De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection

Chemouny, Jonathan; Suberbielle, Caroline; Rabant, Marion; Zuber, Julien; Alyanakian, Marie‐Alexandra; Lebreton, Xavier; Carmagnat, Maryvonnick; Pinheiro, Nathan Carvalho; Loupy, Alexandre; Huyen, Jean-Paul Van; Timsit, Marc‐Olivier; Charron, Dominique; Legendre, Christophe; Anglicheau, Dany

doi:10.1097/tp.0000000000000448

Cited by 29 publications

(21 citation statements)

References 24 publications

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“…4,11,[20][21][22][23][24][25][26][27][28] There is no conclusive information about the effects of purine synthesis inhibitors on dnDSA formation, 29 and we did not find any specific effect of MMF use nor the dosage in it. 4,11,[20][21][22][23][24][25][26][27][28] There is no conclusive information about the effects of purine synthesis inhibitors on dnDSA formation, 29 and we did not find any specific effect of MMF use nor the dosage in it.…”

Section: Discussioncontrasting

confidence: 55%

“…In addition to tacrolimus level variability, we also identified acute rejection and retransplant as risk factors for dnDSA, whereas mismatches, age, sex, and mean tacrolimus levels were not related to dnDSA development. 4,11,24 The AMR has been identified as the main cause of graft loss. 4,22,24 The fact that mean tacrolimus trough levels did not relate to dnDSA is consistent with previous reports 11,25 and stresses the importance of measuring tacrolimus level variability.…”

Section: Discussionmentioning

confidence: 99%

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Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development

et al. 2016

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development

et al. 2016

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“…Generally, TCMR is not more of a refractory problem compared with ABMR. Chemouny et al reported that TCMR might trigger a humoral immune response. Although noninferiority of class l DSA was inconclusive, class II DSA with TAC‐QD was likely less with TAC‐BID (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…The reasons for this are not well understood. One report indicated that T cell‐mediated rejection (TCMR) might trigger a humoral immune response . The incidence of donor‐specific antibodies (DSA) might be associated with this paradoxical result.…”

Section: Introductionmentioning

confidence: 99%

Once‐daily vs twice‐daily tacrolimus for de novo living kidney transplantation patients including ABO/HLA compatible and incompatible: A randomized trial

Okumi

Unagami

Furusawa

et al. 2018

Clinical Transplantation

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Tacrolimus (TAC) is available as a twice‐daily capsule (TAC‐BID), once‐daily capsule (TAC‐QD), and once‐daily tablet. Recipients with ABO‐incompatible/anti‐human leukocyte antigen (HLA)‐incompatible transplantation were excluded in previous trials and have thus not been evaluated. We conducted a 5‐year trial to determine whether TAC‐QD is noninferior to TAC‐BID for transplant outcomes. Adults who underwent de novo living kidney transplantation were randomly assigned (62 TAC‐QD; 63 TAC‐BID). We did not exclude ABO‐/HLA‐ incompatible transplantation. TAC was initiated 7 days preoperatively (0.10 mg/kg/d). Mycophenolate mofetil, methylprednisolone, and basiliximab were administered. The primary endpoint was graft failure (non‐censored for death). We performed a noninferiority test. The noninferiority margin was 10% in risk difference. Five‐year graft failure rates were 6.5% and 9.5% for TAC‐QD and TAC‐BID, respectively (noninferiority, P = 0.009). The estimated glomerular filtration rates were similar between the groups (noninferiority, P < 0.001). TAC‐QD did not have point estimates of risk difference above the inferiority margin in any assessed endpoints. However, a tendency of interaction was observed between biopsy‐proven acute rejection and the follow‐up period. In a living kidney transplant population with 40% of patients with ABO/HLA incompatibility, the effect of TAC‐QD was not appreciably worse on various clinical transplant outcomes than that of TAC‐BID over 5 years.

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“…These factors increase the risk for development of ABMR. Recently, it has been demonstrated that a previous episode of cell-mediated rejection predisposes to formation of de novo antibodies in unsensitized patients [20].…”

Section: Illustrative Casementioning

confidence: 99%

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Singh

Sarwal

2015

Drugs

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Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

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De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection

Abstract: Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.

Cited by 29 publications

References 24 publications

Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development

Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development

Once‐daily vs twice‐daily tacrolimus for de novo living kidney transplantation patients including ABO/HLA compatible and incompatible: A randomized trial

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

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