2187 Everolimus With Reduced Tacrolimus Preserves Long-Term Renal Function in Liver Transplant Recipients: 36 and 48 Months Results From The H2304E1 Study. J. Fung, F. Saliba, G. Kaiser, L. De Carlis, H. Metselaar, F. Nevens, C. Duvoux, P. De Simone, L. Fischer, G. Dong, B. Rauer, G. Junge. H2304E1 Study Group, Cleveland. Purpose: Preserving long-term renal function in liver transplant recipients (LTxRs) remains a major concern. This study evaluates if early introduction of everolimus (EVR) with reduced tacrolimus (rTAC) provides long-term renal benefi ts in LTxRs. Methods: Patients who completed the 24 month (M) randomized H2304 study could continue their assigned treatment regimen during the 12M extension study (H2304E1): EVR+rTAC (N=106, EVR C0 3-8 ng/mL; TAC C0 3-5 ng/mL) or TAC-C (N=125, C0 6-10 ng/mL). In the extension phase, patients in the EVR+rTAC arm were studied for 12M followed by an additional 12M follow-up on the same regimen. Key primary endpoint was renal function assessed by estimated GFR (eGFR) using MDRD4. Additionally, evolution of renal function from M24 to M36 was explored using a mixed-effect model for longitudinal data. Results: At M36, the EVR+rTAC arm had lower incidence of composite effi cacy failure (11.5% vs 14.6% in TAC-C, risk difference -3.2%, 97.5% CI: -10.5, 4.2; p=0.334). Renal function (mean eGFR) was superior with EVR+rTAC vs TAC-C (78.7 vs 63.5 mL/min/1.73m2) with a difference of 15.2 mL/min/1.73m2 in favor of the EVR+rTAC arm (p<0.001; all extension patients). Proportion of patients with eGFR <60 mL/min/1.73m2 was signifi cantly lower with EVR+rTAC (28.0% vs 42.6% in TAC-C, p=0.032). From randomization to M36, decline in eGFR by ≥30% was reported for 20.0% of patients in the EVR+rTAC arm vs 28.7% in the TAC-C arm. At M48, mean eGFR in the EVR+rTAC arm was 80.5 mL/min/1.73m2 and the number of patients with eGFR <60 mL/min/1.73m2 decreased to 15%. From M24 to M36, longitudinal data analysis for eGFR showed no change in renal function for the EVR+rTAC arm vs a decrease for TAC-C arm (0.04 vs -0.26 mL/min/1.73m2/month). Fewer patients in the EVR+rTAC vs TAC-C arm experienced renal failure (2 vs 10) and renal impairment (1 vs 3) with none vs 2 patients discontinuing study medication due to these adverse events. Proteinuria (≥3 g/day) was not reported in either arm. Conclusion: Early introduction of EVR to reduce TAC exposure preserves longterm renal function in LTxRs. The 48M data show that a notable renal function was maintained for patients on EVR with rTAC. DISCLOSURE: Fung, J.: Other, Novartis, Advisory Committee, Vital Therapies, Consultant. Saliba, F.: Grant/Research Support, Novartis, Astellas, Roche and Gambro, Speaker’s Bureau, Schering Plough, MSD and Gambro, Other, Novartis, Astellas, Roche, Genzyme, Advisory committee, Viropharma and Vital Therapies, Advisory committee. Kaiser, G.: Grant/Research Support, Novartis, Astellas, Roche and Pfi zer. Metselaar, H.: Grant/Research Support, Astellas, Biotest and Novartis, Speaker’s Bureau, Astellas, Biotest and Novartis. Nevens, F.: Grant/ Research Support, Ipsen, Roche, MSD, Jansen, CAF, Astellas, Ferring, Eumedica, and Boston Scientifi c. Duvoux, C.: Grant/Research Support, Novartis, Astellas and Roche, Speaker’s Bureau, Astellas, Other, Novartis, Data Safety Monitoring board member. De Simone, P.: Other, Novartis, Consultant. Fischer, L.: Grant/Research Support, Novartis, Astellas, Speaker’s Bureau, Gilead Sciences, Other, Novartis, Advisory committee. Dong, G.: Employee, Novartis. Rauer, B.: Employee, Novartis. Junge, G.: Employee, Novartis. Abstract# 2188 Liver Allograft Provides Immunoprotection Against Both Acute Cellular Immunity and Chronic Humoral Injury in Simultaneous Liver-Kidney (SLK) Transplantation. T. Taner, J. Heimbach, M. Stegall. Mayo Clinic, Rochester, MN. In SLK, the liver appears to protect the kidney from antibody-mediated injury (AMR), however its ability to protect against cell-mediated or chronic injury are less clear. The goal of this study was to compare SLK to kidney transplant (KT) recipients by assessing the; 1) incidence of acute cellular (ACR) and AMR (both clinical and subclinical), and 2) chronic changes seen in kidney allograft protocol biopsies up to 5-yr after transplantation. Methods: 68 SLK recipients were matched (age, race and sex) with 128 KT recipients. Demographic, laboratory, protocol kidney biopsy (4 mo, 1-, 2and 5-yr) and donor-specifi c HLA antibody (DSA) (baseline, 