in that no consistent environ- mental or infectious agent has been shown to be antigenic with an IgA antibody response. Since the original description of the.
DISEASEOF THE MONTH
Immunoglobulin
A Nephropathy:
JAMES
V. DONADIO,
*Dit,isio,t
Mayo
First
described
the
common
Also,
can
we
develop
(initially
thought
periods
of time
glomerulonephritis
IgA
or infectious
an IgA
antibody
attention reported
by
of histopathologic
is unknown
in that
has been
response.
Since
no consistent
temic
disease,
is the
of the
many
of the high
description
of the
disorders
prevalence
of IgAN
This
received
the
and
bulk
offers
of patients
with
Population epidemiologic studies IgAN are meager; most reports
expressed a total
as a percentage biopsy
series
on the
(2,7,
1 1). For
example,
with
glomerulonephnitis,
biopsy
series,
Ibels in
and
Gyory
(7).
The
Japan,
Europe,
in a recent
prevalence
the
Hong
lower
prevalence
from the United Kingdom, Canada, the exception of Native Americans The
low
prevalence
influenced
not
the
States
United
only
rate by
the
are from
from
fact
all
that
rates
in which
reported with (2,7).
States there
of Nephrology,
l()46-6673/0808I 324$03.00/0 Journal of the American Society of Nephrology Copyright 0 1997 by the American Society of Nephrology
renal
asymptomatic,
abnormal
for patients
or both.
outcome
presenting
This
studies
and
practice
recommen-
later.
is is a
Mayo
Asians
of two
high
as
and
less
is a 2: 1 in
patients
in
has a predilection
common
in blacks.
in any
patient
in whom
there
(1) episodic,
presentations:
coincident
than
Caucasian
IgAN
onset
There
1 1 ).
from
6: 1 in
is less
of clinical
(2,7,8,
States.
suspected
often
erythrocytes
in whom
examination
for
(RBC)
with
other
purposes.
hematuria
in
presenting
an upper
mac-
respiratory
median
pain
proteinuric
was
obtained
age
of the
will
grossly
completed,
proteinuria
as part
clinical
patients,
trial
a history
of
under
34
in patients
cohort
the
hema-
that of an individuals.
randomized
study
of
visible
whereas in older
only
of an
accompany
one-third
of episodic,
Unfortunately, abnormalities overlooked or purposely not
and
Loin
106
hematuria the
casts
performed
in younger people, is more frequent
involving
macroscopic
RBC
was
approximately
illness
in a recently
oil
and
the urinalysis
turia is more common abnormal urine sediment
(12).
found on urinalysis may be acted on by further testing until
impairment becomes evident. It is imperative to sediment changes when first detected so as not to
making
of IgAN
age
life
ranging
common
in patients
delay
usual
of
less often a gastroentenitis; or (2) asymptomatic on urinalysis of an abnormal urine sediment
renal function pursue urine
from
as
be highly
containing
The
the
decade
predilection to
infection, findings
fish
with
third
hematuria,
an accurate
requires
diagnosis.
renal
biopsy,
By
definition,
including
a diagnosis
immunofluorescence
microscopy. This
Correspondence to Dr. James V. Donadio. Jr., Division Clinic, 200 First Street, SW, Rochester. MN 55905.
one
yr old,
and
series
be
of
are found
are
the United published
centers
an
practice
and the United
and must
For example, by
Finland,
whites IgAN
macroscopic
of total
and the United States, living in New Mexico
reported referral
rates
sex
Europe
cases.
of patients review
Kong,
for
tract with
studies
4 to 44%
comprehensive
high-end
Australia,
and
from
approach
in recommending
concentration,
at all ages,
patients
epi-
or of
cohort
for 7 to 52%
ranges
a conservative
to be discussed
and
male
roscopic
out-
glomerulonephritis
accounts
which
as reported
Singapore,
southern
IgAN
Pathology,
Features second
and
IgAN.
in referral-based
only
comparative
occurs
the
may
concerning the incidence relate prevalence rates
of primary
originating
by
country
have
creatinine
for treatment
northern
Epidemiology of
who
on
Japanese a
pathology, idiopathic
in
of
a long-term
diagnosis,
serum
usual
because
a perspective
and
been IgA
association
be coincidental
is usually
of
considered
The
also
It is common
bearing
IgAN
a multisys-
arguably
IgAN. that
features,
management
purpura,
may
review
clinical and
common
of idiopathic
secondary
disease.
