Cytokine expression patterns in kidney transplant patients with acute tubular necrosis

Abstract

Utilizing a custom antibody‐microarray we have identified unique expression patterns in the serum of kidney transplant patients with biopsy‐proven acute tubular necrosis (ATN) versus healthy transplant patients. Levels of Activin A, Fas Ligand, Fcγ RII, IL‐1α, IFN γ, MCP‐1, MCP‐2, MIP‐1α, MIP‐1βfz VEGF, BLC/BCA‐1, GM‐CSF, IP‐10 and IL‐1 RI were significantly increased (p<0.05) in patients with ATN, relative to healthy transplants. A hallmark of ATN is regions of ischemia‐reperfusion (IRI) resulting in localized cellular injury within the tubules. Several current reports demonstrate the production of proinflammatory cytokines (MCP‐1, MCP‐2, MIP‐1α, MIP‐1β) by cells in the renal tubule of patients with ischemic renal failure. In addition, we have seen a significant decrease (p<0.05) in Il‐5, Epo R, MIP‐3α, pro‐Cathepsin S, FGF‐6, TGFβ1, TIMP‐4, VEGF R2 and IL‐18 in ATN patients, relative to the stable transplant patients. These altered cytokine expression in patients with ATN associated renal graft dysfunction may occur at different stages of the disease, necessitating additional patients to confirm our findings. These patterns may eventually provide a biomarker signature of ATN, useful to differentiate patients with renal dysfunction, thus providing a sensitive, non‐invasive method to diagnose kidney injury. Work supported in part by NIH RO1 HL0709.