Plus. Chlorambucil. Versus. Methylprednisolone. Plus. Cyclophosphamide ... 6 mo: 3 mo with corticosteroids and. 3 mo with one cytotoxic drug. Among.
A Randomized Study Comparing Methylprednisolone Plus Chlorambucil Versus Methylprednisolone Plus Cyclophosphamide in Idiopathic Membranous Nephropathy CLAUDIO PONTICELLI,* PAOLO ALTIERI,t FRANCESCO SCOLARI, PATRIZIA PASSERINI,* DARIO ROCCATELLO, BRUNO CESANA,” PATRIZIA MELIS,t BRUNELLA VALZORIO, MAURO SASDELLI,1 SONIA PASQUALI,# CLAUDIO POZZI,** GIUSEPPE PICCOLI, ANTONIO SIRO SEGAGNI, FRANCESCO ANTONUCCI,5 MAURO DUGO,111’ MARILENA MINARI,11 ALFIO SCALIA, LUCIANO PEDRINI,*** GABRIELE PISANO,ttt CLAUDIO GRASSI,t MARCO FARINA, and ROBERTO BELLAZZI’1111 *Dj,jsjone
di Nefrologia
Regionale
Spedali
Ospedale
Maggiore
Lecco;
“Ospedale
Provinciale
Feltre;
Zonaie
Uboldo
Magenta;
mide
To may
assess
have
whether
idiopathic merubranous mens based on a 6-mo methylpnednisobone with cycbophosphamide. nous
ncphropathy
domized
and
to be given
3 consecutive mg/kg
per
Civile
1Ospedale
chborarubucil
or index
chborambucib Patients with
by
cycbophospha-
in patients
with
or mcthylprcdnisobone biopsy-proven membrasyndrome
were
ran-
(1 g intravenously
oral
ructhylpnednisobone,
27 d) alternated
d for
(0.2
every other month either per d for 30 d) or cycbophosphamide
rug/kg
with
Among
87 patients followed for at beast 1 yr. 36 of 44 (82%; confidence interval [CI], 67.3 to 91 .8%) assigned to
methylprcdnisobone tial
remission 95%
There
is now
CI, 80.9
methylprednisobonc
3 mo
and chborambucib of
(93%;
whole
the to
controlled and
ncphrotic
98.5%)
treatment with
lasted
one
entered syndrome,
Parma;
##Ospedale
Provinciale
Lodi;
and
hiOspedale
chbonambucil
complete versus
on par40
group
(30.5%)
group
(25%)
had
of
43
and a relapse
(P
remained
0.01)
and
values
in the
in the
phamide
ncphrotic both
and
treatments
developed may
renal
9: 444-450,
two
cancer.
in the
is
but
at least
(1-3)
and
3 yr.
of side
none
in the
zoster.
concluded
One that
in
nephropathy
in favoring
for
Six
cycbophos-
herpes
It
with 3 yr.
because
merubranous
effective
function
2 and
group from
idiopathic
be
attained chloram-
compared for
the treatment
suffered
with
when
chlorambucil
group group
who
cycbophosphamidc syndrome between
followed
group
in the
patients
preserving
groups
did not complete
cycbophosphamide per
unchanged
cohort
patients
patients
1 1 of 36 in the
of plasma creatininc improved in for I yr for both treatment groups
chborambucib
group Four
Of
10 of 40 in the of the nephrotic
reciprocal followed
with
corticosteroids,
a positive
serum
with
albumin
con-
The
per
a
syndrome
for the study.
creatinine
or cycbosporine;
of
and
3.5
were
a plasma
previous
drugs,
bodies antigen
between
gIL),
criteria
deciliter
(150
irumunosupprestest
for anti-DNA
anti-
(and antinuclear antibodies in many patients) or hepatitis B or hepatitis C virus antibodies; a positive Veneral Disease
Research plement
Laboratory component
test: or low serum C3 or C4. A clinical
litus. malignancy. sure to drugs that
chborambucil but
at a dose
count
decreased
dose
wt per d given cycle
concentrations of the diagnosis of diabetes
systemic lupus erythematosus, could induce membranous
infections, nephropathy
was
mg/kg
group
mide
the was
mg/kg
5000
cornmel-
or expowere also
Steroids
period.
