Distinct Role of Complement Receptors C5L2 and C5aR in Acute Kidney Injury and Renal Fibrosis
1Nephrology, Medical School, Hannover, Germany
2Microbiology, Medical School, Hannover, Germany
3Radiology, Medical School, Hannover, Germany
4Imaging Center, Medical School, Hannover, Germany
5Pediatric Surgery, Medical School, Hannover, Germany.
Meeting: 2015 American Transplant Congress
Abstract number: 481
Keywords: Kidney, Renal failure, Renal ischemia
Session Information
Session Name: Concurrent Session: Linking Innate and Adaptive Alloimmune Responses
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Room 118-C
Objective
Acute kidney injury (AKI) is a relevant complication in solid organ transplantation with incidence rates of ∼50-75 % after lung- and heart transplantation. In addition, delayed graft function due to prolonged cold ischemia time can be up to 50% after kidney transplantation. AKI increases morbidity and mortality and also contributes to the progression to chronic kidney disease (CKD). The complement system is activated rapidly in AKI where C5a activation signals via the C5aR and the C5a like 2 (C5L2) receptor. Currently, little is known about the differences between these two receptors.
Methods
AKI was induced by ischemia reperfusion injury by unilateral clipping of the right renal pedicle for 45 min in C5L2 and C5aR deficient and wild type mice (WT). Renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by inulin and PAH clearance. Renal morphology, inflammation and renal fibrosis were investigated by immunohistochemistry. In addition FACS analysis was done to quantify leukocyte subsets at day 7. Functional MRI to analyze RBF was performed at different time points (d1, d7, week3).
Results
Complement receptor deficiency attenuated inflammation and macrophage infiltration after IRI. In addition, collagen deposition was significantly reduced in C5L2-/- mice compared to WT and C5aR-/- mice. Functional MRI showed significantly better renal perfusion in C5L2-/- mice compared to WT at d7 and week 3. These results were in line with PAH clearance measurements. In addition, C5L2-/- had significantly less kidney volume loss. Inflammatory cell infiltration analysed by FACS showed similar activation of myeloid cells but revealed differences in activation of gamma/delta T-cells in C5L2-/- mice.
Conclusion
C5L2 deficiency attenuated AKI and progression to CKD by improvement of renal perfusion. Complement targeted therapies might be promising in prevention of AKI.
To cite this abstract in AMA style:
Thorenz A, Chen R, Hüper K, Hensen B, Klemann C, Meier M, Klos A, Güler F. Distinct Role of Complement Receptors C5L2 and C5aR in Acute Kidney Injury and Renal Fibrosis [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/distinct-role-of-complement-receptors-c5l2-and-c5ar-in-acute-kidney-injury-and-renal-fibrosis/. Accessed May 19, 2025.« Back to 2015 American Transplant Congress