#10#
Revisiones-Ciencias
Básicas-Molecular, Bioquímica, Metabolismo & Genética *** Reviews-Basic
Sciences-Molecular, Biochemistry, Metabolism & Genetics
TRASPLANTE
RENAL *** RENAL TRANSPLANTATION
(Conceptos
/ Keywords: Renal-Kidney transplantation; Kidney donation-procurement; etc).
Enero /
January 2001 --- Marzo / March 2004
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[1]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[2]
TÍTULO / TITLE: - Interleukin 2 receptor antagonists
for renal transplant recipients: a meta-analysis of randomized trials.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):166-76.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000109643.32659.C4
AUTORES
/ AUTHORS: - Webster AC; Playford EG; Higgins G;
Chapman JR; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Cochrane Renal Group, Centre for Kidney
Research, Children’s Hospital at Westmead, Westmead, NSW, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL-2Ra) are increasingly used to treat renal transplant
recipients. This study aims to systematically identify and summarize the
effects of using IL-2Ra as induction immunosuppression, as an addition to
standard therapy, or as an alternative to other antibody therapy. METHODS:
Databases, reference lists, and abstracts of conference proceedings were
searched extensively to identify relevant randomized controlled trials in all
languages. Data were synthesized using the random effects model. Results are
expressed as relative risk (RR), with 95% confidence intervals (CI). RESULTS: A
total of 117 reports from 38 trials involving 4,893 participants were included.
When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss
was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or
3 years (4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly
reduced at 6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10
trials: RR 0.67; CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials:
RR 0.82; CI 0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were
not significantly different. When IL-2Ra were compared with other antibody
therapy, no significant differences in treatment effects were demonstrated, but
IL-2Ra had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL-2Ra in addition to
standard therapy, to prevent one patient from undergoing rejection, with no
definite improvement in graft or patient survival. There is no apparent
difference between basiliximab and daclizumab.
----------------------------------------------------
[3]
TÍTULO / TITLE: - A meta-analysis from
the Cochrane Library reviewing interleukin 2 receptor antagonists in renal
transplantation.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):165.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000112919.54256.8D
AUTORES
/ AUTHORS: - Morris PJ; Monaco AP
----------------------------------------------------
[4]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and
which is the optimal dose of steroids and calcineurin inhibitors beyond the
first year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute
rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy
analysis, severe lesions did not develop in patients with steroid
discontinuation in contrast to patients on standard therapy over follow-up. CsA
reduction did not adversely affect histology. Per-protocol biopsy more than 1
yr after kidney transplantation is a safe procedure to guide change of drug
regimen and to lower the risk of major side effects.
----------------------------------------------------
[5]
TÍTULO / TITLE: - Regulatory T cells in
kidney transplant recipients: active players but to what extent?
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Jun;14(6):1706-8.
AUTORES
/ AUTHORS: - Zhai Y; Kupiec-Weglinski JW N. Ref:: 20
----------------------------------------------------
[6]
TÍTULO / TITLE: - Interleukin 2 receptor
antagonists for kidney transplant recipients.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2004;1:CD003897.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD003897.pub2
AUTORES
/ AUTHORS: - Webster A; Playford E; Higgins G; Chapman
J; Craig J
INSTITUCIÓN
/ INSTITUTION: - Centre for Kidney Research, The Children’s
Hospital at Westmead, Locked Bag 4001, Westmead, NSW, AUSTRALIA, 2145.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute
rejection in kidney transplant recipients. Use of IL2Ra has increased steadily,
with 38% of new kidney transplant recipients in the United States, and 23% in
Australasia receiving IL2Ra in 2002. OBJECTIVES: This study aims to
systematically identify and summarise the effects of using an IL2Ra, as an
addition to standard therapy, or as an alternative to other antibody therapy.
