Effects of anti-adhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts.
Cheadle C, Watkins T, et al.Clinical Transplantation 25(5): 766-775, 2011.
Aims
To explore whether human kidneys would exhibit a brisk, gene-specific inflammatory response during ischemia reperfusion injury, which would be modified by anti-adhesive therapy.
Interventions
Active YSPSL intravenous (IV) push in saline with a YSPSL donor organ flush versus YSPSL IV push in saline with a placebo donor organ flush versus a saline IV push with a vehicle donor organ flush.
Participants
40 deceased-donor kidneys.
Outcomes
Delayed graft function, slow graft function, the incidence of biopsy-confirmed acute cellular rejection. Gene transcription of 10 biomarkers implicated in endothelial activation and leukocyte migration: IL-6, IL-8, interferon-c, MCP-1, E-selectin, hemoxygenase 1, TNFa, TGFb , CD3 and CD25.
Follow-up
1 hour after reperfusion
CET Conclusions
In this study of 40 deceased donor kidneys biopsied prior to implantation and at one hour after reperfusion there was a definite increase in a number of inflammatory gene transcripts at one hour after implantation compared to the control and there was inhibition of leukocyte adhesion using a selectin antagonist (YSPSL). The groups are too small to draw any firm conclusions but the results are suggestive and worthy of further study.
Data analysis
Strict intention-to-treat analysis
Quality notes
This is a subgroup analysis of a previous publication of the same RCT: Gaber AO, Mulgaonkar S, Kahan BD et al. YSPSL (rPSGL-Ig) for improvement of early renal allograft function: a double-blind, placebo-controlled, multi-center phase IIa study. Clin Transplant 2011: 25: 523–533. The methodological quality assessment was based on the original paper.
Trial registration
NCT00298168 (ClinicalTrials.gov)