No abstract

Background and objectives Kidney transplantation is the preferred treatment for ESRD, and donor kidney shortage urges proper donor-recipient matching. Zero-hour biopsies provide predictive values for short-and long-term transplantation outcomes, but are invasive and may not reflect the entire organ. Alternative, more representative methods to predict transplantation outcome are required. We hypothesized that proteins accumulating in preservation fluid during cold ischemic storage can serve as biomarkers to predict posttransplantation graft function. Conclusions We demonstrate that donor kidney preservation fluid harbors biomarkers that, together with information on recipient BMI, predict short-term post-transplantation kidney function. Our approach is safe, easy, and performs better than current prediction algorithms, which are only on the basis of clinical parameters.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival Abstract Background Pretransplant donor-specific anti-HLA antibodies (DSA) are associated with impaired kidney graft survival, while the clinical relevance of non-donor specific anti-HLA antibodies (nDSA) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSA and nDSA. MethodsTo eliminate donor and era-dependent factors, a post-hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995-2005 with available pretransplant serum samples. Anti-HLA antibodies were detected with a luminex single antigen bead assay. ResultsAmong 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies.Patients with pretransplant DSA had a significantly lower 10-year death censored graft survival (55% vs. 82%, p=0.0001). Among 192 pairs with one recipient nDSA positive against either class I or II and the other without anti-HLA antibodies, graft survival did not significantly differ (74% vs. 77%, p=0.79).Only in patients with both nDSA class I and II there was a trend towards a lower graft survival (58%, p=0.06). Lastly, in a small group of 42 recipient pairs 10-year graft survival in recipients with DSA was 49% compared to 68% in recipients with nDSA (p=0.11). ConclusionThis paired kidney analysis confirms that the presence of pretransplant DSA in deceased donor transplantations is a risk marker for graft loss, whereas nDSA in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSA against class I and II, nDSA may be a risk marker for graft loss in the long term.

Complement regulating proteins, including CD46, CD55, and CD59, protect cells against self-damage. Because of their expression on the donor endothelium, they are hypothesized to be involved in accommodation. Polymorphisms in their promoter regions may affect their expression. The aim of this study was to investigate if donor polymorphisms in complement regulating proteins influence kidney transplant outcomes. We included 306 kidney transplantations between 2005 and 2010. Five polymorphisms in the promoters of CD46, CD55, and CD59 were genotyped. A CD59 promoter polymorphism (rs147788946) in donors was associated with a lower 1-year rejection-free survival [adjusted hazard ratio (aHR) 2.18, 95% CI 1.12–4.24] and a trend toward impaired 5-year graft survival (p = 0.08). Patients receiving a kidney with at least one G allele for the CD46 promoter polymorphism rs2796267 (A/G) showed a lower rejection-free survival, though this became borderline significant after adjustment for potential confounders (aHR 1.87, 95% CI 0.96–3.65). A second CD46 promoter polymorphism (rs2796268, A/G), was also associated with a lower freedom from acute rejection in the presence of at least one G allele (aHR 1.95, 95% CI 1.03–3.68). Finally, the combined presence of both favorable genotypes of rs2796267 and rs147788946 had an additional protective effect both on acute rejection (p = 0.006) and graft survival (p = 0.03). These findings could help to identify patients who could benefit from intensified immunosuppressive therapy or novel complement inhibitory therapeutics.