SEARCH STRATEGY: The Cochrane Renal Group’s specialised register (June 2003),
the Cochrane Controlled Trials Register (in The Cochrane Library issue 3,
2002), MEDLINE (1966-November 2002) and EMBASE (1980-November 2002). Reference
lists and abstracts of conference proceedings and scientific meetings were
hand-searched from 1998-2003. Trial groups, authors of included reports and
drug manufacturers were contacted. SELECTION CRITERIA: Randomised controlled
trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other
IL2Ra or other antibody therapy. DATA COLLECTION AND ANALYSIS: Data was
extracted and quality assessed independently by two reviewers, with differences
resolved by discussion. Dichotomous outcomes are reported as relative risk (RR)
with 95% confidence intervals (CI). MAIN RESULTS: One hundred and seventeen
reports from 38 trials involving 4893 participants were included. Where IL2Ra
were compared with placebo (17 trials; 2786 patients), graft loss was not
significantly different at one (RR 0.83, 95% CI 0.66 to 1.04) or three years
(RR 0.88, 95% CI 0.64 to 1.22). Acute rejection (AR) was significantly reduced
at six months (RR 0.66, 95% CI 0.59 to 0.74) and at one year (RR 0.67, 95% CI
0.60 to 0.75). At one year, cytomegalovirus (CMV) infection (RR 0.82, 95% CI
0.65 to 1.03) and malignancy (RR 0.67, 95% CI 0.33 to 1.36) were not
significantly different. Where IL2Ra were compared with other antibody therapy
no significant differences in treatment effects were demonstrated, but adverse
effects strongly favoured IL2Ra. REVIEWER’S CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL2Ra to prevent one
patient having rejection, with no definite improvement in graft or patient
survival. There is no apparent difference between basiliximab and daclizumab.
IL2Ra are as effective as other antibody therapies and with significantly fewer
side effects
----------------------------------------------------
[7]
TÍTULO / TITLE: - Potential role of major
histocompatibility complex class II peptides in regulatory tolerance to
vascularized grafts.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S35-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106472.91343.8D
AUTORES
/ AUTHORS: - LeGuern C
INSTITUCIÓN
/ INSTITUTION: - Transplantation Biology Research Center,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. leguern@helix.mgh.harvard.edu
RESUMEN
/ SUMMARY: - The inactivation of persisting T
lymphocytes reactive to self- and non-self-antigens is a major arm of
operational immune tolerance in mammals. Silencing of such T cells proceeds
mostly by means of suppression, a process that is mediated by regulatory T-cell
subsets and especially by CD4(+)CD(25high) regulatory T cells (Treg). Although
Treg activation and ensuing suppressive activity appear to be major
histocompatibility complex class II dependent, the fine specificity of Treg
T-cell receptors has not yet been elucidated. Recent data from the author’s
laboratory on a class II gene therapy induction of tolerance to allogeneic
kidney grafts suggest that class II peptides are involved as generic signals
for Treg activation. A brief compilation of results that would support this
hypothesis is discussed in the present article. N. Ref:: 31
----------------------------------------------------
[8]
TÍTULO / TITLE: - Transcriptional
regulation of inflammatory genes before transplantation: a role for hypoxia
inducible factor-1alpha?
REVISTA
/ JOURNAL: - Transplantation 2003 Feb 27;75(4):437-8.
AUTORES
/ AUTHORS: - Koo DD; Fuggle SV
INSTITUCIÓN
/ INSTITUTION: - Nuffield Department of Surgery, University
of Oxford, Oxford Transplant Centre, United Kingdom. N. Ref:: 5
----------------------------------------------------
[9]
TÍTULO / TITLE: - Complement and the
kidney.
REVISTA
/ JOURNAL: - J Immunol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jimmunol.org/
●●
Cita: J. of Immunology: <> 2003 Oct 1;171(7):3319-24.
AUTORES
/ AUTHORS: - Quigg RJ
INSTITUCIÓN
/ INSTITUTION: - Section of Nephrology, University of
Chicago, Chicago, IL 60637, USA. rqigg@medicine.uchicago.edu N. Ref:: 94
----------------------------------------------------
[10]
TÍTULO / TITLE: - The economic value of
valacyclovir prophylaxis in transplantation.
REVISTA
/ JOURNAL: - J Infect Dis. Acceso gratuito al texto
completo a partir de los 2 años de la publicación; - http://www.journals.uchicago.edu/
●●
Cita: J. of Infectious Diseases: <> 2002 Oct 15;186 Suppl 1:S116-22.
AUTORES
/ AUTHORS: - Squifflet JP; Legendre C
INSTITUCIÓN
/ INSTITUTION: - University Clinic Saint Luc, 1200
Brussels, Belgium. Jean-Paul.Squifflet@chir.ucl.ac.be
RESUMEN
/ SUMMARY: - Cytomegalovirus (CMV) infection and
disease, with its extensive direct and indirect consequences, adds considerably
to the cost of patient management in both solid organ and bone marrow
transplantation. Antiviral prophylaxis for CMV infection can offer cost
advantages over preemptive therapy and “wait-and-treat” approaches. Valacyclovir
has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow
transplantation and is cost-effective when compared with placebo in renal
transplant recipients at high risk of CMV infection. In reducing CMV infection
and disease, valacyclovir prophylaxis appears to be associated with reductions
in indirect effects of CMV (acute graft rejection, other opportunistic
infections) and, if these effects are considered, the potential exists for even
greater savings to be made with valacyclovir therapy. Benefits of valacyclovir
in transplantation extend beyond CMV to other herpesviruses and may be
increased in some clinical situations by prolonging prophylaxis beyond 3
months. N. Ref:: 32
----------------------------------------------------
[11]
- Castellano -
TÍTULO / TITLE:Polimorfismo del receptor de la
vitamina D y enfermedad osea postrasplante renal. Polymorphism of the vitamin D
receptor and bone disease after renal transplantation.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2001;21 Suppl 1:56-60.
