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.