Transplantation - clinical II

Nephrology Dialysis Transplantation, May 2012

Introduction and Aims: Endothelial progenitor cells (EPCs) participate in regenerative processes of the vasculature, develop incompetence in several states of disease, and also have prognostic value. The effects of various immunosuppressants on EPCs are unknown. Methods: In an open-label, randomized controlled trial cyclosporine A (CSA) treated kidney transplant recipients (KTRs) with stable graft function were assigned to receive tacrolimus (TAC) at target trough levels of 5-8 ng/mL or to continue CSA based immunosuppression at target trough levels of 70-150 ng/mL at a 2:1 ratio. The primary end-point was the effect of TAC on EPC count at 3, 12, and 24 months after conversion from CSA. Secondary objectives included renal function, humoral alloreactivity, pharmakogenetics, traditional cardiovascular disease risk factors, and safety. EPCs were assessed by whole-blood flow cytometry (CD34+CD133+KDR+), cell culture assay (endothelial cell-colony forming units [EC-CFU] and circulating angiogenic cells [CAC]). Between group comparisons were performed by Mann–Whitney-U test. Friedman tests were used to test for changes within groups over time. Results: 148 patients were randomized and 141 were included into the intent to treat analysis (55.6 [46.5-65.0] years old; 67% male; renal graft vintage 6.2 years [3.2 -12.5], with an estimated glomerular filtration rate of 45.8 [37.9 - 57.6] mL/min per 1.73m2). The counts of EPCs, CACs, and EC-CFUs are indicated in Table 1.⇓ View this table: In this window In a new window

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Transplantation - clinical II

Valeria Cademartori 0 3 4 8 11 12 15 18 22 23 Fabio Massarino 0 3 4 8 11 12 15 18 22 23 Emanuele Luigi Parodi 0 3 4 8 11 12 15 18 22 23 Rodolfo Russo 0 3 4 8 11 12 15 18 22 23 Antonella Sofia 0 3 4 8 11 12 15 18 22 23 Iris Fontana 0 2 4 7 10 12 14 17 21 Giorgio L. Viviani 0 1 4 9 12 13 16 Giacomo Garibotto 0 4 12 20 0 Hhemodialysis, Clinical Center , Nis , Serbia 1 Department of Internal Medicine,Genoa University , Genoa , Italy 2 Transplant Section, Genoa University and Aou San Martino , Genoa , Italy 3 Department of Internal Medicine, Nephrology Section, Genoa University , Genoa , Italy 4 Markus Riegersperger 5 Center for Statistics and Informatics, Medical Faculty , Nis , Serbia 6 Clinic for Nephrology 7 University of William and Mary , Williamsburg , USA 8 Mayo Clinic , Jacksonville , USA 9 Ege University School of Medicine, Division of Radiology , Izmir , Turkey 10 Ege University School of Medicine 11 Ege University School of Medicine, Division of Nephrology , Izmir , Turkey 12 Aysegul Cobanoglu Kudu 13 1nephrology and Renal Transplantation, Department of Systematic Pathology, University of Naples federico Ii , 80131 Naples , Italy 14 Department of Neuroscience, Physiology Nutrition Unit, University Federico II , Naples , Italy 15 Nephrology and Renal Transplantation, Department of Systematic Pathology, University of Naples federico Ii , Naples , Italy 16 Department of Nephrology, Baskent University , Ankara , Turkey 17 Baskent University Hospital, Department of Nephrology , Ankara , Turkey 18 Department of Nephrology, Baskent University , Ankara , Turkey. 19 Department of Nephrology, Baskent University , Istanbul , Turkey 20 Department of Internal Medicine, Baskent University , Ankara , Turkey 21 Division of Urology, Kobe University Graduate School of Medicine , Kobe , Japan 22 Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine , Kobe , Japan. 23 University Hospital , Favaloro Fondation, Buenos Aires , Argentina TRANSPLANTATION - CLINICAL II The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: - Introduction and Aims: Endothelial progenitor cells (EPCs) participate in regenerative processes of the vasculature, develop incompetence in several states of disease, and also have prognostic value. The effects of various immunosuppressants on EPCs are unknown. Methods: In an open-label, randomized controlled trial cyclosporine A (CSA) treated kidney transplant recipients (KTRs) with stable graft function were assigned to receive tacrolimus (TAC) at target trough levels of 5-8 ng/mL or to continue CSA based immunosuppression at target trough levels of 70-150 ng/mL at a 2:1 ratio. The primary end-point was the effect of TAC on EPC count at 3, 12, and 24 months after conversion from CSA. Secondary objectives included renal function, humoral alloreactivity, pharmakogenetics, traditional cardiovascular disease risk factors, and safety. EPCs were assessed by whole-blood flow cytometry (CD34+CD133+KDR+), cell culture assay (endothelial cell-colony forming units [EC-CFU] and circulating angiogenic cells [CAC]). Between group comparisons were performed by Mann Whitney-U test. Friedman tests were used to test for changes within groups over time. Results: 148 patients were randomized and 141 were included into the intent to treat analysis (55.6 [46.5-65.0] years old; 67% male; renal graft vintage 6.2 years [3.2 -12.5], with an estimated glomerular filtration rate of 45.8 [37.9 - 57.6] mL/min per 1.73m2). The counts of EPCs, CACs, and EC-CFUs are indicated in Table 1. Conclusions: Our study provides evidence that TAC has no favorable effect on EPCs in stable long-term KTRs. However, the decrease of EPCs over time and the trend for lower EPC counts in TAC treated patients deserves further examination. SAP643 Table 1 EPC endothelial progenitor cells, CD cluster of differentiation, CAC circulating angiogenic cells, EC-CFU endothelial cell colony forming units, CSA ciclosporine A, TAC tacrolimus, P probability, BL baseline, M3 month 3, M12 month 12, M24 month 24. THE EFFECT OF DIFFERENT CALCINEURIN INHIBITORS ON OXIDATIVE STRESS PARAMETERS IN RENAL TRANSPLANT RECIPIENTS Introduction and Aims: Transplanted kidneys are prone to oxidative stress-mediated injury by pre-transplant and post- transplant conditions that cause reperfusion injury or imbalance between oxidants and antioxidants. Oxidative stress can also be caused by immunosuppressive therapy. The most common immunosuppressive drugs used for preventing the rejection of transplanted organs are calcineurin inhibitors (CNI) such as cyclosporine (CsA) and tacrolimus (Tac). The aim of the study was to analyze the relation between oxidative stress parameters (TBA reactive supstances-TBARS, advanced oxidation protein products AOPP, total SH group and catalase activity -CAT) and kidney function in transplanted patients on different calcineurin inhibitors. Methods: A group of 57 renal transplant patients (5,152,85 years after kidney transplantation: Tac group n =34 and CsA group n=23) and control group of healthy people (n=24) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods. TBARS concentrations were measured in plasma and red blood cells by a thiobarbituric acid reaction. The catalase activity was determined by the spectrophotometric method. Based on the ability of hydrogen peroxide to form a stable stained complex with molybdenum salts. Results: All transplanted patients had significantly increased concentration of AOPP ( p<0.005), total SH groups ( p<0.001) and catalase activity ( p<0.05) compared with control group without changes in TBARS content. Between total SH groups and AOPP as well as between catalase activity and SH group we found positive correlation. Our results show that no differences in oxidative stress parameters between patients treated with cyclosporine A or tacrolimus. Conclusions: Our findings suggest that renal transplant recipients display persistent oxidative stress. No significant differences in oxidative stress parameters were found with respect to treatment. EFFECTS OF TWICE-DAILY VS. ONCE-DAILY SLOW RELEASE TACROLIMUS ON THE INSULIN RESISTANCE INDEXES IN KIDNEY TRANSPLANT PATIENTS Introduction and Aims: New onset diabetes after transplantation (NODAT) is a common and a serious complication following kidney transplant. NODAT is associated with reduced patient and graft survival and cardiovascular disease. The use of Tacrolimus (Tac) may induce an impairement of insulin secretion and/or sensitivity and may be involved in the development of NODAT in a dose related manner. The aim of this study was to evaluate the effects of a standard twice-daily formulation of Tac (Prograf ) vs. the once-daily slow release formulation (Advagraf ) on the basal insulin resistance indexes (HOMA and McAuley) in a cohort of kidney transplant patients. Methods: The inclusion and exclusion criteria were defined to select a cohort of patients with stable kidney function ( proteinuria <500 mg/day) and clinical conditions. We retrospectively reviewed data from 20 renal transplant recipients followed at the Nephrology, Dialysis and Transplant Division, University of Genoa, for whom a switch from standard twice-daily formulation of Tac to the once-daily slow release formulation was identified. All patients were on double immunosuppressant regimen (TAC/MMF). Other drugs, including antihypertensive drugs, sodium bicarbonate, calcium carbonate, calcitriol, cinacalcet and erythropoietin were prescribed as appropriate for each patient. Patients had received a kidney graft from more than three months. Blood levels of Tac were analyzed at one-month time points ranging from 6 months before to 8 months after conversion. Homa, McAuley, C- peptide, Insulin, Hb1Ac, TG, LDL and HDL-cholesterol and their associations with blood levels of Tac were also evaluated. Results: After switching we observed a significant decrease in Tac exposure (8.52 ng/ml CV 0,23 vs.6.11.9 ng/ml CV 0.31, Tac vs. Tac slow release, p< 0.00,1). No change in Homa (1.420.4; 1.80.7, Tac vs. Tac slow release p>0.05) and McAuley indexes (7.121; 7.581.4 Tac vs.Tac slow release p>0.05). Observed changes in insulin resistance indexes were not dependent on their respective basal levels. Furthermore we could not observed any association between Tac levels and blood levels of Glucose, Insulin, C-peptide, Hb1Ac, TG, LDL, HDL. Creatinine values remained stable during the observed period (1.20.31 mg/dl; 1.20.39 mg/dl,Tac vs. Tac slow release p>0.05). Conclusions: There was no significant change in basal insulin resistance indexes after switching from Prograf to Advagraf despite a reduced Tac exposure. IMMUNOSUPPRESSION WITH RAPID STEROID TAPER IN KIDNEY TRANSPLANT USING DONATION AFTER CARDIAC DEATH (DCD) DONORS Martin Mai1, William Mai2, Burcin Taner1, Hani Wadei1, Mary Prendergast1 and Thomas Gonwa1 Introduction and Aims: Kidney transplantation using donation after cardiac death (DCD) donors has become more commonplace. Delayed graft function (DGF) incidence in these grafts is higher compared to that of grafts from donation after brain death (DBD). DGF is associated with increased risk of rejection and decreased graft survival. While most studies have shown equal short term graft survival of DCD kidneys to DBD, outcomes of graft survival, function and rejection using rapid steroid taper protocol in DCD transplant is lacking. We retrospectively report on outcomes of 40 DCD primary kidney transplant recipients treated with rabbit anti-thymocyte induction and rapid steroid taper (RST). Methods: Outcomes of 40 consecutive primary DCD kidney transplant recipients performed between Jan 2005 and Dec 2009 were retrospectively reviewed and compared to 142 DBD primary recipients performed during the same interval. All patients were treated with induction using rabbit anti-thymocyte globulin (6 mg/kg total dose) and RST (all steroids stopped 5 days after transplant). Maintenance immunosuppression included tacrolimus and mycophenolate mofetil. Protocol kidney biopsies were obtained at 1, 4, 12 and 24 months. Kidney biopsies for cause were conducted for unexplained elevated creatinine (Cr), decreased measured GFR (mGFR) or new proteinuria. Biopsies were graded for rejection per Banff criteria. All acute cellular rejections (including borderline) were treated and repeat kidney biopsies were obtained 1-8 weeks later. Serum creatinine (Cr) and measured GFR (mGFR - by cold iothalamate, using 24 h ClCr if needed) were collected at 1, 4, 12 and 24 months. Graft survival was available up to 3 years post-transplant. Results: Graft survival at 3 years was 90.0% for DCD recipients and 86.6% for DBD recipients (P= NS). Rejection of any type occurred in 18 DCD (45%) compared to 50 DBD (35%) recipients. In the DCD group, there was no difference in graft survival at 3 years between those with rejection and those without. At 2 years, the meanSEM Cr and mGFR for DCD recipients with rejection was 