka H. Arterial stiffening, wave reflection, and inflammation in habitually exercising systemic lupus erythematosus patients. Am J Hypertens 2011;24(11):1194-200. [Pubmed]
[8]
Temmar M, Liabeuf S, Renard C, Czernichow S, Esper NE, Shahapuni I, et al. Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens 2010;28(1):163-9. [Pubmed]
[9]
Cecelja M, Jiang B, Bevan L, Frost ML, Spector TD, Chowienczyk PJ. Arterial stiffening relates to arterial calcification but not to noncalcified atheroma in women. A twin study. J Am Coll Cardiol 2011;57(13):1480-6. [Pubmed]
[10]
McEniery CM, Spratt M, Munnery M, Yarnell J, Lowe GD, Rumley A, et al. An analysis of prospective risk factors for aortic stiffness in men: 20-year follow-up from the Caerphilly prospective study. Hypertension 2010;56(1):36-43. [Pubmed]
[11]
Bachelet-Rousseau C, Kearney-Schwartz A, Frimat L, Fay R, Kessler M, Benetos A. Evolution of arterial stiffness after kidney transplantation. Nephrol Dial Transplant 2011;26:3386-91. [Pubmed]
[12]
Roullet JB1, Xue H, McCarron DA, Holcomb S, Bennett WM. Vascular mechanisms of cyclosporin-induced hypertension in the rat. J Clin Invest 1994;93(5):2244-50. [Pubmed]
[13]
Ha E, Mun KC. Effects of cyclosporine on metalloproteinase in endothelial cells. Transplant Proc 2012;44(4):991-2. [Pubmed]
[14]
Seibert F, Behrendt C, Schmidt S, van der Giet M, Zidek W, Westhoff TH. Differential effects of cyclosporine and tacrolimus on arterial function. Transpl Int 2011;24:708-15. [Pubmed]
[15]
Strózecki P, Adamowicz A, W¿odarczyk Z, Manitius J. The influence of calcineuin inhibitors on pulse wave velocity in renal trasplant recipients. Ren Fail 2007;29(6):679-84. [Pubmed]
[16]
Martínez-Castelao A, Sarrias X, Bestard O, Gil-Vernet S, Serón D, Cruzado JM, et al. Arterial elasticity measurement in renal transplant patients under anticalcineurin immunosuppression. Transplantation Proceedings 2005;37:3788-90. [Pubmed]
[17]
Ma KL, Varghese Z, Ku Y, Powis SH, Chen Y, Moorhead JF, et al. Sirolimus inhibits endogenous cholesterol synthesis induced by inflammatory stress in human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2010;298:H1646-51. [Pubmed]
[18]
Hester J, Schiopu A, Nadig SN, Wood KJ. Low-dose rapamycin treatment increases the ability of human regulatory t cells to inhibit transplant arteriosclerosis in vivo. Am J Transplant 2012;12:2008-16. [Pubmed]
[19]
Hiemann NE, Wellnhofer E, Lehmkuhl HB, Knosalla C, Hetzer R, Meyer R. Everolimus prevents endomyocardial remodeling after heart transplantation. Transplantation 2011;92(10):1165-72. [Pubmed]
[20]
Joannidès R, Monteil C, de Ligny BH, Westeel PF, Iacob M, Thervet E, et al. Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine. Am J Transplant 2011;11:2414-22. [Pubmed]
[21]
Van Laecke S, Maréchal C, Verbeke F, Peeters P, Van Biesen W, Devuyst O, et al. The relation between hypomagnesaemia and vascular stiffness in renal transplant recipients. Nephrol Dial Transplant 2011;26:2362-9. [Pubmed]
[22]
Gungor O, Kircelli F, Carrero JJ, Hur E, Demirci MS, Asci G, et al. The effect of immunosuppressive treatment on arterial stiffness and matrix Gla protein levels in renal transplant recipients. Clin Nephrol 2011;75:491-6. [Pubmed]
[23]
Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006;113(9):1213-25. [Pubmed]
[24]
Agarwal R. Antihypertensive agents and arterial stiffness: relevance to reducing cardiovascular risk in the chronic kidney disease patient. Curr Opin Nephrol Hypertens 2007;16:409-15. [Pubmed]
[25]
Vincenti F, Larsen CP, Alberu J, Bresnahan B, Garcia VD, Kothari J, et al. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant 2012;12:210-21.
[26]
Durrbach A, Pestana JM, Pearson T, Vincenti F, Garcia VD, Campistol J, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant 2010;10:547-57. [Pubmed]
[27]
Larsen C, Grinyó J, Medina-Pestana J, Vanrenterghem Y, Vincenti F, Breshahan B, et al. Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies. Transplantation 2010;90(12):1528-35. [Pubmed]
[28]
Reference Values for Arterial Stiffness¿ Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ¿establishing normal and reference values¿. Eur Heart J 2010;31:2338-50. [Pubmed]
[29]
Vinh A, Chen W, Blinder Y, Weiss D, Taylor WR, Goronzy JJ, et al. Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation 2010;122:2529-37. [Pubmed]
[30]
Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Levy D, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA 2012;308(9):875-81. [Pubmed]
[31]
Claes K, Meyer-Kriesche HU, Schold JD, Vanrenterghem Y, Halloran PF, Ekberg H. Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Simphony study. Nephrol Dial Transplant 2012;27:850-7. [Pubmed]
[32]
Sjöblom P, Nystrom FH, Länne T, Engvall J, Östgren CJ. Microalbuminuria, but not reduced eGFR, is associated with cardiovascular subclinical organ damage in type 2 diabetes. Diabetes Metab 2014;40(1):49-55. [Pubmed]
[33]
Hashimoto J, Ito S. Central pulse pressure and aortic stiffness determine renal hemodynamics: pathophysiological implication for microalbuminuria in hypertension. Hypertension 2011;58(5):839-46. [Pubmed]
Idiomas
Nefrología
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?