Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p<0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p<0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p<0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p<0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p<0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

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Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612972 ◽

2002 ◽

Vol 87 (02) ◽

pp. 194-198 ◽

Cited By ~ 32

Author(s):

Torsten Slowinski ◽

Ingeborg Hauser ◽

Birgit Vetter ◽

Lutz Fritsche ◽

Daniela Bachert ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Function ◽

Factor V Leiden ◽

Factor V ◽

Transplant Recipients ◽

Graft Dysfunction ◽

Kidney Transplant Recipients ◽

Factor V Leiden Mutation

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.

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Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

F1000Research ◽

10.12688/f1000research.10414.1 ◽

2016 ◽

Vol 5 ◽

pp. 2893 ◽

Cited By ~ 15

Author(s):

Rossana Rosa ◽

Jose F. Suarez ◽

Marco A. Lorio ◽

Michele I. Morris ◽

Lilian M. Abbo ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Acute Rejection ◽

Clinical Outcomes ◽

Kidney Transplant ◽

Graft Survival ◽

Patient Survival ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serious Infections ◽

The Impact

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.

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