1.80.29 mg/dl and 59.28.5 ml/min versus 1.30.11 and 67.07.8 without rejection ( p=NS). For DBD with rejection the mean Cr and mGFR at 2 years was 1.70.12 mg/dl and 54.04.4 ml/ min versus 1.40.11 and 66.63.3 without rejection ( p=NS). In comparing DCD to DBD, there was no statistical difference in mean Cr or mGFR outcomes. Conclusions: DCD primary kidney transplant recipients treated with rabbit anti-thymocyte induction and RST have short-term graft survival and function equivalent to DBD recipients. RST appears to be acceptable immunosuppression for DCD recipients. EARLY CONVERSION FROM TWICE DAILY TACROLIMUS TO THE ONCE DAILY EXTENDED FORMULATION IN RENAL TRANSPLANT PATIENTS BEFORE HOSPITAL DISCHARGE Jannot Martin1, Jannot Martin1, Sury Aurore1, Chabroux Seffert Aline1, Maillard Nicolas1, Medhi Manolie1, Sauron Catherine1, Alamartine Eric1 and Mariat Christophe1 1Chu Saint Etienne Introduction and Aims: In Europe, once daily tacrolimus (ADVAGRAFTM) is approved in renal transplantation to be used immediately after the surgical procedure. As compared to the conventional twice daily tacrolimus, this extended-release formulation is however less flexible for the initial period of transplantation during which many dose adjustments can be necessary. For this reason, we have implemented in our centre a strategy of delayed conversion from PROGRAFTM to ADVAGRAFTM after the first week post-transplant. As part of this strategy, patients are converted before their hospital discharge in order to ensure (i) that exposure to tacrolimus has not been modified by the switch and (ii) that all patients have undergone their therapeutic education under ADVAGRAFTM. We report here our experience of early conversion to ADVAGRAFTM in renal transplantation. Methods: We evaluated tacrolimus exposure (trough levels), dose adjustments over time, as well as the efficacy and safety of an early ADVAGRAFTM conversion strategy (ADVAGRAFTM group) as compared to a conventional PROGRAF-based regimen (PROGRAFTM group). Patients concomitantly received steroids and mycophenolate mofetil in both groups along with a sequential induction therapy. Results: Forty eight transplanted pts were included in each group (69% male, mean age 54). Conversion to ADVAGRAFTM was initiated on average at 12.4 days post tx. Mean (+/-SD) tacrolimus dose was 7.8 (+/-3.1) mg/day and 8.5 (+/-3.3) mg/day before and after the conversion, respectively (NS). Tacrolimus exposure was not significantly impacted by ADVAGRAFTM conversion (tacrolimus C0 of 8.2 ng/ml and 7.5 ng/ml, respectively). No difference between the 2 groups was observed at one year post-transplant, regarding occurrence of acute rejection, level of renal function, mean albuminuria, occurrence of new onset diabetes and proportion of patients with hypertension and hypercholesterolemia. One year post-transplant patient and graft survival was similar in both groups. Conclusions: Early conversion from PROGRAFTM to ADVAGRAFTM after the first week post-transplant is feasible without significant impact on tacrolimus exposure. This strategy appears to be safe and well tolerated and might represent an alternative to the immediate post-transplant introduction of ADVAGRAFTM. EFFECT OF IMMUNOSUPPRESSIVE REGIMEN ON DONOR-SPECIFIC HLA-ANTIBODY FORMATION AFTER KIDNEY TRANSPLANTATION Susanne Brakemeier1, Lutz Liefeldt1, Petra Glander1, Johannes Waiser1, Nils Lachmann2, Constanze Schnemann2, Bianca Zukunft1, Patrick Illigens1, Danilo Schmidt1, Kaiyin Wu3, Birgit Rudolph3, Hans-H. Neumayer1and Klemens Budde1 1Charit, Nephrology, Berlin, Germany, 2Charit, Hla-Laboratory, Berlin, Germany, 3Charit, Pathology, Berlin, Germany Introduction and Aims: Donor-specific HLA-antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. Methods: At 3-4.5 months post-transplant 127 patients were randomized to continue cyclosporine or converted to everolimus-therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Results: Antibody screening was available in 126 cases with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p=0.048). Eight patients on everolimus compared to 2 patients on cyclosporine developed AMR (log-rank: p=0.036). Four of 10 patients with AMR - all in the everolimus- group - lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. Conclusions: This study underlines the usefulness of DSA-screening and demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR. PRETRANSPLANT DONOR-SPECIFIC HLA ANTIBODIES DETECTED BY SINGLE-ANTIGEN BEAD FLOW CYTOMETRY: RISK FACTORS AND OUTCOME AFTER KIDNEY TRANSPLANTATION Luis Pallardo Mateu1, Eva Gavela Martinez2, Asuncion Sancho Calabuig1, Josep Crespo Albiach1, Sandra Beltran Catalan3, Eva Gavela Martinez3 and Julia Kanter Berga3 1Hospital Dr Peset Valencia, Spain, 2Hospital Dr Peset, Valencia, Espaa, 3Hospital Dr Peset Valencia Spain Introduction and Aims: The clinical significance of pretransplant donor-specific antibodies ( pre-Tx DSAs) detected by single antigen bead flow cytometry (SAB-FC) remains unclear. Our aim was to investigate the impact that pre-Tx DSAs detected by SAB-FC have on the early and late clinical outcomes. Methods: We retrospectively tested stored frozen pre-Tx sera from 109 deceased-donor kidney transplants performed between November 1997 and November 2006. All patients had a negative complement dependent cytotoxicity (CDC) X-match with the donor. Median follow up was 9.1 years. Results: 59.6% of patients were men with a mean age of 47.5 +/- 13 years, 5% were retransplants. 10 (9.2%) patients had pre-Tx HLA antibodies detected by CDC. 43% had received pre-Tx transfusions and 33.3% of them received induction therapy with Basiliximab or Thymoglobulin. Pre-Tx HLA antibodies were detected using SAB-FC in the sera of 23 (21%) patients, and pre-Tx DSAs in 16 (14.7%) patients; among pre-Tx DSAs patients 12 had class I antibodies, 8 class II and 4 patients presented both classes. Pre-Tx DSAs group was associated with female sex (69%), a higher percentage of acute tubular necrosis in the first week pos-transplantation (56 vs 34%, p=0.07), and more episodes of acute vascular rejection (37.5 vs 20.4%, p=0.12). Mean pre-Tx DSA Class I/II was 2686 2313/ 1982 560 MFI in non CDC sensitized patients and 8173 7300/ 103815760 MFI in those with CDC-HLA antibodies. 5 years allograft survival was significantly worse in patients with pre-Tx DSA (81 vs 91%, p=0.006), being the chronic allograft rejection the most prevalent cause of renal failure (18.8 vs 4.3%). Among patients with pre-Tx DSAs, 5 years survival was even worse in patients with more than 3000 MFI DSAs (87 vs 75 %, p=0.12) We didnt find differences in patient survival. Conclusions: pre-TX DSAs detected by SAB-FC were more frequent in female ii | Abstracts recipients, and they were associated with acute vascular rejection and a poorer graft outcome. ABO INCOMPATIBLE KIDNEY TRANSPLANTATION IN THE ELDERLY Takaaki Kimura1, Takashi Yagisawa1, Nobuo Ishikawa1, Yasunaru Sakuma1, Takehito Hujiwara1, Akinori Nukui1and Masahiro Yashi2 1Jichi Medical University, 2Jichi Medical University Hospital Introduction and Aims: Recently, ABO incompatible kidney transplantation (ABO-IN Tx) has been performed in patients with various backgrounds such as the elderly and unrelated combination. We compared the results of ABO-IN Tx in patients aged =60 years with in younger patients. Methods: Twenty-four consecutive ABO-IN Tx recipients were included. Patients were divided in two groups according to the recipient age: G1 (=60 yrs, n=9), and G2 (<60 yrs, n=15). Mean recipient/donor age were 63.92.8/63.45.0 yrs in G1 and 46.510.5/54.110.4 yrs in G2. Mean duration of dialysis was 58.946.5 months in G1 and 25.922.9 months in G2, respectively. We compared the difference in the patient and graft survival, and complications, such as acute rejection, cytomegalovirus antigenemia, and surgical complications between the groups. All patients received desensitization with plasmapheresis until pre-transplant ABO IgG titers became <16. Two patients of G1 and 3 patients of G2 received rituximab before transplantation and others underwent splenectomy at the time of transplantation. Results: The patient/graft survival (death censored) were 100%/100% at 1, 3 year(s) in G1, 100%/100% at 1 year and 93%/100% at 3 years in G2. Acute rejection occurred in 2 (22%) of G1 and 2 (13%) of G2. The incidence of cytomegalovirus antigenemia was 67% in G1 and 80% in G2. Surgical complications occurred 3 (33%) of G1 and 4 (27%) of G2. The serum creatinine at 1 year after transplantation was 1.1 mg/dl in both groups. Conclusions: The patient and graft survival, complications, and serum creatinine at 1 year after transplantation were same in both groups. Recipient age had no negative impact on the outcome of ABO incompatible kidney transplantation. EFFECT OF DONOR GENDER IN KIDNEY GRAFT SURVIVAL IN THE AGE-MARGINAL DONOR POOL Jose Duraes1, Jorge Malheiro2, Isabel Fonseca2, Ana Rocha2, La Salete Martins2, Manuela Almeida2, Leonideo Dias2, Antonio Castro-Henriques2and Antnio Cabrita2 1Hospital de Santo Antnio, 2Nephrology Unit, Centro Hospitalar Do Porto, Porto, Portugal Introduction and Aims: Few studies have shown a significant effect of donor gender in kidney transplants (KT) survival. Otherwise, the effect of donor age is well established. The aim of our study was to analyze the effect of donor gender in allograft and patient survival, particularly on the age- marginal donor pool. Methods: We analyzed a total of 1402 recipients from our deceased donor KT recipients database. After exclusion of those with allograft failure or patient death <3 months after KT and recipients of a non-first KT, data from 1195 KT recipients was studied. All analyses were performed separately according to recipients gender. The effect of donor gender in allograft and patient survival was evaluated: first, in all patients studied; second, within two different groups defined according to their donors age [marginal donor if =55 years (n=157) and standard donor if < 55 years (n=932)]. Kaplan-Meier analysis was performed to compare censored graft survival and patient survival according to donor gender. In KT recipients of age-marginal donors, multivariate Cox regression analysis was done to identify significant predictors of censored graft survival; variables included in the model: recipient age, donor age, number of HLA mismatches (0-3 vs 4-6), PRA level (<30% vs >30%), previous transfusions, use of antithymocyte antibody for induction, delayed graft function, acute rejection episode and donor gender. Results: In the overall recipients, no differences were found in censored graft and patient survival according to recipient and donor gender (Graph 1 and 2). However, in KT recipients with age- marginal donors, the censored graft survival of a male recipient that received a KT from a female donor, was significantly less than a KT from a male donor, in the overall follow-up (P=0.005, Graph 3); in female recipients no significant differences were found of whether the donor male or female (Graph 4). Censored graft survival rates in male KT recipients were, at 5 and 10 yr, 86% and 76% with age-marginal male donors, and 76% and 27% with age- marginal female donors, respectively. Censored graft survival rates in female KT recipients were, at 5 and 10 yr, 86% and 65% with age-marginal male donors, and 76% and 51% with age-marginal female donors, respectively. No difference in patient survival was found in male (P=0.614) or female (P=0.235) KT recipients of age-marginal donors according to donor gender. In male KT recipients of age-marginal donors, multivariate regression Cox identified acute rejection episodes (HR: 2.53; P= 0.033) and donor gender (female vs male donors, HR: 3.33; P=0.009) as independent predictors of worse censored graft survival; none of the variables tested was a significant predictor of graft survival in female KT recipients of age- marginal donors. Conclusions: Our results showed no significant role of donor gender in kidney graft and patient survival. Nevertheless, when analyzing the age-marginal donor pool, there was a significant worse censored graft survival when a male recipient was engrafted with a kidney of a female donor. Further studies are needed to corroborate these observations. SUBCLINICAL REJECTION ADVERSELY AFFECTS KIDNEY GRAFT SURVIVAL AND FUNCTION Introduction and Aims: The value of identifying and treating subclinical rejection diagnosed on protocol kidney biopsy with respect to graft survival and function is uncertain. We retrospectively reviewed results of 280 consecutive kidney transplants treated