Prognostic

Significance

Change

Nephrotic

Study

Disease

TARSHISH,*

M. EDELMANN,

*Depart,nent

of Pediatrics,
and

Directors

Social

Network,

New

The ability
to predict
the
diagnosed
minimal
change

Abstract.

newly
(MCNS)

may

have

attempts

been

based

successful.

acterization
and the course

initial

during

of the subsequent
dren with MCNS,
dard prednisone
9.4 yr). They

implications.

lapsers,

infrequent

remission)

of disease

or initial

of patients

syndrome,
and

and

Beaumont

not

were

conduct

characterizes

change

with

the

demonstration

ness

during

the

first

of response

and

relapse.

and

that

and

of

the

6 months

the

January

When

therapy

may

Three-fourths

of

Nephrol

8: 769-776,

laboratory

>

ated
and

the

with

pattern

(4)

the nephrotic
of

MCNS.

adults,

among

among

children)

failure

with MCNS
progression

aids

do
to

in identifying

More

aggressive

individuals.

treatment

agents;

(J

with

and

or exposure

Am

Soc

(5)

to agents

steroids

or other

no evidence
known

of un-

to be associ-

syndrome.

renal biopsy
Of the 521

therapy.

histopathobogically

having

course

these

continued

to renal

outcome.

the

to ESRD

8 wk

of children
or undergo

no prior

underwent

initiation

diagnosed

responsive-

for

disease

All patients

initial

only

during

1997)

< 16 yr;

systemic

before

(MCNS),

indicated

both

course

progression

a poor

or immunosuppressive

derlying

char-

subsequent

and

cytotoxic

therapeutic
course

12 wk

be

for

entire

by progression

of the early
risk

their

proteinuria

during

first

of the

relapsers,

a nonrelapsing

6 months,

Documentation
at increased

initial

followed

proteinuria

the

40%

during

contrast,

Unremitting

was

the subsequent

8 yr of

1967

and

April

1976,

52 1 children

were entered
into a prospective
centers
in 12 countries
in North

with

recent-

study that
America,

Europe,
and Asia. Written
informed
consent was obtained
from all
participants.
Criteria
for admission
were (1) heavy proteinuria,
of 40
mg/lvm2 BSA (0.96
g/daym2),
determined
with an overnight
cob(2)

21%.

during

(nonrelapsers;

achieved

of treatment

Michigan.

This
whom

by the

is in striking

after

ISKDC
contrast

membranous

entry

patients.

into

389

central
to the

the study,

(74.7%)

were

pathologists
experience

gbomerulonephritis

as
with

(a rare

disease

predominates.

Methods

onset nephrotic
syndrome
involved
19 participating

lection:

8 wk

Oak,

in remission
In

of 3 yr.

Clinical

in remission

continued

infrequent,

an average

ESRD.

Patients
Between

and

and

Royal

therapy

rarely.

At

of steroid

predicts

either

of

York,

Institute,

initial

relapsed

those

syndrome

pattern

or

Department

New

occurred
for 35%. Although
95%
well, 4 to 5% die from complications

(con-

long-term

nephrotic

series)

course

York;

remained

after

nonre-

controlled

the

and

Bronx,

who

period

entire

in

New

Research

responders

through

Disease
in Children
study of childhood

clinical

a series

initial

6-month

initial

chilstan-

with

Bronx,

Hospital

after

are predictive

relapsers.

in remission.

BERNSTEIN,

of Medicine,

frequent

steroids

included

frequent

to determine

to

trials ( 1-7). This report

outcome
of minimal

Materials

College

char-

nonresponders

the International
Study of Kidney
began
a multicenter
prospective

nephrotic

of Medicine,

have

whether

classifications

relapsers,

80%

acteristics

College

Previ-

onset

Three
hundred-eighty-nine
at onset,
were treated

Subsequent

JAY

Einstein

Wil!iam

to adrenocortical

months

outcome.
diagnosed

and

investigated

response

the early

(complete
proteinuria).

