Technologies et recherche en matière de transplantation

The current success of renal transplantation (RT) is the result of advancement in the understanding of the transplant immunology from gross allograft rejection to cellular and antibody response to the current molecular level. Laboratory assay technologies have been developed to characterise patient sensitisation and to detect pre-existingdonor-specific antibodies (DSA) in pre-transplant crossmatch, which has helped prevent premature transplant losses from early and late antibody-mediated rejection. After a RT, pre-existing or de novo DSA are routinely monitored for modulation of immunosuppressive regimens. Therefore, it is mandatory for the personnel involved in the management of RT recipients to have clear understanding of the components of transplantation immunology and be familiar with the modern immunological techniques used in RT.

Meniscal allograft transplantation (MAT) is becoming a common procedure in Orthopedic departments worldwide. This procedure has demonstrated good and excellent results in terms of pain relief, improvement in clinical and functional outcomes, return to sports, and patient’s satisfaction. However, MAT is not a universally accepted procedure due to its questionable chondroprotective effects and the relatively high rate of complications and/or reoperations. The present short review summarizes the principal indications, contraindications, outcomes, and complications. Also, it covers several controversial topics like graft preservation, graft sizing, graft fixation, results in MAT associated with concomitant procedures, and the role of MAT in the prevention of knee osteoarthritis.

Background: Despite the implementation of new regulations to increase organ and tissue donation, few regulations have been evaluated for their effectiveness in achieving this goal. Recently, the province of Quebec (Canada) modified Bill 125 to make notification of all potential donors to donation stakeholders mandatory in clinical settings. The purpose of this study was to evaluate the effectiveness of this new regulation on the potential ocular tissue donor notification rate in clinical settings.

Methods: This study used a pre-post design to determine the impact of the new regulation on the ocular tissue donor notification rate. The notification rate of potential ocular tissue donors was measured objectively among 26 departments of five clinical settings over a period of four months, beginning three months after the adoption of the new regulation (post-test measure); the pre-test value consisted in the notification rate during the same four-month period in the previous year. Data were analyzed using generalized estimating equations.

Results: The notification rate of ocular tissue donors prior to the change in the regulation (21.0%) did not increase significantly after legislative changes (21.6%) (χ2=0.01, p=0.93).

Conclusion: Despite making the notification of potential organ and tissue donors mandatory, the new regulation did not change the notification rate of ocular tissue donors. Policy formulation and policy implementation are two possible reasons for this failure. In particular, it is suggested that working closely with all relevant stakeholders at the time of policy formulation should facilitate implementation strategies.

Background: Short-term results of renal transplantation have shown a drastic improvement over time mainly due to changes in immunosuppressive therapy. Non-compliance to therapy is one of the causes of graft loss. Tacrolimus is a cornerstone of immunosuppressive therapy: recently became available Tacrolimus once a day formulation (Advagraf) that could improve the compliance of patients to immunosuppressive therapy. Few are published data about its use in clinical practice. We therefore compared the efficacy and pharmacokinetics of once-daily formulation compared to the classic twice-daily dosing tacrolimus in de novo kidney transplant patients.

Methods: Retrospectively evaluation of 30 de novo transplant recipients treated with Advagraf in 2009-2012 (on dose daily of 0.2-0.3 mg/kg) and 30 treated with Prograf (2 doses daily of 0.2 mg /kg). Comparison between the two groups regarding drugs dose, blood level and clinical variables.

Result: Both Advagraf and Prograf patients reached the drug target level, even if initially with a higher drug dose for Advagraf. Creatinine levels were initially higher in Advagraf group, no differences are detectable two weeks after transplant. There were no differences between groups for rejection episodes, graft loss and adverse events. Lipid metabolism was significantly better in Advagraf patients.

Discussion: Advagraf confirm to offer a similar short-term efficacy compared with the twice a day administration in de novo kidney transplant, with a higher drug dose compared to tacrolimus. The safety profile is comparable with twice-daily administration. Interestingly a better lipid metabolism is present in Advagraf group.