4 mo, 1-yr and yearly thereafter) data were reviewed. Maintenance immunosuppression dose was lower in KT. 232 kidney biopsies in SLK (median 3, range 1-9) and 487 in KT (median 4, range 1-9) were reviewed; incidence of events analyzed by Kaplan-Meier. Mean follow up was 67 months (±40) in both groups. Results: Patient survival was 89.7 vs 85.2%, kidney graft survival was 82.4 vs 70.3%, in SLK and KT, respectively. Four kidney grafts were lost to rejection in KT (2 ACR, 1 AMR, 1 both), none in SLK. The median eGFR at 1and 5-yr were 53 and 53 in SLK; 52 and 48 in KT. Humoral alloimmunity: DSA (MFI>2000) was present at transplant in 14 SLK (10 with +XM, 14.7%) and 7 KT (all with +XM, 5.5%). One patient in each group had persistent class II DSA post-transplant. De novo DSA, predominantly class II, was found in 11 SLK and 9 KT recipients. Patients with de novo DSA were more likely to be non-compliant (5/11 in SLK and 6/9 in KT), and have liver graft dysfunction in SLK (6/11). 5-yr cumulative incidence of AMR was similar in SLK (7.4%) and KT (9.4%). Cellular immunity: ACR was signifi cantly rarer in SLK (7.4%) than in KT (28.9%) (P=0.001).Most of the ACR were subclinical (80% in SLK and 69% in KT). Chronic changes at 5-yr were similar in SLK vs KT (interstitial fi brosis 27.9 vs 22.7%; arteriolar hyalinosis 13.2 vs 14.1%). Importantly, chronic glomerulopathy (usually associated with humoral injury) was more common in KT at 5-yr (8.6% vs 1.5%, P=0.06). Conclusions: Compared to KT, SLK appears to be associated with lower rates of ACR and fewer chronic changes associated with 2188 Liver Allograft Provides Immunoprotection Against Both Acute Cellular Immunity and Chronic Humoral Injury in Simultaneous Liver-Kidney (SLK) Transplantation. T. Taner, J. Heimbach, M. Stegall. Mayo Clinic, Rochester, MN. In SLK, the liver appears to protect the kidney from antibody-mediated injury (AMR), however its ability to protect against cell-mediated or chronic injury are less clear. The goal of this study was to compare SLK to kidney transplant (KT) recipients by assessing the; 1) incidence of acute cellular (ACR) and AMR (both clinical and subclinical), and 2) chronic changes seen in kidney allograft protocol biopsies up to 5-yr after transplantation. Methods: 68 SLK recipients were matched (age, race and sex) with 128 KT recipients. Demographic, laboratory, protocol kidney biopsy (4 mo, 1-, 2and 5-yr) and donor-specifi c HLA antibody (DSA) (baseline, 4 mo, 1-yr and yearly thereafter) data were reviewed. Maintenance immunosuppression dose was lower in KT. 232 kidney biopsies in SLK (median 3, range 1-9) and 487 in KT (median 4, range 1-9) were reviewed; incidence of events analyzed by Kaplan-Meier. Mean follow up was 67 months (±40) in both groups. Results: Patient survival was 89.7 vs 85.2%, kidney graft survival was 82.4 vs 70.3%, in SLK and KT, respectively. Four kidney grafts were lost to rejection in KT (2 ACR, 1 AMR, 1 both), none in SLK. The median eGFR at 1and 5-yr were 53 and 53 in SLK; 52 and 48 in KT. Humoral alloimmunity: DSA (MFI>2000) was present at transplant in 14 SLK (10 with +XM, 14.7%) and 7 KT (all with +XM, 5.5%). One patient in each group had persistent class II DSA post-transplant. De novo DSA, predominantly class II, was found in 11 SLK and 9 KT recipients. Patients with de novo DSA were more likely to be non-compliant (5/11 in SLK and 6/9 in KT), and have liver graft dysfunction in SLK (6/11). 5-yr cumulative incidence of AMR was similar in SLK (7.4%) and KT (9.4%). Cellular immunity: ACR was signifi cantly rarer in SLK (7.4%) than in KT (28.9%) (P=0.001).Most of the ACR were subclinical (80% in SLK and 69% in KT). Chronic changes at 5-yr were similar in SLK vs KT (interstitial fi brosis 27.9 vs 22.7%; arteriolar hyalinosis 13.2 vs 14.1%). Importantly, chronic glomerulopathy (usually associated with humoral injury) was more common in KT at 5-yr (8.6% vs 1.5%, P=0.06). Conclusions: Compared to KT, SLK appears to be associated with lower rates of ACR and fewer chronic changes associated with DSA, although SLK recipients had a higher prevalence of DSA pretransplant and were maintained on lower doses of immunosuppression; suggesting that in SLK, the liver appears to provide immunoprotection against both acute cellular immunity and chronic humoral injury. © The Authors. Compilation © The American Society of Transplant Surgeons, The Transplantation Society and the American Society of Transplantation