AUTORES
/ AUTHORS: - Torres A; Barrios Y; Salido E
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia y, Hospital
Universitario de Canarias, Instituto Reina Sofia de Investigacion Nefrologica,
Tenerife, España. atorres@ull.es N. Ref:: 29
----------------------------------------------------
[12]
- Castellano -
TÍTULO / TITLE:La influencia de los factores
geneticos en la patogenesis de dislipidemias posteriores al trasplante renal.
The effect of genetic factors on the pathogenesis of the dyslipidemias
following kidney transplantation.
REVISTA
/ JOURNAL: - Rev Invest Clin. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.imbiomed.com/
●●
Cita: Revista de Investigacion Clinica: <> 2002 Sep-Oct;54(5):472-3.
AUTORES
/ AUTHORS: - Lerman Garber I
INSTITUCIÓN
/ INSTITUTION: - Departamento de Endocrinologia y
Metabolismo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador
Zubiran. lerman@netservice.com.mx N. Ref:: 11
----------------------------------------------------
[13]
TÍTULO / TITLE: - A benefit-risk
assessment of basiliximab in renal transplantation.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2004;27(2):91-106.
AUTORES
/ AUTHORS: - Boggi U; Danesi R; Vistoli F; Del Chiaro
M; Signori S; Marchetti P; Del Tacca M; Mosca F
INSTITUCIÓN
/ INSTITUTION: - Division of General Surgery and
Transplants, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it
RESUMEN
/ SUMMARY: - Interleukin-2 (IL-2) and its receptor
(IL-2R) play a central role in T lymphocyte activation and immune response
after transplantation. Research on the biology of IL-2R allowed the
identification of key signal transduction pathways involved in the generation
of proliferative and antiapoptotic signals in T cells. The alpha-chain of the
IL-2R is a specific peptide against which monoclonal antibodies have been
raised, with the aim of blunting the immune response by means of inhibiting
proliferation and inducing apoptosis in primed lymphocytes. Indeed,
basiliximab, one of such antibodies, has proved to be effective in reducing the
episodes of acute rejection after kidney and pancreas transplantation. The use
of basiliximab was associated with a significant reduction in the incidence of
any treated rejection episodes after kidney transplantation in the two major
randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European
study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and
equine antithymocyte globulin (ATG) administration resulted in a similar rate
of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months
(19% and 20%, respectively). The use of basiliximab appears not to be
associated with an increased incidence of adverse events as compared with
placebo in immunosuppressive regimens, including calcineurin inhibitors,
mycophenolate mofetil or azathioprine and corticosteroids, and its safety
profile is superior to ATG. Moreover, a similar occurrence of infections is
noted in selected studies (65.5% after basiliximab vs 65.7% of controls),
including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release
syndrome is not observed. Finally, economic analysis demonstrated lower costs of
overall treatment in patients treated with basiliximab. Therefore, the use of
basiliximab entails a very low risk, allows safe reduction of corticosteroid
dosage and reduces the short- and mid-term rejection rates. However, the
improvement in the long-term survival of kidney grafts in patients treated
according to modern immunosuppressive protocols is still to be demonstrated.
These conclusions are based on a systematic review of the scientific
literature, indexed on Medline database, concerning the mechanism of action,
therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in
renal transplantation. N.
Ref:: 62
----------------------------------------------------
[14]
TÍTULO / TITLE: - Renal transplantation
in HBsAg+ patients: is lamivudine your “final answer”?
REVISTA
/ JOURNAL: - J Clin Gastroenterol 2003 Jul;37(1):9-11.
AUTORES
/ AUTHORS: - Fontana RJ N. Ref:: 30
----------------------------------------------------
[15]
TÍTULO / TITLE: - Current treatment
strategies in ANCA-positive renal vasculitis-lessons from European randomized
trials.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Jul;18 Suppl 5:v2-4.