demiology, come,
most
has
Clinical
with
the original
Sch#{246}nlein-Henoch
spectrum
of the
chronic
1).
and
environ-
in the medical literature, but many diseases have that are sporadically associated with mesangial (Table
but
in our
in patients
sediment.
dations
(9-
to be antigenic
has
bias,
by nephrologists
rising of
shown
IgAN
Medicine
with isolated hematuria or mild proteinuria not to receive a renal tissue diagnosis, the renal biopsy being reserved for those people who develop increasing amounts of urine protein or a
constant
deposits lesions
of Laboraton’
selection
taken urine
variable
the
mesangial
tDepartment
biopsy
IgAN
over
t/te
patient as
complex-mediated
morphologically
idiopathic
deposition
part
process)
or codominant
agent
glomerulopathy,
benign
is an immune
idiopathic
with
P. GRANDEt and
in the world renal failure
patients
Perspective
Minnesota.
recognized
that
by a variety
etiology
mental
Medicine
(1),
is now
of
JOSEPH
Rochester,
Hinglais
number
defined
accompanied
Internal
glomerulonephritis as did Berger
IgAN
of predominant
1 1 ). The
and
to be a totally
and
Foundation,
(IgAN)
a substantial
(4-9).
and
Mayo
by Berger
primary appreciate
now
in
presence
and
A nephropathy
most
(2,3).
of Nephrology
Clinic
in 1968
immunoglobulin
JR.*
A Clinical
gists
the ment
that
again
raises
of performing
above-cited
the
spectively
biopsy
presentations
or nephrotic-range
specific
controversial
a renal
without
proteinuria
treatment evaluating
issue under
is not an
available.
asymptomatic
the
renal because
among
nephrolo-
circumstances
function of the
The
approach
patient
was
of
impairperception
of proan
accept-
IgA Nephropathy
Table
1. Classification
of diseases
predominant
associated
mesangial
IgA
with
casts
and
dysmorphic
or microscopic
deposition
bleeding
Idiopathic
IgA
nephropathy
Secondary Sch#{246}nlein-Henoch entity
(Berger
purpura-most
of the
liver:
alcoholic,
cirrhosis;
extension
cryptogenic hepatitis
nephropathy
intestine:
celiac
Crohn’s skin:
disease;
fibrosis,
chronic
ered
to have
tion
of 3.5
colitis;
psoriasis pulmonary
IgA
larynx,
and
monoclonal
pancreas;
gammopathy
immunodeficiency
virus;
systemic/immunologic
disorders:
systemic
cryoglobulinemia;
psoriatic
arthritis;
antineutrophil
associated
vasculitis;
lupus
rheumatoid
ankylosing
syndrome;
spondylitis;
Sjogren’s
cytoplasmic familial
the most
antibody-
until
recently,
now
be
can
rule
for
immune
in that
offered
even
clinical
signs
Gyory
Complete
with
Having
urine
a positive
IgAN
can
the be
the
combination conditions,
proteinuria
to
course
of
the
illness
prolonged
remission 4%).
dis-
is macof all
To
illustrate
examination,
Ibels
correlation
between
the quantity
and
examined
testing
can
be
using
is by
careful
urine
urine
excre-
for
Bence
method
and
to
detect
even
sediment
and
in very
proteinuria
preferably
Serial
discov-
(protein
screened
immunoglobulins
function,
urine
first
precipitation
GFR.
form
by a clear-
measurement
follow-up
of renal
of patients
with
minimal
presence
of circulating
are found biopsy
steroid
for the firm
typical
direct
and by
automatic
light
counter The
with
first
in
specific
finding
microscopy, and,
injury.
but
establishment
microscopic,
that
distributes of renal
diabetic
of
systemic
is
with
in paror
technique cells
to be
(urinary)
can
se-
none
and
complexes,
can
replace
of a diagnosis
(1 1).
immunofluorescence,
segmental
and studies
the
light
nonspecific, demonstrating
diffuse
mesangial
in a number
patients
lesions, microscopic immunofluorescence a predominant
non-
glomer-
IgAN
may
glomerular with lesions
or diffuse features
of other
with
lesions
sclerosing
This
glomerulosclerosis, lesion-associated
microscopic
necrotizing
hypercel-
matrix.
