Circulating angiotensin type II receptor: Possible marker for antibody mediated rejection after renal transplantation?

Kimball, Pamela; Gupta, Gaurav; McDougan, Felecia

doi:10.1016/j.humimm.2017.06.004

Cited by 9 publications

(8 citation statements)

References 25 publications

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“…The early publications suggest that anti‐AT1R antibodies can be associated with AMR and/or might contribute to poorer long‐term outcomes in kidney transplantation . However, Deltombe et al found no increased tendency to acute rejection episodes or long‐term graft outcomes among kidney recipients who were positive for anti‐AT1R prior to transplant, and Kimball reported no increased risk for AMR among presensitized recipients, although sustained elevations of anti‐AT1R were associated with poorer patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti-AT1R antibodies

Oaks

Michel

Downey

et al. 2018

American Journal of Transplantation

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Autoantibodies to the angiotensin II type 1 receptor (AT1R) are thought to be important in antibody-mediated rejection (AMR), especially in the absence of anti-HLA antibodies. We used a variety of methods to examine the specificity of a commercially available kit designed to quantitate anti-AT1R antibodies. We found that fibrin formation in serum samples from patients awaiting cardiac transplantation with ventricular assist devices (VADs) can produce falsely elevated anti-AT1R values. In addition, absorption studies with a variety of cell lines with or without expression of human AT1R, and those that express xenoantigens, suggest that many of the antibodies detected in the AT1R test system are heterophilic and have reactivity to xenoantigens. Furthermore, we provide data that show that reactivity to the sialic acid Neu5Gc is a common finding among samples that are highest in anti-AT1R levels. We conclude that a common laboratory method for quantitation of anti-AT1R antibodies is nonspecific and overestimates the frequency of true positives. A reevaluation of the role that anti-AT1R antibodies play in allograft function and patient outcomes is warranted.

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Section: Discussionmentioning

confidence: 99%

Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti-AT1R antibodies

Oaks

Michel

Downey

et al. 2018

American Journal of Transplantation

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“…Dragun et al [8,13] have shown for the first time their involvement in patients presenting acute rejection episodes (ARE) with severe hypertensive crisis. Since this first observation, the correlation of anti-AT1R antibodies and acute rejection and/or graft failure has become more debated in kidney transplantation sometimes due to a lack of power of studies [15][16][17][18][19][20][21][22][23][24]. In 2013, we showed on a large monocentric cohort (n = 599) of French kidney recipients that patients who displayed a pretransplant AT1R-Ab level above 10 U/ml had higher risk of acute rejection episodes within the first month following transplantation and graft failure beyond 3 years post-transplantation [25,26].…”

Section: Introductionmentioning

confidence: 99%

Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA Luminex era? A retrospective study

Deltombe

Gillaizeau

et al. 2017

Transpl Int

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We aimed to assess the correlation of anti-angiotensin II type 1 receptor antibodies (anti-AT1R-Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008-2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti-HLA immunization. Anti-AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti-angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R-Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)-ARE was 22.5% at 1 year post-transplantation [95% CI (19.9-25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4-13.3%)] and 5.7% [95% CI (4.0-8.1%)] at 3 years post-transplantation, respectively. Multivariate Cox models indicated that pretransplant anti-AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80-1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56-1.33)]. Our study did not confirm an association between pretransplant anti-AT1R antibody levels and kidney transplant outcomes.

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“…This is supported by a prospective study that found the presence of AT1R‐Ab was not associated with elevated donor‐derived cell‐free DNA (dd‐cfDNA), a marker for allograft injury, and did not appear to be associated with risk for rejection (38). Kimball et al also found that pre‐transplant AT1R‐Ab in adult recipients was not associated with increased risk for AMR or allograft failure but was rather associated with poorer outcomes when AT1R‐Ab levels increased during early AMR leading to the speculation that post‐transplant elevations of AT1R‐Ab may be an indicator of ongoing tissue damage (10). In a study by Crespo et al pre‐transplant AT1R‐Ab was frequently found in those with HLA‐DSA positive AMR, but rarely seen in those with HLA‐DSA negative AMR, suggesting pre‐transplant AT1R‐Ab may act synergistically with HLA‐DSA in AMR (39).…”

Section: Discussionmentioning

confidence: 99%

“…Among renal transplant recipients, AT1R‐Ab monitoring is becoming more common as studies have demonstrated adverse allograft outcomes in the presence of pre‐ and/or post‐transplant AT1R‐Ab. (4,7–12,16–18). In this observational study, we showed that pre‐transplant AT1R‐Ab ≥17 U/ml in our small pediatric cohort was not associated with rejection and did not impact graft function or survival, similar to several other studies among adult renal transplant recipients (10,33,34).…”

Section: Discussionmentioning

confidence: 99%

Pre‐transplant angiotensin II receptor type I antibodies in pediatric renal transplant recipients: An observational cohort study

Pizzo

Mirocha

Choi

et al. 2022

Pediatric Transplantation

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Background The role of angiotensin II type 1 receptor antibodies (AT1R‐Ab) in pediatric renal transplantation is unclear. Here, we evaluated pre‐transplant AT1R‐Ab on transplant outcomes in the first 5 years. Secondary analysis compared pre‐transplant AT1R‐Ab levels by age. Methods Thirty‐six patients, 2–20 years old, were divided into two groups: pre‐transplant AT1R‐Ab− (<17 U/ml; n = 18) and pre‐transplant AT1R‐Ab+ (≥17 U/ml; n = 18). eGFR was determined at 6‐month, 1‐, 2‐, and 4‐year post‐transplant. Allograft biopsies were performed in the setting of strong HLA‐DSA (MFI > 10 000), AT1R‐Ab ≥17 U/ml, and/or elevated creatinine. Results Mean age in pre‐transplant AT1R‐Ab− was 13.3 years vs. 11.0 in pre‐transplant AT1R‐Ab+ (p = 0.16). At 6 months, mean eGFR was 111.3 ml/min/1.73 m2 in pre‐transplant AT1R‐Ab− vs. 100.2 in pre‐transplant AT1R‐Ab + at 1 year, 103.6 ml/min/1.73 m2 vs. 100.5; at 2 years, 98.9 ml/min/1.73 m2 vs. and 93.7; at 4 years, 72.6 ml/min/1.73 m2 vs. 80.9. 11/36 patients had acute rejection (6 in pre‐transplant AT1R‐Ab−, 5 in pre‐transplant AT1R‐Ab + ). There was no difference in rejection rates. All 6 subjects with de novo HLA‐DSA and AT1R‐Ab ≥17 U/ml at the time of biopsy experienced rejection. Mean age in those with the AT1R‐Ab ≥40 U/ml was 10.0 years vs. 13.2 in those <40 U/ml (p = 0.07). Conclusion In our small cohort, pre‐transplant AT1R‐Ab ≥17 U/ml was not associated with reduced graft function or rejection. The pathogenicity of pre‐transplant AT1R‐Ab in pediatric kidney transplantation requires further investigation.

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Circulating angiotensin type II receptor: Possible marker for antibody mediated rejection after renal transplantation?

Cited by 9 publications

References 25 publications

Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti-AT1R antibodies

Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti-AT1R antibodies

Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA Luminex era? A retrospective study

Pre‐transplant angiotensin II receptor type I antibodies in pediatric renal transplant recipients: An observational cohort study

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