T-cell ageing in end-stage renal disease patients: Assessment and clinical relevance

Abstract

End-stage renal disease (ESRD) patients have a defective T-cell-mediated immune system which is related to excessive premature ageing of the T-cell compartment. This is likely to be caused by the uremia-associated pro-inflammatory milieu, created by loss of renal function. Therefore, ESRD patients are highly susceptible for infections, have an increased risk for virus-associated cancers, respond poorly to vaccination and have an increased risk for atherosclerotic diseases. Three ageing parameters can be used to assess an immunological T-cell age. First, thymic output can be determined by assessing the T-cell receptor excision circles-content together with CD31 expression within the naïve T cells. Second, the telomere length of T cells and third the T-cell differentiation status are also indicators of T-cell ageing. Analyses based on these parameters in ESRD patients revealed that the immunological T-cell age is increased by on average 20 years compared to the chronological age. After kidney transplantation (KTx) the aged T-cell phenotype persists although the pro-inflammatory milieu is diminished. This might be explained by epigenetic modifications at hematopoietic stem cells level. Assessment of an immunological T-cell age could be an important tool to identify KTx recipients who are at risk for allograft rejection or to prevent over-immunosuppression.

Keywords: End-stage renal disease patients, Kidney transplantation, T-cell ageing, T-cell differentiation, Uremia

Core tip: The uremia-induced inflammatory environment in end-stage renal disease (ESRD) patients is associated with a prematurely aged T-cell compartment, resulting in defective T-cell-mediated immunity. ESRD patients are highly susceptible for infections, have an increased risk for virus-associated cancers, respond poorly to vaccination and have an increased risk for atherosclerotic diseases. Adequate renal replacement therapy in the form of kidney transplantation is able to diminish the uremic pro-inflammatory environment but unsuccessfully reverses the aged T-cell system. Assessment of T-cell ageing might be a tool to facilitate individualization of immunosuppressive regimes and prevent over-immunosuppression and its associated clinical complications in kidney transplant recipients.