AUTORES
/ AUTHORS: - Tesar V; Rihova Z; Jancova E; Rysava R;
Merta M
INSTITUCIÓN
/ INSTITUTION: - First Medical Department, First Medical
Faculty, Charles University, Prague, Czech Republic. tesar@beba.cesnet.cz
RESUMEN
/ SUMMARY: - Antineutrophil cytoplasmic antibody
(ANCA)-positive renal vasculitis is the most common cause of rapidly
progressive (crescentic) glomerulonephritis. Its life-threatening natural
course may be modified substantially by current treatment modalities. The
European Vasculitis Study Group (EUVAS) developed a subclassification of
ANCA-positive vasculitides based on the disease severity at presentation, and
have organized (so far) two waves of clinical trials. The first wave of
randomized clinical trials had the aim of optimizing the existing therapeutic
regimens; the second wave concentrated on testing some newer therapeutic
approaches. Here, the design and available results of the first wave and the
design of some second wave trials are reviewed briefly. The potential of the
new targeted approaches (e.g. anti-tumour necrosis factor therapy) is also
briefly mentioned. N.
Ref:: 9
----------------------------------------------------
[16]
TÍTULO / TITLE: - Angiotensin II type 1
(AT1) receptor antagonists in the treatment of hypertension after renal
transplantation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001;16 Suppl 1:117-20.
AUTORES
/ AUTHORS: - Holgado R; Anaya F; Del Castillo D
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Hospital Reina
Sofia, 14012 Cordoba, España.
RESUMEN
/ SUMMARY: - Hypertension is highly prevalent after
renal transplantation and has been associated with lower graft survival.
Optimum management of post-transplant hypertension remains to be defined.
Losartan, a potent, orally active and selective non-peptide blocker of the
angiotensin subtype 1 receptor, could represent a useful drug for treating
post-transplant hypertension. Recently, a prospective study of 12 weeks
treatment with losartan has showed a satisfactory control of arterial
hypertension associated with a decrease in proteinuria in this high-risk group
of renal transplant patients. A retrospective study was performed to review the
role of losartan as a renoprotective agent (evaluating blood pressure and
proteinuria) in renal transplant recipients in a long-term follow-up. A total
of 150 transplant recipients were included in the study. None of the patients
had a serum creatinine >3 mg/dl, or suspected renal artery stenosis, or
other severe concomitant diseases. The indication for losartan therapy was
hypertension, proteinuria and/or post-transplant erythrocytosis. The values of
blood pressure, results of fasting haematology, blood chemistry and total proteinuria
in 24-h urine samples were recorded at the time of initiation of losartan
therapy, 6 and 3 months before the start, and at 3, 6, 12, 18 and 24 months
thereafter. A tendency analysis by linear regression comparing two slopes
before and after treatment was realized. A decrease in mean blood pressure and
proteinuria, from 106.7+/-0.9 to 98.2+/-2.1 mmHg and from 1253.9+/-188 to
91.2+/-33.7 mg/24 h, P<0.05, respectively, was observed after introduction
of losartan. A progressive increase in creatinine clearance was observed after
the third month of losartan treatment. No significant changes were seen in
haematocrit or serum potassium levels. We can conclude that a progressive
decrease in mean arterial pressure associated with a decrease in proteinuria was
observed during long-term follow-up. Based on the capacity of losartan to
improve renal function, this drug could be decisive for the treatment and
prevention of chronic allograft nephropathy.
N. Ref:: 32
----------------------------------------------------
[17]
TÍTULO / TITLE: - Calcineurin-free
protocols with basiliximab induction allow patients included in “old to old”
programs achieve standard kidney transplant function.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Jun;35(4):1326-7.
AUTORES
/ AUTHORS: - Emparan C; Laukotter M; Wolters H; Dame C;
Heidenreich S; Senninger N
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, Uniklinikum Munster, Munster, Germany. cemparan@teleline.es
RESUMEN
/ SUMMARY: - INTRODUCTION: The EuroTransplant “old to
old” program establishes that patients older than 60 years can receive offers
of organs from donors older than 60 years. The compromised function of these
organs makes it a priority to preserve their initial kidney function.
