Immune cell dysfunction and inflammation in end-stage renal disease

Uraemia causes inflammation and reduces immune system function as evidenced by an increased risk of viral-associated cancers, increased susceptibility to infections and decreased vaccination responses in patients with end-stage renal disease (ESRD). The substantially increased risk of atherosclerosis in these patients is also probably related to uraemia-associated inflammation. Uraemia is associated with a reduction in the number and function of lymphoid cells, whereas numbers of myeloid cells in uraemic patients are normal or increased with increased production of inflammatory cytokines and reactive oxygen species. Similar to healthy elderly individuals, patients with ESRD have increased numbers of specific proinflammatory subsets of T cells and monocytes, suggesting the presence of premature immunological ageing in these patients. These cells might contribute to inflammation and destabilization of atherosclerotic plaques, and have, therefore, been identified as novel nonclassical cardiovascular risk factors. The cellular composition of the immune system does not normalize after successful kidney transplantation despite a rapid reduction in inflammation and oxidative stress. This finding suggests that premature ageing of the immune system in patients with ESRD might be related to a permanent skewing of the haematopoetic stem cell population towards myeloid-generating subsets, similar to that seen in healthy elderly individuals. Betjes, M. G. H. Nat. Rev. Nephrol. 9, 255-265 (2013); published online 19 March 2013; doi:10.1038/nrneph.2013.44