Tubular Epithelial Injury and Inflammation After Ischemia and Reperfusion in Human Kidney Transplantation : Annals of Surgery

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Original Article

Tubular Epithelial Injury and Inflammation After Ischemia and Reperfusion in Human Kidney Transplantation

Snoeijs, Maarten G. J. MD, PhD*; van Bijnen, Annemarie BSc*; Swennen, Els PhD†,‡; Haenen, Guido R. M. M. PhD; Roberts, L. Jackson II MD, PhD§; Christiaans, Maarten H. L. MD, PhD; Peppelenbosch, Arnoud G. MD, PhD*; Buurman, Wim A. PhD*; Ernest van Heurn, L. W. MD, PhD*

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Annals of Surgery 253(3):p 598-604, March 2011. | DOI: 10.1097/SLA.0b013e31820d9ae9

Objective: 

To provide an integrated insight into the kinetics of tubular injury, inflammation, and oxidative stress after human kidney transplantation.

Background: 

Tissue injury due to ischemia and reperfusion is an inevitable consequence of kidney transplantation. Tubular epithelial injury, inflammation, and oxidative stress play major roles in the pathophysiology of acute kidney injury in small animals, but it remains to be established whether this paradigm holds true for human kidney transplantation.

Methods: 

Markers of tubular injury, inflammation, and oxidative stress were compared between recipients of kidneys from donors after cardiac death (DCD; N = 8) with prolonged ischemia and recipients of living donor kidneys with minimal ischemia (N = 8).

Results: 

In the early postoperative period, creatinine clearance and tubular sodium reabsorption were profoundly reduced in DCD kidneys, coinciding with significantly increased urinary concentrations of tubular injury markers (neutrophil gelatinase-associated lipocalin, N-acetyl-β--glucosaminidase, and cystatin C) and an 18-fold increase in renal production of cytokeratin-18, indicating extensive necrotic cell death. Tubular injury in DCD kidneys was followed by greater systemic inflammatory activity and oxidative stress in the postoperative period (measured with 17-plex cytokine arrays and as plasma F2-isoprostanes, respectively). In contrast, no evidence of oxidative damage to either of the 2 kidney types was found in the early reperfusion period.

Conclusions: 

These findings establish the relevance of observations in animal models for human kidney transplantation and form the basis for development of novel therapies to improve early graft function and expand the use of donor kidneys with prolonged ischemia.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.

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