Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial.

Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. METHODS: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. RESULTS: Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months. CONCLUSIONS: EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.

Paid Living Donation and Growth of Deceased Donor Programs.

Limited organ availability in all countries has stimulated discussion about incentives to increase donation. Since 1988, Iran has operated the only government-sponsored paid living donor (LD) kidney transplant program. This article reviews aspects of the Living Unrelated Donor program and development of deceased donation in Iran. Available evidence indicates that in the partially regulated Iranian Model, the direct negotiation between donors and recipients fosters direct monetary relationship with no safeguards against mutual exploitation. Brokers, the black market and transplant tourism exist, and the waiting list has not been eliminated. Through comparison between the large deceased donor program in Shiraz and other centers in Iran, this article explores the association between paid donation and the development of a deceased donor program. Shiraz progressively eliminated paid donor transplants such that by 2011, 85% of kidney transplants in Shiraz compared with 27% across the rest of Iran's other centers were from deceased donors. Among 26 centers, Shiraz undertakes the largest number of deceased donor kidney transplants, most liver transplants, and all pancreas transplants. In conclusion, although many patients with end stage renal disease have received transplants through the paid living donation, the Iranian Model now has serious flaws and is potentially inhibiting substantial growth in deceased donor organ transplants in Iran.