Volume 87, Issue 1, Pages 182-194 (January 2015) A systematic review of the role of C4d in the diagnosis of acute antibody-mediated rejection Ruth Sapir-Pichhadze, Simon P. Curran, Rohan John, Andrea C. Tricco, Elizabeth Uleryk, Andreas Laupacis, Kathryn Tinckam, Banu Sis, Joseph Beyene, Alexander G. Logan, S Joseph Kim Kidney International Volume 87, Issue 1, Pages 182-194 (January 2015) DOI: 10.1038/ki.2014.166 Copyright © 2015 International Society of Nephrology Terms and Conditions
Figure 1 Summary of study inclusion and exclusion process. *Mengel et al.49 included both indications and surveillance biopsies. CCTR, Cochrane Central Register of Controlled Trials; CDSR, Cochrane Database of Systematic Reviews; DSA, donor-specific antibody; Renal DTA, Cochrane Renal Group Reviews of Diagnostic Test Accuracy. Kidney International 2015 87, 182-194DOI: (10.1038/ki.2014.166) Copyright © 2015 International Society of Nephrology Terms and Conditions
Figure 2 Forest plots of diagnostic characteristics of peritubular capillary C4d staining in indication biopsies versus histopathological changes. (a) Glomerulitis, (b) peritubular capillaritis, and (c) microcirculatory inflammation. Studies reporting C4d by immunofluorescence (IF) or immunohistochemistry (IHC) from early allograft biopsies (within first 12 months after transplant) are marked by black and gray arrows, respectively. †Studies using C4d thresholds according to current Banff classification (IF-frozen threshold >10% and any IHC-paraffin staining). Abbreviations: CI, confidence interval; DOR, diagnostic odds ratio; LR+, positive likelihood ratio; LR-, negative likelihood ratio; PTCitis, peritubular capillaritis. Kidney International 2015 87, 182-194DOI: (10.1038/ki.2014.166) Copyright © 2015 International Society of Nephrology Terms and Conditions
Figure 3 Forest plots of diagnostic characteristics of peritubular capillary C4d staining in indication biopsies versus donor-specific antibody (DSA) assays. Studies reporting C4d by immunofluorescence or immunohistochemistry from early allograft biopsies (within first 12 months after transplant) are marked by black and gray arrows, respectively.†Studies using C4d thresholds according to current Banff classification (IF-frozen threshold >10% and any IHC staining). (▪) All studies reporting diagnostic characteristics of IHC staining, other than Herman et al.35 and Lederer et al.,61 used paraffin fixation. CDC, complement-dependent cytotoxicity; CI, confidence interval; DOR, diagnostic odds ratio; IF, immunofluorescence; IHC, immunohistochemistry; LR+, positive likelihood ratio; LR-, negative likelihood ratio; SAB, single antigen beads. Kidney International 2015 87, 182-194DOI: (10.1038/ki.2014.166) Copyright © 2015 International Society of Nephrology Terms and Conditions
Figure 4 Forest plots of diagnostic characteristics of peritubular capillary C4d staining in indication biopsies versus histopathological changes and donor-specific antibody (DSA) assays.†Studies using C4d thresholds according to current Banff classification (IF-frozen threshold >10% and any IHC staining). CI, confidence interval; DOR, diagnostic odds ratio; g, glomerulitis; IF, immunofluorescence; IHC, immunohistochemistry; LR+, positive likelihood ratio; LR-, negative likelihood ratio; MI, microcirculatory inflammation (g+ptc>0); ptc, peritubular capillaritis. Kidney International 2015 87, 182-194DOI: (10.1038/ki.2014.166) Copyright © 2015 International Society of Nephrology Terms and Conditions
Figure 5 Forest plot of diagnostic characteristics of peritubular capillary C4d staining in surveillance biopsies versus histopathological changes and donor-specific antibody (DSA). (a) Glomerulitis, (b) peritubular capillaritis, (c) microcirculatory inflammation, and (d) DSA assays. ▵Studies including high immune risk patients. CI, confidence interval; DOR, diagnostic odds ratio; IF, immunofluorescence; IHC, immunohistochemistry; LR+, positive likelihood ratio; LR-, negative likelihood ratio; PTCitis, peritubular capillaritis; MI, microcirculatory inflammation. Kidney International 2015 87, 182-194DOI: (10.1038/ki.2014.166) Copyright © 2015 International Society of Nephrology Terms and Conditions