Introduction: Microdialysis is one of the methods used clinically for the detection of ischemia. Although microdialysis is reliable, in most clinical settings there is a delay of 1-2 hours before the information is available.

Objective: The aim of this study was to evaluate whether an increase in the Microdialysis per fusion rate from 0.3 to 1.0 or 2.0 μl/min was capable of reducing the delay in the detection of a shift in molecular composition.

Methods and material: Microdialysis was performed in a container with 3 catheters per fused with 0.3, 1.0 and 2.0 μl/min. The molecular composition in the container regarding glucose and lactate was initially as follows: CGlucose=6.0 mmol/L and CLactate=2 mmol/L. At T=90 min the composition was changed to CGlucose=1 mmol/L and CLactate=12 mmol/L. Dialysates were harvested from the three catheters and were analysed regarding the concentration of glucose and lactate. For calculation of the relative recovery, samples were harvested directly from the liquid. The relative recovery and the delay before new steady state were calculated for each of the 3 catheters. The experiment was performed 8 times.

Results: A decrease in relative recovery was found with the higher perfusion rate. For glucose, the relative recovery was 100, 88, and 69% at perfusion rates of 0.3, 1.0 and 2.0 μl/min. For lactate, the corresponding values were 103, 93, and 77%. An increase in the lactate/glucose ratio was found with the higher perfusion rate. The delays in detection of shift in molecular concentration were found to be 60, 20, and 10 minutes for catheters 0.3, 1.0 and 2.0, respectively.

Conclusion: Using microdialysis it is possible to significantly reduce the delay while still detecting a shift in the concentration of glucose and lactate when the perfusionrate is increased.

Background: Combined Liver and Kidney Transplantation (CLKT) is a recognized treatment option for a select group of paediatric patients with severe liver and kidney disease. The aim of this study is to report Indication and outcome of CLKT in our center and to compare the results with the Isolated Kidney Transplantation (IKT).

Patients and method: We retrospectively reviewed children who underwent CLKT between 1997 and 2009. Data analyzed include age, sex, cause of kidney/liver disease, pre-transplant dialysis, donor age, cross-match, and immunosuppression regimen. Additionally, cold ischemia time, Acute Rejection (AR) episodes and patient and graft survival were compared with patients who had IKT in the same period of time.

Results: 9 children (5 females, 4 males) underwent CLKT and 127 IKT. In CLKT group, mean patient age was 10.5 ± 3.9 years. Indications for CLKT were: primary hyperoxaluria (n=3), hemolytic uremic syndrome (n=1), Alagille Syndrome (n=1), nephronoptisis (n=1) and polycystic hepatorenal disease (n=3). Five patients were on dialysis before transplant. In all patients, both grafts were obtained from the same donor and cross-matches were negative. Immunosuppression was induced with Basiliximab and maintained with triple therapy (Tacrolimus+Mycophenolate mofetil+Prednisone). Mean cold ischemia time was shorter in CLKT (10.9 ± 3.5 vs. 16.8 ± 4.6 hours) and hospital stay was longer (35.5 ± 10 vs. 13.9 ± 5.3 days) compared to IKT. Long-term mean Glomerular Filtration Rate (GFR) and cystatin levels were similar in both groups. Rejection tended to be less frequent in CLKT (11 vs. 25%) than in IKT. Patient survival was lower (P=0.008) in CLKT. One patient with chronic liver and kidney rejection due to noncompliance died during re-transplantation 5 years after the first transplant. There were no deaths in the IKT group Mean follow-up time is 5.27 ± 2.9 years the IKT group Mean Follow-up time is 5.27 ± 2.9 years.

Conclusions: Most common indications for CLKT in our children are primary hyperoxaluria and polycystic disease. Long-term results in children receiving CLKT are comparable to those with isolated kidney transplantation.