focal-segmental other glomerular
of light
or global
membranoproliferative Because
be observed
and
in IgAN are illusmicroscopic lesion
extracellular
In addition,
variety
segmental
or
of the
and
diseases.
a wide
is focal
including
nephropathy,
including tion,
IgAN expansion
disorders,
to
Glomer-
dysmorphic
microscopic findings
ular
performed
casts,
with
lularity,
examination
finding
associated
of
In addition
elevated aggregates,
Pathology
presenclue
or
of minimal
immune
IgAN,
two
Prompt
treatment,
including
IgA-containing
with
of the
disorders.
IgA-fibronectin
in patients
by
segmental
proliferation.
expression
variables,
C3 fragments,
rarely
clinicopathologic
or other
after
the phenotypic
of a
marked
and
cellular
this
of one
syndrome
suggests
referral
IgAN
coexisting
change disease (17). There are other laboratory
which
or no
different
late
focal
whether
with severe representing
unusual. may be the
and
with
a variant
two
The not there
syndrome
about
of the nephrotic
rum IgA levels,
is also
associated and
of
will present obviously
of the disease.
nephrotic
represents
diagnosis
urinalysis
of glomerular
suspected
to size.
The
bright-field
leukocytes,
an
renal
sample.
proteinuria,
of a Coulter
according
biopsy.
unstained,
RBC,
a clinical
a definitive
renal
all indicative
also
RBC,
has
voided for
using
casts,
the lines
by
freshly
to identify
injury
are
range be
in the long-term
consensus or
the renal
and the number of hyaline casts in a cohort of 121 Australian
a patient
diagnosis
morning,
RBC
along
and
deposits
spontaneously,
the
sediment
descriptions, only
sediment,
required ular
that
made
physicochemical
the urine
voided
who
electrophoresis
of renal
expansion
re-
risk
The
above
a proper
on a first
glomerular
chains
to estimate
is no
for
at
IgAN.
determined
fitting
this
urologic
protein/osmo-
electron microscopic alterations observed trated in Figure 1 . The most common light
tatioh
ticular,
yr old
h) should
of an abnormal
mesangial
There
inter-
Diagnosis
making
24
undiagnosed patient on immunofluorescence
remission and
presenting
and
of RBC per milliliter of urine and progressive renal disease patients
50
immunofixation
coexistent
recently
are
on
(approximately
of direct
(7) showed
who
based
whose
is uncommon
the importance
patients
throughout
patients
hematuria.
therapeutic
hematuria
amounts
in those
roscopic
to
rational
renal disease (12-15).
microscopic
in variable
ease,
per
aggressive
previously Likewise, reported,
developing progressive ported treatment studies persist
over
by the sulfosalicylic
is essential
mesangial
It is the
undergo
morning,
in the nephrotic
more
technique,
IgA
ventions
on first
A small group of patients with IgAN azotemia, some even requiring dialysis,
arthritis;
thrombocytopenia
practice
to
that
and
IgAN.
erythematosus;
able
adults
by
function
having
ratios
measurement
ance
leprosy;
in origin,
or by semiquantitative
proteinuria g or
presence
require
toxoplasmosis
Other
Also,
monoclonal light low concentrations.
hemosiderosis;
macroscopic
to the clinician
is glomerular
from
protein
proteinuria
The
of lung,
fungoides;
human
(16).
Jones
sarcoidosis
carcinoma
mycosis
urine
areas);
ulcerative
herpetiformis; : idiopathic
cystic
or protein/creatinine
examination
dermatitis
Neoplasia:
total
lality samples
disease
bronchus/lung
Infection:
chronic
patient
24-h
biliary
B (endemic
the
tract
either
indicate
such as cystoscopy and retrograde pyelography. proteinuria can be assessed further by measuring
primary
schistosomiasis
accompanying
clearly
urinary
spare
procedures Qualitative
a distinct
of IgA
and
in the
should
common;
or a multisystemic
Diseases
disease)
RBC
hematuria
I 325
crescent with
forma-
hyalinosis,
proliferative of or
IgAN
present
lesions,
lesions. are
variable
immunoperoxidase
or codominant
deposition
I 326
Journal
of the American
Society
of Nephrology
Figure
1. Characteristic
nephropathy
morphologic
(IgAN).
