In Search of a Better Outcome: Opting Into the Live Donor Paired Kidney Exchange Program

Background: Live donor (LD) kidney transplantation is the best option for patients with end-stage kidney disease (ESKD). However, this may not be the best option if a patient’s donor is older and considerably smaller in weight. Patient (A) with a less than ideal donor (Donor A) might enter into a live donor paired exchange (LDPE) program with the hopes of swapping for a better-quality organ. A second patient (B) who is in the LDPE may or may not benefit from this exchange with Donor A. Methods: This medical decision analysis examines the conditions that favor Patient A entering into the LDPE compared to directly accepting a kidney from their intended donor, as well as the circumstances where Patient B also benefits by accepting a lower-quality organ. Results: Under select circumstances, a paired exchange could benefit both Patients A and B. For example, a 30-year-old Patient A with a lower-quality donor might gain 1.201.521.84 quality adjusted life years (QALYs) by entering into a LDPE for a better-quality kidney, whereas a 60-year-old Patient B might gain 0.931.031.13 QALYs by accepting Donor A’s kidney rather than waiting longer in the LDPE. The net benefit (or loss) of entering the LDPE differs by recipient age, donor organ quality, likelihood of Patient B being transplanted in LDPE, and likelihood of Patient A finding an ideal donor in the LDPE. Conclusion: This study shows there are ways to increase live donor utilization and effectiveness that require further research and potentially changes to the LDPE process.

Medical Decision Analysis: Choosing Second Line Treatment in Adults with Immune Thrombocytopenia (ITP)

Introduction ITP is an autoimmune bleeding disorder characterized by accelerated destruction and reduced production of platelets. Steroids +/- IVIG are first line treatment, but there is no clear consensus on second line therapy. No randomized trials are available comparing the 3 most commonly considered second line options: thrombopoetin receptor agonists (TPO-RA), rituximab (Ritux) and splenectomy (SPL).This study used medical decision analysis, a mathematical Markov-model-based method, to compare second line treatments in adults with newly-diagnosed and persistent ITP. Methods Base case analysis considered 40-year old women with ITP lasting for at least 1 month, in daily need of corticosteroid treatment to maintain platelet counts above 30 x 109 /L. We modeled three treatment strategies: SPL; TPO-RAs, and Ritux (with dexamethasone and mycophenolate mofetil). Patients who were unresponsive or relapsed after initial therapy received alternate treatment. Six different treatment strategies were evaluated (Table 1). We simulated the course of identical patients using Markov processes which enabled complex time-dependent and recurrent clinical events, including side effects of treatments, to be modelled. At monthly intervals, patients could move from one clinical state to another based on probabilities assigned to these transitions. To facilitate estimating probabilities of transitioning between states, the cohort of patients was first divided into three categories according to the possible responsiveness to each treatment: i) responsive and curable- platelet count would increase above 50 x 109/L after the treatment and remain there without further treatment, ii) responsive but incurable - platelet count would increase above 50 x 109/L with treatment, but decrease below 30 x 109/L if treatment was not continued, iii) non-responsive - platelet count would not increase above 30 x 109/L despite treatment. This yielded 27 groups of patients for each treatment strategy since there are 3 possible groups for each of 3 strategies (3 x 3 x 3). Patients were followed for their entire lifetime. Probability values and costs were collected from published data and expert opinions. Within each monthly cycle of the Markov process, patients could fail the current treatment and switch to another. Complications - bleeding, thrombosis, or fever/sepsis - either minor or fatal, could occur. Sensitivity analysis was done to evaluate the accuracy of the input parameters and to determine for ranges of variables whether the outcomes were substantially affected. Results The results of estimated costs and years of lifespan for each treatment are presented in Table 2. Discussion This medical decision analysis fills the gap created by the absence of comparative second line treatment studies. In our model, patients suffering treatment-related toxicity or failing one treatment, attempt a second treatment and, failing that, progress to the third treatment. As a result, all treatable patients would eventually receive appropriate treatment. That explains why the lifespan with each of these 3 treatments in any order was within one year of each other at approximately 81 years of age. The order resulting in the longest lifespan was T-D-S which was driven by delay of SPL since SPL had the highest mortality composed of small contributions from the procedure itself, risk of thrombosis, and post-splenectomy sepsis. The D-T-S strategy, also delaying SPL, had almost the same lifespan at a significant cost savings. The lowest estimated cost was the S-D-T arm in which costs of additional therapy were reduced by doing SPL first and using TPO agents, if necessary, last. Of note, the cost estimates were based on costs of treatments obtained in the United States. Costs in Europe were estimated and were so much lower that the arms were essentially even. The major limitation to our study is that quality of life was not included. Conclusion: In the USA, TDS has the longest lifespan at a cost of approximately $130,000 per additional year of life. In Europe the cost for the additional year of life is < $20,000. If USA costs were as low as they are in Europe, there would be no compelling economic reason to select one of the specific second line therapies so treatment could be individualized according to physician and patient preference. Disclosures Bussel: Amgen Inc.: Consultancy, Research Funding; Uptodate: Honoraria; Momenta: Consultancy; Protalex: Consultancy; Prophylix: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Rigel: Consultancy, Research Funding.

Lifetime risks of kidney donation: a medical decision analysis

ObjectiveThis study estimated the potential loss of life and the lifetime cumulative risk of end-stage renal disease (ESRD) from live kidney donation.DesignMarkov medical decision analysis.SettingUSA.Participants40-year-old live kidney donors of both sexes and black/white race.InterventionLive donor nephrectomy.Main outcome and measuresPotential remaining life years lost, quality-adjusted life years (QALYs) lost and added lifetime cumulative risk of ESRD from donation.ResultsOverall 0.532–0.884 remaining life years were lost from donating a kidney. This was equivalent to 1.20%–2.34% of remaining life years (or 0.76%–1.51% remaining QALYs). The risk was higher in male and black individuals. The study showed that 1%–5% of average-age current live kidney donors might develop ESRD as a result of nephrectomy. The added risk of ESRD resulted in a loss of only 0.126–0.344 remaining life years. Most of the loss of life was predicted to be associated with chronic kidney disease (CKD) not ESRD. Most events occurred 25 or more years after donation. Reducing the increased risk of death associated with CKD had a modest overall effect on the per cent loss of remaining life years (0.72%–1.9%) and QALYs (0.58%–1.33%). Smoking and obesity reduced life expectancy and increased overall lifetime risks of ESRD in non-donors. However the percentage loss of remaining life years from donation was not very different in those with or without these risk factors.ConclusionLive kidney donation may reduce life expectancy by 0.5–1 year in most donors. The development of ESRD in donors may not be the only measure of risk as most of the predicted loss of life predates ESRD. The study identifies the potential importance of following donors and treating risk factors aggressively to prevent ESRD and to improve donor survival.