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The significance of Focal C4d+: The WU experience. Helen Liapis, M.D. Professor of Pathology & immunology. Kedainis RL et al. Am J Transplant . 2009 Apr;9(4):812-9. Patients & Methods. Retrospective review of 301 patients (368 biopsies) 2002-2007 Inclusion criteria: - indication bx
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The significance of Focal C4d+: The WU experience Helen Liapis, M.D. Professor of Pathology & immunology Kedainis RL et al. Am J Transplant. 2009 Apr;9(4):812-9.
Patients & Methods • Retrospective review of 301 patients (368 biopsies) • 2002-2007 • Inclusion criteria: - indication bx - adequate tissue for evaluation - at least 6 month follow up - DSA test results
Patient demographics • Cause of ESRD • Therapy (>90% Thymo); CNI (Tacrolimus) antimetabolite and prednisone for maintenance • Hx of previous transplantation • Donor source • HLA match/mismatch • Time interval to transplantation • Renal function at the time of bx • Follow-up period • Graft failure (return to dialysis or re-transplt)
Question Focal , diffuse C4d+,C4d- correlation with histopathological findings and graft survival Statistics: Chi-square, ANOVA, Cox regression
C4d+ as defined by BANFF by IF • >50% = diffusely + • 10-50% = focal +
C4d results Diffuse C4d+ = 9.5% Focal C4d+ = 20.9% C4d- = 69.4%
Diffuse C4d+ & PTC 2 PTC 2 = ≥10% with max 5 to 10 luminal inflammatory cells
Focal C4d+ and PTC1 PTC1 = ≥10% max 3 to 4 luminal inflammatory cells
C4d+ & DSA 132/301 (43%) had DSA
Conclusions • Focal C4d+ has histopathology similar to diffuse C4d+ • Correlation with DSA is similar • Focal C4d+ and TGP not significant but there is a trend association • Allograft loss: worse prognosis trend at 1 year • Overall, focal C4d+ should be taken into account in treatment strategies
Caveats • Retrospective study • Relatively short follow up • DSA only in ~ 50% (44%) • C4d- cases were less frequently tested