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Introduction: Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (Basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model, demonstrating the usefulness of combining simulation with Bayesian estimation methods for analysis of cost-effectiveness data collected alongside a clinical trial. We sought to determine whether calcineurin-sparing protocols using anti-interleukin-2/antibody induction (Simulect) would show a beneficial effect on initial kidney function and reduce transplantation costs upon admission, clinical incidences, graft function, and complications during the first month after transplant., Patients and Methods: A Markov Chain Monte Carlo (MCMC) was used to estimate a system of generalized linear models relating costs and outcomes to a kidney transplant process affected by treatment under alternative therapies. The Markov simulation model was established following three chains: a calcineurin-free regimen with Basiliximab induction (chain A); a calcineurin-sparing protocol with Basiliximab induction (chain B); and a conventional immunosuppressive regimen (chain C). The MCMC draws were used as parameters in simulations that yielded inferences about the relative cost-effectiveness of the novel therapy under a variety of scenarios. After designing the Markov chain and cohorts, 31 patients from the "old-to-old" program were assigned; eight to chain A; eight to chain B; and 15 to chain C. A year after transplantation a cost-benefit study was performed guided by the three branches of the Markov model., Results: The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a year, there was a clear benefit from calcineurin-free plus Basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols., Conclusions: Markov models are extremely useful when introducing new clinical therapies. The approach allows flexibility in assessing treatment using various premises and quantifies the global effect of parametric uncertainty on a decision maker's confidence to adopt one therapy over another. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with Basixilimab induction.

Introduction: EuroTransplant old-to-old program allows patients older than 60 years to receive offers from donors older than 60. The long-term results of kidney transplantation in this model are still under discussion, due to the impaired kidney function of the donor and cumulative diseases in the recipient., Hypothesis: Calcineurin-sparing protocols with IL-2 antibody induction (Simulect) may benefit long-term kidney function in these patients avoiding overimmunosuppression. The main outcome measures are: graft function and rejection rate during the first year after transplant., Patients and Methods: A cohort of 15 consecutive older subjects were prospectively compared with 30 conventional cadaveric kidney transplants. Study patients were induced with Simulect (20 mg, 30 minutes before reperfusion and 4 days after transplantation) and steroids allowing the introduction of CsA to be delayed to the time at which the creatinine is below 3 mg/dL. Conventional patients were immunosuppresed with Tacrolimus (trough 8-12 ng/mL), MMF (1 g/d) and identical steroid tape. The graft and patient survival, kidney function in terms of diuresis, creatinine clearance, rejection episodes and grades were compared between both groups during the first year posttransplantation., Results: Except for the age of the donors and recipients in both groups (72 vs 54 in donors, and 67 versus 52 years in recipients), no significant differences were observed. Patient survival rates were 97% in control patients and 100% in the Simulect group. Graft survival was 97% in the control group and 100% in the old-to-old study group. Acute rejection episodes were decreased among study patients (6.6% vs 13.2%), and corticoid sparing protocols were applied in 75% of Simulect patients but only 50% of control patients. All 44 patients and grafts showed excellent kidney function after one year with equal creatinine levels in both groups (mean 1.42)., Conclusions: Calcineurin free protocols with IL-2 therapy as the main initial suppression allows patients in an old-to-old ET program to have superior results to conventional cadaveric kidney transplants.

Introduction: The EuroTransplant "old to old" program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years. The compromised function of these organs makes it a priority to preserve their initial kidney function., Hypothesis: Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R) antibody induction (Simulect) may benefit initial kidney function in these patients, as assessed by the rates of delayed graft function and of rejection during the first month after transplant., Patients and Methods: A cohort of 15 consecutive elderly patients were prospectively compared with 30 cadaveric kidney transplants in younger recipients. Study patients were induced with Simulect (20 mg, 30 minutes before reperfusion and 4 days after transplantation) and steroids, delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF, 1 g/d), and an identical taper of steroids. The analysis compared donor and recipient ages, mean cold ischemic time, incidence of initial kidney function (diuresis in the first 24 h) serum creatinine levels, glomerular filtration rate (GFR), number of dialysis sessions, and rejection rate in the two groups., Results: Except for the donor and recipient ages (72 vs 54 in donors, and 67 versus 52 years in recipients), no significant differences were observed between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed graft function (13.2% required dialysis), or infection (6.6%). Within 1 month all 45 grafts showed primary function with equal creatinine levels (mean 1.65)., Conclusions: Calcineurin-free protocols using IL-2 therapy as the initial suppression allow patients in the "old to old" ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists.

Introduction: Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model., Hypothesis: Calcineurin-sparing protocols using anti-IL-2/antibody induction (Simulect) show a beneficial effect on initial kidney function, reducing transplantation costs reception based upon mean length of stay, mean admission cost, and incidences of delayed graft function and complications during the first month after transplant., Patients and Methods: A Markov simulation model was established following three different chains. A calcineurin-free regimen with basiliximab induction (chain A), a calcineurin-sparing protocol with basiliximab induction (chain B), and a conventional immunosuppressive regimen (chain C). After designing the Markov chain and cohorts, 31 patients from the "old to old" program were assigned to each chain eight to chain A, (eight to chain B, and 15 to chain C). A month after transplantation a cost-benefit study was performed guided by the three branches of the Markov model., Results: The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a month there was a clear benefit from Calcineurin=free plus basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols., Conclusions: Markov models are extremely useful when introducing new clinical therapies. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with basixilimab induction.