HYPOTHESIS: Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R)
antibody induction (Simulect) may benefit initial kidney function in these
patients, as assessed by the rates of delayed graft function and of rejection
during the first month after transplant. PATIENTS AND METHODS: A cohort of 15
consecutive elderly patients were prospectively compared with 30 cadaveric
kidney transplants in younger recipients. Study patients were induced with
Simulect (20 mg, 30 minutes before reperfusion and 4 days after
transplantation) and steroids, delaying the introduction of CsA until the serum
creatinine was below 3 mg/dL. The other cohort of patients were
immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF,
1 g/d), and an identical taper of steroids. The analysis compared donor and
recipient ages, mean cold ischemic time, incidence of initial kidney function
(diuresis in the first 24 h) serum creatinine levels, glomerular filtration
rate (GFR), number of dialysis sessions, and rejection rate in the two groups.
RESULTS: Except for the donor and recipient ages (72 vs 54 in donors, and 67
versus 52 years in recipients), no significant differences were observed
between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed
graft function (13.2% required dialysis), or infection (6.6%). Within 1 month
all 45 grafts showed primary function with equal creatinine levels (mean 1.65).
CONCLUSIONS: Calcineurin-free protocols using IL-2 therapy as the initial
suppression allow patients in the “old to old” ET program to display equal
results to cadaveric kidney transplants with initial treatment with calcineurin
antagonists.
----------------------------------------------------
[18]
TÍTULO / TITLE: - ACE inhibitors and AII
receptor antagonists in the treatment and prevention of bone marrow transplant
nephropathy.
REVISTA
/ JOURNAL: - Curr Pharm Des 2003;9(9):737-49.
AUTORES
/ AUTHORS: - Moulder JE; Fish BL; Cohen EP
INSTITUCIÓN
/ INSTITUTION: - Department of Radiation Oncology, Medical
College of Wisconsin, Milwaukee, WI 53226, USA. jmoulder@its.mcw.edu
RESUMEN
/ SUMMARY: - Radiation nephropathy has emerged as a
major complication of bone marrow transplantation (BMT) when total body
irradiation (TBI) is used as part of the regimen. Classically, radiation
nephropathy has been assumed to be inevitable, progressive, and untreatable.
However, in the early 1990’s, it was demonstrated that experimental radiation
nephropathy could be treated with a thiol-containing ACE inhibitor, captopril.
Further studies showed that enalapril (a non-thiol ACE inhibitor) was also
effective in the treatment of experimental radiation nephropathy, as was an AII
receptor antagonist. Studies also showed that ACE inhibitors and AII receptor
antagonists were effective in the prophylaxis of radiation nephropathy.
Interestingly, other types of antihypertensive drugs were ineffective in
prophylaxis, but brief use of a high-salt diet in the immediate
post-irradiation period decreased renal injury. A placebo-controlled trial of
captopril to prevent BMT nephropathy in adults is now underway. Since excess
activity of the renin-angiotensin system (RAS) causes hypertension, and
hypertension is a major feature of radiation nephropathy; an explanation for
the efficacy of RAS antagonism in the prophylaxis of radiation nephropathy
would be that radiation leads to RAS activation. However, current studies favor
an alternative explanation, namely that the normal activity of the RAS is
deleterious in the presence of radiation injury. On-going studies suggest that
efficacy of RAS antagonists may involve interactions with a radiation-induced
decrease in renal nitric oxide activity or with radiation-induced tubular cell
proliferation. We hypothesize that while prevention (prophylaxis) of radiation
nephropathy with ACE inhibitors, AII receptor antagonists, or a high-salt diet
work by suppression of the RAS, the efficacy of ACE inhibitors and AII receptor
antagonists in treatment of established radiation nephropathy depends on blood
pressure control. N.
Ref:: 108
----------------------------------------------------
[19]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.1 Long-term immunosuppression. Late steroid or
cyclosporine withdrawal.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:19-20.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In order to reduce or avoid
long-term serious adverse effects of corticosteroids, such as bone fractures,
diabetes mellitus, arterial hypertension, osteoporosis and eye complications,
steroid withdrawal should be considered. B. Steroid withdrawal is safe only in
a proportion of graft recipients and is recommended only in low-risk patients.
The efficacy of the remaining immunosuppression should be considered. C. After
steroid withdrawal, graft function has to be monitored very carefully because
of the risk of a delayed but continuous loss of function due to chronic graft
dysfunction. In the case of functional deterioration or dysfunction, steroids
should be re-administered. D. Cyclosporine withdrawal might be considered in
order to ameliorate nephrotoxicity, arterial hypertension, lipid disorders and
hypertrichosis. This can be carried out with no significant long-term risk of
progressive graft loss. The efficacy of the remaining immunosuppression should
be considered. After cyclosporine withdrawal, careful monitoring for acute
rejection is recommended.
