Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed. © 1994

Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64330/1/21877_ftp.pd

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Review of major clinical trials with mycophenolate mofetil in renal transplantation

Mycophenolate mofetil (MMF) was approved for the prevention of acute rejection following renal transplantation based on the results of three groundbreaking, large, clinical trials that demonstrated a significantly reduced risk of acute rejection in patients receiving MMF when compared with those receiving placebo or azathioprine. These three multicenter, prospective, double-blind trials performed at 55 transplant centers on three continents were the largest immunosuppressive drug trials ever attempted and the first prospective, randomized, double-blind trials ever performed in transplantation. These pivotal trials established a foundation for widespread acceptance of MMF in combination with cyclosporine and steroids as a maintenance regimen for renal transplant patients. The findings of these initial trials that led to the approval of MMF for renal transplantation, including long-term follow-up data, will be reviewed in this paper. The expanding scope of major trials of MMF, including trials in pediatric patients, combination regimens with novel induction therapies or other maintenance agents, and trials in special patient populations such as those at high immunological risk or with deteriorating kidney function, will also be discussed

Regional Variation in Kidney Transplant Outcomes: Trends Over Time

Background and objectives: Clinical outcomes after kidney transplant have improved considerably in the United States over the past several decades. However, the degree to which this has occurred uniformly across the country is unknown

Preliminary Report on the Effect of Mesenchymal Stem Cell Therapy in Patients with Chronic Lung Allograft Dysfunction

Background: Mesenchymal stem cell (MSC) effects can shift immune responses toward anti-inflammatory and tolerogenic phenotypes, potentially helping patients with bronchiolitis obliterans syndrome (BOS). Methods: We evaluated the effect of infusing allogeneic MSC intravenously in 9 patients with moderate BOS refractory to standard therapy who were not candidates for retransplant, dividing them into 3 dosing groups: Group 1, 1×106 MSC/kg (n=3); Group 2, 2×106 MSC/kg (n=3); and Group 3, 4×106 MSC/kg (n=3). We recorded pulmonary function tests, laboratory variables, and serum biomarkers pre- and post-MSC infusion. Results: These patients had significant decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over 1 year pre-MSC infusion (mean ± SD) FVC, 3.11±0.98 L, and FEV1 1.99+0.64 L versus FVC 2.58±1.03 and FEV1 1.61±0.52 just before infusion (P<0.05); representing a mean loss of 530 mL in FVC and 374 mL in FEV1 over 12 months. One year post-MSC infusion, mean FVC and FEV1 increased to 2.66±1.01 L and 1.63±0.55 L, respectively (changes no longer significant compared to before MSC infusion). Patients in Group 1 showed elevation of tolerance-inducing T regulatory cells and increased levels of epidermal growth factor. Tolerance-inducing Th-2 cytokines increased in Groups 1 and 2. These changes were not significantly different in these small sub-groups. Conclusion: MSC infusion appears to slow down or reverse the progressive decline in lung function in some patients with moderate BOS, possibly by inducing anti-inflammatory effects and promoting cell proliferation and angiogenesis