(A)
Light
alterations microscopy
pansion of mesangial regions. both with acid-Schiff stain). Original magnification. cence microscopy demonstrating brightly predominantly X200.
(C)
its within ment
within Electron the
membranes
mesangial micrograph
mesangial (right)
are
regions. The
normal.
A
mild
ex-
cells and matrix (periodic X200. (B) Immunofluonesstaining deposits of IgA.
demonstrating
region.
in immunoglobulin demonstrating
peripheral Original
Original
magnification.
electron-dense capillary magnification,
deposloop
baseX7l25.
IgA Nephropathy
Table
2.
Renal
survival
time
in large
of renal
cohorts
of patients
with
IgAN
relates
to prevalence
of renal
Geographic
Renal Survivalb
n
Area
Germany
New
South
Upper
(21)
France
United Kingdom Fukuoka, Japan
(22)
(23) (24)
Wales,
Australia
Midwestern
U.S.
(7)
(9)
IgAN, immunoglobulin A nephropathy; 10 yr after renal biopsy. After clinical onset of disease.
a 1 C
of IgA
are
deposits
essential
NA,
in establishing
are predominantly
within
239
81
282
94C
220
gial
and
immunofluorescence
hypercellularity
and
an increase
deposition of electron-dense A number of tubulointerstitial seen
in patients
with
bular
atrophy,
interstitial
casts,
or
may
provide
vascular
IgAN,
3
225
74
36
22
16
121
86
36
31
16
148
67
59
47
30
U.S.,
with
sclerosis.
important
and
United
The
stitial
fibrosis,
both
glomerular
include
mi-
mesan-
matrix,
interstitial of
information
with
areas. may be
fibrosis,
tu-
tubular
renal
is characterized from a totally
function patients function
Many
renal clinical
course
around
the
alterations
stitial
IgAN
has been world
on
that
(2,4-9, independently
decreased
renal
We
in a number
clinical,
predict
laboratory,
development
Clinical associated
the presence
na. Histologic renal failure
addressed the
19-24).
include
mesangial
by a highly variable benign condition and
clinical course, well-maintained
for decades to rapidly progressive have a chronic, slowly progressive over 10 to 20 yr (2-9). The wide
characteristics
and with
function,
and
of reviews
of
renal
the degree
persistent
failure
features
progressive
rates
renal
to
disease
of proteinuria, hematu-
predictors fibrosis,
of and
hypercellulanity. recently
reported
study
of the clinical
IgAN in North America and a number of the previously
histopathologic
ease. Although a large univariately associated
features
associated
with
number of histopathologic with adverse outcome,
the first reported progressive features including
course in I 3 yr clinical
total
that
change
with
fibrosis).
This
in IgAN,
interstitial
alterations. score
was
dictor
of adverse with
changes
may
end-point
in
overall
been
not correof inter-
that,
at least
to the glomer-
we found
that
total
gbpre-
histopathologic
hypercellularity
either
the
patient
survival
did
not
or
the
univariate was
97 ± 1%
at 5 yr and 89 ± 4% at 10 yr (9). Ultimately, developed end-stage renal failure, the pri-
of our study.
to be
has
index
be secondary
mesangial
failure
analysis,
(an
independent
outcome,
In our recent
mary
the possibility
although
are the
did
raises
renal models.
(estimate ± SEM) 39 of 148 patients
biopsies
finding
best
(9).
changes damage.
IgAN
volume
the
analysis
serial renal biopsies in creatinine clear-
in interstitial
In addition,
merular
final
as-
score
independent
that tubulointerstitial progression of renal
and
as
glomerular
provided
in patients
and
activity
in a multivariate
the initial
the
79
± 4%
with
survival
at 5 yr and
free
67
±
of renal
5%
at
failure
10 yr.
The
overall below
10-yr renal the percentage
survival of 67% in our study group survivals reported in five recent
was large
cohort
studies
Europe.