with rapid steroid taper and followed with protocol kidney biopsies to determine the impact of subclinical rejection on graft survival and function. Methods: Data was retrospectively collected on 280 primary kidney transplant recipients from Jan 2005 to Dec 2009 (132 DBD, 40 DCD, 10 ECD and 98 LD). Patients were treated with rabbit anti- thymocyte globulin induction (6 mg/kg total dose) with rapid steroid taper (stopped after 5 days) and maintenance tacrolimus and mycophenolate mofetil. Protocol kidney biopsies were obtained at 1, 4, 12 and 24 months. Kidney biopsies for cause were conducted for unexplained elevated creatinine, decreased measured GFR or new proteinuria. Biopsies were interpreted by renal pathologists and graded for rejection per Banff criteria. All rejections were treated and repeat kidney biopsies were obtained 1-8 weeks later. Treatment options TRANSURETHRAL RESECTION OF THE PROSTATE FOR BLADDER OUTLET OBSTRUCTION DUE TO BENIGN PROSTATIC HYPERPLASIA IN KIDNEY TRANSPLANT RECIPIENTS: LONG-TERM UROLOGICAL AND RENAL FUNCTIONAL OUTCOMES IN A PROSPECTIVE STUDY Alessandro Volpe1, Marco Quaglia2, Alberto Menegotto1, Roberta Fenoglio1, Cristina Izzo1, Andrea Airoldi1, Carlo Terrone1and Piero Stratta1 1Amedeo Avogadro University, Maggiore Della Carit Hospital, Novara, Italy, 2Amedeo Avogadro University; Maggiore Della Carit Hospital, Novara Introduction and Aims: The results of TURP after renal transplant (RTx) have been described mainly in retrospective series and most studies on this topic focused only on urological outcomes. Aim of this prospective study was to confirm safety and efficacy of TURP in RTx recipients and to assess the impact of the procedure on long-term graft function. Methods: From January 1998 to July 2009, 696 patients underwent RTx at our centre. Overall, 103 (22.8%) males developed bladder outlet obstruction (BOO) symptoms after RTx and were treated with a-blockers and dutasteride for at least 6 months. Indications to TURP were: PVR >100 ml, Qmax = 10 ml/sec, increased or stable IPSS, urinary retention requiring indwelling urethral catheter or increasing serum creatinine levels likely due to BOO. Only patients (n=32) with a minimum follow up of 24 months were included in the analysis in order to evaluate long-term outcomes. Serum PSA, IPSS, Qmax at uroflowmetry, PVR, Hb, proteinuria and serum creatinine were determined before TURP and 1,6, 24 and 48 months after the procedure. Complications were also recorded. Change of the above mentioned variables over time was assessed in order to evaluate the efficacy of the procedure and its effects on long term graft function. Statistical analysis was performed with SPSS v.15. Results: Median age was 58 (40-76) years. Median operative time, catheterization time and hospital stay were 41 (30-60) minutes, 2 (2-4) days and 3 days (2-6), respectively. Seven (20%) complications were observed. No patient required a second TURP. The Table shows preoperative and post operative variables 1,6,24,48 months after TURP. Qmax, PVR and IPSS improved significantly postoperatively and the improvement was maintained at 48 months. Serum creatinine level decreased 1 and 6 months after TURP and did not increase significantly at long term follow-up. SAP653 Table 1. reoperative and post operative variables 1,6,24,48 months after TURP. Conclusions: TURP in RT recipients is a safe and effective procedure and allows an early significant improvement of graft function that remains stable up to 48 months. A CASE-CONTROL STUDY OF THE IMPACT OF TICLOPIDINE AND CLOPIDOGREL ON SURGICAL RISK IN RENAL TRANSPLANTATION Benahmed Ahmed1, Kianda Mireille1, Broeders Nilufer1, Massart Annick1, Wissing Karl Martin2, Hoang Anh-Dung1, Mikhalski Dimitri1, Madhoun Philippe1, Racap Judith1and Abramowicz Daniel1 1Hopital Erasme, 2Uz Brussel Introduction and Aims: Some kidney transplant candidates are treated with anti-platelet agents such as ticlopidine or clopidogrel for either the prevention of thrombosis of vascular access, or recurrent stroke, or ischemic heart disease. Some teams refuse to list these patients for fear of the risk of bleeding during transplant surgery, although this has not been demonstrated. We have studied this issue in the context of a retrospective case-control study. Methods: We retrospectively reviewed the records of 702 adult patients with a kidney transplant alone (excluding combined grafts) between 2000 and 2010. Nineteen for borderline rejection included either increasing maintenance immunosuppression and repeat kidney biopsy or methylprednisolone 5 mg/kg IV daily for 1-5 doses. Serum creatinine (Cr) and measured GFR (mGFR - by cold iothalamate, using 24 h ClCr if needed) were collected at 1, 4, 12 and 24 months. Graft survival was available up to 3 years post-transplant. Results: Rejection of any type was present on 81 protocol biopsies and 30 for cause biopsies. Overall graft survival was 88.9% at 3 years (yrs). Rejection occurred in 111 recipients graded as borderline -70, 1A -31, 1B -1, 2A -6 and AMR -3. Graft survival in those recipients without rejection was 90.8% at 3 yrs versus 85.9% for those with any type of rejection, p=0.008. Graft survival at 3 yrs for rejection type was: borderline-87%, 1A-87%, 2A-83% and AMR-67%, p=0.027 comparing no rejection to borderline and 1A. Interestingly, the graft survival at 3 years was 91% in those with rejection diagnosed by biopsy for cause, versus 83% in protocol biopsy rejection, p=0.005. Overall meanSD serum Cr and mGFR at 2 yrs was 1.40.76 mg/dl and 63.625.5 ml/min respectively. MeanSEM Cr and mGFR in those without rejection at 2 yrs was 1.30.06 mg/dl and 66.92.4 ml/min compared to 1.60.08 mg/dl and 58.53.2 ml/min in those with rejection, p<0.05. The meanSEM Cr and mGFR at 2 yrs for borderline rejection was 1.60.11 mg/dl and 58.53.9 ml/min, with 1A rejection 1.50.11 and 54.35.3 respectively. In those with rejection on protocol kidney biopsy, meanSEM Cr was 1.50.11 with mGFR 60.93.9 versus 1.90.16 and 53.46.0 in for cause biopsies, not statistically different. Conclusions: 1) Subclinical rejection is common on protocol biopsy. 2) Despite treatment, subclinical rejection detected on protocol biopsies was associated with decreased graft survival compared to those with rejection diagnosed by for cause biopsy. 3) Borderline rejection had negative impact on graft survival and mGFR at 2 yrs. 4) Borderline rejection has no better graft survival and function than 1A rejection. ii | Abstracts patients (2.7%) were taking Clopidogrel or ticlopidine when called in for transplant. The indications were: prevention of thrombosis of catheter or arterio-venous fistula (N = 4), cardiovascular disease (N = 10) or unknown cause (N = 5). We compared the risk of bleeding per and post-operatively, and the occurrence of cardiovascular complications, within 30 days after the kidney transplant between 19 cases and 39 controls selected randomly within the cohort. Results: A single case (5.3%) presented significant bleeding during surgery following an implantation biopsy. Within 24 h of transplantation, red blood cell transfusions were required in 3 cases (16%) vs. 1 control (2.6%) (P = 0.1). Seven cases (37%) received platelet transfusions, which was preventive in 3 patients (vs 0 controls, P <0.0001). No reoperation has been performed for bleeding. After the transplant, clopidogrel or ticlopidine were prescribed in only two patients: one for stented coronary heart disease and one for ileo-bi-femoral by-pass with stenting. The platelet count and hemoglobin were similar between cases and controls 30 days after renal transplantation. No cardiovascular event has occurred in cases or controls during the first month of transplantation. The rates of acute rejection were below 10% in the 2 groups. At 5 year, graft survival censored for death was 75% among cases and 78% in controls (P = 0.46). Patient survival was 100% in cases and 93% in controls (P = 0.32). Conclusions: Clopidogrel or ticlopidine is associated with a low risk of bleeding after kidney transplant surgery, and does not appear to be a contra-indication for transplantation. DETERMINANTS OF OUTCOME AFTER KTX IN ELDERLY PATIENTS Lutz Liefeldt1, Petra Glander1, Petra Glander1, Yang Lan1, Danilo Schmidt1, Christoph Heine1, Klemens Budde1and Hans-H. Neumayer1 1Charit, Nephrology, Berlin, Germany Introduction and Aims: The Eurotransplant Senior Program (ESP) has been implemented to utilize kidneys from elderly deceased donors for transplantation of age-matched recipients. In order to assess the suitability of kidney transplantation (KTX) in elderly patients and the ESP in particular we have analyzed the outcome of those KTX in a single center analysis between 1999 and 2011. Methods: All candidates for KTX beyond the 65th birthday were identified using a clinical database. Outcome-analysis included the outcome on the waiting list, KTX, graft- and patient-survival. Risk factors for worse outcome after KTX were identified using a multivariate model. For this purpose recipient-related factors (age at start of dialysis, age at transplantation, diabetes mellitus, coronary artery disease) and donor-related factors (age, gender, diabetes mellitus, hypertension) were analyzed. End of observation was 31st of December 2010 for waiting list and 31st of December 2011 for KTX and follow-up data. Results: 334 KTX-candidates were identified. In this cohort until 31st December 2011 219 patients received a kidney graft. Median follow-up of graft recipients was 32.8 (range: 0-145) months. Waiting list mortality (removals) was 32.1% for blood group O and 14.7% for patients with non-O. The rate of transplantation was dependant on the blood group of the recipient too and ranged from 46.7 (blood group O) to 78.7% (non-O). Significant risk factors in the multivariate model for death-censored graft-survival were diabetes mellitus of the recipient and donor-age. Significant risk factors for death were diabetes mellitus of the recipient and age at KTX. Uncensored graft survival was impaired by diabetes mellitus of the recipient, age at KTX 70+ and donor age 70+, whereas the latter did not reach statistical significance. Conclusions: From a statistical point of view elderly patients above 70 years and those with diabetes mellitus (irrespective of age) are high risk candidates for KTX. In our analysis donor-related parameters were not associated with a significant impairment of patient outcome. DETERMINANTS AND DURATION OF HOSPITALISATIONS AFTER KTX IN ELDERLY PATIENTS Danilo Schmidt1, Petra Glander1, Petra Glander1, Klemens Budde1, Hans-H. Neumayer1and Lutz Liefeldt1 1Charit, Nephrology, Berlin, Germany Introduction and Aims: Economical aspects of kidney transplantation (KTX) in elderly patients are not well established. This is the background for attempts to analyse costs of this treatment in our centre. Since hospitalisations are one important part of medical costs we have assessed the duration of hospitalisations of kidney graft recipients 65+ years of age. Methods: All candidates for kidney transplantation beyond the 65th birthday were identified using a clinical database. Outcome-analysis of graft recipients included all hospitalisations after kidney transplantation. Age at KTX, diabetes mellitus at time of transplantation, coronary artery disease at time of transplantation, the occurrence of delayed graft function (DGF), the occurrence of acute rejection (AR) and donor age were analyzed on their effect on the hospitalisation rate by chi-square tests. For this purpose the duration of hospitalisation for KTX was grouped into 3 groups: up to 14 days, 15 to 29 days, =30 days. For the overall hospitalisation rate patients were grouped into those with <10%, 10-20% and >20% hospitalisation per observation time. Results: From a cohort of 334 elderly KTX-candidates (65+ years) 219 patients received a kidney graft between 1999 and 2011. Median follow-up of graft recipients was 32.8 (range: 0-145) months. In 27.1% of recipients a prolonged initial hospitalisation for KTX (=30 days) was observed. Univariate analysis revealed DGF, AR and age of =70 years as significant factors ( p<0.05). 