In 1967,
(ISKDC)

Albert

regimens
and monitored
for up to 1 7 yr (mean,
were classified,
after 8 wk of therapy,
as initial

tinued
follow-up,

Einstein

at disease

it was

N. TOBIN,t

course
in children
with
nephrotic
syndrome

available

of the International

JR*

Albert

therapeutic

data

Therefore,

of the

responders

significant
on

of Minimal

in Children

Medicine,

York;

Course

Report

JONATHAN

CHESTER
Epidemiology

ous

Syndrome:

of Kidney
PENINA

of the Early

hypoalbuminemia,

of 2.5

g/dL

(25

g/L):

(3)

age

of

Prednisone

Regimens

The

treatment

was

60 mg/24

hm2

80 mg/24

hm2)

in three

divided

daily

initial
dosage,

followed

by 40 mg/24

in divided

doses

of relapse
was 60 mg/24
imum
of 4 wk), followed
consecutive

days

Response
Received
May 7, 1996. Accepted
September
24. 1996.
Correspondence
to Dr. Chester
M. Edelmann.
Albert
Medicine.
1300 Morris Park Avenue, Bronx, NY 10461.
I 046-6673/0805-0769$03.00/0
Journal of the American
Society of Nephrology
Copyright
U 1997 by the American
Society of Nephrobogy

Einstein

College

of

hm2

to <4

Relapse
(Albustix,

involved

were
during

Some

mg/lvm2

who

Initial
the initial
of the

(maximum

doses for 4 wk,

60 mg/24 hm2)

of 7 for 4 wk.

hm2 in divided
by 40 mg/24

The

treatment

doses until response

(maxhm2 in divided
doses
on 3

as a reduction
(Albustix,

in the rate of urinary

0 to trace)

responded

during

nonresponders

were

8 wk of prednisone
patients

subsequently

days.

of 40
mg/lvm2
Initial responders

the 8 wk of the initial

patients

excretion

for 3 consecutive

a reappearance
of proteinuria
+ + or greater)
for 3 consecutive
days.

patients

regimen.

daily

days

daily
dosage,

of 7 for 4 wk.

was defined

of protein

(maximum

on 3 consecutive

prednisone

who

failed

entered

into

prednisone
to respond

therapy.
were

therapeutic

770

Journal

trials

of the American

incorporating

that

included

initial

different

Society

dosages

cycbophosphamide

2 yr of inclusion

in the trial,

by their own physicians.

trials, very few patients

However,
received

of Nephrology

of prednisone

(5) and

regimens

( 1 ) or azathioprine

(7).

patients

as determined

were

treated

After

except
for those included
drugs other than prednisone.

Table

of Clinical

For the purpose

into three
quent

course,

each

1 yr of follow-up

For

assessing

after

annually

the

initial

I and

status
the

8 wk after

therapy;

on the basis

(Tables

yr with

of the patients

( 1 ) the initial

period

classified

consecutive

the courses

as follows:

(2) the 6-month

study:

classifications

no

Infrequent

relapse

relapser:

Frequent

one

relapser:

Nonresponder

to three

four

followed

followed
Nonresponder

relapses

or more
by

relapses

remission:

by remission
not followed

8 weeks

by remission:

were divided

entrance

unremitting

proteinuria

Results

into the

of data

over

classification

Characteristics

and (3) the subsereported

The

during

and

2).

of patients

same

terize the course of the patients

changes.
This allowed transient

time,

was

a period

of 2

required

to charac-

and to identify clinically

changes
in the frequency

significant
of relapses

at Onset

389
34%

(mean

patients
female

SD).

0.87

to 14.8.

been

published

with

MCNS

included

66%

patients.

Age

at onset

was

Age

at entry

A figure

showing

(4).

cal and laboratory

4.9
the

age

As previously

distribution

reported

data did not correlate

Histopathologv
tissue

correlations

was processed,
as previously

between

clinical

course,

evaluated,
and classified
into histodescribed
(2.9). Because
there were no

histologic

data

for

subtypes

all

of MCNS

patients

were

and

pooled

the long-term

for

the

Geographic

present

Histopathobogic

Methods

and

for quantitative

dence

limits

differences

were

for categorical

measures

using

and

measures
estimated

between

means

to describe

patient

subgroups

SD.

response

The

times

( 10). Patients

95%
and

were

confl-

to assess

evaluated

irregular
intervals
during the follow-up
period. Annual assessments
were obtained
for all patients. and the clinical courses were classified
according
to the criteria
listed in Table 2. Analysis
of the subsequent
courses was based on the proportion
of patient reports in each annual
classification.

among

at

341

patients

1. Initial

Initial

and

responder:
cessation

attainment

Initial

of complete
within

children

at 2 yr from

(93%)

initial

nonrelapser:

no

initial

infrequent

relapser:

initial

frequent

relapser:

histopatho-

no correlations
was present

and,

were
at onset

6-month

Europe,
16.5%
North America.
classifications

entry,

(Table

301

months,

at 5 yr.

