Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies.
OBJECTIVE
This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies.


METHODS
Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n=1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n=5) were combined with those identified in the 51-month period of review (n=6).


RESULTS
One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at ≤90 days and one at 213 days). Early (≤90 days) C4d+ biopsies (n=5) had more frequent TMA (11.9% C4d+ versus 3.4% C4d-; odds ratio, 3.84; P=0.03). Graft loss was significantly greater in an early C4d+TMA+ group (n=5 study+2 archival patients) than in C4d+ controls without TMA (n=21) (57% versus 9.5%; P=0.02). Early TMA+C4d+ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMA+C4d- and had more frequent neutrophilic capillaritis than TMA-C4d+ biopsies.


CONCLUSIONS
TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss.
Department of Pathology, MC 6101, AMB S-630, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA. shane.meehan@uchospitals.edu
Shane M
SM
Meehan
Joseph
J
Kremer
Farah N
FN
Ali
Jessica
J
Curley
Susana
S
Marino
Anthony
A
Chang
Pradeep V
PV
Kadambi
D000328:Adult; D001706:Biopsy; D002196:Capillaries / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002641:Chicago; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010446:Peptide Fragments / Q000032:analysis*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D057049:Thrombotic Microangiopathies / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d