2).
comparing hypertension, creased studies),
Midwestern
observed cases
patients
were inter-
enzyme
are
Recent
Australia,
and
Japan
(Table
risks, seen
emphasizing
in referral
are coming studies (ACE)IDD
States)
populations. renal
to renal have
shown
genotype
was
much
Many that,
that was
in the
more United
late in their the
cohort group
than
of our patients
in general,
centers
biopsy
greater
advanced States
disease
with
that
carried and
course.
angiotensin-converting
associated
In
(i.e., and in-
as reported in these large of all three risks in our study
United
in the other
all of these
dis-
from
the three most consistent risks for progression elevated serum creatinine concentration, protein excretion, the percentage
(Upper the largest
marker
relationship
between
with
estimated in
found
microscopic
as independent interstitial
from
histologic
the
outcome accepted in the
of this
correlate multivariate
renal failure. decline in variability in and
laboratory
of hypertension,
features identified were glomerulosclerosis,
of patients with (9). We identified and
ance
ular
IgAN ranging
pathologic
regarding
inflammation,
proliferative
questioned. In a series of 39 patients with reported by Bennett et al. (25), the change
these
Outcome
NA
interstitial
interstitial
1 immunostaining,
only
primacy
late
IgAN.
be
the
atrophy,
and
Mib-
information
or protein with
by
was
RBC
in patients
h)
States.
focal
light
mesangial changes
Identification
prognostic
by
infiltrates,
g/24
32
observed
including
cellular
(>3
26
of IgAN.
within vascular
Hypertension
28
in mesangial
deposits and
.
Proteinuna
.
83
regions
studies
(%)
9
a diagnosis
those
Factor
19
Although generally major determinants
parallel
Risk
2
by
microscopy
Indicated
Creatinine Concentration
sessed
croscopy
at the
34
not available;
mesangial
with
Serum
paramesangial/subendothelial extension. Other immune reactants frequently codistnibute with IgA, including IgG, 1gM, C3, lambda light chain, and kappa light chain ( 1 ,1 8). The findings electron
factors
Increased
(%)
Saint-Etienne,
risk
biopsy’ Patients
TUbingen,
progression
1327
an increased
1328
Journal
Table
3.
of the American
Nonrandomized
Society
of Nephrology
controlled
long-term
studies
of corticosteroid No.
Group
Children
and
Adults a h
rate
of
adolescents
derived from other to treatment according
Japanese
(28)
renal
cohorts
the Japanese
excretion not
(28).
notype
may
system,
These
resulting
findings
that
progressive
IgAN.
In
angiotensin
system
may
the
ACEIDD
In summary,
placed
at an
who
carry
addition,
this
renal
high-risk
role
with
function studies
the
developing can
now
shown
no
therapeutic
agent
favorably ventions
influence reported
renal function in spite over the past 17 yr (29).
recently
published
studies,
has
treatment inhibitors who had
chronic,
form
uncontrolled was shown IgAN (30). daily
Table
proteinuric
interin four
n-3
(12
with high-dose immunoglobulins function in 1 1 adults with severe
of alternate-day
prednisone
prednisolone
in adults
Controlled
clinical
(14)
trials
has
in children been
of fish
shown
mediators
for
has
using
long side
fish
polyunsaturated
study
been
involved
were
tested
with
of these followed
in patients
varying
oil in IgAN
acids
in ongoing
control
Each
who
fatty
groups
published
(3 1-33).
studies
in a double-blind,
of
a 30%
results
is based
alter
by the thereby
damage
placebo-controlled
were were
treated untreated
of
eicosapentanoic
because
in renal
yet of little
clinical
were significance
decline might
6-mo
small
(35).
Japanese Australian
EPA,
37
(36)
Swedish (35) U.S. American a
20
(34)
eicosapentanoic
32 106
(12) acid;
DHA,
docosahexanoic
1.6/1.0 1.8/1.2
1 2
3.3/1.8
0.5 2
1.8/1.2 acid.
Treatment Duration (yr)
and
study who
in 1 1 who have failed
follow-up but
period;
statistically In the Australian
Effect of Treatment on Renal Function
Stabilized Declined Declined Stabilized
of oil
proteinfunction
(12). In the in 9 patients
1 yr but did from Sweden
of the short,
function
con-
acid
persistent renal
3.5 g/24 h hypertension
and
Glomerulonephritis
normotensive
Mayo
(U.S.)
acids
fish
clearly
and
of these
oil-treated
U.S. American patients. b ACEi, angiotensin-converting
1995,
the
North
comprised
nephrologists.
an increased
The
amount
of both
IgAN
is being
of n-3
(Donadio
conducted
trials, the ACEi
by
our
enalapril
collaborative
is being
results
used
to
are not yet available. patient
ACE1-
There
had a stabilization
less
progressive
these
study
loss
for
Hence,
renal
our
disease
this
function.
function
which
seems
who was fish oil, or was
in a subset
there
rudimentary
is the
disease
for
a lack
in
to be no effective
understanding
reason
relent-
of patients
of progres-
of effective
therapies
in all patients.
