Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies.
Reports have associated non-HLA antibodies, specifically those against angiotensin II type-1 receptor (AT1R), with antibody-mediated kidney graft rejection. However, association of anti-AT1R with graft failure had not been demonstrated. We tested anti-AT1R and donor-specific HLA antibodies (DSA) in pre- and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy-proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG's rate of anti-AT1R was significantly higher than the CG's (18% vs. 6%, p < 0.001). Moreover, 79% of ABG patients with anti-AT1R lost their grafts (vs. 0%, CG), anti-AT1R levels in 58% of those failed grafts increasing posttransplant. With anti-AT1R detectable before DSA, time to graft failure was 31 months-but 63 months with DSA detectable before anti-AT1R. Patients with both anti-AT1R and DSA had lower graft survival than those with DSA alone (log-rank p = 0.007). Multivariate analysis showed that de novo anti-AT1R was an independent predictor of graft failure in the ABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti-AT1R with graft failure. Further study is needed to establish causality between anti-AT1R and graft failure and, thus, the importance of routine anti-AT1R monitoring and therapeutic targeting.
Terasaki Foundation Laboratory, Los Angeles, CA.
M
M
Taniguchi
L M
LM
Rebellato
J
J
Cai
J
J
Hopfield
K P
KP
Briley
C E
CE
Haisch
P G
PG
Catrou
P
P
Bolin
K
K
Parker
W T
WT
Kendrick
S A
SA
Kendrick
R C
RC
Harland
P I
PI
Terasaki
D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001706:Biopsy; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007674:Kidney Diseases / Q000097:blood / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D015996:Survival Rate; D014184:Transplantation, Homologous
D001323:Autoantibodies; D006680:HLA Antigens; D044140:Receptor, Angiotensin, Type 1
AT1R; Angiotensin II type-1 receptor antibodies; DSA; kidney transplantation; rejection