Decision making around living and deceased donor kidney transplantation: a qualitative study exploring the importance of expected relationship changes

Transplant surger

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Contains fulltext : 208426.pdf (publisher's version ) (Open Access)Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals

PIRCHE-II is related to graft failure after kidney transplantation

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient\'s HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals

Antibodies against ARHGDIB are associated with long-term kidney graft loss

The clinical significance of non‐HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large‐scale studies incorporating analysis of multiple non‐HLA antibodies simultaneously. We developed a multiplex non‐HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non‐HLA antibodies was corre

[e-Health in chronic diseases: not yet feasible for everyone in every setting]

Item does not contain fulltexte-Health is a hot item: governments, healthcare insurers and manufacturers of medical appliances state that the expected epidemic of chronic diseases can only be countered by broad application of e-health. However, sound scientific data to support this claim is currently lacking. Several recent large trials demonstrate that results do not always keep up with expectations. The WSD Trial, published in last months' BMJ, shows the discrepancy between scientific reality and political planning. In addition to a critical comment, we attempt to make recommendations on aspects of e-health that do hold promise

Model-Informed Precision Dosing of Everolimus: External Validation in Adult Renal Transplant Recipients

Contains fulltext : 232471.pdf (Publisher’s version ) (Open Access)BACKGROUND AND OBJECTIVE: The immunosuppressant everolimus is increasingly applied in renal transplantation. Its extensive pharmacokinetic variability necessitates therapeutic drug monitoring, typically based on whole-blood trough concentrations (C(0)). Unfortunately, therapeutic drug monitoring target attainment rates are often unsatisfactory and patients with on-target exposure may still develop organ rejection. As everolimus displays erythrocyte partitioning, haematocrit-normalised whole-blood exposure has been suggested as a more informative therapeutic drug monitoring marker. Furthermore, model-informed precision dosing has introduced options for more sophisticated dose adaptation. We have previously developed a mechanistic population pharmacokinetic model, which described everolimus plasma pharmacokinetics and enabled estimation of haematocrit-normalised whole-blood exposure. Here, we externally evaluated this model for its utility for model-informed precision dosing. METHODS: The retrospective dataset included 4123 pharmacokinetic observations from routine clinical therapeutic drug monitoring in 173 renal transplant recipients. Model appropriateness was confirmed with a visual predictive check. A fit-for-purpose analysis was conducted to evaluate whether the model accurately and precisely predicted a future C(0) or area under the concentration-time curve (AUC) from prior pharmacokinetic observations. Bias and imprecision were expressed as the mean percentage prediction error (MPPE) and mean absolute percentage prediction error (MAPE), stratified on 6 months post-transplant. Additionally, we compared dose adaptation recommendations of conventional C(0)-based therapeutic drug monitoring and C(0)- or AUC-based model-informed precision dosing, and assessed the percentage of differences between observed and haematocrit-normalised C(0) (∆C(0)) and AUC (∆AUC) exceeding ± 20%. RESULTS: The model showed adequate accuracy and precision for C(0) and AUC prediction at ≤ 6 months (MPPE(C0): 8.1 ± 2.5%, MAPE(C0): 26.8 ± 2.1%; MPPE(AUC): - 9.7 ± 5.1%, MAPE(AUC): 13.3 ± 3.9%) and > 6 months post-transplant (MPPE(C0): 4.7 ± 2.0%, MAPE(C0): 25.4 ± 1.4%; MPPE(AUC): - 0.13 ± 4.8%, MAPE(AUC): 13.3 ± 2.8%). On average, dose adaptation recommendations derived from C(0)-based and AUC-based model-informed precision dosing were 2.91 ± 0.01% and 13.7 ±��0.18% lower than for conventional C(0)-based therapeutic drug monitoring at ≤ 6 months, and 0.93 ± 0.01% and 3.14 ± 0.04% lower at > 6 months post-transplant. The ∆C(0) and ∆AUC exceeded ± 20% on 13.6% and 14.3% of occasions, respectively. CONCLUSIONS: We demonstrated that our population pharmacokinetic model was able to accurately and precisely predict future everolimus exposure from prior pharmacokinetic measurements. In addition, we illustrated the potential added value of performing everolimus therapeutic drug monitoring with haematocrit-normalised whole-blood concentrations. Our results provide reassurance to implement this methodology in clinical practice for further evaluation

Contribution of donor and recipient characteristics to short- and long-term pancreas graft survival

Transplant surger

Contribution of donor and recipient characteristics to short- and long-term pancreas graft survival

Background: Many donor and recipient factors are known to affect pancreas graft survival. However, their relative importance in explaining differences in graft survival is unknown. Purpose of this study was to retrospectively evaluate the impact of donor and recipient factors on pancreas graft survival, and compare their contribution in explaining graft survival differences. Material/Methods: Patient records of all 170 pancreas transplantations (158 Simultaneous Pancreas-Kidney; 12 Pancreas-after-kidney) in the period 1997-2008 were reviewed retrospectively to assess recipient factors before/during transplantation, and to assess graft survival. Eurotransplant reports were reviewed to assess donor factors. Results: Death-censored 1-year graft survival was 88.4% and 82.3% at 3 years. Several factors significantly influenced graft survival: female recipient gender (Hazard Ratio (HR) 2.81[1.10-7.14]), enteric graft drainage (HR 2.85[1.15-7.05]), and donor-recipient match on BMI (HR 2.46[1.01-6.02]). None of the donor factors significantly affected survival. Similar results were found for 1-year survival, except for enteric graft drainage and donor-recipient BMI matching. In total, donor factors explained 3.6% and recipient factors 10.0% of the variance in graft survival. Donor factors were more important for 1-year survival (3.1%), but still less important than recipient factors which explained 6.4%. Conclusions: Recipient factors are more important in explaining differences in pancreas graft survival than donor factors.Transplant surger