Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation.

Abstract Background Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. Methods In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Δ) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). Results Positive transrenal gradients of tPA antigen occurred at 1 minute [Δ = 14 (3–46) ng/mL, P <.01] and 5 minutes [Δ = 5 (-3 to 27) ng/mL, P <.01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Δ = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P <.001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P =.006). Conclusions The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation. Highlights • Inflammation and coagulation both contribute to ischemia and reperfusion injury. • Kidney tissue plasminogen activator release was associated with graft neutrophil sequestration. • Tissue plasminogen activator may have a proinflammatory role in human kidney transplantation. [ABSTRACT FROM AUTHOR]

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