42.4% of our patients spent more than 10% of the total observation time in the hospital. Age, diabetes, DGF and AR were identified as significant risk factors for the overall hospitalisation rate. A prolonged initial hospitalisation after KTX has also a worse impact on the uncensored graft survival (1-y survival 77% vs. 95%, 5-y survival 45.5 vs. 73.6%). Conclusions: High risk elderly patients for long lasting and/or repeated hospitalisations after KTX are patients =70 years and those with diabetes mellitus. DGF and AR are other costly circumstances. From an economical point of view average costs of KTX should be compared to costs of maintenance dialysis in elderly patients. ADULT MALE DONOR INTO FEMALE RECIPIENT INCREASES THE RISK OF KIDNEY GRAFT LOSS ONLY IN YOUNG-FOR-YOUNG RENAL TRANSPLANT. Marco Quaglia1, Marco Quaglia2, Valentina Capone3, Cristina Izzo3, Alberto Menegotto4, Roberta Fenoglio5, Andrea Airoldi5and Piero Stratta6 1Amedeo Avogadro University, Novara, Italy., 2Amedeo Avogadro University; Maggiore Della Carit Hospital, Novara, 3Amedeo Avogadro University, 4Maggiore Della Carit Hospital, 5Maggiore Della Carit Hospital, Novara, Italy, 6Amedeo Avogadro University, "Maggiore Della Carit" Hospital, Novara, Italy. Introduction and Aims: It is known that the Eichwald-Silmser effect, first demonstrated in female mice rejecting skin graft from male donors of the same strain, depends on the loci controlling weak transplantation antigens on the Y chromosome, responsible for H-Y incompatibility in transplants across a sex difference. This has been shown to have an impact on female recipients of male bone marrow transplant in humans, whereas conflicting results were reported in renal transplant. Aim of this study was to assess the clinical impact of the Eichwald-Silmser effect on a population of renal transplanted patients. Methods: We performed a retrospective cohort study (1998-2010) at our Transplant Center and analysed correlations between donor-recipient sex match and graft survival. Results: Overall, 289 women (mean age 5012 years, min 20 max 75) received single allografts from deceased donors (mean age 5017 years, min 15 max 83), 134 of them from male donors and 135 from female donors. Graft loss was more common in female patients receiving kidneys from male donors than in the specular situation ( p<0.04) only in the subgroup of patients receiving donors aged below 50 years, but not in other subgroups with older age (Table I). Furthermore, women recipients from donors <50 years were significantly younger than those in other subgroups (42 10 years versus 51 10 years and 60 9 years, p<0.001). Therefore an SAP657 Table I. Impact of donor-recipient sex match on graft survival, according to different donor ages. increased risk of kidney graft loss was only demonstrated in young female recipients being transplanted from young male donors. Conclusions: Our results suggest that a role for H-Y minor histocompatibility in affecting human kidney transplantation has to be analysed specifically in the setting of young-for-young transplant, and that this age-related effect could explain previous conflicting results. TRANSPLANTATION RATES FOR LIVE-DONOR, BUT NOT DECEASED-DONOR KIDNEYS VARY WITH SOCIO-ECONOMIC STATUS IN AUSTRALIA Blair Grace1, Philip Clayton2, Alan Cass3and Stephen Mcdonald2 1Anzdata Registry, Adelaide, Australia, 2Australia and New Zealand Dialysis and Transplant Registry, 3The George Institute for Global Health Introduction and Aims: Socio-economic disadvantage has been linked to reduced access to kidney transplantation. This has not been examined in Australia, where renal replacement therapy (RRT) is predominantly provided through a universal-access public hospital system. Methods: Using national registry data (ANZDATA), we examined rates of primary kidney transplantation among non-Indigenous patients, aged 18 or over, who commenced chronic RRT in Australia 2000-2009. Patients residential postal codes were classified as either advantaged or disadvantaged, using national standard indices of area SES. Analyses used competing risk regression for access to transplantation for patients who did not receive pre- emptive transplants. Live-donor and deceased donor transplants were investigated separately. Results: Overall 19,042 patients commenced RRT, and 3% of these received pre-emptive transplants (all from living donors). Patients from advantaged areas were 50% more likely to receive pre- emptive transplantation (incidence rate ratio 1.50, 95% CI 1.19 1.89), and 39% more likely to receive a live-donor transplantation (sub-hazard ratio 1.39, 95% CI 1.21 1.59) if they did not receive a pre-emptive transplant. There was no association between SES and access to deceased-donor kidneys (sub-hazard ratio 0.95, 95% CI 0.86 1.06). Conclusions: Associations between SES and access to live-donor kidneys suggests that disadvantaged patients may face financial barriers, have reduced access to specialist care, as well as a higher prevalence of risk factors for potential donors. In contrast, SES was not associated with access to deceased-donor kidneys, suggesting equitable access to the transplant waiting list and organ allocation process. LONGITUDINAL OBSERVATION OF RENAL FUNCTIONS FOLLOWING LIVE KIDNEY TRANSPLANTATION: FEASIBILITY AND LIMITATION TO USE ELDERLY KIDNEY Takashi Yagisawa1, Takashi Yagisawa2, Masahiro Yashi1, Takaaki Kimura1, Akinori Nukui1, Takehito Fujiwara1, Yasunaru Sakuma1, Nobuo Ishikawa1, Toshihisa Iwabuchi1and Osamu Muraishi3 1Jichi Medical University Hospital, 2Jichi Medical University, 3St. Lukes International Hospital, Introduction and Aims: Recent outcome studies indicate that the overall survival and risk of end-stage renal disease in kidney transplant donors are similar to the general population. Although the long-term safety is justified, the outcome study focused on the elderly donors is lacking. This study was conducted to elucidate the residual renal function of the donors and the graft function of the recipients in the longitudinal follow-up following live kidney transplantation. Methods: One hundred and eight pairs of donor and recipient were eligible for the study, and 23 of the 108 (21.3 %) were donated from elderly donors over than 65 years old. Functional parameters were compared between younger and elderly donor groups, between recipients with and without diabetes, and their combination groups. The median follow-up period was 49.5 months, ranging from 13 to 105 months. Results: Perioperative characteristics, such as gender, side of donor kidney, body mass index, operative time, blood loss, and rate of complications, did not significantly differ between groups. More than half of the donors developed chronic kidney disease stage 3 immediately after kidney donation, and 70% of elderly donors displayed estimated glomerular filtration rate (eGFR) below 60ml/min/1.73m2 but without subsequent deterioration. Percent eGFR of its pre-donation value in the younger donors improved 10 to 20%, whereas the elderly donors remained unchanged until four years post-donation. The graft function of the recipients with diabetes did not show uniform results, and the combination of elderly donor and diabetic recipient showed deteriorated graft function in the three years post-transplantation: the average creatinine value over than 2.5mg/dl. Conclusions: The tolerable difference in recovery of renal function following kidney donation was observed between younger and elderly donors. Low GFR itself does not necessarily indicate a bad prognosis unless it is accompanied by risk factors represented by albuminuria and hypertension. Therefore, elderly donors need careful evaluation before kidney donation to confirm that they are competent as donors. The future evaluation based on a larger donor series may provide a conclusion for the continued use of kidneys from elderly donors, but the combination of elderly donor and diabetic recipient should be carefully managed. ROLE OF FGF23 IN KIDNEY TRANSPLANT: IS THERE ANY DIFFERENCE BETWEEN RECIPIENTS OF PREEMPTIVE TRANSPLANTS AND PATIENTS WHO HAD BEEN ON DIALYSIS? Vicente Torregrosa1, Xoana Barros1, M Jess Martinez de Osaba1, Raphael Paschoalin2and Josep Mara Campistol1 1Hospital Clinic, Barcelona, Spain, 2Hospital Clinic - Barcelona, Spain Introduction and Aims: FGF23 is a bone-derived hormone implicated in bone metabolism disorders of CKD, which levels increase 100 to 1000-fold times above normal range in dialysis patients. The objective of our study was to determine the behavior of FGF23 in transplanted kidney patients who had been on dialysis compared with CKD patients who underwent a preemptive transplant and the FGF23 influence over development of hypophosphatemia and vitamin D deficiency during the initial post-transplant period. Methods: Prospective study of longitudinal follow-up of 6 months in a single center. All kidney transplant (KT) patients between May 2010 and June 2011 were included. Patients with delayed graft function were excluded. We measured sCr, MDRD, sPO4, sCa, iPTH, 25(OH)D3, 1,25(OH)2D3 and FGF23 at baseline and day 15, 30, 90 and 180 after KT and calculated Fractional excretion of phosphate (FEPO4). FGF23 was measured by a 2nd generation ELISA (Inmunotopics, San Clemente, USA). Any patient received treatment with phosphate binders, calcimimetics, bisphosphonates or vitamin D during the follow-up. Statistical analysis was performed with SPSS 15.0. Results: Patients who underwent a preemptive KT were younger (39,958,6 vs 53,3 12; p<0.001) and had lower levels of FGF23 at baseline than patients who had been on dialysis before KT (843,4840,1 vs 3099,23296,2; P=0.001). Other clinical and biochemical parameters didnt show significant differences. FGF23 decreased significantly during the 1st month after transplant in both groups. Preemptive recipients had lower levels of FGF23, higher of sPO4 (3.130.72 vs 2.54 0.85 mg/dl; P=0.028) and lower FEPO4 (249% vs 4016%; P=0.000) at 1st month, with similar levels afterwards. PTH levels were lower during all the follow-up (PTH at 6th month: 177.994.1 vs 112.951.1 pg/ml; P=0.01). At 1st month, patients who had been on dialysis reached sPO4<2.5 mg/dl in more % than patients who underwent a preemptive KT. In contrast, more % of preemptive recipients reached FGF23 < 120 mg/dl than patients on dialysis (Table 1). In both groups, 1,25(OH)2D3 increased significantly from 18,47,2 at baseline to 32.413 pg/ml at 1st month (P=0.000) and progressively until 6th month (41.120.1 pg/ml). sCr also improved during the 1st month (1.40.4 mg/dl) and remained stable until 6th month (1.30.3 mg/dl), similarly in both groups. Regression analysis showed that FGF23 at baseline was the main predictor of sPO4 and 1,25(OH)2D3 levels at 1st month and PTH at 6th month was the main predictor of sPO4 at the same month. Conclusions: Patients who received a preemptive transplant had lower levels of FGF23 and less risk of development of hypophosphatemia during the initial post-transplant period. FGF23 at baseline was the main predictor of levels of sPO4 and 1,25(OH)2D3 during early post-transplant. SAP660 Table 1. Differences in evolution of FGF23 and sPO4 between preemptive KT and patients who had been on dialysis before KT. KIDNEY TRANSPLANTATION AND ITS IMPACT ON FEMALE SEXUAL FUNCTION. Rashad Hassan1, Ahmed El-Hefnawy2, Shady Soliman2and Ahmed Shokeir2 1Urology and Nephrology Center, Mansoura, Egypt, 2Urology & Nephrology Center, Mansoura, Egypt Introduction and Aims: The impact of renal transplantation on female sexual function is still controversial. Although literature showed better sexual function in females after transplantation compared with patients with end stage kidney disease and those on hemodialysis, data comparing female sexual function after kidney transplantation with data from normal population is still lacking. Therefore, this study was conducted to assess sexual outcome in females after kidney transplantation in comparison with normal females. Methods: Sixty-six women who underwent renal transplant were asked to fulfill Arabic version of sexual questionnaire utilizing Female Sexual Function Index (FSFI). Six domains were assessed including lubrication, pain, arousal, desire, orgasm and satisfaction. Inclusion criteria included sexually active females, stable marital status, normal serum creatinine, and renal transplantation = 6 months. Patients with associated co-morbidities that may impair sexual activity were excluded. FSFI was compared with 65 normal non-transplant females of the same age group. A power calculation suggested 64 sample size in each group to get 80% power. Independent student t-test was utilized to compare means with P value < 0.05 considered as significant. Results: The mean age SD of transplanted women and non-transplanted women was 30.76 vs 30.16 years respectively, P =0.75). No difference was found between both groups in total score and every domain except for lubrication in which the difference approaching statistical significance (P=0.055) in favor of