The appropriate dose of thymoglobulin induction therapy in kidney transplantation

Nafar, Mohsen; Dalili, Nooshin; Poorrezagholi, Fatemeh; Ahmadpoor, Pedram; Samadian, Fariba; Samavat, Shiva

doi:10.1111/ctr.12977

Cited by 16 publications

(11 citation statements)

References 26 publications

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“…Dendritic cells and macrophages are key initiators, potentiators, and effectors of innate immunity in kidney IRI, inducing injury through inflammatory signals or directly through the release of soluble mediators 13 Macrophages appear in the kidney within 1-5 days of IRI, and the early activation of macrophages and dendritic cells leads to the infiltration of neutrophils and generation of proinflammatory cytokines 13 The only difference observed between groups was the doses of thymoglobulin, higher in the DSA + group. Although the optimal dosage of thymoglobulin used in the induction therapy is still not well established, previous studies showed that cumulative doses of thymoglobulin ranging from 4.2 to 7.4 mg/kg appear to be effective in prevention of acute rejection during the first year post-transplantation 14 . Nafar et al 14 compared three transplant recipient groups according to thymoglobulin dose: 4.5 mg/kg in 3 days, 4.5 mg/kg single bolus dose, and 6 mg/kg in 3 days.…”

Section: Discussionmentioning

confidence: 99%

“…Although the optimal dosage of thymoglobulin used in the induction therapy is still not well established, previous studies showed that cumulative doses of thymoglobulin ranging from 4.2 to 7.4 mg/kg appear to be effective in prevention of acute rejection during the first year post-transplantation 14 . Nafar et al 14 compared three transplant recipient groups according to thymoglobulin dose: 4.5 mg/kg in 3 days, 4.5 mg/kg single bolus dose, and 6 mg/kg in 3 days. They found no significant difference in rejection among groups, but the incidence of glomerulitis and peritubular capilaritis was higher in the divided lower dose group.…”

Section: Discussionmentioning

confidence: 99%

“…The only difference observed between groups was the doses of thymoglobulin, higher in the DSA + group. Although the optimal dosage of thymoglobulin used in the induction therapy is still not well established, previous studies showed that cumulative doses of thymoglobulin ranging from 4.2 to 7.4 mg/kg appear to be effective in prevention of acute rejection during the first year post-transplantation 14 . Nafar et al 14 compared three transplant recipient groups according to thymoglobulin dose: 4.5 mg/kg in 3 days, 4.5 mg/kg single bolus dose, and 6 mg/kg in 3 days.…”

Section: Discussionmentioning

confidence: 99%

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Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

2020

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Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

2020

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“…A higher incidence of death due to infection was observed in the groups with pre-transplant anti-HLA antibodies (DSA+ and non-DSA). In these cases, immunosuppressive induction with higher doses of thymoglobulin could justify the higher incidence of opportunistic infections, compared to patients who received lower doses of thymoglobulin or basiliximab as induction therapy [ 24 ]. However, we did not find any cases of graft failure due to rejection in these groups during the 1-year follow-up.…”

Section: Discussionmentioning

confidence: 99%

Effect of Preformed or De Novo Anti-HLA Antibodies on Function and Graft Survival in Kidney Transplant Recipients

et al. 2018

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BackgroundDonor-specific antibodies (DSA), directed against human leucocyte antigens (HLA), are associated with increased risk for graft rejection in kidney transplantation. Anti-HLA antibodies detection by Luminex™ present high sensitivity and accuracy, but its interpretation after transplantation is not completely clear.The aim of this study was to evaluate the impact of anti-HLA antibodies, preformed or de novo, on renal function, graft survival, and incidence of antibody-mediated acute rejection (AMR).Material/MethodsA retrospective cohort of 86 kidney transplant recipients was divided into 3 groups according to the presence of anti-HLA antibodies before transplantation: donor-specific antibodies (DSA+, n=15), non-DSA (non-DSA, n=39), and negative pre-transplant panel reactive antibodies (PRA) that became positive after transplantation (PRA−, n=22). Forty-nine recipients with negative PRA pre- and post-transplantation were excluded. Antibody specificity and intensity of fluorescence (MFI) and their relationship with renal function, proteinuria, AMR, and graft failure were evaluated.ResultsAmong patients who completed 1 year of follow-up, there was no significant difference in serum creatinine, estimated glomerular filtration rate, or proteinuria. AMR incidence was 9.5% in the DSA group, 2.3% in the non-DSA group, and 9.1% in the PRA− group. There was no correlation between fluorescence intensity and/or antibodies class (I or II) with increased risk of AMR. Thirteen grafts failed within 1 year post-transplant, there were 9 deaths due to infection, and only 1 due to AMR (PRA− group, DSA de novo at 3 months).ConclusionsIn contrast to previous reports, we did not find a correlation between incidence of AMR and MFI intensity in this series.

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“…To prevent AMR, rabbit antithymocyte globulin (rATG) induction immunosuppression is widely used to eliminate T helper cells, decrease donor-specific antigen (DSA) antibody titers, and reduce B-cell differentiation to plasma cells. 2-4 However, antibodies against rATG can negate its therapeutic purpose. 5 This is particularly important when deliberating follow-up rATG to combat suspected AMR.…”

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confidence: 99%

Antithymocyte Globulin Antibody Titer Congruent With Kidney Transplantation: Analysis of Incidence, Outcomes, Cost, and Alternative Targets

Lattimore

Skill

Maluccio

et al. 2019

Transplantation Direct

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Background.Rabbit antithymocyte globulin (rATG) use for immunosuppression induction is widespread but is contraindicated by the presence of anti-rATG antibodies. This study reports the incidence of positive anti-rATG antibody titers in patients before and after renal transplant and evaluates associated outcomes and costs. In addition, it will correlate CD40L and interleukin (IL)-21 with anti-rATG antibody titers.Methods.Clinical and billing records from the Indiana University Transplant Laboratory were reviewed for positive versus negative anti-rATG antibody titers, graft survival, and 7-day readmission costs between 2004 and 2018. Serum from patients with positive and negative rATG antibody titers were quantitated for CD40L and IL-21 by enzyme-linked immunosorbent assay.Results.On average, between 2004 and May 2018, 163 kidney transplants per year were performed. Anti-rATG antibody titers were ordered for 17 patients/year, of which 18.2% were positive at 1:100 titer either pre- or post-transplant. Time to graft loss correlated with a positive rATG titer at time of readmission. Moreover, second kidney transplant increased the anti-rATG positive rate. A weak correlation was observed between anti-rATG titer and recipient age. Seven-day readmission treatment costs were significantly lower in patients with positive anti-rATG titer. IL-21 and CD40L were significantly greater in patients with positive anti-rATG titers after transplant when compared with negative anti rATG patients.Conclusions.Positive anti-rATG antibody titer is associated with a significant negative impact on outcomes. Monitoring of anti-rATG antibody titer is recommended to optimize treatment options in patients, especially in the setting of second transplants. Elucidation of the mechanisms associated with positive anti-rATG antibody is required. IL-21 and CD40L are potential targets for future study.

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The appropriate dose of thymoglobulin induction therapy in kidney transplantation

Abstract: Although all regimens showed the same efficacy regarding the rate of rejection episodes, 3-day 4.5 mg/kg Thymoglobulin had significantly fewer complications.

Cited by 16 publications

References 26 publications

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

Effect of Preformed or De Novo Anti-HLA Antibodies on Function and Graft Survival in Kidney Transplant Recipients

Antithymocyte Globulin Antibody Titer Congruent With Kidney Transplantation: Analysis of Incidence, Outcomes, Cost, and Alternative Targets

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