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CONNEXI 2016-08 Nephrologie

Kidney Experts Forum Old

Kidney Experts Forum Old donor • Immunogenicity • Acute rejection rates • Impaired graft function Recipient Old Young Risk of rejection Demographic and clinical factors affecting risk of graft rejection Prof. Thomas Müller provided a summary of relevant background information on non-immunological factors affecting immunological factors which include recipient age, older donor age, female recipient gender, black ethnicity, deceased vs. living donor and other factors. Graft survival Old recipient • Comorbidities • Acute rejection rates Donor +Young +Old Risk of rejection There is little difference in terms of risk between deceased- and living-donor recipients [17]. Older donor age and gender mismatch may portend worse clinical outcomes [18, 19]. The other possible variables including HIV or HCV infection, BMI, cause of End Stage Renal Disease, diabetes and dialysis may significantly affect graft outcome [20-22]. Considering the absence of a clear and precise definition of immunogenicity, other variables were listed as potential contributory factors at the time of transplant; the kidney allograft itself should be considered in the assessment of risk through all the different aspects related to organs such as The kidney allograft itself should be considered in the assessment of risk Education Kidney Experts Forum Figure 3: Interaction between donor and recipient age Non-immunological factors related to recipient and donor demographics and clinical factors, and contributing to graft outcome are age, adherence, gender, ethnicity, donor type and others like concomitant viral infection or disease, obesity, diabetes, cause of death, duration of dialysis, etc [12]. A qualitative assessment of the leading risk factors has been developed even if it is difficult to have clear consensus on which parameters should be taken into account. Younger recipient age coincidence with higher rates of non-adherence in adolescence as well as black ethnicity are associated with increased graft failure and should be taken into account when assessing immunological risk in kidney transplantation [13-16] (Figure 3). endothelial dysfunction, systemic immunogenicity and functional capacity of the kidney. Even if it is difficult to establish conclusively the contribution of these different risk factors on graft outcome, some non-immunological parameters were persistent independent risk factors affecting graft survival rate. Effect of pre-transplant sensitization on rejection risk Prof. Duska Dragun presented an overview of the effect of pre-transplant sensitization on rejection risk. Three levels of immunological risk associated with kidney transplantation are currently defined high, intermediate and low [12]. High immunologic risk consists in patients on desensitization protocols who were cross-match positive and were 40

Kidney Experts Forum desensitized for the case of high panel reactive antibodies (PRA) after previous transplant loss, or female recipients of living related donation in constellation of pregnancy-induced HLA-DSA. Intermediate risk includes two groups of patients, re-transplantations with increased PRA or female patients with pregnancy-induced increased HLA- DSA. Low immunological risk is indicated when the cross-match result is negative and the patient has never been sensitized [23]. Because no consensus between centers has been reached on the definition of risk categories there is a need for refining classification of immunological risks. Pregnancy has the highest impact on the change of HLA antibodies from pre-transplantation level [24]. The contribution of different classes of HLA-DSA, HLA non-DSA, complement (C1q) fixing HLA-DSA and non-HLA antibodies to immunological risk remains controversial [12]. There is a debate regarding which antibodies are the most or least aggressive. However, in a retrospective analysis of pre-transplant sera from a cohort of 837 cross-match-negative kidney transplant recipients, There is a need for refining classification of immunological risks Otten et al. showed that the presence of class-I + -II IgG DSA as detected by Luminex single-antigen bead (SAB) was indicative of an increased risk for graft failure [25]. Non-HLA antibodies directed against autoantigens such as angiotensin type 1 negative HLA-DSA negative AT1R-Abs negative ELISPOT low immunologic risk negative or low non-cytotoxic HLA-DSA low/intermediate positive AT1R-Abs positive ELISPOT intermediate immunologic risk HLA-DSA desensitization protocols highly positive AT1R-Abs highly positive ELISPOT high immunologic risk Pre-Tx close monitoring of de-novo HLA sensitization required clinicians alert about risk and danger of immunosuppression weaning and choice of induction Post-Tx Figure 4: Expanding definition of pre-transplant risk in low-, intermediate- and high-risk renal transplant recipients ! Education Kidney Experts Forum 41

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