non-transplanted women. Conclusions: Successful renal transplant has positive impact on female sexual function with results comparable with normal population. DETERMINANTS OF CAROTID ATHEROSCLEROSIS CHANGES IN RENAL TRANSPLANT PATIENTS:THE ROLE OF ASYMMETRIC DIMETHYLARGININE Introduction and Aims: Atherosclerotic cardiovascular diseases are among the major causes for mortality in renal transplant patients. Carotid intima media thickness (CA-IMT) measurement is a validated and reliable method for diagnosis of atherosclerosis. In addition, plasma Asymmetric dimethylarginine (ADMA) concentrations are higher in patients with clinically manifest atherosclerosis than in those without atherosclerosis In this study, we aimed to investigate the role of ADMA, oxidized LDL (oxLDL) and anti-oxidized LDL (anti-oxLDL) on progression of atherosclerosis in renal transplant patients. Methods: 180 renal transplant patients being followed at our renal transplant unit were studied. Baseline and mean 25th month CA-IMT were determined by B-mode Doppler ultrasonography. ADMA, oxLDL and anti-oxLDL were measured by commercial ELISA. Results: Mean age was 41 9 and time after transplantation 60 44 months. Baseline CA-IMT was 0.61 0.15 mm. Age, cardiovascular disease and diabetes history, proteinuria and trygliserid levels were positively and HDL and albumin negatively correlated with baseline CA-IMT. 92 patients underwent CA-IMT measurement at mean 25th month. Mean 25th month CA-IMT was 0.68 0.18 mm. Second CA-IMT measurement was positively correlated with age, donor age, cardiovascular disease and diabetes history, proteinuria, HCV positivity, HbA1c and baseline ADMA levels negatively with albumin levels. ADMA levels, HCV positivity and albumin levels were predictors for CA-IMT progression in the multivariate analysis including age, donor age, ADMA, HCV positivity, albumin, glucose and proteinuria. oxLDL and anti- oxLDL were not associated with CA-IMT progression. Conclusions: HCV positivity, albumin and ADMA levels were predictor for progression of atherosclerosis in renal transplant patients. THE TREATMENT OF ACUTE HUMORAL REJECTION (AHR): A TASK STILL FAR AT HAND Silvio Sandrini1, Gisella Setti2, Francesca Valerio3, Stefano Possenti4 and Irene Torrisi1 1A.O. Spedali Civili, Brescia, Italy, 2A.O. Spedali Civili, Brescia. Italy, 3A.O. Spedali Civili , Brescia Italy, 4A.O Spedali Civili, Brescia, Italy Introduction and Aims: The treatment of AHR after renal transplantation (Tx) is still an open issue. This study aimed at evaluating by control renal biopsies (CB), the efficacy of therapy in reversing the main morphological markers of AHR, e.i: transplant glomerulitis, peritubular capillaritis and C4d+ Methods: Between February 2008 and October 2011, 26 patients ( pts) underwent 38 anti AHR treatments. Each treatment was made after biopsy-proven diagnosis and followed by CB, 3.62.3 months (mo) later. The 1st biopsies (B0) were carried out 12.810.6 mo after Tx; the interval between B0 and the last CB was 6.45.9 mo. (median 4.5 mo). The diagnosis of AHR was based on Banff 1997-2005 classification. At B0, 47% of pts were on steroids, 47% either on CsA or Tacrolimus; 58% on MMF and 18% on mTORi. The AHR therapy included different treatment modalities: Plasmapheresis (n:64; in all pts), high-dose IVIG (1-2 gr/Kg; in 21 pts), Rituximab (Rtx:375 mg/m2 in single dose; in 15 pts); Bortezomib (1.3 mg/m2 x 2-7 doses; in 9 pts), steroids (1080 745 mg; in 19 pts). The last biopsy was to be considered for the assessment of any morphological improvements after therapy. Pts follow-up was 31 16 months. Results: Serum creatinine (sCr; mg/dL) was 1.50.5 six months after tx, 3.02.7 at B0, 2.31.7 at CB (B0 vs CB:p<0.05) and 1.90.8 at the end of study (1812 mo after B0) (end of study vs B0, p<0.02). At B0, Donor Specific Antibodies (DSA) were positive in 21 patients (75%) and associated with non-DSA (NDSA) in 14 cases (66%). 5 patients were positive only for NDSA; 2 patients negative for both. Biopsy features are summarised hereafter. Three grafts (12%) were lost: one for urologic complication, two for rejection. At 30 months, pts and graft survival rate were 100% and 89%. Conclusions: While renal function improved, all therapies failed in reversing the morphological lesions referred to AHR. Therefore, in these patients, progression to SAP663 Table 1 1st biopsy (B0) C4d inter, infilt, tubulitis glomerulitis arteritis capillaritis glomerulopathy chronic humoral rejection likely occurs more frequently than anticipated by clinical data. Effective therapy for AHR is still far from having been established. BK VIRUS NEPHROPATHY TREATED WITH MTOR INHIBITORS-BASED IMMUNOSUPPRESSION Natalia Polanco1, Laura Garcia-Puente1, Esther Gonzalez Monte1, Enrique Morales1, Eduardo Gutierrez1, Ignacio Bengoa1, Ana Hernandez1, Jorge Caballero1, Jose Maria Morales1and Amado Andres1 112 de Octubre University Hospital Introduction and Aims: The incidence of renal allograft dysfunction due to BK virus nephropathy (BKVN) has increased over the last decade. Previous studies have analysed the influence of different immunosuppressive strategies in this pathology. Over the last few years mTOR-inhibitors (mTOR-i) have gained strength as a plausible treatment option, because of their demonstrated in-vitro antiviral effectiveness and the restored T-cell mediated immune response in renal transplant patients with anticalcineurinic-free therapy. Based on this data, an anticalcineurinic-free regime based on mTOR-i conversion protocol was initiated on 2007 in our medical center, in those patients with BKVN and without other medical contraindication. To evaluate renal allograft survival and the evolution of BK viral load in those patients with a diagnosed BKVN after conversion to an mTOR-i based immunosuppressive therapy. Methods: Retrospective study of a series of cases from a single medical center. Diagnostic criteria for BKVN: biopsy proven infection and/or positive serum viral load>10000 copies demonstrated by PCR on at least two consecutive measurements. Of the 796 renal transplants done in our center between 2007 and 2011, 18 cases of BKN were diagnosed (2.3 % incidence). Results: Of the 18 diagnosed cases, 9 were converted to an mTor-inhbitor based regime (everolimus), being the rest excluded for proteinuria levels >0.8 gr per day. Patients mean age (4 male/5 female) at diagnosis was 40.516.7 years. Follow up time was 2813.9 months. Six of them received their first renal allograft and 3 of them their second. Only 1 patient was at high immunologic risk (PRA>50%) but 8 of them received induction therapy (3 thymoglobulin and 5 basiliximab). Maintenance immunosuppressive therapy was the same in all patients: tacrolimus, mycophenolate mofetil and corticosteroids. Post-transplant renal function in our recipients was excellent with a mean serum creatinine (sCr) level of 1.20.19 mg/dl. Evolution over time is shown on figure number 1. The time between the transplant and the diagnosis of BKVN was of 13.6 months (4-45). At diagnosis the pathology report showed both findings of BKVN and acute rejection in 4 patients. Treatment with mycophenolate was stopped in all patients and conversion from tacrolimus to SAP664 Figure 1.: Renal function over follow up. everolimus performed. Renal function improved in all of our patients and the viral load became negative in 6 of them and diminished over 80% in the other two. None of them developed an acute rejection after mTOR-I treatment was initiated. At the end of the follow-up period all renal allografts were functioning and all the cases presented a viral load under 10000 BK copies. Conclusions: BKVN treatment is still controversial though the benefit of lowering immunossuppression is well established. Even though our results are limited by the reduced number of patients in our study we can infer that treatment with mTOR-i has some additional benefit and in selected patients could preserve renal allograft function and lower BK viral load. PROSPECTIVE STUDY ON THE CLINICAL AND PROGNOSTIC SIGNIFICANCE OF POLYOMAVIRUS JC INFECTION IN KIDNEY TRANSPLANT Introduction and Aims: The introduction of a more effective post-transplant immunosuppressive therapy on one hand allowed a drastic reduction of acute rejection incidence, on the other hand led to an increased susceptibility to infective complications, together with the occurrence of new and still little known infections such as those from Polyomavirus. Polyomavirus JC is an emerging infectious agent in renal transplantation. Currently there are few available data investigating the correlation of this infection with renal function and transplant outcome. The purpose of this study was to evaluate the incidence of Polyomavirus JC after renal transplantation and its impact on graft function. Methods: Eighty-three renal transplant recipients were evaluated at 3, 6, 12 and 24 months post- transplant for serum creatinine, GFR (MDRD), blood drug concentrations, search of decoy cells, JC viremia and viruria. Maintenance immunosuppressive therapy was based on steroids, tacrolimus (range 7-9 ng/ml) and mycophenolate mofetil (1g/day) in 48 patients (57.8%). In the remaining 35 patients (42.2%), therapy included steroids, cyclosporine (range 500-700 ng/ml) and mycophenolate mofetil (2 g/day). Graft function was then compared between patients who developed viruria and those who did not. Results: A total of 83 patients and 1992 urine and blood samples were evaluated during the study. Incidence and prevalence of JC viruria and viremia were 26.5 % and 6%. The maximum incidence was found after 12 months. The highest average urinary viral load was detected at month 6 and corresponded approximately to 1.3*108 copies/ml, although it remained elevated in all subsequent determinations. The mean serum viral load was observed at month 24 (3193 copies/ml). No significant differences were found between the two groups ( presence vs absence of viruria), except for recipient age, which was statistically higher in patients who developed the infection. When we compared serum creatinine in the two groups of patients, we found significantly higher values at month 24 in the patients who developed viruria ( p=0.03). Conclusions: JC Polyomavirus infection is common after renal transplantation. The infection appears to persist over time and not to be limited to the first year post-transplant. The onset of infection is correlated with a worse renal function at two years post-transplant. These findings suggest that a screening for this infection searching the JC viruria in the first two years post-transplant seems to be an appropriate approach. Further studies are needed to verify the progression of the infection and the incidence of nephropathy performing renal biopsies. EFFICACY AND APPROPRIATENESS OF HISTOLOGICAL SCORE IN PREDICTION OF THE 3-YEAR OUTCOME OF KIDNEY TRANSPLANTATION Introduction and Aims: The number of patients on the waiting list for kidney transplant increases every year. In an effort to narrow the gap between the demand and supply of organs from deceased donors, various strategies have been proposed aimed to expand the existing donor selection criteria and hence those for organ allocation. One of these approaches is the use of expanded criteria donors (ECD), namely elderly donors with a high number of clinical risk factors. There are still no well-established shared standard criteria of marginality (systems based on histological, clinical, or mixed evaluation). The Karpinski's scoring system, based on histological evaluation, considers the degree of microscopic damage observed in glomeruli, tubuli, interstitial tissue, vessels, following a previously proposed scheme. The main purpose of this study was to assess the reliability of Karpinski's histological score in predicting the course of graft function during the 3-year period after renal transplantation. Methods: One hundred fifty-six marginal donors were evaluated using Karpinski's score and kidneys were allocated following the criteria proposed by Remuzzi et al (score from 0 to 4 single transplant, score from 5 to 6 double transplant, score 7 discard). Serum creatinine (mg/dL) and its conversion into estimated-GFR (eGFR) were recorded at 1, 2 and 3 years post- transplant using the Modification of Diet in Renal Disease (MDRD) equation. The follow-up time after transplantation was 3 years. Results: A total of 156 marginal donor were evaluated. Twenty-two were discarded owing to a Karpinski's score > 7. Karpinski's scores were: 0-1 (n=10), 2 (n=31), 3 (n=47), 4 (n= 25), score >5 (dual