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Background. HLA matching has been the cornerstone of deceased donor kidney allocation policies worldwide but can lead to racial inequity. Although HLA matching has been shown to improve clinical outcomes, the long-term impacts of nonallogenic factors are being increasingly recognized. This has led some transplant programs to include points for nonallogenic factors, for example, age. Our study looks at long-term graft and patient outcomes based on allocation cohorts rather than individual number of HLA mismatches. Methods. Using the Australia and New Zealand Dialysis and Transplant Registry, we analyzed 7440 adult deceased donor transplant events from 2000 to 2018. Transplants were classified as HLA matched or nonmatched according to the OrganMatch score and the local allocation algorithms. Graft function was studied with linear mixed modeling and graft rejection with logistic and binomial regression. Time to graft failure and recipient survival were examined with Kaplan–Meier curve and Cox regression models. Results. Forty percent of transplants were HLA matched. Mean glomerular filtration rate was 1.76 mL/min/1.73 m2 higher in the matched transplants (P

Background. Repetitive endothelial damage from dialysis membrane incompatibility is a probable cause of accelerated atherosclerosis in haemodialysis patients. Consequently pulse wave velocity (PWV), a measure of arterial stiffness, was utilized as a surrogate marker of vascular dysfunction during dialysis with two commonly used synthetic dialysers.Methods. PWV was monitored before, during and after haemodialysis using both polysulphone and polyamide membranes. PWV, an arterial stiffness measure, was calculated from the carotid to the femoral (C-F) and also to the radial (C-R) artery. In a further group, PWV was monitored while polysulphone and polyamide membranes were perfused with blood without dialysate.Results. Mean aortic (C-F) PWV was lower during dialysis with the polyamide membrane, being 14 and 16% less following 75 and 135 min of dialysis (P<0.05) in 24 patients. Because intradialytic intravascular volume changes alter PWV, a subgroup analysis in 11 patients where dialysis fluid removal during both periods was minimal (<1?kg) was performed, and a persistent and significant increase in aortic PWV was detected with the polysulphone kidney being maximal (40%) at 75?min (P<0.01). This increase was negatively correlated with pre-dialysis PWV (P<0.01). In contrast, the polyamide dialyser did not change PWV. An increase in C-R PWV was also noted with the polysulphone membrane (P<0.05). In the nine patients where membranes were perfused with blood without dialysate, aortic PWV was again significantly increased by the polysulphone (P<0.01), but not the polyamide dialyser.Conclusions. Haemodialysis with polysulphone but not polyamide membranes acutely alters aortic stiffness, an effect postulated to be due to membrane bioincompatibility. However, factors including age, time on dialysis and underlying vascular disease, were also found to impact on these acute dialysis-induced changes to vascular function. Since these acute changes disappear post-dialysis, their long-term consequences are uncertain. [ABSTRACT FROM AUTHOR]

Background. Cytokine gene polymorphisms have been associated with poor outcomes after renal transplantation such as chronic allograft nephropathy (CAN), graft rejection (GR) and graft failure (GF), but the effects of these polymorphisms are still controversial. We therefore conducted a systematic review, with individual patient data (IPD) where possible, to determine the association between cytokine polymorphisms (TGF-β1, TNF-α and IL-10) and outcomes after renal transplantation. Methods. Five investigators were willing to participate and provided IPD. The outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age. Results. One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6–1.8 for ≥3 HLA-A, -B, -DR mismatches compared with those with <3 mismatches) and age (OR = 1.2–1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-β1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0–2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-β1 at c10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0–2.3). Three polymorphisms of the IL-10 gene at −1082, −819, −592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6–1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events com- pared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9–1.6). Conclusion. Pooled results to date suggest possible association between both the TGF-β1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]