Is the level of HLA eplet mismatch a risk factor for graft loss among kidney transplant recipients who have already formed de novo donor specific antibody?

BackgroundCalcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.MethodsStable adult kidney transplant recipients 6–60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.ResultsOverall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, −2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.ConclusionsSwitching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA.Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572

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Clinical significance of de novo donor-specific antibody in kidney transplant recipients with chronic antibody-mediated rejection

Korean Journal of Transplantation ◽

10.4285/kjt.20.0052 ◽

2021 ◽

Author(s):

Woo Yeong Park ◽

Yaerim Kim ◽

Jin Hyuk Paek ◽

Kyubok Jin ◽

Seungyeup Han

Keyword(s):

Kidney Transplant ◽

Clinical Significance ◽

Specific Antibody ◽

De Novo ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection

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Immunosuppressive Management of Pediatric Kidney Transplant Recipients

Current Pharmaceutical Design ◽

10.2174/1381612826666200708133429 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3451-3459

Author(s):

Tomáš Seeman

Keyword(s):

Immunosuppressive Therapy ◽

Kidney Transplant ◽

Induction Therapy ◽

Graft Loss ◽

Calcineurin Inhibitors ◽

Mtor Inhibitors ◽

Therapeutic Drug ◽

High Dose ◽

Transplant Recipients ◽

Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

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BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Viruses ◽

10.3390/v13020351 ◽

2021 ◽

Vol 13 (2) ◽

pp. 351

Author(s):

Baptiste Demey ◽

Véronique Descamps ◽

Claire Presne ◽

Francois Helle ◽

Catherine Francois ◽

...

Keyword(s):

Viral Replication ◽

Kidney Transplant ◽

Clinical Relevance ◽

Graft Loss ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplantation ◽

Bk Polyomavirus ◽

Micro Rnas

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.

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Glomerular C3 Deposition Is an Independent Risk Factor for Allograft Failure in Kidney Transplant Recipients With Transplant Glomerulopathy

Kidney International Reports ◽

10.1016/j.ekir.2019.01.018 ◽

2019 ◽

Vol 4 (4) ◽

pp. 582-593 ◽

Cited By ~ 3

Author(s):

Sarah E. Panzer ◽

Emily Joachim ◽

Sandesh Parajuli ◽

Weixiong Zhong ◽

Brad C. Astor ◽

...

Keyword(s):

Risk Factor ◽

Kidney Transplant ◽

Independent Risk Factor ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Allograft Failure ◽

Transplant Glomerulopathy

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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