1) BK virus nephropathy in kidney tranplant.
2) Evaluation of bioptic score on kidney tranplant to evaluated
the allocation for single or double kidney tranplant.
3) Role of anti-HLA specific antibody on developement of chronic
rejection. Eveluation of early markers of immunological
activation.
4) Pregnancy after organ tranplantation: follow up of new born
and mother.
5) Predictive factors on chronic allograft nephropathy
6) VDR expression of on endothelial progenitor cells in dialysis
patients
7) New immunosuppression strategy in kidney trasplant
patient
8) Evaluation of NGAL (Neutrophil Gelatinase-Associatel
Lipocalin) as a mediator of biological and pathological states.
9) Vascular complications after kidney transplant (Atrial
Fibrillation, Deep Venous Thrombosis)
10) Genetic cardiovascular risk factors after renal
transplantation: role of cytokine polymorphisms
11) De novo malignancies after organ transplantation:
epidemiology and focus on viral infection
12) Reduction of oxidative damage and kidney transplantation
outcome
13) New insight in artificial renal replacement
treatments: automatic adaptive system dialysis for
hemodialysis-associated hypotension and disequilibrium symptoms
14) Restless-leg sindrome in uremia
15) pregnancy after solid organ transplant: outcome and immunosuppressive therapy
Early diagnosis of polyomavirus type BK infection in
tailoring immunosuppression for kidney transplant patients:
screening with urine qualitative polymerase chain reaction
assay
Polyomavirus type BK (BKV) nephropathy is increasingly a
significant cause of graft dysfunction and even failure. Early
diagnosis followed by reduction of immunosuppression has been
associated with an improved prognosis. The aim of the study
is to screen patients with the urine qualitative
polymerase chain reaction (PCR) for BKV DNA. We followed with blood
BKV PCR if the urine screen was positive and then reduced
immunosuppression in viremic patients. An early diagnosis of BKV
infection with reduction of immunosuppression may reverse viremia
and retard progression of BKV nephropathy. BKV screening by PCR
assays should be considered in kidney transplant recipients,
especially those with impaired graft function.
Evaluation of bioptic score on kidney tranplant to evaluated
the allocation for single or double kidney tranplant.
Marginal organs not suitable for single kidney transplantation
are considered for double kidney transplantation (DKT).
Double-kidney transplantation is performed using organs from
marginal donors with a histological score not suitable for single
kidney transplantation. The number of patients on the waiting list
for renal transplantation has progressively increased in the last
decade, while the number of potential donors have remained the
same. The expansion of the donor pool using marginal donors may
represent a possible, although partial solution to this problem.
Dual transplant of marginal kidneys otherwise not considered for
single transplant may give access to an expanded pool of cadaveric
organs without exposing recipients to the drawbacks of a limited
nephron mass supply The aim of the study is to verify the results
obtained with double-kidney transplantation in terms of graft and
patient survival and complications in comparation with patients
that received a kidney transpant with bipoptic score suitrable
for single transplant. Moreover the score used in this study
is useful to determine whether a kidney should be refused or
suitable for single or dual-kidney transplantation.
Impact of early humoral alloreactivity after
transplantation on the long-term survival of renal
allografts.
She is active involved in a multicentric study in collaboration
with the Departiment of Transplant Immunology of General Hospidal
of Padua about the role of antibody immunoresponse in developement
of acute and cronic rejection. The primary end point of the study
is the detection of early immunological markers involved in
the umoral response against renal transplantation in the aim
of developement of immunomodulation strathegic protocol
. The study involved the evaluation of several blood samples
to decected serum antibody against kidney transplant. A kidney
biopsy will be done in the patient who developed antibody,
associated with plasmepheresis and increase of immunosuppression
therapy.The study is divided in an obsevational phase and in a
interventistic phase. in the observational phase we analyze blood
sample of transplant patient to dectect early specific antibody
involved in humoral rejection; in interventistic phase we perform
plasmapheresis on patien who develop specific antibody.
Outcome of pregnancy after organ transplantation: a
retrospective survey in Italy.
We are strictly involved in a multicenter retrospective study
describes pregnancies after kidney transplantation and is the first
such survey in Italy.The number of women who decide to have a child
after organ transplantation has increased. We determined the
outcomes of over 100 pregnancies of women who had undergone
kidney, liver or heart transplantation. All recipients had been
maintained on immunosuppressive therapy before and during
pregnancyIn the last few years advances in surgical techniques and
immunosuppression have improved not only survival, but also quality
of life in organ transplanted patients. Hence, the number of women
of child-bearing age who decide to have a child--which means
resuming a normal life--has increased.
The study analize the outcomes of pregnancies in kidney transplant
recipients from data collected in questionnaires, hospital records,
and phone interviews. All recipients were maintained on
cyclosporine (CsA), azathioprine (AZA), corticosteroids or
tacrolimus (FK506) before and during pregnancy Preliminare data
showed that in kidney transplant recipients who became pregnant the
incidence of spontaneous abortion and preterm delivery was
increased. Newborns delivered to these patients had low birth
weight, but no congenital defects were noted and their development
was normal.
