Successful Treatment of Anti–angiotensin II Type 1 Receptor Antibody–Associated Rejection in Kidney Transplantation: A Case Report

Wiwattanathum, Punlop; Ingsathit, Atiporn; Thammanichanond, Duangtawan; Worawichawong, Suchin

doi:10.1016/j.transproceed.2017.11.027

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…We do not advocate for modifying organ allocation protocols according to preformed AT1R-AA. Attempts have been made to eliminate AT1R-AA in kidney transplant recipients with refractory rejection using antibody-removal regimens such as plasmapheresis and rituximab, with (27) or without intravenous immune globulin (1). Bortezomib was added to the protocols to treat aggressive rejection in renal transplant recipients when both DSA and AT1R-AA were positive (28).…”

Section: Accepted Articlementioning

confidence: 99%

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

McAlister

Leckie

et al. 2020

American Journal of Transplantation

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Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R-AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R-AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R-AA before transplantation were higher (p=0.019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R-AA>17U/ml before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R-AA (defined as >40U/ml) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan-Meier analysis, patients with strong positive AT1R-AA had significantly worse graft survival than those with Accepted Article This article is protected by copyright. All rights reserved. AT1R-AA<40U/ml (p=0.035). In multivariate Cox models that included confounders such as sex and age, either AT1R-AA>40U/ml [HR=1.999 (1.085-3.682), p=0.026] or increased concentrations of AT1R-AA [HR=1.003 (1.001-1.006) per incremental U/ml, p=0.019] were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R-AA in candidates for second liver transplantation and that their presence is associated with inferior long-term outcomes of the second graft.

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Section: Accepted Articlementioning

confidence: 99%

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

McAlister

Leckie

et al. 2020

American Journal of Transplantation

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“…One patient (patient #6) was not treated with an ARB due to hyperkalemia but recovered good graft function following use of pulse steroid. A similar treatment was reported in a case study for treatment of rejection in the presence of AT1R-Ab [31]. AT1R expression increases during inflammation [9], therefore use of steroids to reduce inflammation may be an effective approach to reduce the availability of the target AT1R on the endothelium to which circulating antibodies can bind.…”

Section: Discussionmentioning

confidence: 69%

Management of heart transplant recipients with hemodynamically significant clinical rejection in the presence of antibodies against angiotensin II type 1 receptor: A retrospective study

Randhawa¹,

Philogene²,

Jeresano³

et al. 2018

Trends in Transplant

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Antibodies against Angiotensin II Type 1 Receptor (AT1R-Abs) have been associated with allograft rejection in heart transplantation. Data is lacking for modalities to mitigate their effect on cardiac function. We describe a case series consisting of patients with clinical and/or biopsy indication of rejection with detectable AT1R-Ab and present treatment regimen and outcome. Clinical dysfunction was defined as hemodynamically significant cardiac dysfunction on echocardiogram including a decrease in ejection fraction greater than or equal to 20%, shortness of breath, palpitations, chest tightness, and/or prolonged inotrope/vasopressor requirements during hospitalization. All patients selected for AT1R-Ab assessment had very low level or no donor specific HLA antibodies. Five of 9 patients with positive AT1R-Ab recovered good graft function following treatment with either losartan alone or in combination with plasmapheresis and IVIG. Two patients did not recover normal graft function and died despite the use of similar treatments. Losartan and plasmapheresis are obvious therapeutic approaches for heart transplant recipients with clinical dysfunction and positive AT1R-Ab. Losartan blocks activation of AT1 receptor, and plasmapheresis reduces circulating antibodies. Additional considerations such as patient characteristics, comorbidities, the use of ARBs other than losartan and appropriate time for treatment administration need to be evaluated in larger studies.

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“…Antibody levels decreased and an endothelial crossmatch became negative after 9 PP sessions and treatment with low-dose IVIG (100 mg/kg), 5–8 mg/ml tacrolimus, and mycophenolate mofetil (MMF) (2000 mg daily). Other case reports 82-84 also showed that PP was successful in treating AMR in renal transplant patients with anti-AT1R antibodies but without DSAs. Although AT1R antibody titers sometimes returned to the maximal detection level after treatment, refractory AMR was not observed.…”

Section: Therapeutic Approachesmentioning

confidence: 87%

A Comprehensive Overview of the Clinical Relevance and Treatment Options for Antibody-mediated Rejection Associated With Non-HLA Antibodies

Kardol‐Hoefnagel

Otten²

2020

Transplantation

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Although solid organ transplant results have improved significantly in recent decades, a pivotal cause of impaired long-term outcome is the development of antibody-mediated rejection (AMR), a condition characterized by the presence of donor-specific antibodies to HLA or non-HLA antigens. Highly HLA-sensitized recipients are treated with desensitization protocols to rescue the transplantation. These and other therapies are also applied for the treatment of AMR. Therapeutic protocols include removal of antibodies, depletion of plasma and B cells, inhibition of the complement cascade, and suppression of the T-cell–dependent antibody response. As mounting evidence illustrates the importance of non-HLA antibodies in transplant outcome, there is a need to evaluate the efficacy of treatment protocols on non-HLA antibody levels and graft function. Many reviews have been recently published that provide an overview of the literature describing the association of non-HLA antibodies with rejection in transplantation, whereas an overview of the treatment options for non-HLA AMR is still lacking. In this review, we will therefore provide such an overview. Most reports showed positive effects of non-HLA antibody clearance on graft function. However, monitoring non-HLA antibody levels after treatment along with standardization of therapies is needed to optimally treat solid organ transplant recipients.

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Successful Treatment of Anti–angiotensin II Type 1 Receptor Antibody–Associated Rejection in Kidney Transplantation: A Case Report

Cited by 6 publications

References 14 publications

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

Management of heart transplant recipients with hemodynamically significant clinical rejection in the presence of antibodies against angiotensin II type 1 receptor: A retrospective study

A Comprehensive Overview of the Clinical Relevance and Treatment Options for Antibody-mediated Rejection Associated With Non-HLA Antibodies

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