scholarly journals Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wai H. Lim ◽  
Brigitte Adams ◽  
Stephen Alexander ◽  
Antonia H. M. Bouts ◽  
Frans Claas ◽  
...  
Keyword(s):  
New Zealand ◽  
Acute Rejection ◽  
Children And Adolescents ◽  
Kidney Transplant ◽  
Kidney Failure ◽  
De Novo ◽  
Hla Typing ◽  
Trial Registration ◽  
Donor Kidney ◽  
Allograft Loss

Abstract Background Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. Methods This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. Discussion The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. Trial registration The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

COMPARISON OF MICROEMULSION AND CONVENTIONAL FORMULATIONS OF CYCLOSPORINE A IN PREVENTING ACUTE REJECTION IN DE NOVO KIDNEY TRANSPLANT PATIENTS1

1999 ◽  
Vol 68 (9) ◽  
pp. 1325-1331 ◽  
Author(s):  
Stephen G. Pollard ◽  
Paul A. Lear ◽  
Andrew R. Ready ◽  
Richard H. Moore ◽  
Robert W.G. Johnson
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Cyclosporine A ◽  
De Novo

Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss

2009 ◽  
Vol 9 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
M. J. Everly ◽  
J. J. Everly ◽  
L. J. Arend ◽  
P. Brailey ◽  
B. Susskind ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Specific Antibody ◽  
Renal Allograft ◽  
De Novo ◽  
Renal Allograft Loss ◽  
Allograft Loss ◽  
Antibody Levels

MO1001THE OUTCOME OF PLASMA CELL-RICH ACUTE REJECTION IN KIDNEY TRANSPLANTATION, IS IT REALLY POOR?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Tarek S H Mahmoud ◽  
Osama Gheith ◽  
Jude Yagan ◽  
Ahmad Al-Taleb ◽  
Medhat MA Halim ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Plasma Cell ◽  
Membranous Nephropathy ◽  
Post Treatment ◽  
Hla Typing ◽  
Antibody Mediated Rejection ◽  
Banff Classification ◽  
Associated Conditions

Abstract Background and Aims The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR which can be associated with any type of rejection, may not be considered as independent morphological prognostic feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Method Out of 1920 kidney transplant recipients under follow up in our centre from 1996 till 2019, four patients were reported to have PCAR according to 2007 Banff classification. They were re-evaluated based on 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. Results The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded well to treatment and the mean improvement in eGFR was 12.8%, 24.9%, 40.3% and 39.1% at 1-, 3-, 6- and 12-months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Conclusion Outcome of PCAR management was favourable among our patients irrespective of the type of rejection and associated conditions.

SLCO1B3 polymorphisms and clinical outcomes in kidney transplant recipients receiving mycophenolate

2021 ◽  
Author(s):  
Lauren Schumacher ◽  
Fang Fang ◽  
Kelley M Kidwell ◽  
Faisal Shakeel ◽  
Daniel L Hertz ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Patient Survival ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Primary Analysis ◽  
Adult Kidney ◽  
Increased Risk

Aim: Determine the influence of SLCO1B3 polymorphisms on outcomes in kidney transplant recipients. Materials & methods: We retrospectively evaluated 181 adult kidney transplant recipients receiving mycophenolate. Outcomes included treated biopsy-proven acute rejection (tBPAR), de novo donor specific antibody (dnDSA) formation, graft survival, patient survival and mycophenolate-related adverse effects among SLCO1B3 genotypes. Results: The presence of SLCO1B3 variants was not associated with increased risk of tBPAR (HR: 1.45, 95% CI: 0.76–2.74), dnDSA (HR: 0.46, 95% CI: 0.16–1.36) or composite of tBPAR or dnDSA (HR: 1.14, 95% CI: 0.64–2.03). Graft and patient survival were reduced among variant carriers; however, inconsistent findings with the primary analysis suggest these associations were not due to genotype. Adverse effects were similar between groups. Conclusion: Presence of SLCO1B3 polymorphisms were not predictive of rejection or dnDSA in kidney transplant recipients.

scholarly journals Clinical characteristics, risk factors and outcome of severe Norovirus infection in kidney transplant patients: a case-control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Julien Gras ◽  
Moustafa Abdel-Nabey ◽  
Axelle Dupont ◽  
Jérôme Le Goff ◽  
Jean-Michel Molina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Case Control Study ◽  
De Novo ◽  
Case Control ◽  
Duration Of Symptoms ◽  
Factors Associated ◽  
Control Study

Abstract Background Human Norovirus (HuNoV) has recently been identified as a major cause of diarrhea among kidney transplant recipients (KTR). Data regarding risk factors associated with the occurrence of HuNoV infection, and its long-term impact on kidney function are lacking. Methods We conducted a retrospective case-control study including all KTR with a diagnosis of HuNoV diarrhea. Each case was matched to a single control according to age and date of transplantation, randomly selected among our KTR cohort and who did not develop HuNoV infection. Risk factors associated with HuNoV infection were identified using conditional logistic regression, and survival was estimated using Kaplan-Meier estimator. Results From January 2012 to April 2018, 72 cases of NoV diarrhea were identified among 985 new KT, leading to a prevalence of HuNoV infection of 7.3%. Median time between kidney transplantation and diagnosis was 46.5 months (Inter Quartile Range [IQR]:17.8–81.5), and the median duration of symptoms 40 days (IQR: 15–66.2). Following diagnosis, 93% of the cases had a reduction of immunosuppression. During follow-up, de novo Donor Specific Antibody (DSA) were observed in 8 (9%) cases but none of the controls (p = 0.01). Acute rejection episodes were significantly more frequent among cases (13.8% versus 4.2% in controls; p = 0,03), but there was no difference in serum creatinine level at last follow-up between the two groups (p = 0.08). Pre-transplant diabetes and lymphopenia below 1000/mm3 were identified as risks factors for HuNoV infection in multivariate analysis. Conclusion HuNoV infection is a late-onset and prolonged infection among KTR. The current management, based on the reduction of immunosuppressive treatment, is responsible for the appearance of de novo DSA and an increase in acute rejection episodes.

scholarly journals Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

2018 ◽  
Vol 29 (7) ◽  
pp. 1979-1991 ◽  
Author(s):  
Julio Pascual ◽  
Stefan P. Berger ◽  
Oliver Witzke ◽  
Helio Tedesco ◽  
Shamkant Mulgaonkar ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Confidence Interval ◽  
Kidney Transplant ◽  
Calcineurin Inhibitor ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
End Point

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

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