Local Expression of C-Reactive Protein Is Associated with Deteriorating Graft Function in Acute and Chronic Failure of Kidney Transplants

Abstract

Background: C-reactive protein (CRP) is a key molecule in inflammation and tissue homeostasis and is produced locally by renal tubular epithelial cells. Its significance of expression in contrast to expression of cytotoxic T cell (CTL) markers remains to be elucidated. Methods: By means of real-time PCR, we determined mRNA levels of CRP in 66 renal allograft biopsies with acute allograft failure and in 34 biopsies with chronic dysfunction. Results were compared to expression of CTL components (perforin, granzyme B) and were correlated with histologic diagnoses and outcome. Results: CTL markers were found in most biopsies, and thus were not specific for particular histologies, although expression levels increased significantly with Banff rejection grades. Expression of CRP was highly specific for rejection episodes in acute failure (p < 0.0001) as well as for transplant glomerulopathy or de novo/recurrent glomerulonephritis in chronic failure (p < 0.005). Finally, the presence of CRP expression in renal allografts was associated with a deteriorating 1-year graft function in acute (p < 0.01) as well as chronic allograft dysfunction (p = 0.077). Conclusions: Our data suggest local CRP expression of kidney transplants as an indicator for pathologic entities associated with unfavorable outcomes in the early and late course of kidney transplants.

Symmetric Dimethylarginine as Predictor of Graft loss and All-Cause Mortality in Renal Transplant Recipients

“…We and others have shown that markers of inflammation are associated with impaired long-term patient and graft outcome ( 3–5 ). Inflammation seems to correlate with endothelial dysfunction and early atherosclerotic changes in patients with chronic kidney disease (CKD) ( 6 ).…”

C-reactive protein exacerbates renal ischemia-reperfusion injury

“…Blood CRP generally increases as kidney function decreases (26,36), and CRP levels are positively associated with worse outcomes and increased mortality in AKI (48,49). In the context of renal transplantation, elevated CRP levels in graft recipients associate with graft failure, and local expression of CRP mRNA in donated kidneys correlates with both acute and chronic rejection (14,31,43). There is evidence from animal models of chronic kidney disease suggesting that CRP actively increases inflammation (21,23).…”