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CONNEXI 2016-08 Nephrologie

Kidney Experts Forum

Kidney Experts Forum Education Kidney Experts Forum Odds ratio for acute rejection 2 1.5 1 0.5 0 42 receptor contribute to the process of antibody-mediated acute and chronic rejection. By assessing donor-specific alloreactive memory/effector T cell responses, the use of T cell allospecific ELISPOT assays have helped evaluate the cellular immune risk in renal transplantation [26] (Figure 4). Similarly, the presence of soluble CD30, reflecting memory response in the patient, has been proposed as a biomarker for increased risk of kidney graft rejection [27]. Adjusted odds ratio for acute rejection by year 1 USRDS (1995–2002); N=27,707 1.0 0 mismatch (n=1,468) 1.39 1-3 mismatches (n=11,859) 1.56 4-6 mismatches (n=14,380) Figure 5: HLA mismatch & risk of acute rejection In conclusion, a need clearly exists to consider additional parameters for refining risk stratification. Instead of only measuring HLA antibodies, functional non-HLA antibodies should also be taken into account. The T cell ELISPOT assay and shortcut methods should be used for a general overview of the recipient’s individual response. In this regard help from HLA laboratories to extend this method is critical. A consensus emerged amongst panelists on the need for defining which group would benefit from full-scale pre-transplant monitoring. Influence of immunological and viral serostatus matching Prof. Friedrich Thaiss presented an overview of the influence of immunological and viral serostatus matching on graft outcome. Well-established data have shown a correlation between degree of HLA mismatch and risk of acute rejection [28] (Figure 5). HLA mismatch in DR loci is particularly unfavorable for both acute and antibody-mediated rejection [1]. Complement-dependent cytotoxic test (CDC) was used as the gold standard to identify clinically relevant HLA antibodies [29]. This methodology was nourished by solid phase assays of solubilized HLA antigens. The limitations of these tests which should be performed before transplantation remain a matter of debate. However, not all pre-transplant DSA are perfectly predictive of poor outcome [29]. Serial testing should be performed before and after transplant even if no DSA is detectable before transplantation. Only 6 % of highly sensitized patients are transplanted each year Sensitization remains a major barrier to kidney transplantation. Desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized patients. Most centers use one of three different desensitization strategies for living kidney donors or sensitized patients on the waiting list. Current protocols include intravenous immunoglobulin (IVIG) or pre-transplant plasmapheresis (PP) or immunosuppression together with

Kidney Experts Forum IVIG or IVIG with or without rituximab [30]. Sensitized patients comprise about 30% of the kidney transplant waiting list but only 6% of highly sensitized patients are transplanted each year [31]. No clear data showed that CMV, EBV and BK viruses , per se, induced acute rejection Viral infections represent a potential contributor to graft failure. However, there is no clear data supporting that cytomegalovirus (CMV), Epstein- Barr (EBV) and BK viruses, per se, induced acute rejection [32]. Thus, the impact of CMV mismatch on acute rejection appears negligible in the era of widespread prophylaxis and EBV is unlikely to play an important role in rejection risk in adult patients [13, 32]. Importantly, there is a risk of rejection when lowering or discontinuing immunosuppressive therapy to treat these viruses. In conclusion, desensitization strategies need to be further refined to improve long-term allograft outcome in these patients. The cut-off at which desensitization protocols should be started and which protocol for individual patients should be used are key questions that require further debate and await answers. Overall, available data do not allow for establishing a clear-cut relationship between EBV, CMV viruses per se and graft rejection. Rejection risk according to transplant-related factors J. Pratschke presented a brief overview of the rejection risk according to transplant-related factors. Longer cold ischemia time (CIT) is a well-established risk factor for graft loss [33]. Less conclusive evidence exists for effect of CIT on acute rejection; CIT longer or shorter than 8 hours has no effect on rejection rates. CIT may exert an effect by exacerbating ischemia-perfusion injury and predisposing to delayed graft function (DGF) [12]. There are currently two approaches for preservation of organs, static or dynamic. Cold storage is the main method for static preservation. Perfusion-based methods are among the methods for dynamic preservation (hypothermic-, normothermic- and oxygenated-perfusion). Randomized control trials (RCTs) have shown that marginal organs benefit from machine perfusion. However, overall, there is no evidence supporting a clear relationship between type of preservation system and risk of rejection [34]. CIT may exert an effect by exacerbating ischemiaperfusion injury and predisposing to delayed graft function Overall conclusion Prediction of graft outcome proves to be a multi - faceted problem. There are numerous immunological as well as non-immunological factors that can contribute to graft loss (Table 2). The continuum of risk factors briefly described here should be useful to transplant clinicians in their assessment of at-risk kidney transplant Education Kidney Experts Forum 43

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