The
were use
discouraged
but
Clinical
excretion
a remission.
at
I wk.
a normal
plasma
syndrome
was
3.5 g/d
worsening
was
Gbomerular
stages
reich
ci’
with
tubular
were
atrophy
biopsies
were
were
was an open-label by the institutional patient
ruent
regimens,
sample
size
probability
gave were
informed
written
assigned
according a decrease
to of about
ruethylprednisobone
25%
with
year,
and
plus
every
side were
cytotoxic
effects
of therapy.
measured
every
drug,
and
In our previous criteria,
only
start
early,
to prevent
24-h was
syndrome
without complications
a run-in
period,
was from
of
treat-
order.
thereafter. urinary questioned
At each protein about
of efficacy
and
administration
rates and platelet of the
visit.
patients
had a spontaneous
6 mo (4). Therefore, a potentially
of the nephrotic
with
syndrome.
the same
reciprocal
beneficial Patients
treatment assigned
to
remission 0.2 1 and
2
concentration. as an
increase
in
who
had
in plasma
the baseline
value.
remission,
complete
was estimated according to of the hazard functions
performed
on
or partial
of the plasma
creatinine
treatments were compared measurements (10), with
patient”
the
cumulative
remission.
A further
of the remission
factor
at two
levels
(every
and
and
time
6 mo).
proteinuria
cedure icance
for correction of the degrees of freedom of the within-patient terms was followed. been
carried
trend (second degree). creasing-increasing-decreasing
out
The
as a fixed,
at 2 1 levels
has
by
two
values
for
“within-patient”
Geisser-Greenhouse
means
( I I ) pro-
for statistical In addition,
of orthogonal
of a linear and then
signifa trend
polynomial
increasing/decreasing decreasing (or
higher than the have therapeutic
third). Indeed, impact.
trend versa)
vice
of an increasing-decreasing-increasing trend (third degree) of a mean
ating pattern (degree overall pattern could
time
The test.
by mixed-factorial ANOVA for treatment as a fixed, “between-
factor
or defluctu-
the shape
of an
Results Among tion,
97 patients
two
were
underlying after
remission
we preferred
partial
(partial or complete) on the total follow-up for each patient. treatments were then compared by the Wilcoxon rank sum
of
excretion symptoms
remission.
as an increase
as the percentage
a baseline
plasma
been
was obtained
contrasts to assess the presence (first degree), of an increasing
at of
was
permitted.
fulfilled as suggested by the log have been shown for illustrative
complete
analysis
visit,
selected
have
with
A
erythrocyte,
patients
tests
of patients
to
of about
and
complete/partial
be considered survival curves
necessary
(2) at power
10 d during
with
within
random
of response
at each
experience
was apcenter,
of the two
per group
Leukocyte,
one of 39 untreated
of the nephrotic
fob-
0.05). Patients were examined 6 ruo. every 2 mo until the end
7 to
repeated
to one
chborambucil =
3 to 6 ruo
creatinine concentrations and were measured, and the patient counts
No
At the coordinating
a center-stratified 50 patients
with a two-tailed test (alpha every month during the first
possible
fibrosis
or absent.
consent.
consecutively
80%
first
index
cannot plots,
only;
proportion
The
0.80 least the
interstitial
as present
purposes
of Ehren-
multicenter study. The protocol review board of the coordinating
of approximately
demonstrate
and
biopsy
microscopy.
to the system
sclerosis
classified
renal
study
Analyses
Cumulative
the two repeated
Design
patients
according
each electron
performed.
This proved center,
examined and
glornerular
Study
each
center
classified
al. (8). Mesangial
low-up
and
study
immunofluorescence.
the
I wk in patients
over
proportionality (-log) survival
at each
were
defined
50%
Histology light.
of
creatinine
defined
of at least
Renal
by
less of
inhibitors
to between
for at least
remission alone, and thereafter of relapses Kaplan and Meier (9). Because assumption
pathologist
end
drugs
excretion
for exclusion.
The
the
discon-
3 ruo with the same of the two cytotoxic the
Hypolipemic
criteria
specimen
it was
enzyme
of protein
with
concentration
Statistical
stopped
g/d for at least
than
Stable
and
or partial
nephrotic
creatinine
by 50%.
leukocyte b0’1L),
X
in the rate of urinary
Relapse
the
(5
as a complete
1 wk,
to more
cycbophospha-
as a reduction
g/d for at least of
by oral
to the
of methyl-
defined
in the rate
proteinuria
cycles
was defined to 0.2
as a reduction
three
6 mo for both groups; and 3 mo with either
was
of treatment
assigned
cycle if the leukocyte count was (3 X b0#{176}IL).The total duration
not prohibited.
remission
protein
Patients
angiotensin-converting
response
Complete
with days
27 d, in a single 1 mo
millimeter
reduced
completely
of
for by
same
cubic
was
treatment
wt per d. If a patient’s
per
agent
orally
replaced
body
of
445
on 3 consecutive
followed
received
below
cycles
per d, orally).
chlorambucil
of 2.5
of the cytotoxic
drugs.
three
each (0.2
Nephropathy
intravenously
body
and
treatment, therefore, was doses of methylprednisobone
exceeding
of
