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E. P. Lasmar; M.F.Lasmar;L.F.Lasmar;L.F. C. Giordano; F.
L. Junior; J. M. Borges (*)
Abstract
The aim of this study was to compare the
progression of renal grafts following treatment
of an acute rejection event based on the
histological diagnosis of a graft biopsy
compared to a presumptive (clinical and
laboratory) diagnosis. A historical cohort was
used to
study 44 patients undergoing a live haploidentical
related donor renal transplant, using a
similar immunosuppressive treatment: cyclosporine,
azathioprine and prednisone. Treatment
of
the acute rejection event was made using
methylprednisolone 250 mg during 3 to 5
days based on a histological examination diagnosis
(biopsy group = 14) or on a clinical and
laboratory diagnosis (presumptive group
=
30) which consisted of an over 20% elevation
in plasma creatinine in 24 hours and renal
ultrasound or cintigraphy findings. The
study demonstrated no significant difference in
renal function (plasma creatinine) and
other
outcomes 2 years following transplantation
in both groups.
The results show that treatment of acute
rejection based on a presumptive diagnosis
is not a risk factor for unfavorable outcomes following 2 years of renal transplantation
monitoring.
Keywords: kidney transplantation, biopsy, acute rejection
Material and methods
An historical cohort was used to assess 44
patients who had undergone a live haploidentical
donor renal transplant between 1990 and
1999. The biopsy group (n=14) was defined as that
in which diagnosis of acute rejection
was made based on a percutaneous renal biopsy
and pathology. Diagnosis in the presumptive
group (n=30) was made based on clinical
criteria (fever with no evidence of infection, pain
over the graft site, a fall in urinary
output), laboratory findings (rise in plasma creatinine
at least 20% over baseline values) and
image studies (Doppler ultrasound or cintigraphy).
Treatment of acute rejection was the
same in both groups, using methylprednisolone
250 mg during 3 to 5 days. No group required
mono or policlonal antibody salvage treatment.
Both groups used the same immunosuppression
regimen (cyclosporine, azathioprine and
prednisone) and there was no difference in donor and
receptor age, type, race, gender, HLA
mismatches and PRA between both groups (Table1).The
cohort was interrupted two years following
the diagnosis of rejection and plasma
creatinine
values were compared between both groups
(primary outcome). Secondary outcomes
assessed were death, graft loss, infection and
other
complications. The Mann-Whitney test
was used for variable analysis in both groups
and a 5% significance level was considered
for all outcomes.
Results
There was no significant difference in
plasma creatinine in both groups two
years following
treatment for acute rejection. The
p value was 0.115, with a 5% significance level.
There was no difference (5% significance
level) between both groups in the variables
under study: death, graft loss, infection
and other complications (Table 2).
Discussion
Acute graft rejection still occurs in around
10 to 20% of cases2 even with new immunosuppressant
drugs. Pathology remains the gold standard
for the diagnosis3 but other non-invasive
methods have been used, such as the plasma
creatinine, the creatinine clearance,
Doppler ultrasound and cintigraphy.4 Doppler ultrasound
with analysis of the diastolic/systolic
ratio, the pulsatility index and the resistivity
index has both advantages and disadvantages – it
is limited to large vessels (main artery,
arcuate and interlobar arteries) – while
a biopsy allows the study of small vessels
in which rejection begins. Cintilography
has a 96% positive predictive value – based
on calculation of the ?P – but only
a 50% negative predictive value.1,5 Two clinical
studies comparing the accuracy of the clinical
diagnosis and histology showed contradictory
results.3 The first study demonstrated an
excellent and the second study showed a poor
correlation (83.3% and 43%). In this study,
creatinine had significantly higher values
in the biopsy group patients at the onset
of rejection compared to the presumptive
group, which may have led to an indication
for biopsies to assess the severity of rejection,
leading to a selection bias. Creatinine values
two years following the rejection event were
not superior in the biopsy group compared
to the presumptive group. There were no statistically
significant differences between both groups
in secondary outcomes (death, graft loss,
infection and other complications).
In conclusion notwithstanding the limited
number of patients in this study, we
may conclude that the presumptive treatment
of acute rejection is unrelated to a
less
favorable
graft function after a two-year follow-up
and is also not a risk factor for graft
loss, death or infection.
Bibliography
1. Távora ERF, Lasmar EP, Drummond
RS et al: Atualidades em Nefrologia 5. 1ª ed.,
São Paulo, SP, Sarvier, 326, 1998
2. Al-Awwa I A, Hariharan S, First M R
et al: Am J. Kidney Dis 31: 6 (suppl.1):
8,
1998
3. Salaman JR: Immunol Lett 29(1-2) et
al: 139, 1991
4. Bertoni E, Di Maria L, Piperno R et
al: J Nephr 12(2): 100, 1999
5. Castro MCR, Chocair PR, Saldanha LB
et al: Rev Ass Med Bras 44(2): 155, 1998
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