Immunosuppressive therapy and chronic allograft
nephropathy
In the kidney graft field she focused her studies on CAN.
Chronic allograft nephropathy (CAN) is an anatomical and clinical
alteration, characterized by proteinuria, hypertension and a
progressive decline of kidney function, that begins at variable
times (months, years) and that can lead to the loss of the
transplanted organ. The pathogenesis of CAN involves both
immunological (early acute rejection, hyperimmunization,
HLA-mismatches between donor and recipient, suboptimal
immunosuppression, etc) and non-immunological factors
(ischemia/reperfusion injury, reduced nephron mass, age differences
between donor and recipient, dialysis time, hypertension,
dislipidemia, proteinuria, etc.). The possible strategies for
prevention of CAN consist of procedures aimed at the reduction of
some potential risk factors like optimization of the
conditions for organ explantation, diminution of
ischemia/reperfusion injury etc. Moreover, some categories of
immunosuppressive drugs, such as calcineurin inhibitors, can have a
nephrotoxic effect, often regardless of therapeutic dosage.
The introduction in clinical practice of novel immunosuppressive
drugs with no nephrotoxicity, like mycophenolate mofetil and
rapamycin, makes therapeutical strategies able to decrease of the
incidence of CAN feasable .
New trend in the field of immunosuppressive therapy in renal
transplant
The prevention of allograft rejection a foremost challenge for
the clinicians involved in transplant. Among the regimens aimed to
suppress transplant recipient immune response against the graft,
tacrolimus represents a milestone of immunosuppressive therapy. The
formulation of Prograf capsules requires twice-a-day
administration. Advagraf is a recently developed slow-release
once-a-day oral formulation of tacrolimus, with similar efficacy
and safety profile of 12-hour formulation (Prograf). It been shown
that poor compliance is one relevant factor associated with graft
loss: once-daily dosing can contribute to improved patient
adherence. Few data are currently available on Advagraf use in
clinical practice, especially as early immunosuppressive therapy in
transplants. We therefore evaluated the efficacy and
pharmacokinetics of single-dose formulation compared to the
traditional Prograf twice-daily dosing in de novo renal
transplants.The groups did not differ significantly in terms of
patient characteristics and drug efficacy. Drug blood levels tended
to be lower in the first weeks post-transplant, particularly in
Advagraf-treated patients who required higher drug doses The groups
did not differ significantly in terms of patient characteristics
and drug efficacy. Drug blood levels tended to be lower in the
first weeks post-transplant, particularly in Advagraf-treated
patients who required higher drug doses . This study suggests that
in de novo kidney transplant, single-dose formulation of tacrolimus
has a similar short-term efficacy compared with twice-a-day
administration. The data also highlight the necessity to increase
Advagraf dosage in the first week post-transplant to achieve
effective therapeutic levels (11-15 ng/ml). .An emerging finding is
the reduction of lipids with a considerable importance for
cardiovascular risk.
Genetic cardiovascular risk factors after renal
transplantation: role of cytokine polymorphisms
Cardiovascular disease (CVD) represents the main cause of
morbidity and mortality after renal transplantation. A pathogenetic
link between inflammation, atherosclerosis and CVD have been
demonstrated. For this reason, genetic factors regulating cytokine
production and the balance between pro- and anti- inflammatory
molecules could have a deep influence on CVD risk. In the view of
the modern paradigm of atherosclerosis as an inflammatory disease,
the present study was undertaken to investigate the impact of
inflammatory cytokine polymorphisms on post-renal transplant CVD.
To evaluate the association between cytokine polymorphisms and CVD,
a case-control study was carried out on 798 renal allograft
recipients transplanted between 1997 and 2008, 196 of them with CVD
(CVD group) and 602 controls free of cardiovascular complications
(no-CVD group). TNF-α/G-308A, TGF-β1/L10P, TGF-β1/R25P,
IL-10/G-1082A, IL-10/C-819T, IL-10/C-592A, IL-6/G-174C,
IFN-γ/T+874A, IL-8/T-251A and VEGF/C+936T polymorphisms were
genotyped using PCR-SSP and RFLP. The patients in CVD and no-CVD
group differed significantly in IL-10 and TNF-α genotype
frequencies. Using multivariate analyses to test the association
with CVD, the high producer genotype of the pro-inflammatory
cytokine TNF-α was significantly associated with a 4.41-fold
increased cardiovascular risk. Conversely, the carriage of high
producer genotype of the anti-inflammatory cytokine IL-10 resulted
protective against post-transplant CVD, with an adjusted OR of 0.2
(0.02-0.29). This work seems to indicate that gene polymorphisms
involved in inflammatory response might represent cardiovascular
risk markers in renal allograft recipients and suggests a
prognostic value of TNF-α and IL-10 genotypes. Further studies are
necessary to evaluate if patients with a CVD "predisposing"
genotype should be treated more aggressively.
