Macrophage activation is associated with poorer long-term outcomes in renal transplant patients

Long-term graft and patient survival after renal transplantation are largely determined by progression of chronic allograft dysfunction and cardiovascular disease. Inflammation plays a crucial role in both disease processes. We prospectively analyzed the association of early peri-transplant inflammatory burden on long-term outcomes in 144 consecutive deceased donor renal allograft recipients. Single time point and cumulative levels of markers of acute phase response (serum amyloid A [SAA] and C-reactive protein [SCRP]) and macrophage activation (serum and urine neopterin) were measured daily during the immediate post-operative period. Mean patient follow-up was 16 yr. Graft and patient survival rates at one-, five-, and 10-yr were 90%, 70%, and 51%, and 97%, 77%, and 59%, respectively. Graft loss occurred in 90 patients, of whom 71 died with a functioning graft and 19 returned to dialysis. CRP, SAA and neopterin (NEOP) levels were all elevated post-operatively. High levels of NEOP, in contrast to SAA or SCRP, were associated with poorer graft and patient survival (p < 0.05), specifically with death from cardiovascular events and cytomegalovirus IgG positivity. These findings strongly suggest that early post-transplant macrophage activation, as reflected by NEOP levels, is associated with poorer long-term graft and patient survival.