1445 Symmetric Dimethylarginine as Predictor of Graft Loss and All-Cause Mortality in Renal Transplant Recipients. H. Pihlstrom,1 G. Mjoen,2 D. Dahle,1 S. Pilz,3,4 K. Midtvedt,1 W. Maerz,5,6,7 S. Abedini,8 I. Holme,9 B. Fellstrom,10 H. Holdaas.1 1Department of Organ Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; 2Department of Medicine, Oslo University Hospital Ullevaal, Oslo, Norway; 3Department of Internal Medicine, Medical University of Graz, Graz, Austria; 4Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, Amsterdam, Netherlands; 5Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; 6Synlab Center of Laboratory Diagnostics, Heidelberg, Germany; 7Mannheim Institute of of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany; 8Department of Medicine, Sykehuset i Vestfold, Tonsberg, Norway; 9Department of Research and Development, Oslo University Hospital Ullevaal, Oslo, Norway; 10Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated. We analysed SDMA in the placebo arm of the ALERT study, a randomized controlled trial of fl uvastatin in RTR. Mean follow up of was 5.1 years. Patients were grouped into quartiles based on SDMA-levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analysed in 925 RTR using uniand multivariable survival analysis. In univariate analysis SDMA was signifi cantly associated with renal graft loss, all-cause death and major cardiovascular events. After adjustment for established risk factors including estimated glomerular fi ltration rate, an elevated SDMA level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR) 5.51 (95% CI 1.95-15.57, p=0.001) compared to the 1st quartile. Similarly,SDMA in the 4th quartile was independently associated with all-cause mortality (HR 4.56 95% CI 2.15-9.71, p<0.001), and there was a strong borderline signifi cant trend for an association with cardiovascular mortality (HR 2.86, 95% CI 0.99-8.21, p=0.051). In stable RTR an elevated SDMA-level is independently associated with increased risk of all-cause mortality and renal graft loss. Abstract# 1446 Renin Angiotensin Aldosterone System (RAAS) Blockers Are Nephroprotective If Used Immediately After Renal Transplantation. C. Chatzikyrkou,1 J. Eichler,1 A. Müller-Heine,2 J. Menne,1 F. Lehner,3 H. Haller,1 M. Schiffer.1 1Nephrology and Hypertension, Hannover Medical School, Hanover, Germany; 2Department of Biostatistics, Hannover Medical School, Hanover, Germany; 3Clinic for General Abdominal and Transplant Surgery, Hannover Medical School, Hanover, Germany. Aim: We have previously shown, that the use of RAAS blockers in the in the very early postoperative period after renal transplantation is safe. The aim of this study was to investigate the long term effects of this therapeutic approach. Methods: We conducted a case-control study including 142 kidney transplant recipients, who received a RAAS blocker one week after transplantation and 114 controls (group I). The RAAS blocker was given only for blood pressure control. Cases and controls were matched by age, sex, year of transplantation and serum creatinine at the time of administration of the RAAS blocker. 117 cases continued to receive and 50 controls remained continuously free of the RAAS blocker in the fi rst year (group II). Only outcomes in group II are presented here. Results: The creatinine clearance at one year was signifi cantly better in cases (78 vs.61 ml/min, p=0.005). The mean duration of follow-up in group II was 4.3 years. Cases exhibited less proteinuria at the end of follow-up (0.27 vs. 0.33 g/day, p=0.07). There were no differences in blood pressure levels at one year and at the end of follow-up, but cases needed much more antihypertensive agents for blood pressure control (3.1 vs 2.1, p <0.0001 and 2.8 vs. 2.1, p=0.005). The endpoints graft failure and graft failure or death from any cause were signifi cantly better in cases (p=0.03 and p=0.04 respectively). The treatment effects in the RAAS blocker group persisted even after adjustment for demographic parameters, immunological risk factors, peritransplant risk factors, duration of dialysis prior to transplantation and medical comorbidities. Conclusion: The use of RAAS blockers immediately after transplantation is nephroprotective, especially in patients with diffi culties in blood pressure control. Desensitization Protocols in Kidney Transplantation Tuesday, July 29, 2014 4:00 PM 5:30 PM Room 2005/2007 Abstract# 1454 A Phase I/II Placebo-Controlled Trial of C1 Inhibitor for Prevention of Antibody-Mediated Rejection in HLA Sensitized Patients. A. Vo, J. Choi, K. Cisneros, J. Kahwaji, A. Peng, R. Villicana, S. Jordan. Kidney Transplant, Cedars-Sinai Medical Center, Los Angeles, CA. Introduction: Antibody-mediated rejection (ABMR) is a severe form of rejection, mediated by complement (C). C1 inhibitor (C1INH, Berinert®) inhibits classic and (MBL/MBLSP) pathways of C activation. Here we undertook a placebo-controlled, single center study using C1INH in highly sensitized (HS) patients for prevention of ABMR. Patients & Methods: From 12/2011 to 4/2012, 20 consecutive HS patients {CPRA >50%, DSA(+) and FCMX(+)} desensitized with IVIG + rituximab were enrolled and randomized 1:1 to receive C1INH (20u/kg/dose) vs. Placebo (NS) administered intra-operatively, then 2X weekly for 7 additional doses. Posttransplant, evidence of DVT (Wells Criteria), other AEs/SAEs and C3, C4, C1INH levels were monitored. All patients received Campath-1H induction and were maintained on Prograf/Cellcept/Pred. Results: Two patients (20%) in C1INH vs. 3 patients (30%) in NS developed SAEs. C1INH levels {C1 function (p = 0.0007) & C1INH antigen % (p = 0.013)} increased with C1INH treatment. C3 levels on day 30 increased in the C1INH group (p= 0.005). C4 levels were signifi cantly higher in the C1INH group at all time points. 1454 A Phase I/II Placebo-Controlled Trial of C1 Inhibitor for Prevention of Antibody-Mediated Rejection in HLA Sensitized Patients. A. Vo, J. Choi, K. Cisneros, J. Kahwaji, A. Peng, R. Villicana, S. Jordan. Kidney Transplant, Cedars-Sinai Medical Center, Los Angeles, CA. Introduction: Antibody-mediated rejection (ABMR) is a severe form of rejection, mediated by complement (C). C1 inhibitor (C1INH, Berinert®) inhibits classic and (MBL/MBLSP) pathways of C activation. Here we undertook a placebo-controlled, single center study using C1INH in highly sensitized (HS) patients for prevention of ABMR. Patients & Methods: From 12/2011 to 4/2012, 20 consecutive HS patients {CPRA >50%, DSA(+) and FCMX(+)} desensitized with IVIG + rituximab were enrolled and randomized 1:1 to receive C1INH (20u/kg/dose) vs. Placebo (NS) administered intra-operatively, then 2X weekly for 7 additional doses. Posttransplant, evidence of DVT (Wells Criteria), other AEs/SAEs and C3, C4, C1INH levels were monitored. All patients received Campath-1H induction and were maintained on Prograf/Cellcept/Pred. Results: Two patients (20%) in C1INH vs. 3 patients (30%) in NS developed SAEs. C1INH levels {C1 function (p = 0.0007) & C1INH antigen % (p = 0.013)} increased with C1INH treatment. C3 levels on day 30 increased in the C1INH group (p= 0.005). C4 levels were signifi cantly higher in the C1INH group at all time points. No patient in the C1INH group developed ABMR during the study period. Two patients (20%) developed ABMR outside of study period. 