Three-year results of renal function in liver transplant recipients on low-dose sirolimus and tacrolimus: a multicenter, randomized, controlled trial

Abstract

The aim of this study was to investigate whether the combination of low-dose sirolimus (SRL) and low-dose extended-release tacrolimus (TAC) compared to normal-dose extended-release TAC results in a difference in the renal function and comparable rates of rejection, graft and patient survival at 36 months after transplantation. This study was an open-label, multicenter randomized, controlled trial. Patients were randomized to once-daily normal-dose extended-release TAC (control group) or once-daily combination therapy of SRL and low-dose extended-release TAC (interventional group). The primary endpoint was the cumulative incidence of chronic kidney disease (CKD) defined as grade ≥3 (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) at 36 months after transplantation. In total, 196 patients were included. CKD at 36 months was not different between the control and interventional group (50.8%, 95% CI: 39.7%–59.9%) vs. 43.7%, 95% CI: 32.8%–52.8%). Only at 6 months after transplantation, the eGFR was higher in the interventional group compared to the control group (mean eGFR 73.1±15 vs. 67.6±16 mL/min/1.73 m2, p=0.02) in the intention-to-treat population. No differences in the secondary endpoints and the number of serious adverse events were found between the groups. Once daily low-dose SRL combined with low-dose extended-release TAC does ultimately not provide less CKD grade ≥3 at 36 months compared to normal-dose extended-release TAC.

Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus: A Multicenter, Randomized Controlled Trial

“…Figure 2 shows the proportion of LT recipients reaching the composite primary endpoint and the separate components of the composite primary endpoint in the ITT and PP populations. In the ITT population, a statistically significant lower proportion of LT recipients in the LCPtacrolimus group reached the composite primary endpoint at 12 Sensitivity analyses for new-onset and PTDM showed similar event rates in both groups when LT recipients with pretransplant hypertension or diabetes were included in the analysis (and considered not to have new-onset disease) as well as when every LT recipients with hypertension or diabetes was considered new-onset hypertension or PTDM. S1 (SDC, http://links.lww.com/TXD/A636).…”

Health-related Quality of Life and Fatigue in Liver Transplant Recipients Receiving Tacrolimus Versus Sirolimus-based Immunosuppression: Results From a Randomized Trial

“…An extensive description of the LOLIII study design has been published previously. 10 In brief, the LOLIII study randomized patients 90 d after transplantation in a 1:1 ratio to (1) once daily normal-dose TAC with target trough levels 5 to 10 µg/L (control group) or (2) once daily combination therapy of SRL and low-dose TAC with target trough levels 3 to 5 µg/L for both SRL and TAC (interventional group). During the 3-y follow-up, a switch in immunosuppressive therapy occurred in 48.9% (48/98) of the patients in the control group and in 44.9% (44/98) of the patients in the interventional group.…”

“…In the control group, the main reason for the switch in immunosuppressive therapy was deterioration of the kidney function (43/48, 89.6%). 10 In the interventional group, multiple reasons for switching applied. The main reasons for a switch were side effects of SRL and/or preference of the treating physician with another immunosuppressive agent in the case of deterioration of kidney function (29/44, 65.9%).…”

“…The side effects consisted mainly of pancytopenia, malaise, and skin problems. 10 The majority of the LT recipients were switched within the first year after transplantation (69/92, 75%) to mycophenolic acid.…”

Health-related Quality of Life After Liver Transplantation—An Important Goal, but One Definition (or Size) Does Not Fit All

“…Most of the technical aspects of liver transplantation have been worked out, and there are several immunosuppression agents from which to choose. In this issue of Transplantation , Mulder et al 1 examined the effect of immunosuppressive agents on the overall health-related quality of life (HRQOL) and fatigue levels in a cohort of Dutch liver transplant recipients. They found no consistent quality differences attributable to either tacrolimus or sirolimus-based immunosuppression.…”