Transplantation IgAN renal
is more
failure
failure,
and
of renal
Frohnert
are
common
in young
adults,
those
generally
in good
health,
except
at an ideal
to the circumstances Transplant programs in every
IgA
recipient
(42,45)
deposition
more
that
in patients IgAN
(42-48).
This
tend
Clinic
has been large
1963
accounted primary
to
for
glomer-
shown
to recur
variability
in
probably
recurrence is diagserial allograft biop-
to uncover and
for In a
from
IgAN with
under which that perform often
who
transplantation.
Mayo
reported
done
grafts
for renal
at the
Stenoff
transplantation, of
age
transplantation
and
renal
to 60%
angial
of renal
of renal
cohorts
recurrent
earlier
than
mes-
those
that
reserve graft biopsies for clinical indication only (44,46,48). Initially considered a benign condition (47), allograft losses from recurrent IgAN have been reported in the last 2 yr. casting doubt with
on the 5 1 grafts
responsible inhibitor.
by
Group
in late
sies
enzyme
conducted
It is evident, of course, that not every treated with any of these regimens-corticosteroids,
relates nosed.
a Average annual slopes of Cr-ethylenediamine tetra-acetic acid clearance for at least 1 yr in Swedish patients, median annual slopes of creatinine clearance for at least 3 mo in Toronto patients, and mean annual slopes of creatinine clearance for at least 2 yr in
trial
study
20
-0.3
hypothesis
volve
-8.4>
55
the
IgA
hypertensive
27
01
tests
two
with
patients. Both of these prospective studies in2 yr of treatment, and because patients were entered in the
treat
10% of renal transplants ulonephritis (41).
1
of
patients
trial
Study
progressive
-6.0
-7.
study
of
first
medicine
33
5 1
comparative
treatment
The
that
In both
review
Study
placebo-treated
internal
(Omacor’)
group.
-4.0
(12)
acids-
study fatty
After
Collaborative
Group
or n-3 fatty
study
-8.8
1
of results
in an
A prospective
OmacorTM
to curtail
1.4
effective
disease-corticosteroids
Group: of
treatment.
(38)
histology
laborative
sive
all patients advanced
the
and
treatment
renal
cebo-controlled
(Table
a more
two randomized clinical trials are currently under way in the United States (39; and Donadio JV Jr. Bergstralh EJ, Offord KP, Spencer DC, Grande JP, for the Mayo Nephrology Col-
Yet Ca-
suggesting
oil
is the better
pa-
patients were group, providing
oil in slowing
fish
that alternate-day decline in renal moderate IgAN
IgANa No. of Patients
Group
testing
and
ACE1-treated
patients,
and
by ACE1 inhibitors. with the discrepancy
doses
ACE1-
determined
disease
pain
protective
to the normotensive
of GFR
normotensive
Annualized
Stockholm,
patients
patients, and the placebo-treated greater than the fish oil-treated
evidence
Table
a renal
in estimated
estimates
decreases
hypertensive
further
the hypertensive
suggesting
not only
other
but also to the high-risk patients reported from and the placebo-treated group in our fish oil trial
in whom
5).
similar
agents
hypertensive
with
agents,
with
normotensive rates of decline
ACE1-treated
decline
was
provided However,
trials
on a comparison of patients with ACE1
antihypertensive
in hypertensive
annual
renal
that
progressive
that treatment
of untreated but lower
compared
other
sive
were
associated
Glomerulonephri-
reported
with
group similar
between
normotensive treated
they
not
which
and associates
and a third There were
creatinine
risk
did
failure.
group
than ACE1, tients (15).
in a study and
important
ACE1 attenuated the decline in GFR based treatment of one group of hypertensive drugs,
oil
patients
subjects
is an
study
Cattran
37
I 329
17 biopsy-proven
initial
premise
in 46 patients for significant cases
(45,48,49). revealed functional
and in 36%
An
Australian
that recurrent deterioration ofthose
who
study
IgAN was in 29% of also
had signs
1330
Journal
of the
American
Society
of Nephrology
(9) 1 00
(6)
(2)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
90I
Lb
80
( 1 1)
-
%
>
70
C,,
60-
-
-
-
(9)
-
CAD
m
-
-
-
.
lI
(2)
0
12
LRD-0
‘I,
-
(7)
No. at time .
