Immunoglobulin A Nephropathy: A Clinical Perspective - Journal of the ...

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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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