Proactive treatment of angiotensin receptor antibodies in kidney transplantation with plasma exchange and/or candesartan is safe and associated with excellent graft survival at 4 years: A single centre Australian experience

Carroll, Robert; Deayton, Sue; Emery, Timothy J.; Munasinghe, Watsala; Tsiopelas, Eleni; Fleet, A; Lake, Meg; Humphreys, Ian R.; Jalalonmuhali, Maisarah; Coates, P. Toby

doi:10.1016/j.humimm.2019.04.005

Cited by 13 publications

(12 citation statements)

References 16 publications

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“…This treatment resulted in similar rejection rates at 90 days and same death-censored graft survival at 4 years as those for recipients of kidney transplants who have antibody levels < 17 U/ml. 93 Similar results were reported in heart transplantation including therapies of AT 1 R blockers, plasmapheresis, immunoglobulins, and rituximab. 94 Future therapeutic options include use of epitope-binding peptides abolishing autoantibodies' activity or synthetic nanobodies as AT 1 R blockers.…”

Section: Discussionsupporting

confidence: 70%

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

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Wischnewski

Chen

et al. 2022

Kidney International

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Section: Discussionsupporting

confidence: 70%

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

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Wischnewski

Chen

et al. 2022

Kidney International

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“…Ig, plasmapheresis, and angiotensin receptor blockade. 7,60,61 However, the role of ETAR blockade in transplantation has not yet been explored. The successful use of ETAR blockers to treat complications associated with ETAR-Ab has been reported in scleroderma.…”

Section: Discussionmentioning

confidence: 99%

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

Pearl

Chen

ElChaki

et al. 2020

Kidney International Reports

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Introduction: Autoantibody to angiotensin II type 1 receptor (AT1R-Ab) has been recognized as a non-human leukocyte antigen (HLA) antibody relevant in transplantation. Endothelin type A receptor antibody (ETAR-Ab) has been strongly associated with AT1R-Ab, but the data in kidney transplantation are scarce. Methods: We examined the relationship of ETAR-Ab and AT1R-Ab with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibody (DSA) in a cohort of pediatric renal transplant recipients. Sixty-five patients were longitudinally monitored for ETAR-Ab, AT1R-Ab, HLA DSA, interleukin (IL)-8, tumor necrosis factor-a, IL-1b, interferon-g, IL-17, IL-6, renal dysfunction, hypertension, rejection, and allograft loss during the first 2 years post-transplant. Results: Fifteen patients (23%) had AT1R-Ab alone, 1 (2%) had ETAR-Ab alone, 23 (35%) had both ETAR-Ab and AT1R-Ab, and 26 (40%) were negative for both antibodies at all timepoints. Having both ETAR-Ab and AT1R-Ab was associated with >30% decline in estimated glomerular filtration rate (P ¼ 0.024), arteritis (P ¼ 0.016), and elevated IL-8 levels (P ¼ 0.010), but not rejection, HLA DSA, or allograft loss. Having both antibodies resulted in greater increases in IL-8 compared with AT1R-Ab alone, even when controlled for additional clinical factors, including HLA DSA (P ¼ 0.012). Conclusion: Our study demonstrates that, in pediatric kidney transplantation, ETAR-Ab is highly associated with AT1R-Ab, but there are a subset of patients with AT1R-Ab alone. Having both antibodies is significantly associated with arteritis, elevated IL-8, and decline in renal function, and our results suggest possible interaction effects. Better understanding of this interaction may be informative in developing protocols for testing, treatment, and prevention of allograft injury.

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“…More recent studies have indicated similarly improved clinical course and histologic outcomes using AT1R blockers for treating kidney transplant recipients with anti-AT1R-mediated rejection and for preventing allograft rejection in patients with high levels of circulating anti-AT1R antibodies. 118,119 These AT1R antibody status-based stratified treatment protocols may thus provide durable means to reduce immunologic risk in kidney transplantation 120 ; therefore, the use of AT1R blockers as prophylaxis for patients with circulating anti-AT1R antibodies is promising, but available data remain preliminary. Regarding the treatment of ABMR related to anti-AT1R antibodies, little experience exists for the use of standard-of-care treatment of ABMR (plasmapheresis, i.v.…”

Section: Inactive Activementioning

confidence: 99%

The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

Lefaucheur

Louis

Philippe

et al. 2021

Kidney International

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Proactive treatment of angiotensin receptor antibodies in kidney transplantation with plasma exchange and/or candesartan is safe and associated with excellent graft survival at 4 years: A single centre Australian experience

Cited by 13 publications

References 16 publications

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

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Proactive treatment of angiotensin receptor antibodies in kidney transplantation with plasma exchange and/or candesartan is safe and associated with excellent graft survival at 4 years: A single centre Australian experience

Cited by 13 publications

References 16 publications

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

Non-HLA antibodies targeting angiotensin II Type 1 receptor and endothelin-1 Type A receptors induce endothelial injury via β2-arrestin link to mTOR pathway

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

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Product

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Proactive treatment of angiotensin receptor antibodies in kidney transplantation with plasma exchange and/or candesartan is safe and associated with excellent graft survival at 4 years: A single centre Australian experience