T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune condition that commonly causes kidney impairment and can be fatal. The key participation of B-lymphocytes as ANCA producers and neutrophils as target of these antibodies is widely described as the mechanism of endothelial damage in this disease. There has been a rising interest in the role of T-lymphocytes in AAV in recent years. Evidence is strong from animal models, and T-lymphocytes can be found infiltrating kidney tissue and other tissue sites in AAV patients. Furthermore, the different subsets of T-lymphocytes are also key players in the aberrant immune response observed in AAV. Polarization towards a predominant Th1 and Th17 response in the acute phase of the disease has been described, along with a decline in the number of T-regulatory lymphocytes, which, in turn, show functional impairment. Interactions between different T-cell subsets, and between T-cells and neutrophils and B-cells, also enhance the inflammatory response, constituting a complex network. Novel therapies targeting T-cell immunity are emerging in this scenario and may constitute an interesting alternative to conventional therapy in selected patients. This review aims to summarize the available evidence regarding T-cell imbalances and functional impairment, especially focusing on renal involvement of AAV.

Arterial stiffness in kidney transplantation: a single center case-control study comparing belatacept versus calcineurin inhibitor immunosuppressive based regimen

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 (AU)

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 (AU)

Arterial stiffness in kidney transplantation: a single center case-control study comparing belatacept versus calcineurin inhibitor immunosuppressive based regimen.

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.