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

Abstract

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.

Neopterin is associated with cardiovascular events and all‐cause mortality in renal transplant patients

“…Elevated neopterin was not significantly associated with renal graft loss after adjusting for level of proteinuria. While Grebe et al 37 were primarily interested in early post-transplant macrophage activation associated with elevated neopterin, our study suggests that in clinically stable allograft recipients, serum neopterin is not independently associated with renal graft failure and does not add significantly to the prognostic information given by the degree of proteinuria. Weimer et al 39,40 reported significant associations between neopterin concentration at one yr post-transplant and the development of chronic rejection and chronic allograft dysfunction within two yr, but proteinuria was not included in their multivariable analysis, possibly explaining this discrepancy.…”

“…In a smaller cohort of patients, Grebe et al 37 observed that elevated neopterin levels following transplantation were associated with inferior graft and patient survival, while a recent prospective study in 216 KTR showed an association between higher levels of neopterin and acute rejection in the first year of follow-up 38. Our population was recruited five yr after transplantation and was clinically stable with a reasonably good renal function.…”

The Role of Serum C-Reactive Protein Measured by High-Sensitive Method in Thyroid Disease

“…Limited inflammatory disorders, such as Crohn’s disease, are better managed with the implementation of a regular Hs-CRP measurement (Erlinger et al 2004 ; Owczarek et al 2012 ). Hs-CRP is also useful in determining renal transplant rejection (Grebe et al 2011 ; Roshdy et al 2012 ). A moderate increase in the concentration of Hs-CRP occurs in liver diseases (Komoriya et al 2012 ), autoimmune diseases (Rezaieyazdi et al 2011 ), and neoplasms (Hopkins et al 2012 ).…”

Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

“…Studies have shown that infiltrating inflammatory cells are detected in IF/TA and contribute to long-term renal allograft failure [ 58 , 59 ]. For example, infiltrating monocytes/macrophages and their related chemokines/cytokines influence the long-term survival of renal allografts [ 60 , 61 ]. The infiltrating inflammatory cells contribute to IF/TA of chronic kidney transplant recipients through an HIF-1α signaling-dependent pathway.…”