Despite progress made in the field of immunosuppression, graft rejection remains a major cause of morbidity and mortality of patients after solid organ transplantation. There are several genetic causes which could influence the outcome of renal transplantation. One of the main determining factors of success in renal transplantation is human leukocyte antigen (HLA) compatibility between donor and recipient, particularly at HLA-A, HLA-B and HLA-DR loci. HLA compatibility remains an essential immunological barrier, despite modern immunosuppressive treatments. There is also evidence that natural killer (NK) cell alloreactivity contributes to the immune response which modulates the outcome of renal transplantation. However, the clinical impact of combinations of KIR genes (family of NK cell receptors) and their HLA ligands in donor and recipient still remains to be clearly established. Furthermore, cytokines are involved in the immune reaction against the renal transplant, but the implication of the genetic polymorphism of cytokines is strongly debated. Therefore, while HLA compatibility remains a primordial component for any renal transplantation, it would be premature to use the two other genetic aspects as criteria for organ allocation and as prognostic factors.

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).

Immunological factors influencing renal graft survival. The results of clinical renal transplantation are determined mainly by immunological factors, the most important of which are compatibility for the HLA chromosomes and pretransplant blood transfusions. Other factors include HLA matching in cadaver transplantation, compatibility for the Lewis blood group system, and sensitization to lymphocyte panels or to endothelial-monocyte antigens. Performance of the previous graft is the most reliable predictor of success in recipients of retransplants. Because several immunological factors may interact, multiple variables must be considered simultaneously. Published in Annual review of medicine (1983)

called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. Its name comes from its discovery during the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. Its name comes from its discovery during the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due to incompatibility is only a facet of the full function of MHC molecules, which is to bind an antigen derived from self-proteins, or from pathogens, and bring the antigen presentation to the cell surface for recognition by the appropriate T-cells. MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases. In a cell, protein molecules of the host's own phenotype or of other biologic entities are continually synthesized and degraded. Each MHC molecule on the cell surface displays a small peptide (a molecular fraction of a protein) called an epitope. The presented self-antigens prevent an organism's immune system from targeting its own cells. The presentation of pathogen-derived proteins results in the elimination of the infected cell by the immune system. Diversity of an individual's self-antigen presentation, mediated by MHC self-antigens, is attained in at least three ways: (1) an organism's MHC repertoire is polygenic (via multiple, interacting genes); (2) MHC expression is codominant (from both sets of inherited alleles); (3) MHC gene variants are highly polymorphic (diversely varying from organism to organism within a species). Sexual selection has been observed in male mice choosing to mate with females with different MHCs. Also, at least for MHC I presentation, there has been evidence of antigenic peptide splicing, which can combine peptides from different proteins, vastly increasing antigen diversity. Hyperacute rejection occurs when, before the transplantation, the recipient has preformed anti-HLA antibodies, perhaps by previous blood transfusions (donor tissue that…

<h4>Background and aims</h4>Long-term kidney transplant survival is a critical challenge in nephrology, which might be influenced by a myriad of recipient, donor, and post-transplant factors. Despite advancements in medical care, some issues, like transplant rejection and comorbidities, continue to hinder progress. This scoping review aimed to identify predictors of long-term kidney transplant survival.<h4>Methods</h4>Following Arksey and O'Malley's framework, this scoping review analyzed studies published between 2014 and 2025 across seven databases. Studies addressing recipient-, donor-, and post-transplant factors as predictors of long-term kidney transplant survival were included. The findings were categorized by timeframes and predicting factors, and finally, synthesized descriptively.<h4>Results</h4>Overall, 37 studies were included. Key predictors of long-term survival included recipient-related factors such as age, BMI, comorbidities, and serum creatinine levels. Donor-related factors like age, HLA mismatches, and kidney quality also emerged as significant contributors. Post-transplant factors, including acute rejection episodes, use of immunosuppressive drugs, and hospital readmissions, were strongly associated with graft outcomes.<h4>Conclusion</h4>This review highlighted the multifaceted predictors of long-term kidney transplant survival, emphasizing the need for personalized management strategies. Tailored interventions targeting high-risk patients and enhanced donor selection protocols are vital for improving outcomes. Future research should focus on examining predictive algorithms to predict transplant survival.