262

60 at 15 yr.
was possible
3).

For

with

were

onset

nor

Table

3.

patients,

334

initial

for

I 3 patients.

GFR

(92%)

were

nonresponders
at last

included

at 7 yr.

363

there

initial

(Table

follow-up

a maxi-

monitoring

223

of the
were

cient data to characterize

the courses
during
the first
for I 3 patients,
there were no follow-up
data beyond
(8%)

did

examination

and

Neither

two

8 weeks

of

Six-month

Initial responder
nonrelapser

continuous
of therapy

relapse
or more

proteinuria

29

GFR

correlated

at
with

remission

initial

relapse

one

389

6 months;
entrance.

responders
3).

at

insuffi-

classifications
% of Total

% of Subgroup

6 months

nonresponder:

nonresponder:
initial
8 weeks

the

No.

subsequent

clini-

course

from
from

averaged
1 13 62
(17.6 yr). Follow-up

therapy

during

subsequent

classifications

of proteinuria

prednisone
Course

6-month

has

baseline

groups.

10 yr. 186 at 12 yr, and

Six-month
classification

Of the 363

Table

and

these

Course
Follow-up
times
mum of 2 1 1 months

using proportions

yr

of

at onset

(4),

or subsequent

47.8%
patients
Kong, and 35.7%

subtypes

not differ

The data were evaluated

2.9

a range

Distribution

The series
included
from Japan and Hong

analysis.

Statistical

to therapy,

patients

with renal

therefore,
are not reported
here. Similarly,
found with microscopic
hematuria,
which
in one-third
of patients.

subgroups

response

male
4.8

2.9 yr. with

logic

Renal

findings,

was

to be disregarded.

logic

of proteinuria

Courses

of analysis.

phases.

Annual

Nonrelapser:

in these

Methods used for data collection,

coding, reporting
of clinical and
laboratory
examinations,
and standardization
of age- and genderdependent
variables
have been described
previously
(2,4). Values of
GFR were estimated
using the Schwartz
formula (8).

Analysis

2.

the

infrequent

relapses

for

proteinuria

frequent

weeks
during

Course
during
subsequent
6 months
continued
nonresponder:
unremitting
proteinuria
subsequent
responder:
loss of proteinuria

the

with

with
Total

92%)

relapser
relapser

subsequent
Initial

(334,

nonresponder

nonresponder
continued

subsequent

(29,

148

40.8

44.3

73

20.1

21.8

102

28.1

30.6

I1

3.0

8%)

3.3
100

nonresponse

17

4.7

58.6

response

12
363

3.3
100

41.4
100

Significance

classification
at 6 months
or
except
for initial nonresponders,
throughout

their

courses

Of the

148 initial

pattern

throughout

ing

rarely,
(Figure

(see
their

16%
entire

and

half

of their

sustained

course

subsequent

60%

one relapse
each
became
frequent

annual

came
wk)

relapsed

year
re-

assessments

the

seven

quently

73 initial
infrequent
relapsers,
within
0.3 to 7.7 yr (median,
2.7
initial

classified

infrequent

within

nonrelapse

or

prednisone,

period

infrequent

equally
The
Figure
gradually

with

three

with

pattern

63%

no significant

became

alone

difference

among

(1),

long-term
be seen

increased,

nisone

nonre-

those

in time
who

all

of

plus
relapsers,
these

to

For

received

singly

for

the
the

reaching

ultimately

within

the

predcom-

prednisone
(two

initial
alone

patients),

tients),

and

entire

group

proportion

is shown

in

therapy

approximately

80%

by

or were

was observed

of nonrelapsers
8 yr.

(7).