transplant, n=21). Repeated measures ANOVA to analyze the effect of the Karpinski's scores (0-1, 2, 3, 4) and double transplant confirmed that creatinine level over time is statistically associated with Karpinskis score (F=5.76, p<0.001). Patient and graft survival did not differ significantly between the score groups. Conclusions: The Karpinskis score provides a substantially accurate prediction of the course of renal function within three years after kidney transplant. The functional trend over time was statistically correlated with patients initial histological score. SHORT-TERM EFFECTS OF AN -3 (N-3) RICH DIET ON METABOLIC AND INFLAMMATORY MARKERS IN RENAL TRANSPLANT RECIPIENTS Introduction and Aims: Elevated levels of C-reactive protein (CRP) and interleukin 6 (IL-6) are associated with a worse graft outcome in kidney transplant recipients. Several clinical studies suggested that dietary manipulation of essential fatty acids (EFA) may decrease the production of inflammatory mediators. Aim of the study was to evaluate the effects of a n-3 rich diet on some metabolic and inflammatory markers in kidney transplanted patients. Methods: This study was conducted on 20 clinically stable transplanted patients (group DIET), in periodic follow-up at our clinic. In each patient we prescribed a diet, naturally rich in n-3 (with no exogenous source). The diet did not change caloric and proteic intake in any patient, but suggested the regular consumption of foods naturally rich in n-3 as fish (salmon, sardines, herring and blue fish) and fruits and vegetables (oranges, strawberries, bananas, zucchini, artichokes, mushrooms, cauliflower, pumpkin). The intake of n-6, conversely, was reduced by limiting eggs, meat, whole grains and cereals. The control group (CON) consisted of 19 transplanted patients who maintained their usual diet. All the patients were followed up for 6 months. Results: After 3 months the Group DIET showed a reduction versus baseline of sodium intake ( p<0.002), serum glucose ( p<0.03), cholesterol and triglyceride levels (both p<0.0004), without significant modifications in body weight and serum albumin. Microalbuminuria, factored by eGFR, was also significantly reduced in Group DIET ( p<0.03 vs basal). These changes were associated with a significant reduction of CRP ( p<0.007 vs basal), IL-6 ( p<0.01), Ferritin ( p<0.001) and Fibrinogen ( p<0.001). These positive effects persisted after 6 months, despite a slightly reduced compliance to the diet, as assessed by questionnaires. In CON group, ii | Abstracts all the metabolic, clinical and inflammatory parameters were unchanged. These changes occurred with no significant modification in body composition, assessed by bioelectrical impedance in both Groups. The evaluation of dietary intakes showed a drastic increase of n-3 EFA Intake (+103%, P<0.0001), that resulted in a significant reduction in the n-6/n-3 EFA ratio (-39%, P<0.0001). Conclusions: In conclusion, an n-3 rich diet leads to a significant improvement of the microinflammation typically associated with organ transplantation, with beneficial effects on metabolism and microalbuminuria. PRE TRANSPLANT BIOPSY AND 1 YEAR GRAFT OUTCOMES IN MARGINAL KIDNEY. A MONOCENTRIC STUDY Paolo Carta1, Maria Zanazzi2, Lorenzo DI Maria1, Leonardo Caroti2, Anduela Miejshtri1, Aris Tsalouchos1and Elisabetta Bertoni1 1Nephrology Unit, Careggi University Hospital, 2Nephrology Unit, Careggi University Hospital, Florence, Italy Introduction and Aims: Renal biopsy is commonly used in assessing a potential non-living donor to decide if marginal kidneys must be allocated as single or double transplant. However it is not clear whether the histological evaluation is really predictive of the outcome or remains just a pathologic parameter. In our allocation system kidneys with a Karpinskis histological score of 4 or 5 can be allocated as single transplant if donor renal function is optimal and no other risk factor is present. The aim of this study is to compare the outcomes among patients who received a single kidney graft from a marginal donor with optimal renal function but with different histological scores Methods: In this retrospective observational study we evaluated 77 patients that received a single renal transplantation from a non-living donor older than 65 with a histological evaluation at the time of transplantation. Patients were divided in 2 groups according to their Karpinskis histological score. Group A included 40 patients who received a transplant from a Karpinskis histological score <4 while group B 37 patients who received a transplant from a donor with a score of 4 or 5. We analyzed the difference between the 2 groups in terms of recipient serum creatinine, creatinine clearance, the incidence of delayed graft function and the rate of graft loss after one year of transplantation. Statistical analysis included ? square statistical tests, Student's t test when appropriate. Results: Donors characteristics between the two groups were similar with respect to the following parameters of the donor: creatinine (0.86 0.26 mg / dl vs. 0.81 0.20 mg/dl , creatinine clearance 73.5 27, 5 ml / min vs 85.2 24.68 ml/min p: 0.052). Only donor age was slightly lower in group B 72.48 years 4.11 vs. 70.54 3.4. ( p: 0.02) There was no statistically significant difference between the two groups after one year of transplantation with respect to the following recipient parameters: creatinine 1.71 0.54 mg / dl vs. 1.70 0.46 mg/dl; creatinine clearance 45.87 11.59 ml / min vs 49.57 16.03 ml/min, the onset delayed graft function and rates of graft loss (9 in group A vs 5 in group B) Conclusions: In our small monocentric experience the difference in pre-transplant histological score of kidneys with very good renal function from marginal non-living donor did not have a significative influence on outcome after one year of kidney transplantation. DETERMINANTS OF LEFT VENTRICULAR MASS INDEX IN RENAL ALLOGRAFT RECIPIENTS Introduction and Aims: Left ventricular hypertrophy (LVH) is frequently observed in patients with end stage renal disease and renal allograft recipients, and is an independent and strong predictor of morbidity and mortality. Renal resistive index (RRI) is an important determinator of graft function in transplant recipients. In essential hypertension increased RRI is associated to reduction of renal function and tubulo-interstisial damage. In this present study, we investigated the effects of graft function and ambulatory blood pressure monitoring on left ventricular mass index (LVMI) in renal transplant recipients. Methods: Patient charts of 79 (25 female, age 40.5 10.8 years) renal transplant recipients with echocardiography and ambulatory blood pressure monitoring at the end of posttransplant 1 year were included in the study. Laboratory tests including creatinine, glomerular filtration rate and CRP level were collected. LVMI was calculated by Devereux formula with echocardiographic findings. Results: LVMI was positively correlated with mean nighttime systolic blood pressure (r:0.312, p:0.007), mean nighttime diastolic blood pressure (r:0.427, p:0.005), mean systolic blood pressure (r:0.512, p:0.0001), mean diastolic blood pressure (r:0.373, p:0.014), renal resistive index (RRI) (r:0.312, p:0.007) and age (r:0.371, p:0.001). Multiple logistic regression analysis revealed that mean and maximum nighttime systolic blood pressure and renal resistive index were independent risk factors for LVMI ( p:0.001, 0.035 and 0.05 respectively). RRI was positively correlated with older age (r:0.342, p:0.003). Conclusions: High RRI is one of the main indicators of cardiovascular disease in renal transplant patients. Additionally, older age, high blood pressure and non-dipper pattern are important associates of left ventricular hypertrophy. MEDICAL FACTORS ASSOCIATED TO THE REGISTRATION ON THE KIDNEY WAITING LIST IN FRANCE Christian Jacquelinet1and Sahar Bayat2 1Agene de la Biomedecine, 2Ehesp Introduction and Aims: In a context of major differences between dialysis and transplantation in terms of quality of life and survival, the selection of ESRD patients for their registration on waiting list and for renal transplantation remains a ethical issue, increasing with the scarcity of organs available for transplantation. Efforts realized to improve equity and efficacy of organ allocation can be jeopardized by registration practices. The main objective of this study is to identify the medical and non medical factors related to the registration on the kidney waiting list in France, in a cohort of ESRD patients starting a renal replacement therapy. Methods: Population enrolled in the study: (i) 8549 incident cases of chronic renal failure who started dialysis from January 1 2006 to December 31, 2008, (ii) aged 18-80 years, (iii) residing in 12 out of 24 French regions contributing to the REIN registry from 2006 (Auvergne, Normandy, Burgundy, Brittany, Champagne-Ardenne Corsica Upper Normandy, Languedoc Roussillon, Limousin, Midi-Pyrenees, PACA and Rhone-Alpes). Patient outcomes (death, registration) were checked to December 31, 2010, providing a 2 years minimal follow-up. The registration was the event of interest and the death prior to registration was a competing event. Data were analysed according to the Fine & Gray model for competing risks. Determinants of registration were the socio-demographic characteristics of patients, their comorbidities at the start of RRT and the context of RRT start (emergency, catheter). Results: Mean age was 64 13 years (median 68 yrs). The 2-yrs overall cumulative incidence was 24.6% (CI95 = 23.7 to 25.5%) for registration on the waiting list and 22.2% (CI95 = 21.3 to 23.0) for deaths prior to registration. Multivariate analysis of each risk event (registration, death) showed that a younger age, the absence of emergency or catheter at initiation of RRT, the absence of HIV infection, cancer, cirrhosis, respiratory insufficiency, co-morbid cardiovascular, behavioural disorders or diabetes were independent factors significantly associated with both an increased probability of registration and a lower risk of death before registration; the same for the type of kidney disease: polycystic kidney disease or glomerulo- nephritis. All of these medical factors taken into account, we observed that: (i) the male was an independent factor associated with both an increased probability of registration and an increased risk of death, (ii) the persistence of a professional activity was an independent factor associated with both a greater probability of being enrolled and lower risk of death (iii) PD, out-center HD and limited care centres (LCU) patients had an increased probability of registration than in-center HD patients; and (iv) the existence of significant regional variations. Conclusions: These results showed that the registration on the waiting list in France is mainly related to the existence of medical factors: age, comorbidities and primary renal disease. These factors considered, we observe the influence of non-medical determinants that also affect registration. The question remains open whether age or diabetes, at equal comorbidities, should have as much impact on the process of registration on the waiting list, including the decision to refer or not the patient to a transplant centre for pre-transplant evaluation. LYMPHOCYTE RECONSTITUTION AFTER INDUCTION WITH THYMOGLOBULIN IN RENAL TRANSPLANTATION: IMPACT OF THE MODE OF ADMINISTRATION (DAILY VS INTERMITTENT TREATMENT BASED ON T LYMPHOCYTE MONITORING) Vincent Pernin1, Pierre Portales2, Ilan Szwarc1, Valerie Garrigue1, Fernando Vetromile1, Sylvie Delmas1, Jean Francois Eliaou1 and Georges Mourad1 1Chu Lapeyronie Montpellier, 2Chu St Eloi Montpellier Introduction and Aims: Antithymocyte induction after renal transplantation induces a profound and sometimes prolonged lymphopenia, associated with an increased incidence of opportunistic infections or cancers, as well as excess mortality. The determinants of lymphocyte reconstitution are not well known. The aim of our study was to analyze whether mode of Thymoglobulin administration influences lymphocyte reconstitution. Methods: T cell reconstitution (LyT) during the first year was studied in 31 patients, randomized 1:1, according to two different modalities of administration of Thymoglobulin: "daily treatment" (1mg/kg/j from day 0 to day 4) or "monitored treatment " (1mg/kg on days 0 and 1, and then only if the number of circulating Lyt-CD3+ was above 10 cells/mm3, until day 10). The LyT subpopulations were analyzed by flow cytometry at day 