Investigating the immune system in chrONIC kidney disease - the SONIC study

Chronic kidney disease (CKD) is associated with a high infective burden and poorer vaccine responses. This thesis presents findings of a prospective observational study, where a non-biased approach was taken to systematically characterise the immune “landscape” in CKD and examine adaptive immune cell phenotypes associated with responses to two vaccines - seasonal trivalent influenza (TIV) and 23-valent pneumococcal polysaccharide (PPV23) - in older adults with and without CKD. Despite significantly higher rates of self-reported infections, reductions in humoral responses to vaccination in patients with CKD were subtle, but with evidence of hyporesponsiveness to repeat PPV23 vaccination. CKD patients had fewer circulating B lymphocytes than controls, greater proportions of “Th2-like” (CCR4+CCR6- CXCR3-) and Treg cells (CD4+CD25+/highFoxP3+) and fewer Bregs (CD19+CD24highCD38high), but similar naïve/memory populations and “senescence”- associated T cells (defined by loss of surface CD27/28 and/or gain of CD57/KLRG1). Unexpectedly, CMV was the main determinant of T cell phenotype in both study groups and was also associated with poorer responses to both vaccines. Examination of neutrophil function demonstrated reduced oxidative burst capacity, reduced NETs generation and impaired migratory accuracy to fMLP in patients with CKD. This study highlights the complexity of CKD-associated immune dysfunction and the important role played by CMV