In the

their

trial

of these

1 2 patients
azathioprine

cyclophosphamide
It was
resulted

3).

resolved
included

plus

However,

nonresponders

was

administration

patient).

experi-

(Table

proteinuria

remissions

spontaneous.

among

nonresponders

prednisone

(one

for

and

Treatment

plus

drugs

except

steroid-responsive

the

patient),

prednisone

whether

to prednisone,

one with azathiofour received

prednonresponsive,

of prednisone

(one

all three

determine

initial

non-

relapsers,

steroid-nonresponsive

6 months.

8 wk

of two

In addition

of total),

the subsequent

after

did

consisted

remained

were

(3.3%

were
be-

two frequent

persistently
who

became

12 of them

or in

patients

became

relapser

at the

few

steroid-responsive

patients

nonresponders.

None

frequent

very

(i.e. over a period of at least 8

of follow-up
monitoring.
The
relapsers,

enced
renal failure.
Twenty-nine
patients

within

monitoring.
that

alone.

771

to relapse

although

initially

of these

infrequent

subsequent

8 yr but

34%

relapsers

or cyclophosphamide,

of response

4. It can

2).

subse-

continued

were

of MCNS

were treated
with cycbophosphamide,
and three with both of these drugs;

for one

infrequent

relapse

prednisone

well

(Figure
were

combination.
Thus,
although
cycbophosphamide
nisone
improved
the early course
forfrequent
pared

seven
prime,

became

of 3 yr; and an additional

became

was

azathioprine,

yr)

(9.6%)

relapsers,

relapsers
3). There

70%

who

classification

relapsers,

relapsers.

frequent

an average

of initialfrequent
2 yr (Figure

relapsers

as frequent

Of the 102 initial

lapsers

patients

and eight

Among
nonrelapsers

of patients

Course

examination,

transiently
nonresponsive
during
the latter
years

6-month

were

10%

follow-up

relapsers.

Fifteen

a nonrelaps-

and

as nonrelapsers.

Only

5 to

of last

frequent

i.e. no 2-yr period

with at least
1 ). Only six initial
nonrelapsers

lapsers,

time

below).

nonrelapsers,

Nevertheless,

with histopathobogic
findings,
who remained
nonresponsive

of the Early

(eight

pa-

not possible
from

to

continued

no beneficial

effect

in the trial of azathioprine

of cycbophosphamide

(1),

proteinuria

subsided

Subsequent Annual
Classification:
Rare Relapse

Subsequent Annual
Classifications:
No Relapse
69%
Infr Relapse
29%
Freq Relapse
2%

4%

No Further

Relapse

No Relapse
Rare

::::

Relapse

lnfreq

Relapse

Freq Relapse

Figure
is defined

1. Subsequent
as no 2-yr

classification
period

(Infreq or Infr) relapsers

frequent.

with

of 148 patients
at least

is presented

one

who were nonrelapsers

relapse

in tabular

form,

each

year.)

showing,

The

percent

for example,

at 6 months.
distribution

that there

Three-fourths

relapsed

of subsequent

were no relapses

annual

rarely

or not at all. (Rare

classifications

relapse

of the infrequent

in 69% of the follow-up

years.

Freq,

772

Journal

of the American

Society

of Nephrology

Subsequent

Annual

Classifications:

34%
28%
32%

No Relapse

lnfr Relapse
Freq

Relapse

Subsequent

Annual

Subsequent

Classifications:

Annual

Classifications:

No Relapse

21 %

No Relapse

lnfr Relapse

57%

lnfr Relapse
Transient
Non-Response

00/

Freq Relapse
Transient
Non-Response

90%
,_,

/0

,.)

/0

/0

Intermittent Proteinuria

/0

/0

12%

Intermittent Proteinuria

No Relapse
lnfreq Relapse
Freq Relapse

Figure 2. Subsequent
classification
of 73 patients
who were infrequent
relapsers
at 6 months.
The classification
for 70% was as a nonrelapser,
and a similar percentage
of the following
annual classifications
was as a nonrelapser.
The subsequent
classifications
of infrequent
and frequent
relapsers

are shown

earlier
pared

in tabular

among
patients
with those who

portions
of
were similar

patients
in the

patients,
one with
onset ( 1 1 ). Seven
One

other

Intermittent

proteinuria

an

relapser

infrequent

relapsers

findings

series,

and

did

none

Seventeen
to those

not

within

0.6

(median,

3 yr.

