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

• Published in: Clinical transplantation Vol. 25; no. 5; pp. 744 - 754
• Main Authors: Grebe, Scott O., Kuhlmann, Uwe, Fogl, Dominik, Luyckx, Valerie A., Mueller, Thomas F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2011; Wiley
• Subjects: acute phase response; Acute-Phase Reaction; Adult; Biological and medical sciences; C-Reactive Protein - metabolism; cardiovascular disease; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - etiology; Graft Rejection - mortality; Graft Survival - physiology; Humans; Kidney - physiopathology; kidney graft outcome; Kidney Transplantation - adverse effects; Kidney Transplantation - mortality; Macrophage Activation; macrophages; Male; Medical sciences; Middle Aged; neopterin; Neopterin - blood; patient survival; Prognosis; Prospective Studies; Serum Amyloid A Protein - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Survival Rate; Tissue, organ and graft immunology; Human; acute phase response; Poverty; Prognosis; patient survival; cardiovascular disease-kidney graft outcome-macrophages; Acute; Patient; Cardiovascular disease; Activation; Homotransplantation; Long term; Survival; Kidney; Medicine; Response; Association; Treatment; Urinary system; Surgery; Evolution; Neopterin; Macrophage
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2010.01345.x

Grebe SO, Kuhlmann U, Fogl D, Luyckx VA, Mueller TF. Macrophage activation is associated with poorer long‐term outcomes in renal transplant patients.
Clin Transplant 2011: 25: 744–754. © 2010 John Wiley & Sons A/S. :  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.