0, M1, M2, M3, M6 and M12. Results: In the "monitored treatment" group, despite a higher total dose of Thymoglobulin (6.0 +/- 1.5mg/kg vs 4.6 +/- 1.0mg/kg), lymphocyte reconstitution was significantly higher, especially for LyT-CD8+. At M12, total number of lymphocytes was 1063 +/- 673/mm3 vs 626 +/- 333/mm3 ( p = 0.13), the number of LyT-CD3+ 796 +/- 565/mm3 vs 356 +/- 186/mm3 ( p = 0.009), the number of LyT-CD4+ 183 +/- 93/mm3 vs 107 +/- 69/mm3 ( p=0,012) and the number of LyT-CD8+ 613 +/- 250/mm3 vs 472 +/- 118/mm3 ( p = 0.04) in the "monitored treatment" vs "daily treatment" groups respectively. The number of regulatory T cells with CD4+ CD25+ Foxp3+ CD127Low phenotype and the incidence of opportunistic infections or acute rejections were not significantly different between the two groups. Conclusions: In our study, the modality of administration of Thymoglobulin affects lymphocyte reconstitution after renal transplantation. Treatment monitoring appears to decrease the risk of prolonged lymphopenia. POSTTRANSPLANT HYPOPHOSPHATEMIA IS FREQUENT AND ASSOCIATED WITH BETTER OUTCOMES Lu Huber1, Lu Huber2, Torsten Slowinski1, Marcel Naik1, Petra Glander1, Lutz Liefeldt1, Danilo Schmidt1, Hans-Hellmut Neumayer1and Klemens Budde1 1Charit - Universittsmedizin Berlin, 2Charit - Universittsmedizin Berlin, Germany Introduction and Aims: Despite growing knowledge of its pathophysiological mechanism, the clinical course and its effect on patient and graft outcomes of posttransplant hypophosphatemia remains a neglected theme. We investigated prevalence, associated factors and outcomes of hypophosphatemia in our centre. Methods: Serum calcium, phosphate, PTH, magnesium and Vitamin D levels were followed on 838 kidney only adult transplantations (Tx) performed during 1.1.2000 to 1.1.2011. Overall mortality and graft failure rate of patients ( pts) with serum phosphate low (<0.8), normal (0.8- 1.5) or high (>1.5 mmol/L) at 6 month (m) post Tx were estimated with Kaplan-Meier survival analysis. Results: Incidence of hypophosphatemia was 36% at 6m and 30.7% at 1 year(y) post Tx. This frequency (25 to 30%) persisted up to 10y, significantly higher than that of the CKD population (16%, P<0.001). Only 17 pts (2.2%) had high phosphate at 6m, with significantly worse patient (80.2%, P=0.003) and graft survival (76.6%, P<0.001) at 8y. Compared with normal phosphate group, pts with low 6m phosphate were slightly younger at time of transplantation (4814 vs. 5015y, P=0.04), had more male pts (68% vs. 57.4%, p=0.003) and had younger donor age (50.814.9 vs. 53.7 15y, P=0.01). No difference was observed in pre-Tx calcium, phosphate, calcium x phosphorus product, magnesium, PTH, or the percentage of living donation. From 6m to 5y post Tx, hypophosphatemia pts had higher eGFR (6m: 5419.5 vs. 44.6 20.8, 5y: 51.720.9 vs. 43.417.5 ml/min, P<0.001 for both), higher serum calcium (both albumin and protein corrected), lower phosphate and calcium x phosphorus product. There was no difference in PTH or calcidiol at any time point, whereas calcitriol levels were significantly higher in low phosphate group at 6m, 1y and 3y. 252 pts (32.5%) received phosphorus supplement, which significantly increased phosphate level. 236 (93.7%) had it stopped in less than 1y. Hypophosphatemia pts had significantly longer survival time (10.720.22, 95%CI 10.2911.16y, P=0.017), time to non death-censored graft failure (11.080.17, 95%CI 10.7311.42y, P=0.004) and time to death-censored graft loss (10.270.25, 95%CI 9.77-10.76y, P<0.001). Their 8y patient survival was 84.7% and graft survival was 91.5%, compared to pts with normal phosphate, 80.5% and 81.5%, respectively. Pts who received phosphate supplement had better 8y graft survival (94.1%, P=0.001) than those who were not (78%), but pts survival were the same. Multivariate analysis demonstrated that 6m eGFR was a strong predictor for both pts survival and graft survival. Conclusions: There is high frequency of hypophosphatemia after renal transplantation, which persists up to 10 years. Patients with hypophosphatemia have better GFR and a distinctive bone-mineral metabolic profile along with higher patient and graft survival, reflecting a better renal function. HYPERPARATHYROIDISM IN KIDNEY TRANSPLANT PATIENTS DISCONTINUING CINACALCET AFTER LONG-TERM HEMODIALYSIS Introduction and Aims: Chronic kidney disease-mineral and bone disorder is a common complication in long-term hemodialysis patients. Cinacalcet is a promising alternative to parathyroidectomy in patients with severe hyperparathyroidism resistant to conventional therapy. This drug was launched in 2008 and approved in Japan only for secondary hyperparathyroidism in dialysis patients. Because retention of uremic toxins and phosphorus can worsen secondary hyperparathyroidism in hemodialysis patients, kidney transplantation decreases serum phosphorus levels together with a subsequent decline in serum parathyroid hormone (PTH) levels. Moreover, cinacalcet may be associated with an increase in serum creatinine levels, urinary calcium excretion, and nephrocalcinosis in kidney transplant patients. Therefore, cinacalcet is usually discontinued at kidney transplantation. The aim of this study was to evaluate the clinical changes in patients discontinuing cinacalcet at kidney transplantation. Methods: We performed a retrospective observational study of patients who had undergone kidney transplantation at our institute between 2008 and 2011. Five patients (all males, aged 2664 years) who had received cinacalcet during dialysis were followed for 19 11 months after kidney transplantation. Mean duration of dialysis before transplantation was 132 (50235) months, and mean cinacalcet dose was 25 (2550) mg/day. Creatinine, corrected calcium, phosphorus, alkaline phosphatase (ALP), and intact PTH levels were assessed. Furthermore, ultrasonography of parathyroid glands was performed. Results: Three months after transplantation, serum phosphorus levels decreased below the normal range ( from 6.8 1.9 mg/dl to 1.9 0.3 mg/dl), corrected calcium levels increased above the normal range (from 8.9 0.6 mg/dl to 11.1 0.9 mg/dl), ALP levels increased from 202.8 66.7 IU/l to 459.0 107.8 IU/l, and intact PTH levels continued to remain high (from 246 96 pg/ml to 137 22 pg/ml). At this point, serum calcium levels were above 11 mg/dl in 3 patients, and parathyroidectomy was performed in one patient. Of the remaining 2 patients, one was prescribed cinacalcet again. Ultrasonography of the parathyroid glands revealed that one or more parathyroid glands had enlarged in the 3 patients and the maximum diameter was 0.821.61 cm. Conclusions: In kidney transplant patients discontinuing cinacalcet after long-term hemodialysis, especially those with enlarged parathyroid glands, mineral abnormalities may persist after transplantation. Therefore, parathyroidectomy may be preferred over cinacalcet treatment in kidney transplant candidates with severe hyperparathyroidism resistant to conventional therapy. KIDNEY TRANSPLANT PATIENTS ON CINACALCET BEFORE SURGERY SHOW LESS GRAFT CALCIFICATION DURING THE FIRST YEAR AFTER TRANSPLANT THAN THE ONES THAT HAVE NEVER RECEIVED IT. Raphael Pereira Paschoalin1, Raphael Paschoalin1, Jose Vicente Torregrosa1, Xoana Barros Freiria1, Carlos Edoardo Durn Rebolledo1, Ana Sanchez Escuredo1, Manel Sol1and Josep Maria Campistol1 1Hospital Clinic - Barcelona, Spain Introduction and Aims: It has been described recently that patients who were receiving cinacalcet before kidney transplantation (KT) would have, after transplant, a greater probability to develop graft calcification. The aim was to evaluate the effect of withdraw cinacalcet at surgery on allograft calcification at 3 and 12 months after transplantation. Methods: We evaluated the protocol biopsies (PB) at 3 and/ 12 months after transplant. of all recipients between January 2009 and March 2011. 347 PB (198 PB at 3 months and 149 PB at 12 months) in 224 patients (149 men) were performed. . 125 of patients had PB at 3 and 12 months. Immunosuppression was: at 3 months (Calcineurin inhibitor: CNI): 148; mTOR: 31; CNI + mTOR: 19) and at 12 months (CNI: 112; mTOR: 34; CNI + mTOR: 3). Mean age: 49 + 12.8 years. Forty-three patients were receiving cinacalcet at the moment of transplant. Results: At light microscopy, 17 (4.9%) of the total biopsies (16 patients) showed calcifications (intratubular or in the parenchyma). In the calcification group, only one patient had been received cinacalcet before surgery (dose of 120 mg/day) and the others had never used cinacalcet before. The group receiving cinacalcet before KT showed serum calcium ( p = 0.000) and iPTH ( p = 0.003) significantly higher and, and lower serum phosphorus although not statistically significant. Renal function was similar (Table). There were no significant differences in serum creatinine, calcium, phosphorus and iPTH between patients with calcifications and no calcifications. Conclusions: Patients receiving Cinacalcet before KT show less graft calcification during the first year after KT than the ones who had never received cinacalcet. SAP674 Table 1. ANALYSIS OF CHARACTERISTICS AND OUTCOMES OF A SINGLE CENTRE CLUSTER OF PNEUMOCYSTIS JIROVECII PNEUMONIA IN THE UK 1University Hospitals Leicester Introduction and Aims: Penumocystis Jirovecii Pneumonia (PJP) is a potentially life-threatening opportunistic infection in immunocompromised individuals, with a mortality of 13-38% in one review1. Recently several UK centres have reported an increase in the incidence of PJP in their immunosuppressed and renal transplant populations2. Registry data and case control studies have identified several potential risk factors for the development of PJP, with evidence of person to person transmission in some series. We describe a cluster of 16 cases of PJP in a single centre in the UK, including complications and outcome. Methods: We identified a cohort of patients with suspected and proven (by sputum or bronchoalveolar lavage) PJP and undertook a retrospective review of case notes and laboratory results to identify risk factors for development of the infection. Data collected included type of immunosuppression, rejection episodes, CMV status, complications of treatment, ITU admission and outcome. Results: From January-December 2011 we identified 16 patients with clinically suspected and proven PJP. Age range was 24-69 years. Twelve patients had functioning renal transplants, one patient was on dialysis following failure of his transplant, one was HIV-positive, one had vasculitis and one was on treatment for myeloma. Twelve patients (75%) were on prednisolone and 12 were taking mycophenolate mofetil (MMF). Four patients had received methylprednisolone for acute rejection, and two had received anti-thymocyte globulin. Duration on immunosuppression ranged from 6-138 months. No patient was on PJP prophylaxis at presentation but 2 had just completed 6 months prophylaxis following transplantation. Four patients had been treated for CMV disease in the past. All but one patient had been lymphopenic for at least three months prior to presentation. All patients were treated with co-trimoxazole except one who received primaquine and atovaquone. Four patients 925%) developed bone marrow toxicity as a result of therapy. Seven patients 944%) were admitted to ITU, with time on ITU ranging from 5-46 days; 5 patients received invasive ventilation. There were no deaths. Six patients developed acute kidney injury, and 3 of 12 renal transplant patients went on to develop graft failure. Conclusions: We report a significant cluster of PJP cases in our population. Our results are notable for the length of time post transplantation the disease occurred. Possible explanations for this outbreak include changes in the pathogenicity of the organism, improved detection techniques, or person to person transmission. There may be an association with MMF use, additional immunosuppression for rejection, and chronic lymphopenia. PJP resulted in significant morbidity, but with 100% patient survival. Increased vigilance and early detection may be key to a successful outcome. 1. de Boer MG, de Fijter JW, Kroon FP. Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review. Med Mycol. 