16 yr. Their
prednisone

0.5

and

logic

tients).

it was

to any

patients),

not

included

thickening
and

with

remainder

of the

Ten

and continued
were similar

of them

entrance

and

the trial

periods

form
nil

all three
to

relate

of therapy.
disease

of 2 to

gbomerular

drugs
their

The

(three

mild mesangial
obsolescence

proteinuria

The
nitis

(three

than

One

but

died

a relapse.

continued

from
into

of them

ultimately

to define

and

who

of entrance

ESRD.

to time

required

initial

one

6 months

developed

that

seven

4) included
within

time

less

remaining

(Table

nonresponders

pneumococcab
the

study.

responded

returned

of the

patients

prednisone
Follow-up
patients

received

alone.
biopsies
physicians

with

were

the baseline

to

to focal

do

well,

ESRD.
low-up
focal

The four
biopsies
segmental

developed

the

half

The
Half
received

only

of the

65

patients.

the classifications

of the

by the ISKDC
pathologists,
For 13 the biopsy
diagnosis
Nine

other

patients
showed

four

of the

(see

who developed
focal
global

glomerulosclerosis

proliferative

for

readings,

gbomerulosclerosis.

whereas

state

at the discretion

available

follow-up
biopsies,
performed
were discordant
for 19 (29%).

six

from

monitoring.
throughout.
and

performed

were

other

to a nonresponding

cycbophosphamide,

and

perito-

The

to prednisone

and experienced
ESRD by year 9 of follow-up
other five maintained
nonresponsive
courses

changed

responded
into

follow-up

transient

Compared

ESRD.

were initial
distributions

possible

(one patient),
focal

1 .5 yr).

prednisone
alone (one patient),
(four patients),
prednisone
plus

patients),

particular

classifications

mesangial
(three

(two

Again,

remissions

well,

treatment
included
plus azathioprine

cycbophosphamide
patients).

did

three

for 69% of the

of histopatho-

developed

to 3.6 yr from

and

yr (median,

of the

population.

resolved
these
12

7 months
after
2.3 yr of entry.

at

to 3.9

that

patients

study

within
0.8 yr).

from

(4.7% of total)
age and gender

of the entire

subsequently,

differ

of these

patients
Their

nonresponders.

comthe pro-

for whom
the proteinuria
was
two treatment
groups.
Among

The 1 1 surviving
patients
were nonrebapsers
follow-up
time of 6 to 1 3 yr. The distribution
logic

reflects

who received
cycbophosphamide,
received
prednisone
alone,
but

nil disease
died of septicemia
became
nonrelapsers
within

became

becamefrequent

form.

1 3 continued

above)

developed

ESRD
and had
glomerubosclerosis

(FSGS);

gbomerubonephritis

one

of them

(Table

4).

fobor
later

ultimate

histopatho-

patients),

mild

Among

hyperplasia
(three

Discussion

pa-

with
courses

the difficult

MCNS
and

are

tasks

predicting

determining

facing
both

the

clinicians
the

prognosis.

initial
These

treating
and

children
subsequent

evaluations

are

Significance

subsequent

courses.

transient

and

/0

during
was
for

courses

more

for
Subsequent

Annual

Annual

Classifications:

Classifications:

those

No Relapse
lnfr Relapse

59%

No Relapse

91%

32%

Infr Relapse

9%

Freq Relapse
Transient
Non-Response
Intermittent
Proteinuria

1%

course.

4%

remission

series)
course

classification

Note
ing

the small

either

In contrast,
only

Non-Response

of 102 patients

of patients

who

were

frequent

maintaining

a frequently

relaps-

course.

after

initial

to the

impression

to find

such

failure

treatment
nisone,

of frequent
because
the
infrequent

relapsers
time frame

relapsers

parents

and

in making

therapeutic

deci-

95%

sions.