-
3
---
LAD-I
29
---
LRD-2
9
I
I
I
I
I
I
0
2
4
6
8
10
Years Figure matched
2. Actuarial renal allograft survival according to donor kidney living related donor (LRD)-2, 88% in HLA-l haplotype-matched
HLA-mismatched Reprinted
(LRD-0)
with
kidneys
permission
from
IgAN.
C/in Transplant
1997,
Table
6.
of IgAN
Recurrence graft
source
were
functioning
Frohnert
source.
There LRD-l,
for up to I .6 yr (longest
PP. Donadio
IV In, Vebosa
IA,
follow-up)
Holley
KE,
in renal
in several
patien
albografts
according
to
and
peared
t group?
No. of Transplants
CAD
Source
LRD-1
of
San
(42)
Francisco,
1986
kidneys
LRD-2
should
data
1994
CA,
12
1/4
1/1
5/7
13
1/7
4/4
1/2
MN,
50b
4/1 2
9/29
1/9
(48,
75
6/23
14/34
7/18
1.43
=
CAD, cadaver; LRD-l, one haplotype HLA-matched LRD-2. two haplotype HLA-matched kidney. a
of
recurrent
transplants
biopsy-proven
were three additional LRD kidneys. and follow-up of I .6 yr.
disease given
IgAN,
(45). to
51
there
at risk
at a given
transplants
patients transplanted none had a recurrence
time).
in patients
with
patients
our
experience (41
was excellent
men,
ing
available
for
difference
analysis,
(Figure
1 and
in Table
in LRD-2
6. A total of 75
incidence
kidneys.
23 There
of IgAN
in our patients.
glomerular
filtration
that
seen
there in 14
in patients
was
grafts
CAD was
between
a 7 1% incidence with
without
recurrent
kidney;
53
reapIf the
representing
18 LRD-2
and
in the
in LRD-
results
The interval of 2 yr between transplantation recurrence of IgAN and 3 yr to significant
women)
in CAD kidneys and in the different LRD warnings against the use of LRD kidneys,
of recurrence
then (52).
and recipient HLA-identical with sufficient
donor
far exceeds
with 10
between
recurrence, then rate. All studies
with our own
kidneys,
opinion
(NS)
no
these
of declinIgAN,
recurrence
renal with 2).
groups
does
which
were
disease
and the rate of IgAN
which
(14%)
(49).
development
and
loss
of
recurrence,
which
a previous observation by Berger et al. (42). It appears that D’Amico’s observation concerning
of
albograft
function coincides with the Australian study (45). Finally, series, there was no relationship between the aggressiveness
with HLAafter a
graft survival
antigens
rates
are listed
(50,5 1) and
patient categories. Thus, LRD transplantation should not be discouraged for fear of disease recurrence. In addition to a recurrence
primary
In
data
as an unreferenced
HLA
were
statistical
However, IgAN recurred in 14 (26%) allografts with equal frequency in cadaveric donor (CAD) and living related donor (LRD) grafts (48,49). Our experience with an equal frequency of IgAN recurrence not support
of renal
the risk of IgAN suffer the highest
34 LRD-1
rate of 26%
x2
h There mismatched maximum
grafts,
49)
Total
text
to determine
grafts (2.5)
(50)
Rochester,
of recipients fate
nonsignificant
shared
increase
transplants
1975
5: The
in a nephrology
should
(Recurrence/Total Transplants)
France,
number
=
on statistically
based number
Group Year
(,t
Sterioff
haplotypeAll three
in press.
Graft Study
was 5-yr graft survival of 100% in HLA-2 and 74% in cadavenic donor (CAD) kidneys.
in our of the supports primary
IgAN slowly
that the most frequent clinical course is an indolent, progressing chronic disease (2) also applies to recurrent
IgAN
in the renal
albograft.
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