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Sirolimus Is Associated With Worse Renal Function in a Tacrolimus Based Immunosuppressive Regimen in Lung Transplantation
Abstracts S291 802 Implementation and Medium-Term Outcomes of a Center-Specific High-Urgency Anti-HLA Antibody Policy A. Stoddart ,1 M.I. Hertz,2 M. David,2 K. Rosemary,2 S. Sara,2 J. Patil.2 1Medicine, University of Vermont, Burlington, VT; 2Medicine, University of Minnesota, Minneapolis, MN.
8( 01) Sirolimus Is Associated With Worse Renal Function in a Tacrolimus Based Immunosuppressive Regimen in Lung Transplantation M. Robinson ,1 C. Liao,2 J. Koyner,3 S. Bhorade,4 (on behalf of the AIRSAC investigators). 1Internal Medicine, University of Chicago, Chicago, IL; 2Health Studies, University of Chicago, Chicago, IL; 3Nephrology, University of Chicago, Chicago, IL; 4Pulmonary and Critical Care, University of Chicago, Chicago, IL. Purpose: As outcomes after lung transplantation have improved, renal function is now becoming an important contributor to morbidity and mortality after transplantation. Calcineurin inhibitors are a major cause of worsening renal function in lung transplantation and several studies have suggested the addition of sirolimus or everolimus improves renal function in transplantation. We evaluated the effect of sirolimus in a post hoc analysis of renal function in patients enrolled in a multicenter randomized, open label trial. Methods: Data were collected from the AIRSAC study comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus (TAC)-based regimen. Renal function using the Chronic Kidney Disease Epidemiology Collaboration equation was compared at multiple time points post-transplant. Confounding variables were accounted for using a generalized estimating equation. Results: 180 patients were randomized in the study and included in the analysis. Baseline demographics and the incidence of diabetes and hypertension were similar between the AZA and SIR arms. Hypertension and TAC levels were associated with decreased renal function in both arms (P< 0.05). TAC levels were lower in the SIR arm (6 ng/ml) compared to the AZA arm (8 ng/ml)(P< 0.05). There was a significant decline in renal function over three years in both arms, becoming significantly worse in the SIR arm by three years post-transplant (P = 0.03) (Figure 1). Conclusion: In our post-hoc analysis, sirolimus was associated worsening renal function after three years post transplantation, despite lower TAC levels. These data differ from previous small, single center studies in which sirolimus is associated with improved renal function and suggests further investigation of immunosuppression effects on renal function should be conducted prospective randomized studies.
Purpose: Circulating recipient pre-transplant anti-HLA antibodies present a challenge in identifying a suitable lung donor. To address this challenge, we initiated a high-urgency protocol, for selected candidates judged to have high wait list mortality risk. Methods: Historically, only donors to whom recipients had no donor-specific anti-HLA antibodies (DSA)(mfi < 500) were considered acceptable for transplant at our program. In the high-urgency protocol, we increased the anti-HLA threshold to mfi < 3000 for selected patients with high wait list mortality risk. Results: 18 patients with at least one anti-HLA antibody level between mfi 500-3000 were entered in the high-urgency protocol. 2 patients expired before transplant; outcomes for the remaining 16 patients were examined. Average lung allocation score was 59. Median number of days between listing and changing to high-urgency status was 91 days (range 0-3696 days). Median number of days between being listed as high urgency and transplant was 51 days (range 7-428 days). Six recipients had low levels of pre-transplant DSA (i.e. mfi 500-3000), of which only two were T-cell crossmatch positive. The remaining recipients were virtual crossmatch as well as T/B cell crossmatch negative. 15/16 transplanted patients are currently alive with mean posttransplant follow-up of 375 days. Only one patient developed bronchiolitis obliterans syndrome stage ≥ 2 at 474 days post-transplant. 3 patients showed at least one acute rejection (A+ B ≥ 2). All three patients had at least two or more rejections, and only two of these patients had pre-tx DSAs. 2 patients developed post transplant DSAs. Conclusion: Increasing the anti-HLA antibody threshold for lung transplant wait list patients is associated with a reduced time to transplant. Low levels of circulating DSA are compatible with good medium-term post-transplant outcomes. 