The

goals

of the ISKDC

therapeutic
that

trials

predict

and

characteristics

teristics

and

predicted

with

nonresponsiveness
dicated
gbomerular
with

MCNS.

indicators

The

to conduct
early

course.

controlled

clinical

with

except

that

a high

degree

Undetermined

initial

outcome

current

report

is based

of an unselected,

the
on

(3,4).

nonspecific
outcomes

initial

with

previously

few

studies

the

only

frequent

nonrelapsers

biopsy

of patients

did

not

correlate

4) is somewhat

better

from 66% at 9 yr to
be explained
by the

or treatment,
with

state
relapsers.

other
than predrelapsers
to be-

avoiding

disease

that

the

is difficult

to manage.

charac-

Most
patients
who
prednisone
ultimately

fail to respond
to an
attain
a full remission,

Steroid-

Nevertheless,

initial
course
independent

the treatment

regimen.

state

greatly

increases

small

number

were

during
the initial 8 wk of prednisone
therapy
was followed
by
progression
to ESRD
in 21%. In addition,
9 of the 10 deaths

the

large

prospective

occurred

series

of children

nisone

of initial

in patients
or who

the

risk

an initially

of
of

but inthan that

MCNS.

untreated

before

referral

course

from the literature.

be explained
by the

used.
rate at 8 yr (Figure

of patients

of selected

one-

a nonrelapsing

that reported
in other series,
ranging
at 15 to 20 yr (12,15-17).
This might

enrollment
bias

steroid-responsiveness

of accuracy

in

long-term

reported,

histopathobogic

was histopathobogically
diseases
with poorer

of

clinical

characteristics

As previously

correlated

outcome,

MCNS

were

to identify

the long-term

clinical

study

than

their

of subsequent

and

gathers
cannot

the

nonrebapsing

a nonrelapsing

with drugs
for frequent

or

in
of

approximately

to achieve

one
a difference

in contrast

The

(40%

early

frequency

the

remained

throughout

this

infrequent

initial

that

subsequent

who

achieved

of time

between

(3)

period

for

of 3 yr. The

that

a subsequent

of the

remission

is in

concluded

impression

Thus,

relapsers

with the drug regimen

The 80% remission
in counseling

in

This

of

6-month

rarely.

the length

differ

who

responders

continued

relapsed

an average
and

not

come

used

initial

in agree-

(12,13).

predictive

subsequent

of the
course

prognosis,

predictive

pattern
augurs
an excellent
prognosis
third of children
with MCNS.

Two-thirds
were classified
as nonrelapsers,
and
annual classifications
were as nonrelapsers.

percentage

the

or

be

an early

of

during

relapses
3. Subsequent

to

34 to 47%

et a!.

et a!. (14),

is highly

Three-fourths

entire

did

relapsers at 6 months.
91% of the following

required

classification

entire

lnfreq Relapse

Figure

of Lewis

nonrelapsing
course.
These
analyses
confirmed

4%

Transient

was

of Habib

relapsers

a nonrelapsing

an excellent

observation

6-month

frequent

only
that

were

nonrelapsing

of their

were

etc.)

who

their

nonrebapsers

be reassured

yr augurs

the

period

6-month

No Relapse

can

on

yr. The

those

regardless
who

ignore

relapser.

that

yr continued

yr were

to

analyses

2 consecutive

finding

of the time,

to the findings

a 4-yr

the

86%

2 consecutive

contrast

of at least

by

773

designed

infrequent

contrast,

thus

with

was

In

Patients

ment
Subsequent

a period

of MCNS

long-term

(nonrelapser,

2 consecutive

for 2 consecutive

Course

the

than

classification.

time.

base

validated

nonrelapsers

Early

approach

to

pattern

persisted

approach

1)0/

This

changes

response/relapse
that

of the

of poor

nonresponders,

who

relapsed

were
during

nonresponsive

outcome.

Despite

unremitting

initially

nonresponsive

the

8-wk

first

the

proteinuria

period

to predof therapy.

renal biopsies
are no longer
routinely
performed
for children
thought
to have MCNS
(or, in operational
terms,
who have

One-third
of 17 patients
who had unremitting
proteinuria
during the initial
8 wk of therapy
and the subsequent
6 months
progressed
to renal failure,
making
this an even more ominous

steroid-responsive

predictor

with

recent-onset

MCNS

disease),

and

renal

biopsy

it is unlikely

that

ever be duplicated.
On the basis of preliminary
data (3), patients
according
to their course
during
the 6 months
8-wk
period
of therapy.
Because
patterns
of relapses,
a method
was

at entry.

such

Because

a study

will

As

were
after

classified
the initial

of the variability
in
devised
to characterize

the
the

within

reported

of outcome.
reported

in 1984,

2 yr of disease

here.

