Ann Lab Med.  2020 Sep;40(5):398-408. 10.3343/alm.2020.40.5.398.

Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting

• Yu S
• Huh HJ
• Lee KW
• Park JB
• Kim SJ
• Huh W
• Jang HR
• Kwon GY
• Moon HH
• Kang ES

• KMID: 2502570
• DOI: http://doi.org/10.3343/alm.2020.40.5.398

Abstract

Background
Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients.
Methods
In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes.
Results
Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant.
Conclusions
Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.

Keyword

Non-HLA antibodies; Anti- angiotensin II type 1 receptor antibodies; Anti-endothelial cell antibodies; Endothelial cell crossmatch; Kidney transplantation; Outcome; Low-risk

Figure

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  Fig. 1 Clinical outcomes according to the anti-AT1R levels and AECA status using ECXM assay. (A) No significant differences in AR or MVI only free survival rates are seen between recipients with anti-AT1R ≥11.5 U/mL (N=36) and those with anti-AT1R <11.5 U/mL (N=58). (B) Recipients with anti-AT1R ≥11.5 U/mL have a higher risk of AR than those with anti-AT1R <11.5 U/mL (P=0.039). (C) AECA (+) recipients (N=22) have a higher risk of AR or MVI only than AECA (−) recipients (N=72) (P=0.006); (D) There is no significant difference in the AR free survival rates. (E) AECA (+) recipients with anti-AT1R <11.5 U/mL (N=11) have a higher risk of AR or MVI only than other recipients (P=0.006); (F) There are no significant differences in AR free survival rates among the four groups. Abbreviations: Anti-AT1R, anti-angiotensin II type 1 receptor antibodies; AECA, anti-endothelial cell antibodies; ECXM, endothelial cell crossmatch; AR, acute rejection; MVI, microvascular inflammation.

• 

  Fig. 2 Effect of anti-AT1R levels and AECA status using ECXM assay on renal function during the post-KT period. Recipients with pre-transplant anti-AT1R ≥11.5 U/mL show significantly lower eGFR (B) but not creatinine levels (A) at 6 and 12 months post KT (P=0.012; P=0.012, respectively), compared with those at one month post-KT. AECA (+) recipients have significantly higher creatinine levels (C) and lower eGFRs (D) at six (P=0.003; P=0.028, respectively) and 12 months (P<0.001; P=0.011, respectively), compared with those at one month post-KT. The change in the pattern of creatinine levels in AECA (+) recipients from one to 12 months post-KT is significantly different compared with that in AECA (−) recipients (P=0.038) (C). AECA (+) recipients with anti-AT1R ≥11.5 U/mL show significantly different changes in the pattern of creatinine levels (E) from one to 12 months post-KT (P=0.045) compared with other recipients, and significantly higher creatinine levels and lower eGFRs (F) at 12 months (P<0.001; P=0.028) compared with those at one month post-KT. Abbreviations: Anti-AT1R, anti-angiotensin II type 1 receptor antibodies; AECA, anti-endothelial cell antibodies; ECXM, endothelial cell crossmatch; KT, kidney transplantation; eGFR, estimated glomerular filtration rate; MVI, microvascular inflammation.

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