8( 03) Extracorporeal Photoimmune Therapy (ECP) with UVADEX in Conjunction with Standard Therapy Compared to Standard Therapy Alone for the Prevention of Rejection in Lung Transplantation Patients P. Jaksch ,1 G. Murakoezy,1 C. Lambers,1 A. Scheed,1 W. Klepetko,1 R. Knobler.2 1Thoracic Surgery, Medical University Vienna, Vienna, Austria; 2Dept Dermatology, Medical University Vienna, Vienna, Austria. Purpose: Extracorporeal photopheresis has been shown to be beneficial in acute and chronic rejection in heart transplant patients, and has although been used in lung transplant recipients with acute rejection or bronchiolitis obliterans. Methods: We performed a retrospective study to document the efficacy of photoimmune therapy in the prevention of acute rejections and chronic after lung transplantation. 18 lung transplant recipients with COPD were analysed: 2 groups were defined: Group A (9 pat) received in total 16 ECP treatments (starting 1-2 weeks after TX) and group B (9 pats) without ECP or any other kind of induction therapy, both groups receiving standard triple immunosuppression with Tacrolimus, Mycophenolate and steroids. Surveillance bronchoscopies with biopsies were performed after 2, 4,8,12, 26 and 52 weeks. Primary objectives were the incidence of biopsy proven rejections ISHLT grade > A1, high grade airway inflammation (B2R) and freedom from BOS. Secondary objectives were number of infections (CMV, bacterial, fungal, viral non-CMV, tuberculosis, parasitic), patient and graft survival. Results: Demographics in both groups were similar . Five year survival rates were equal in both groups (5 years survival 66% in both groups) The incidence of higher grade lymphocytic bronchiolitis (R2) in the ECP treated group was significant lower (p= 0.05) than in the group with photopheresis . There was also a significant difference in freedom from BOS after 5 years of follow up with zero cases of CLAD in the ECP treated cohort vs. 50% in the non ECP group . Furthermore there was a trend towards a lower incidence of CMV disease in the photopheresis group.
8( 01) Sirolimus Is Associated With Worse Renal Function in a Tacrolimus Based Immunosuppressive Regimen in Lung Transplantation M. Robinson ,1 C. Liao,2 J. Koyner,3 S. Bhorade,4 (on behalf of the AIRSAC investigators). 1Internal Medicine, University of Chicago, Chicago, IL; 2Health Studies, University of Chicago, Chicago, IL; 3Nephrology, University of Chicago, Chicago, IL; 4Pulmonary and Critical Care, University of Chicago, Chicago, IL. Purpose: As outcomes after lung transplantation have improved, renal function is now becoming an important contributor to morbidity and mortality after transplantation. Calcineurin inhibitors are a major cause of worsening renal function in lung transplantation and several studies have suggested the addition of sirolimus or everolimus improves renal function in transplantation. We evaluated the effect of sirolimus in a post hoc analysis of renal function in patients enrolled in a multicenter randomized, open label trial. Methods: Data were collected from the AIRSAC study comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus (TAC)-based regimen. Renal function using the Chronic Kidney Disease Epidemiology Collaboration equation was compared at multiple time points post-transplant. Confounding variables were accounted for using a generalized estimating equation. Results: 180 patients were randomized in the study and included in the analysis. Baseline demographics and the incidence of diabetes and hypertension were similar between the AZA and SIR arms. Hypertension and TAC levels were associated with decreased renal function in both arms (P< 0.05). TAC levels were lower in the SIR arm (6 ng/ml) compared to the AZA arm (8 ng/ml)(P< 0.05). There was a significant decline in renal function over three years in both arms, becoming significantly worse in the SIR arm by three years post-transplant (P = 0.03) (Figure 1). Conclusion: In our post-hoc analysis, sirolimus was associated worsening renal function after three years post transplantation, despite lower TAC levels. These data differ from previous small, single center studies in which sirolimus is associated with improved renal function and suggests further investigation of immunosuppression effects on renal function should be conducted prospective randomized studies.