Nine

a total
onset

of the

not at all. The additional

earlier
observation
that

of

10 patients

(1 1 ), including

10 responded

in this
four

initially

series

of the

only

died

patients

briefly

or

follow-up
monitoring
confirms
early
nonresponse
marks
a group

the
of

774

Journal

of the

American

Society

of Nephrobogy

100

(1)

80

U)
0

60

0
c:
a)
C.)

40

1.

ci)
Q20

0
1

10

11

12

13

14-18

Year of Follow-up

F
L
4. Annual

Figure

frequently

Table

classification
categories.

relapsing

4. Clinical

data

Age at
Onset (yr)

of patients

and

course

Nonrelapser
Frequent

according

Annual

3.6

Never

i .6

Occasional

initial

category,

demonstrating

continued

the progressive

nonresponders

who

Initial
Pathology

Classification

responded
responses

FTC

Never

responded;

died

FTC

5.6

Never

responded

NIL

FSGS/3

2.6

Never

responded

FGO

FGGS

nil disease;

See reference

patients
here
others,

at risk

FGO,

Never
responded;
pneumococcal
focal

glomerular

gbomerubonephntis;
1 1.

of early

is on the low
whereas

the

end

death.

The

death

of the range

renal

failure

diffuse

rate

of 2.5
rate

died from
peritonitis

obsolescence;

DPGN.

1.4
3
with

of 2.5%

the relationship

MCNS

glomerular

the finding

of focal

focal

reported

changes;

(20%)

by

0 to 3.5%
between

lesions

tubular

0.5

FGGS,

focal

global

gbomerubosclerosis;

MCGN,

glomerubonephritis.

reported

the

reported
in other studies
(12,14-16,18).
Although
this study did not address
and FSGS,

FTC,

atrophy/3

NIL

proliferative

to 6.7%

is within

died

14.6

NIL,

FSGS/l,
DPGN/5

course

tubular

(4

Total Years
of Data

responded;

mesangiocapillary

and

or died

FTC

Never

ESRD

in the infrequent

Pathobogy/
Year

FGGS/0.25,
MCGN/5,

3.0

decline

developed

Follow-up

FGO

followed
by
nonresponsive
1 .6

and

Relapser

Other

LI

Relapser

to response

for the seven

Gender

Infrequent

in 13

of

common

65

second

biopsies

pathogenetic

two

histopathobogic

dren

is not uniform

may

mechanisms
patterns

(19 -22).

in histopathobogic

course,
and responsiveness
differences
may relate

reflect

the

operation

in the development

of

of these

FSGS

in nephrotic

chil-

severity

or clinical

onset,

to steroid
therapy,
and some of the
to the variable
severity
of giomerular

Significance

injury

(20).

Approximatel,

initial

FSGS

30%

respond

to

of

steroid

nephrotic

therapy,

continue
to do well (19). Nine (69%)
FSGS
and global
gbomerubosclerosis,
well.

These

rather

than

gbomerular

Careful
can

outcome,

help

warranted

for

sponders

patients

may eventually

not

found

two

some
in

with

sporin

alone.

five

Nephrobogy
21

patients

is no

of

Collaborative

(30),

studying

with

the time

(27,28)
and

with

Group

of the French

form

the observations

of

suggest

(30).

therapy

that

these

two

drugs

4.

ing

95%

as one-third
state

of children

maintaining

throughout

excellent
cations

with

their

MCNS

a nonrelapsing
entire

outcomes,

4 to 5%

or progress

to ESRD.

course.

Study

Study

laboratory

may

be

6.

of patients

may

with

as

relaps-

these

overall

die from

compli-

7.

8.

mann,
and

Jr. (Directors),
A. Spitzer

I. Greifer

(Directors

Coordinator),

(Secretarial
Assistant);
Kuijten,
and LB. Travis;
(New
phis).

0.

95:

Hallman

(New

(Heidelberg),
(Cincinnati),
ham,

White

Hsieh,

SM.

Grant

(Helsinki),

work

Mongeau

I. Strauss
and

Einstein),

R.H.R.

White

Consultants:

Houston

supported

and

Oetliker

and
by National

the

(Bern),

I. Churg,

National

K. Freeman,
IN.

Tobin

Institutes

Kidney

Foundation

Nephrotic

comparing

two

pred-

patients
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iroJccts

Research

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not

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topathobogic

several

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Institute

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The

universally

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