Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.

Survival Outcomes in Split Compared With Whole Liver Transplantation.

Split-liver transplantation (SLT) should be cautiously considered because the right trisection (RTS) graft can be a marginal graft in adult recipients. Herein, we analyzed the outcomes of RTS-SLT in Korea, where >75% of adult liver transplantations are performed with living donor liver transplantation. Among 2462 patients who underwent deceased donor liver transplantations (DDLTs) from 2005 to 2014, we retrospectively reviewed 86 (3.5%) adult patients who received a RTS graft (RTS-SLT group). The outcomes of the RTS-SLT group were compared with those of 303 recipients of whole liver (WL; WL-DDLT group). Recipient age, laboratory Model for End-Stage-Liver Disease (L-MELD) score, ischemia time, and donor-to-recipient weight ratio (DRWR) were not different between the 2 groups (P > 0.05). However, malignancy was uncommon (4.7% versus 36.3%), and the donor was younger (25.2 versus 42.7 years) in the RST-SLT group than in the WL-DDLT group (P < 0.05). The technical complication rates and the 5-year graft survival rates (89.0% versus 92.8%) were not different between the 2 groups (P > 0.05). The 5-year overall survival (OS) rate (63.1%) and graft-failure-free survival rate (63.1%) of the RTS-SLT group were worse than that of the WL-DDLT group (79.3% and 79.3%; P < 0.05). The factors affecting graft survival rates were not definite. However, the factors affecting OS in the RTS-SLT group were L-MELD score >30 and DRWR ≤1.0. In the subgroup analysis, OS was not different between the 2 groups if the DRWR was >1.0, regardless of the L-MELD score (P > 0.05). In conclusion, a sufficient volume of the graft estimated from DRWR-matching could lead to better outcomes of adult SLTs with a RTS graft, even in patients with high L-MELD scores.

Evidence that the ratio of donor kidney weight to recipient body weight, donor age, and episodes of acute rejection correlate independently with live-donor graft function.

BACKGROUND: We demonstrated that higher donor kidney weight-to-recipient body weight (KW/BW) ratio showed better graft function in acute rejection-free renal recipients. METHODS: We investigated the impacts of KW/BW ratios on the graft function including acute rejection and donor's age in 259 live-donor renal recipients. Renal parameters were measured yearly. Correlations between the variables and each parameter were assessed by mixed regression and analysis of variance. RESULTS: Renal function showed a positive correlation with the KW/BW ratio, but an inverse correlation with the rejection episodes and donor's age. The regression slope for serum creatinine or creatinine clearance by these covariants was consistent each year. On comparing the lower KW/BW ratios (<3.0) with higher ratios (> or =4.5), the higher was associated with better graft function. Increased donor's age was associated with worse graft function. CONCLUSIONS: KW/BW ratio, donor's age, and the number of acute rejections are independent covariants for graft function.