Transplantation - clinical II
Emanuele Luigi Parodi
Giorgio L. Viviani
Hhemodialysis, Clinical Center
Department of Internal Medicine,Genoa University
Transplant Section, Genoa University and Aou San Martino
Department of Internal Medicine, Nephrology Section, Genoa University
Center for Statistics and Informatics, Medical Faculty
Clinic for Nephrology
University of William and Mary
Ege University School of Medicine, Division of Radiology
Ege University School of Medicine
Ege University School of Medicine, Division of Nephrology
Aysegul Cobanoglu Kudu
1nephrology and Renal Transplantation, Department of Systematic Pathology, University of Naples federico Ii
Department of Neuroscience, Physiology Nutrition Unit, University Federico II
Nephrology and Renal Transplantation, Department of Systematic Pathology, University of Naples federico Ii
Department of Nephrology, Baskent University
Baskent University Hospital, Department of Nephrology
Department of Nephrology, Baskent University
Department of Nephrology, Baskent University
Department of Internal Medicine, Baskent University
Division of Urology, Kobe University Graduate School of Medicine
Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine
Favaloro Fondation, Buenos Aires
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
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
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
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
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
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
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
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
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
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
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
ABO INCOMPATIBLE KIDNEY TRANSPLANTATION IN THE
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,
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
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
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
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),
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
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
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
DETERMINANTS OF OUTCOME AFTER KTX IN ELDERLY
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
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
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
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,
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
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
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
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
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
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,
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
FGF23 at baseline was the main predictor of levels of sPO4 and 1,25(OH)2D3 during
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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,
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
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
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
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
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
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
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
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.
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