Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

Abstract

Background: Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys.

Methods: Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables.

Results: Normal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied.

Conclusions: PIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients.

FIGURE 1

Relative mRNA expression of FOXP3, TGF-B, MCP-1, RANTES, and IL-10 genes in PIBx. Box-plot representation of median and quartile values. The whiskers are indicating range and asterisks represent outliers.

FIGURE 2

Relative mRNA expression of FOXP3, TGF-B, MCP-1, RANTES and IL-10 genes in preimplantation biopsies according to donor type and histological findings. *P < 0.05 vs normal/ECD; **P < 0.05 vs IFTA ≥ 1/ECD; ***P < 0.01 vs IFTA ≥ 1/ECD; ^#P < 0.001 vs. IFTA ≥ 1/ECD.