30% of NS treated developed ABMR, one during study period. © The Authors. Compilation © The American Society of Transplant Surgeons, The Transplantation Society and the American Society of Transplantation 103 Conclusions: Important observations from this initial trial in human transplantation of C1INH include: C1INH appears safe in the post-transplant period. Second, C1INH administration resulted in signifi cant elevations of C1INH, C3 and C4 levels, suggesting inhibition of systemic C activation by C1INH. Finally, no ABMR episodes were observed during the treatment period with C1INH. IND #14363, NCT01134510. DISCLOSURE: Jordan, S.: Grant/Research Support, CSL-Behring. Abstract# 1455 Refining The Prediction of Early Antibody Mediated Rejection After Antibody Incompatible Renal Transplantation; Importance of Pregnancy-Induced Sensitisation. R. Higgins,1 D. Lowe,2 M. Hathaway,2 C. Williams,2 C. Imray,1 N. Krishnan,1 S. Daga,3 D. Briggs,2 D. Zehnder.3 1Renal Transplantation, University Hospital, Coventry, United Kingdom; 2H&I Laboratory, NHS BT, Birmingham, United Kingdom; 3Warwick Medical School, University of Warwick, Coventry, United Kingdom. 1455 Refining The Prediction of Early Antibody Mediated Rejection After Antibody Incompatible Renal Transplantation; Importance of Pregnancy-Induced Sensitisation. R. Higgins,1 D. Lowe,2 M. Hathaway,2 C. Williams,2 C. Imray,1 N. Krishnan,1 S. Daga,3 D. Briggs,2 D. Zehnder.3 1Renal Transplantation, University Hospital, Coventry, United Kingdom; 2H&I Laboratory, NHS BT, Birmingham, United Kingdom; 3Warwick Medical School, University of Warwick, Coventry, United Kingdom. Background. Acute antibody mediated rejection (AMR) after HLA antibody incompatible renal transplantation is related to donor specifi c HLA antibody (DSA) levels. However, pre-treatment DSA levels have a low predictive value for AMR, partly because of rapid changes in DSA levels post-transplant. This study examined changes in DSA according to the primary sensitising event. Methods. Responses to 220 HLA specifi cities in 64 patients over the fi rst 30 days after

Purpose New-onset diabetes after transplantation [NODAT] is associated with increased cardiovascular risk and reduced patient survival. We have also shown that patients who develop NODAT, despite the use of a steroid sparing immunosuppressive regime have reduced patient survival. In this study, we investigate the causes of death in these patients developing NODAT. Methods In a retrospective, single centre study, we report the outcomes of 920 patients [552m, 368f, mean age 47±13.3 yrs, range 18-78, mean follow up 57.6±30 mths], receiving a steroid sparing, tacrolimus based regime after monoclonal antibody induction. Steroids were stopped 7 days post kidney transplantation and only reintroduced to treat rejection. We excluded patients with history of diabetes mellitus. Results Overall, 169/920 [18.4%] patients developed NODAT, defined as diabetes requiring diet control [19.9%], oral hypoglycaemics [62.0%], insulin [15.7%] or both [2.4%]. Cumulative patient survival in the NODAT+ and NODAT- groups at 1, 3, 5 years post transplant was 98.2%, 93.6%, 90.2% and 98.5%, 97%, 94.8%, respectively (p=0.032). Cumulative graft survival in the NODAT+ and NODAT- groups at 1,3 and 5 years was 98.2%, 92.3%, 87% and 95.7%, 92%, 87.9%, respectively (p=0.547). The cumulative incidence of NODAT was 9.5%, 14.2% and 16.5% at 1, 3 and 5 years after transplantation, respectively. During follow up, there were 71 cardiac events, 22 of which occurred in patients with NODAT [1 STEMI, 9 non-STEMIs, 9 episodes of cardiac arrhythmia and 3 cardiac deaths]. In NODAT- patients, there were 49 cardiac events (4 STEMI, 18 NSTEMI, 24 episodes of cardiac arrhythmia and 3 cardiac deaths). The NODAT+ group had an increased risk of cardiac events (12.4% vs. 6.5%, p=0.009) and death (10.1% vs. 4.9%, p=0.011). Patients with NODAT had reduced coronary event-free survival (log rank p=0.017) and overall survival (log rank p=0.032). Older age (p<0.001) and development of NODAT (p=0.041) increased the risk for a cardiac event. Conclusions This study shows that patients who develop NODAT despite the use of a steroid-sparing regime have a higher incidence of cardiac events and impaired patient survival.