----------------------------------------------------
[20]
TÍTULO / TITLE: - Angiopoietin growth
factors and Tie receptor tyrosine kinases in renal vascular development.
REVISTA
/ JOURNAL: - Pediatr Nephrol 2001 Feb;16(2):177-84.
AUTORES
/ AUTHORS: - Woolf AS; Yuan HT
INSTITUCIÓN
/ INSTITUTION: - Nephro-Urology Unit, Institute of Child
Health, University College London, UK. a.woolf@ich.ucl.ac.uk
RESUMEN
/ SUMMARY: - Angiopoietin-1 (Ang-1) is a secreted
growth factor which binds to and activates the Tie-2 receptor tyrosine kinase.
The factor enhances endothelial cell survival and capillary morphogenesis, and
also limits capillary permeability. Ang-2 binds the same receptor but fails to
activate it: hence, it is a natural inhibitor of Ang-1. Ang-2 destabilises
capillary integrity, facilitating sprouting when ambient vascular endothelial
growth factor (VEGF) levels are high, but causing vessel regression when VEGF
levels are low. Tie-1 is a Tie-2 homologue but its ligands are unknown.
Angiopoietin and Tie genes are expressed in the mammalian metanephros, the
precursor of the adult kidney, where they may play a role in endothelial
precursor growth. Tie-1-expressing cells can be detected in the metanephros
when it first forms and, based on transplantation experiments, these precursors
contribute to the generation of glomerular capillaries. During glomerular
maturation, podocyte-derived Ang-1 and mesangial-cell-derived Ang-2 may affect
growth of nascent capillaries. After birth, vasa rectae acquire their mature
configuration and Ang-2 expressed by descending limbs of loops of Henle would
be well placed to affect the growth of this medullary microcirculation.
Finally, preliminary data implicate angiopoietins in deregulated vessel growth
in Wilms’ kidney tumours and in vascular remodelling after nephrotoxicity. N. Ref:: 64
----------------------------------------------------
[21]
TÍTULO / TITLE: - Early prognosis of the
development of renal chronic allograft rejection by gene expression profiling
of human protocol biopsies.
REVISTA
/ JOURNAL: - Transplantation 2003 Apr 27;75(8):1323-30.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000068481.98801.10
AUTORES
/ AUTHORS: - Scherer A; Krause A; Walker JR; Korn A;
Niese D; Raulf F
INSTITUCIÓN
/ INSTITUTION: - Novartis Institutes for BioMedical
Research/Transplantation, Novartis Pharma AG, Basel, Switzerland.
RESUMEN
/ SUMMARY: - BACKGROUND: Chronic allograft rejection
(CR) is the major cause of failure of long-term graft survival and is so far
irreversible. Early prognosis of CR by molecular markers before overt
histologic manifestation would be a valuable aid for the optimization of
treatment regimens and the design of clinical CR trials. Oligonucleotide
microarray-based approaches have proven to be useful for the diagnosis and
prognosis of a variety of diseases and were chosen for the unbiased
identification of prognostic biomarkers. METHODS: Renal allograft biopsies were
taken at month 6 posttransplantation (PT) from two groups who were, at that
time, healthy recipients: one group developed CR at month-12 PT, the other
group remained healthy. Gene expression profiles from the two groups at month-6
PT biopsies were analyzed to identify differentially expressed genes with
prognostic value for CR development at month 12. RESULTS: A set of 10 genes was
identified that showed differential expression profiles between the two patient
groups and had a complete separation of the 15% to 85% quantile range for each
individual gene. This set of genes was sufficient to allow the correct
prediction of the occurrence or nonoccurrence of CR in 15 of 17 (88%) patients
using cross-validation (occurrence for a patient was predicted on the basis of
the other patients’ data only). In addition, a correct prediction could be made
that a recipient with a normal biopsy 12 months PT developed CR within the
following 6 months. CONCLUSIONS: Identified expression patterns seem to be
highly prognostic of the development of renal CR.
----------------------------------------------------
[22]
TÍTULO / TITLE: - Calcium metabolism and
skeletal problems after transplantation.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2002 Feb;13(2):551-8.
AUTORES
/ AUTHORS: - Torres A; Lorenzo V; Salido E
INSTITUCIÓN
/ INSTITUTION: - Nephrology Section and Research Unit,
University Hospital of the Canary Islands, Instituto Reina Sofia de
Investigacion, Tenerife, España. atorres@ull.es N. Ref:: 59
----------------------------------------------------
[23]
TÍTULO / TITLE: - The impact of impaired
insulin release and insulin resistance on glucose intolerance after renal
transplantation.
