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C5b-9 Deposition in Renal Transplant Biopsies Associates With Prolonged Delayed Graft Function in Kidneys Donated
Laura W D Knijff1, Mieke F van Essen1,2, Daniëlle J van Gijlswijk-Janssen1,2
1Division of Nephrology and Transplant Medicine, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Complement activation marker C5b-9 correlates with prolonged delayed graft function in donation after circulatory death kidney transplants, offering insights beyond standard histology. Higher levels in expanded criteria donors suggest intrinsic donor factors influence early complement activation.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pathology
Background:
- Ischemia-reperfusion injury is a significant risk factor for delayed graft function (DGF) in kidney transplantation.
- Complement activation during reperfusion contributes to DGF, particularly in donation after circulatory death (DCD) kidney transplants.
- Assessing complement activation may provide additional diagnostic information beyond histology for DGF.
Purpose of the Study:
- To investigate the correlation between complement activation and the duration of DGF in DCD kidney transplants.
- To determine if complement deposition offers additional predictive value compared to standard Banff classification for DGF.
- To explore the role of donor factors in early complement activation post-transplant.
Main Methods:
- Protocol biopsies from 64 DCD kidney transplant recipients were analyzed on day 10.
- Immunohistochemistry was used to assess and quantify complement deposition (C4d, C3d, C5b-9).
- Complement deposition was correlated with DGF duration (early, intermediate, prolonged) and Banff classification scores.
Main Results:
- C4d and C3d deposition did not differ significantly across DGF durations.
- C5b-9 deposition was significantly higher in recipients with prolonged DGF compared to early and intermediate DGF.
- Kidneys from expanded criteria donors showed higher C5b-9 deposition than standard criteria donors, independent of ischemia times. C5b-9 did not correlate with Banff scores.
Conclusions:
- Increased C5b-9 deposition is associated with prolonged DGF in DCD kidney transplants and is not captured by Banff scoring.
- Elevated C5b-9 levels in expanded criteria donor kidneys suggest intrinsic donor characteristics contribute to early post-transplant complement activation.
- C5b-9 may serve as a valuable biomarker for predicting DGF severity and understanding donor-related risks in kidney transplantation.
Background:
Ischemia-reperfusion injury is a risk factor for delayed graft function (DGF). During reperfusion, the damaged tissues and cells are exposed to blood, thereby contributing to complement activation. The aim of this study was to investigate if complement activation correlates with the duration of DGF in donation after circulatory death (DCD) kidney transplants and whether it provides additional information beyond regular histology.
Methods:
In day-10 protocol, biopsies from 64 DCD recipients, complement deposition (C4d, C3d, C5b-9) was assessed by immunohistochemistry, quantified and correlated with fDGF duration (early graft function [≤7 d], intermediate [8-20 d], and prolonged duration [≥21 d]), as well as with Banff classification.
Results:
C4d and C3d deposition was not different between fDGF durations. In contrast, C5b-9 deposition was higher in recipients with prolonged DGF (median 8.1%) compared with those with early graft function (median 5.6%) and intermediate DGF (median 5.6%). Kidneys from expanded criteria donors exhibited significantly higher C5b-9 deposition compared with standard criteria donors ( P = 0.001), but no correlation with warm or cold ischemia times. Banff classification scores showed only significant associations of C4d with interstitial inflammation (i), total inflammation (ti), and arteriolar hyalinosis (ah). Similar results were found with semiquantitative complement scoring in specific kidney compartments. No significant associations were observed between C5b-9 deposition and any of the Banff scores.
Conclusions:
C5b-9 deposition is increased in DCD kidneys with prolonged fDGF, representing a marker not reflected by Banff scoring. Higher C5b-9 levels in expanded criteria donors kidneys suggest that intrinsic donor factors contributes to early complement activation after transplantation.
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