Purpose: Circulating recipient pre-transplant anti-HLA antibodies present a challenge in identifying a suitable lung donor. To address this challenge, we initiated a high-urgency protocol, for selected candidates judged to have high wait list mortality risk. Methods: Historically, only donors to whom recipients had no donor-specific anti-HLA antibodies (DSA)(mfi < 500) were considered acceptable for transplant at our program. In the high-urgency protocol, we increased the anti-HLA threshold to mfi < 3000 for selected patients with high wait list mortality risk. Results: 18 patients with at least one anti-HLA antibody level between mfi 500-3000 were entered in the high-urgency protocol. 2 patients expired before transplant; outcomes for the remaining 16 patients were examined. Average lung allocation score was 59. Median number of days between listing and changing to high-urgency status was 91 days (range 0-3696 days). Median number of days between being listed as high urgency and transplant was 51 days (range 7-428 days). Six recipients had low levels of pre-transplant DSA (i.e. mfi 500-3000), of which only two were T-cell crossmatch positive. The remaining recipients were virtual crossmatch as well as T/B cell crossmatch negative. 15/16 transplanted patients are currently alive with mean posttransplant follow-up of 375 days. Only one patient developed bronchiolitis obliterans syndrome stage ≥ 2 at 474 days post-transplant. 3 patients showed at least one acute rejection (A+ B ≥ 2). All three patients had at least two or more rejections, and only two of these patients had pre-tx DSAs. 2 patients developed post transplant DSAs. Conclusion: Increasing the anti-HLA antibody threshold for lung transplant wait list patients is associated with a reduced time to transplant. Low levels of circulating DSA are compatible with good medium-term post-transplant outcomes. 8( 03) Extracorporeal Photoimmune Therapy (ECP) with UVADEX in Conjunction with Standard Therapy Compared to Standard Therapy Alone for the Prevention of Rejection in Lung Transplantation Patients P. Jaksch ,1 G. Murakoezy,1 C. Lambers,1 A. Scheed,1 W. Klepetko,1 R. Knobler.2 1Thoracic Surgery, Medical University Vienna, Vienna, Austria; 2Dept Dermatology, Medical University Vienna, Vienna, Austria. Purpose: Extracorporeal photopheresis has been shown to be beneficial in acute and chronic rejection in heart transplant patients, and has although been used in lung transplant recipients with acute rejection or bronchiolitis obliterans. Methods: We performed a retrospective study to document the efficacy of photoimmune therapy in the prevention of acute rejections and chronic after lung transplantation. 18 lung transplant recipients with COPD were analysed: 2 groups were defined: Group A (9 pat) received in total 16 ECP treatments (starting 1-2 weeks after TX) and group B (9 pats) without ECP or any other kind of induction therapy, both groups receiving standard triple immunosuppression with Tacrolimus, Mycophenolate and steroids. Surveillance bronchoscopies with biopsies were performed after 2, 4,8,12, 26 and 52 weeks. Primary objectives were the incidence of biopsy proven rejections ISHLT grade > A1, high grade airway inflammation (B2R) and freedom from BOS. Secondary objectives were number of infections (CMV, bacterial, fungal, viral non-CMV, tuberculosis, parasitic), patient and graft survival. Results: Demographics in both groups were similar . Five year survival rates were equal in both groups (5 years survival 66% in both groups) The incidence of higher grade lymphocytic bronchiolitis (R2) in the ECP treated group was significant lower (p= 0.05) than in the group with photopheresis . There was also a significant difference in freedom from BOS after 5 years of follow up with zero cases of CLAD in the ECP treated cohort vs. 50% in the non ECP group . Furthermore there was a trend towards a lower incidence of CMV disease in the photopheresis group.