Incidence of late deep venous thrombosis in renal
transplant patients
Kidney transplant recipients (KTR) manifest a hypercoagulable
state that contributes to increase the incidence of deep vein
thrombosis (DVT), also occurring late in stable patients..It
has been proven an imbalance of hemostatic mechanisms in KTR, with
a multifactorial rise in procoagulant factors, partly related to
traditional risk factors (diabetes, pregnancy, obesity, preexisting
thrombophilic states), partly transplant-related (surgery per se,
immunosuppressive therapy, primary nephropathy disease,
pretransplant dialysis mode, post-transplant erythrocytosis,
post-transplant infections).We observed a group of patients with an
episode of DVT at least 4 months after transplant. who developed
DVT (lower limbs, lower limbs complicated by pulmonary embolism,
retinal) at least 4 months after transplantation. Primary
nephropathy, immunosuppressive regimen, post-transplant infections
and erythrocytosis were recorded All patients received low dose
subcutaneous low molecular weight heparin (LMWH) as trombophylactic
treatment for the first week after transplantation and then with
oral anticoagulants. DVT was diagnosed by color duplex
ultrasonography . Significant increased incidence of DVT was
observed in patients receiving cyclosporine or cyclosporine+mTOR
inhibitors, in those with polycystic kidney diseases, systemic
lupus erythematosus, nephrotic syndrome (especially if
steroid-sensitive) and in those with rapid and excessive correction
of hematocrit values after transplant. DVT was not significantly
related to acute infection (CMV) or dialysis modality.
Hypercoagulability in KTR is a multifactorial condition
representing a severe complication in stable transplants. The
prevention may consist either in an accurate pre-transplant
thrombophilia screening or in identification of patients at higher
DVT risk requiring long-term antiplatelet therapy. A longer
observation period is needed to assess the optimal duration and
type of anticoagulant therapy in these patients.
Influence of the immunogenetic KIR and HLA systems on long-term
renal transplant outcome.
Numerous studies have established the importance of innate
immunity, particularly natural killer (NK) cells, in
transplantation tolerance. NK cells express killer cell
immunoglobulin-like receptors (KIRs) on their surface. By
recognizing and binding major histocompatibility complex class I
antigens, KIRs prevent autologous cell killing and promote lysis of
non-self antigen-presenting cells. This study investigated the role
of 16 KIR genes and donor-recipient KIR/HLA combinations on 5-year
outcomes in a population of deceased donor kidney transplant
recipients.We genotyped 126 renal transplant patients and their
donors for HLA A, B, C, DR, and KIR genes. Patients underwent
standardized transplantation and immunosuppressive protocols and
were followed-up for 5 years. Graft function was evaluated by serum
creatinine level and glomerular filtration rate calculated using
the 4-variable modification of diet in renal disease (MDRD)
equation. The presence of KIR2DS3 in the recipients was associated
with better graft function indexes over time (p<0.05), but
Conversely, the presence KIR2DS3 in the recipients combined with
the presence of its HLA ligand in the donor had a detrimental
effect on the trends of serum creatinine levels and eGFR trends,
also confirmed by multivariate analysis. Kidney transplant
recipients negative for the KIR2DL1 gene displayed higher
creatinine levels after 5 years. The present study demonstrates an
important role of the KIR immunogenetic system in the long-term
immune response to kidney transplantation
De novo malignancies after organ transplantation: focus
on viral infections.
Organ transplantation is an increasingly used medical procedure
for treating otherwise fatal end stage organ diseases Newly developed
anti-rejection drugs greatly helped to prolong long-term survival
of both the individual and the transplanted organ. Presently,
5-year patient survival rates are around 90% after kidney
transplant and 70% after liver transplant. However, the prolonged
chronic use of immunosuppressive drugs is well known to increase
the risks of opportunistic diseases, particularly infections and
virus-related malignancies. Although transplant recipients
experience a nearly 2-fold elevated risk for all types of de-novo
cancers, persistent infections with oncogenic viruses - such as
Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and
Epstein-Barr virus - are associated with up to 100-fold increased
cancer risks. This review, focusing on kidney and liver
transplants, highlights updated evidences linking iatrogenic
immunosuppression, persistent infections with oncogenic viruses and
cancer risk. The implicit capacity of oncogenic viruses to
immortalise infected cells by disrupting the cell-cycle control can
lead, in a setting of induced lowered immune surveillance, to
tumorigenesis and this ability is thought to closely correlate with
cumulative exposure to immunosuppressive drugs. Mechanisms
underlying the relationship between viral infections,
immunosuppressive drugs and the risk of skin cancers,
post-transplant lymphoproliferative disorders, Kaposi sarcoma,
cervical and other ano-genital cancers are reviewed in details.