2011 Oct;49(7):673-80 2. Alderson, H. et al., A UK Single Centre Cluster of Pneumocystis Jirovecii Pneumonia in Renal Patients. Poster presentation BRA/RA conference 2011 THE NEW SPECTRUM OF PNEUMOCYSTIS JIROVECII PNEUMONIA : A MULTICENTER STUDY Anne Grall1, Laeticia Treguer2, Marie Essig3, Caroline Lecaque4, Natacha Nol5, Matthias Bchler6, Dominique Bertrand7, Joseph Rivalan8, Laura Braun9, Florence Villemain10, Bruno Hurault de Ligny11, Anne Totet4, Nathalie Pestourie3, Dominique Toubas5, Gilles Nevez12and Yannick Le Meur1 1Chu, Brest France, 2Chru Brest France, 3Chu, Limoges France, 4Chu, Amiens France, 5Chu, Reims France, 6Chu, Tours France, 7Chu, Rouen France, 8Chu, Rennes France, 9Chu, Strasbourg France, 10Chu, Angers France, 11Chu, Caen France, 12Chu Brest France Introduction and Aims: Pneumocystis jirovecii pneumonia (PCP) is a potentially life-threatening opportunistic infection in immunocompromised patients. The last three years, our group (12 transplant centers) have faced an increasing number of PCP with unusual clinical presentations and evidence of interhuman transmission. Methods: We retrospectively analysed 69 cases of PCP between 2008 and 2011. The diagnosis of PCP was confirmed if Pneumocystis jirovecii was detected by direct microscopy and/or PCR in a bronchoalveolar lavage fluid specimen (BAL). Demographic and clinical data, immunosuppressive medication, PCP prophylaxis and treatment as well as biological and radiological features were collected. Genotyping of Pneumocystis isolates was performed in the 4 renal transplant centers which experienced local outbreaks. Results: All patients received prophylaxis and none of them developped PCP during this prophylactic period. Previous acute rejection was reported for 41% of the patients. At diagnosis, immunosuppressive therapy included calcineurin inhibitors (78%), antimetabolites (87%), mTOR inhibitors (20%) and steroids (67%) (mean dose 10.4 mg/d). The clinical presentation was different than classically reported. 1) The majority of cases occured late after transplantation, median delay 51 months. 2) The typical presentation (fever, cough, dyspnea) was not present in 70% of cases with 10% of the patients without respiratory symptoms at onset. 3) CD4 count was not predictive of the PCP risk: in our study mean CD4 count before PCP was 518/ mm3 with 66% > 300/mm3. Moreover, 65% had a CD19 count <80/mm3 suggesting a role for B cells in immune response to PCP. 4) Interhuman transmission was suspected: 83% of the cases were concentrated in 4 centers. Genotyping was performed for these cases. The results supported the hypothesis of an interhuman transmission. Finally, prognosis was poor with 27% requiring mechanical ventilation and 13% leading to death. Conclusions: In conclusion, in renal transplant units, we observed an increasing number of PCP with unusual presentation and late onset. Our data suggest that prolonged prophylaxis and isolation mesures should be considered. ORGAN DONATION : OPINION OF DOCTORS Bassit Nour el Houda1, Habiblah Mustapha1, Fadili Wafaa1and Laouad Inass1 1Chu Mohammed VI OF Marrakech Introduction and Aims: Organ and human tissue donation in Morocco falls short of needs. This is due in part to the refusal of families but also to a lack of awareness. We conducted a survey of a representative sample of medical interns and residents to assess their knowledge and attitudes to organ donation and their training needs. Methods: This is a cross-sectional study of medical interns and residents, an anonymous questionnaire adapted to Moroccan context containing 29 questions (open and closed) assessing the knowledge, opinions, attitudes and needs organ donation was given to doctors. Results: 130 forms were distributed, 115 completed by 45 men and 70 women, 87 residents and 28 interns, 80% were aged 25 to 34 years, 60% practice their profession of 1 to 5 years, 28% do not know that the organ removal of dead is made in Morocco. 74% know the structures authorized to organ removal. Only 6% are aware of the organs and tissues that can be taken. 76% know the definition of brain death. 88% were for the removal of organs and tissue of deceased persons. 35% do not believe that brain death is the death of the individual. 10% do not know that Islam allows organ donation from a living donor and cadaveric. 98% believe that organ donation saves lives, 62% will give their organs and tissues after death. 25% refuse organ donation of a parent and 30% refuse it of their children after death. 40% think that the hospital coordinating must act after the expression by the family of the deceased's wishes. 91% would receive training in this area. Conclusions: A medical, psychological and sociological study is needed to better understand the obstacles to organ donation and target the necessary training. The promotion of organ donation requires good training of medical and paramedical teams to sensitize the population USE OF EXPANDED CRITERIA LIVING DONORS: POSSIBLE SOLUTION OF SEVERE ORGAN SHORTAGE IN THE BALKANS Irena Rambabova Bushljetikj1, Irena Rambabova Bushljetikj1, Jelka Masin-Spasovska1, Goce Spasovski1, Zivko Popov1, Aleksandar Sikole1and Ninoslav Ivanovski1 1University Clinic of Nephrology and Urology , Skopje, R. Macedonia Introduction and Aims: The Balkan region is dramatically changed over the past 20 years. Despite the efforts for renal transplants, dialysis remains the usual way for treatment of ESRD. Due to the lack od deceased organ donation, the living renal transplantation is predominant transplant activity. Trying to solve the problem, we started accepting so called expanded criteria living donors ( ECLD) Methods: Two hundried and twenty living renal transplants are performed in our Kidney Transplant Center in the last 20 years. As ECLD were accepted 88 donors older than 65 years, 4 ABO incompatible, 21 unrelated ( predominantly spausal), 10 with mild arterial hypertension, 4 with large simple cyst, 2 with multiple renal arteries and one with double ureter ( ECLD Group) The quadruple sequential immunosuppressive protocol was used in all cases including induction with ATG or Il-2R antagonists, Cyclosporin A, MMF/AZA and Steroids. In ABO incompatible transplants a special preconditioning regimen for recipients was used including laparoscopic splenectomy, Rituximab, plasmapheresis and IvIg. The Kaplan-Meier one, three and five years graft survival rate, rejection episodes, DGF and actual renal function were analysed.The results were compared with the group of 90 recipeints with standard criteria living donors ( SCLD) performed in the same time. Results: One, three and five years Kaplan-Meier graft survival rate for ECLD group was 94%, 83%, 74%, respectively, compared with 95%, 87%, 78% in the SCLD group. The difference were not statistically significant. The percentage of Delayed Graft Function was 14% in ECLD group compared with 6% in SCLD group ( p<0.05). The rejection episodes rate was 18% ( ECLD) compared with 16% (SCLD). The actual serum creatinin 5 years after the surgery was 170 and 154 micromol/lit in ECLD and SCLD, respectively ( p< 0.05). Conclusions: Our study justifies the use of ECLD especially in the regions where the Living Renal transplantation is predominant transplant activity. It may ameliorate the actaul organ shortage in the Balkan region. INTERMEDIATE EARLY GRAFT FUNCTION IS A RISK FACTOR FOR GRAFT LOSS AND WORSE LONG-TERM GRAFT FUNCTION IN KIDNEY TRANSPLANT PATIENTS Mrio Raimundo1, Jos Guerra2, Catarina Teixeira2, Alice Santana2, Snia Silva2, Clara Mil Homens2and Antnio Gomes Da Costa2 1Hospital de Santa Maria, Lisbon, Portugal, 2Hospital de Santa Maria, Department of Nephrology & Renal Transplantation, Lisbon, Portugal Introduction and Aims: It is well established that delayed graft function (DGF) is associated with premature graft loss, increased rate of allograft function decline and increased rate of acute rejections (AR). However, regarding early intermediate graft function (IGF), also referred as slow graft function, these prognostic observations have not been clearly made. Our objective was to investigate the impact of IGF, as compared to excellent graft function (EGF), on relevant renal allograft outcomes: graft survival, long term graft function and incidence of AR. Methods: We retrospectively reviewed the medical records of all patients transplanted in a tertiary care center between 1989 and 2009. DGF was defined as the need for dialysis in the first 7 days post-transplantation, EGF as a level of serum creatinine below 3 mg/dl at 5 days post transplantation and IGF as the absence of dialysis need but with a serum creatinine above 3 mg/dl at 5 days post-transplantation. Glomerular filtration rate was estimated with the 4- variable MDRD equation. Univariate analysis was performed with the Students t-test or the Mann-Whitney test for continuous variables, as appropriate, and with the Chi-square test for categorical variables. Kaplan-Meier method was used to determine survival curves and log- rank test was used for comparison. Multivariate logistic regression analysis was employed to determine independent predictors of IGF and of graft survival. Results: 570 patients were transplanted during the 20-year period, of whom 69.0% had EGF, 22.6% IGF and 8.4% DGF. Patients with IGF had worse graft survival (censored to mortality) at 5 and 10 years post-transplantation (75% versus 93% and 69% versus 85%, respectively; p < 0.001 for both comparisons) and higher incidence of AR (27% vs 41%; p = 0.001), compared to patients with EGF. In multivariate analysis, EGF was independently associated with a reduced risk of graft loss [Odds ratio (OR) compared to IGF: 0.44; 95% CI 0.22 0.88; p=0.019] after adjustment for the occurrence of AR and other covariates. As expected, the absence of AR episodes was also independently associated with better graft survival (OR 0.11; 95% CI 0.06 0.22; p=0.001). Higher donor age was the only independent predictor of the occurrence of IGF (OR 1.03 per year; 95% CI 1.01 1.05; p=0.001), while warm and cold ischemia times and recipient age were not. IGF was also associated with worse long-term graft function until 7 years post-transplantation (mean GFR 48.3 18.9 vs 57.4 20.4 ml/min/1.73m2; p=0.008). At 10 years post-transplantation, patients with IGF had a numerically lower mean GFR (48.1 22.2 vs 54.8 21.6 ml/min/1.73m2), not reaching statistical significance probably due to the lower number of patients analyzed. Conclusions: The results of this study suggest that IGF, as DGF, is associated with worse clinical outcomes: increased rate of graft loss and AR and worse long-term kidney graft function. Efforts should be undertaken to minimize the incidence of IGF and DGF. Donor age was the only factor associated with the occurrence of IGF. This is especially relevant regarding the increasing use of extended donor criteria. RESULTS OF LIVER AND COMBINED LIVER-KIDNEY TRASPLANT WITH MELD SCORE: WHAT CHANGED AFTER THE INCLUSION OF RENAL FUNCTION AS A DETERMINANT OF LIVER ALLOCATION? Introduction and Aims: The implementation of MELD score for the distribution of organs determined that renal function has a significant role in the allocation of liver and liver-kidney transplant. However, the benefit of this strategy is controversial. Aims: To evaluate the results of liver (LT) and liver-kidney transplantation (LKT) before and after the implementation of MELD system. Methods: 524 charts of patients who received liver transplantation (LT) or LKT since Jun /1999 to Jul/ 2011, were evaluated retrospectively, dividing their follow up in pre MELD (until June/ 2005) and MELD era (since July 2005 to Jul/2011).Prevalence and actuarial survival of LKT was assess in both periods. Statistical Analysis: Chi Square, Student Test, Log Rank Test/Kaplan Meier. SPSS 17.0 Results: The overall prevalence of LKT was 5.7% (30/524). In pre-MELD 4.4% (11/ 248) and in MELD era 7% (19/275) ( p = NS).Main indications for LKT in pre-MELD and MELD era were HCV cirrhosis (63/23% p=0.04), previous renal graft loss (54/20% p=NS) and polycystic diseases (27/21% p=NS) Median time in the waiting list in pre-MELD and MELD era was 179/70 days ( p=0.02),warm ischemia time ?5030/328 min( p<0,01?) and induction with basiliximab 63/94%( p=0.04). There were not significant differences in age, MELD, pre transplant dialysis and time of dialysis at the recipient, as well as age, DRI of the donor, and immediate perioperative complications between the two eras. Conclusions: 1. Overall survival of LKT was comparable to isolated LT 2. Implementation of the MELD system did not led to a significant increase in the number of LKT but favoured a short stay on the waiting list 3. The lower survival of LKT in the MELD was not statistically significant and was not associated with the variables analysed 3) More patients and follow-up studies are required to validate these results


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