REVISTA
/ JOURNAL: - Clin Transplant 2002 Dec;16(6):389-96.
AUTORES
/ AUTHORS: - Hjelmesaeth J; Hagen M; Hartmann A;
Midtvedt K; Egeland T; Jenssen T
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Section of
Nephrology, Oslo, Norway. joran@online.no
RESUMEN
/ SUMMARY: - The current knowledge of the pathogenesis
of post-transplant glucose intolerance is sparse. This study was undertaken to
assess the relative importance of insulin secretion (ISec) and insulin
sensitivity (IS) in the pathogenesis of post-transplant diabetes mellitus
(PTDM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)
after renal transplantation. An oral glucose tolerance test (OGTT) was
performed in 167 non-diabetic recipients 10 wk after renal transplantation.
Fasting, 1-h and 2-h insulin and glucose levels were used to estimate the
insulin secretory response and IS. One year after transplantation 89 patients
were re-examined with an OGTT including measurements of fasting and 2 h glucose.
Ten weeks after transplantation the PTDM-patients had significantly lower ISec
and IS than patients with IGT/IFG, who again had lower ISec and IS than those
with normal glucose tolerance (NGT). One year later, a similar difference in
baseline ISec was observed between the three groups, whereas baseline IS did
not differ significantly. Patients who improved their glucose tolerance during
the first year, were mainly characterized by a significantly greater baseline
ISec, and they received a significantly higher median prednisolone dose at
baseline with a subsequent larger dose reduction during the first year, than
the patients who had their glucose tolerance unchanged or worsened. In
conclusion, both impaired ISec and IS characterize patients with PTDM and IGT/IFG
in the early course after renal transplantation. The presence of defects in
insulin release, rather than insulin action, indicates a poor prognosis
regarding later normalization of glucose tolerance. N. Ref:: 29
----------------------------------------------------
[24]
TÍTULO / TITLE: - Basiliximab: a review
of its use as induction therapy in renal transplantation.
REVISTA
/ JOURNAL: - Drugs 2003;63(24):2803-35.
AUTORES
/ AUTHORS: - Chapman TM; Keating GM
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - Basiliximab (Simulect), a chimeric
(human/murine) monoclonal antibody, is indicated for the prevention of acute
organ rejection in adult and paediatric renal transplant recipients in
combination with other immunosuppressive agents.Basiliximab significantly
reduced acute rejection compared with placebo in renal transplant recipients
receiving dual- (cyclosporin microemulsion and corticosteroids) or
triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and
patient survival rates at 12 months were similar. Significantly more
basiliximab than placebo recipients were free from the combined endpoint of
death, graft loss or acute rejection 3 years, but not 5 years, after
transplantation.The incidence of adverse events was similar in basiliximab and
placebo recipients, with no increase in the incidence of infection, including
cytomegalovirus (CMV) infection. Malignancies or post-transplant
lymphoproliferative disorders after treatment with basiliximab were rare, with
a similar incidence to that seen with placebo at 12 months or 5 years
post-transplantation. Rare cases of hypersensitivity reactions to basiliximab
have been reported.The efficacy of basiliximab was similar to that of equine
antithymocyte globulin (ATG) and daclizumab, and similar to or greater than
that of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte
globulin (RATG) in patients at relatively low risk of acute rejection, but less
effective in high-risk patients. Numerically or significantly fewer patients
receiving basiliximab experienced adverse events considered to be related to
the study drug than ATG or RATG recipients. The incidence of infection,
including CMV infection, was similar with basiliximab and ATG or
RATG.Basiliximab plus baseline immunosuppression resulted in no significant
differences in acute rejection rates compared with baseline immunosuppression
with or without ATG or antilymphocyte globulin in retrospective analyses
conducted for small numbers of paediatric patients. Limited data from
paediatric renal transplant recipients suggest a similar tolerability profile
to that in adults. Basiliximab appears to allow the withdrawal of
corticosteroids or the use of corticosteroid-free or calcineurin
inhibitor-sparing regimens in renal transplant recipients.Basiliximab did not
increase the overall costs of therapy in pharmacoeconomic studies.CONCLUSION:
Basiliximab reduces acute rejection without increasing the incidence of adverse
events, including infection and malignancy, in renal transplant recipients when
combined with standard dual- or triple-immunotherapy. The overall incidence of
death, graft loss or acute rejection was significantly reduced at 3 years;
there was no significant difference for this endpoint 5 years after
transplantation. Malignancy was not increased at 5 years. The overall efficacy,
tolerability, ease of administration and cost effectiveness of basiliximab make
it an attractive option for the prophylaxis of acute renal transplant
rejection. N. Ref:: 85
----------------------------------------------------
[25]
TÍTULO / TITLE: - Pharmacokinetics of
tacrolimus-based combination therapies.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i12-5.
