Objective

The complement receptors C5aR1 and C5aR2 serve distinct roles in immune regulation. In kidney transplantation the early post-implant ischemia reperfusion injury (IRI) causes rapid complement activation. So far, there is little known about the distinct role of C5aR1 and C5aR1. In this study C5aR1 and C5aR2 deficient mice were tested in two different models: renal ischemia reperfusion injury (IRI) and in isogenic cross over kidney transplantation (ktx).

Methods

IRI was inducedby unilateral clipping of the right renal pedicle for 45 min in C5aR1, C5aR2 deficient and wild type mice (WT). Functional magnetic resonance imaging (MRI) to analyze renal perfusion was performed at different time points (d1, d7, week3) and glomerular filtration rate (GFR) were assessed by inulin clearance. Renal morphology, inflammation and renal fibrosis were investigated by immunohistochemistry. In a second model isogenic ktx with prolonged cold ischemia time of 90 min was performed. C5aR1, C5aR2 or WT mice served as donors or recipients.

Results

C5aR2 deficiency resulted in attenuated inflammation and renal fibrosis 3 weeks are IRI. Kidney regeneration was enhanced in C5aR2 deficient mice which showed significantly improved renal perfusion. In the ktx model C5R2 deficiency of the recipient showed the best renal morphology with attenuated renal injury. By FACS analysis differential activation in gd-Tcells in C5aR2 deficient mice was observed and may have contributed to enhanced regeneration.

Conclusion

C5aR2 deficiency attenuates renal damage in AKI and ktx via modulation of T-cell signalling.

CITATION INFORMATION: Thorenz A, Chen R, Hueper K, Hensen B, Klemann C, Meier M, Klos A, Gueler F. Complement Receptor C5aR2 Deletion in Kidney Transplantation in Mice Attenuates Renal Damage. Am J Transplant. 2016;16 (suppl 3).

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