AUTORES
/ AUTHORS: - Undre NA
INSTITUCIÓN
/ INSTITUTION: - Fujisawa GmbH, Neumarkter Str. 61, D-81673
Munich, Germany. nas.undre@fujisawa.de
RESUMEN
/ SUMMARY: - This paper reviews the pharmacokinetics of
tacrolimus, with special reference to its combination with adjunctive
immunosuppressants. Oral bioavailability of tacrolimus, which is variable
between patients, averages approximately 25%. This is largely due to extrahepatic
metabolism of tacrolimus in the gastrointestinal epithelium. Nevertheless,
intra-patient variability is low, as evidenced by the small number of dose
changes required to maintain patients within the recommended tacrolimus target
levels. Tacrolimus is distributed extensively in the body with most partitioned
outside the blood compartment. Concentrations of tacrolimus in blood are used
as a surrogate marker of clinically relevant concentration of the drug at the
site(s) of action. Convenient whole-blood sampling within a +/-2-h window
around 12 h post-dose (C(min)) is highly predictive of systemic exposure to
tacrolimus and is thus used to optimise therapy. Sampling at other time-points
offers no advantage over C(min) monitoring. The interactions of tacrolimus with
other immunosuppressive agents are well characterized. After cessation of
concomitant corticosteroid treatment, exposure to tacrolimus increases by
approximately 25%. In contrast, there is no pharmacokinetic interaction between
mycophenolate mofetil (MMF) and tacrolimus. Therefore, systemic exposure to the
active metabolite of MMF, mycophenolic acid, is higher with MMF-tacrolimus
combination than with MMF-cyclosporin combination. Therefore, 1 g/day MMF may
be an adequate maintenance dose in tacrolimus-based regimens. Co-administration
of tacrolimus and sirolimus, while having no effect on exposure to sirolimus,
results in reduced exposure to tacrolimus at sirolimus doses of 2 mg/day and
above. In conclusion, tacrolimus levels should be monitored when sirolimus is
co-administered at doses >2 mg/day and after cessation of corticosteroid
treatment. N. Ref:: 13
----------------------------------------------------
[26]
- Castellano -
TÍTULO / TITLE:La enfermedad linfoproliferativa
difusa postrasplante renal y su relacion con el virus Epstein-Barr. Experiencia
de un centro. Diffuse lymphoproliferative disease after renal transplantation
and its relation with Epstein-Barr virus. Experience at one center.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2002;22(5):463-9.
AUTORES
/ AUTHORS: - Franco A; Jimenez L; Aranda I; Alvarez L;
Gonzalez M; Rocamora N; Olivares J
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia Hospital General
Alicante Maestro Alonso, 109 03010 Alicante. franco_ant@gva.es
RESUMEN
/ SUMMARY: - Post-transplant lymphoproliferative
disorders (PTLD) are a group of heterogeneous lymphoid proliferations in
chronic immunosuppressed recipients which appear to be related to Epstein Barr
Virus (EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and
CMV disease have been identified as risk factors that may tigger development of
PTLD. We have studied the incidence of PTLD and its relationship with EBV in
588 adult renal transplant recipients who were transplanted in our hospital
from 1988 to 2001. We have also evaluated the diagnostic and therapeutic
methods used, the risk factors and outcome of the patients who developed PTLD.
We identified 8 recipients (4 males and 4 females), range from 18 to 67 years
(mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years
(0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had
CMV disease, two of them (25%) had been treated with hight doses of
prednisolone, another was EBV seronegative, but the rest of them (50%) had no
risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was
based on the histology of biopsy and the last one by CT scans of chest-abdomen
and cytology. The presence of EBV in the lymphoproliferative cells was assessed
in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was
poor. Five out of 8 patients died shortly after diagnosis as a direct
consecuence of PTLD and another of an infectious complication of the treatment
(75%). The 2 patients alive started dialysis and 1 of them died 2 years later
of a non-related cause. In conclusion, PTLD is a relatively frequent disease
with a poor prognosis in renal transplant patients. It seems to have a close
relationship with EBV and can develop in the absence of the classical risk
factors. N. Ref:: 18
----------------------------------------------------
[27]
TÍTULO / TITLE: