f32-Microglobulin Amyloidosis in Chronic Dialysis Patients: A Case ...

AMERICAN RENAL TRAINING CENTER SERIES

f32-Microglobulin Amyloidosis in Chronic Case Report and Review of the Literature JOHN

FARRELL

Division

Abstract.

and

of Nephrologv,

Dialysis-related

BAHAR

University

secondary

to

amyboidosis

morbidity sity

with

potential

to deposit

bones carpal

in the

mortality.

2m

osteoarticular

tissues,

has a propen-

particularly

of dialysis are of this disease.

Dialysis-related

two important The high-flux,

amyboidosis

of chronic

dialysis

(DRA)

therapy.

The

is a serious

identified as a modified form levels of which are universally

of beta-2 elevated

However,

also

2m

other level

development screening logic

factors

is

not

specific

and

a remarkable bony

of DRA.

DRA.

Although

do not

serum

DRA.

The

in their

there

f32m

osteoarticular

result

of diabetic

nephropathy.

hemodialysis, acetate,

koA

930;

=

a white

ESRD

She

3 h each

was

session,

Baxter

IL) membrane. She was veboped a painful, swollen revealed

showed

very

tendon

sheets.

on

subject

nights

and

during

thumb

and

index

this

in

treated using

HealthCare

1984

diagnosis

staining

classic

the

the

material,

with

a CA2 Co.,

thrice-

stroke.

10 (cellu-

McGaw

levels

Park,

F80

had

and

the

reduced

blood

cell

count

of

10,400,

a red

blood

cell

Immunohistochemical

formaldehyde.

worse

polyclonal

antiserum

cisco,

to 2m,

joint

unremarkable. She continued over the next 18 months.

effusions pain

in her

left

hand,

which

was

Synovial

at

and

carpal

tissue

were CA)

tendon

tunnel

January

Correspondence University Louis,

Health MO

17, to

1996.

Dr. Sciences

Accepted

May

Bastani,

Bahar

Center,

8. 1996.

Division 3635

Vista

er’s of

Nephrology,

Avenue,

63104.

1046-6673/0803-0509$03.00/0 Journal of the American Society Copyright

© 1997

by the

of

the

showed

the

amyloid

pres-

antisera was I 20.7

dialysis

membrane

KOA = 945; Fresenius for I yr and then to a CT 920;

Baxter

HealthCare

1994

Co.),

after

a massive

membranes,

to approximately

American

9-North

St. FDT,

Louis St.

her

35

on the CTI9O

used

protocol

throughout of Nephrology Society

of Nephrology

tissue

mgIL

32m on

the

membranes.

for

(Zymed using

labeled

a blocking

the antibody showed between the collagen

Inc.

,

with

rabbit

San

Fran-

streptavidine-biotin

according Corp.,

in which solution, (Figure

buffered

of paraffin-blocked staining

Laboratories

the specimen

in 10%

Laboratories,

the

slides.

intraoperatively

fixed

immunohistochemical

(DAKO

with

was sections

technique

control

obtained

surgery

Four-micrometer

the negative replaced

sheet

release

oxidase-antiperoxidase Received

material

Staining

to have In March

noted

a

(H &

never transplanted. In 1993, she deleft knee. This knee was tapped and

barity, but was otherwise she

with

on July

45 mgfL

and

staining

light,

patient’s

=

death

left

intraoperatively red

biocompatible

approximately

during

1994,

The

KOA her

more

markedly

(CTS)

eosinophilic

polarized

(Polysulfone, Germany)

her

and eosin

consistent

mgIL).

until

count of 53,000, with a 32m bevel of 27.8 mgIL. A magnetic resonance imaging scan of the knee revealed synovial noduintermittent

of

Soc

confirmed

syndrome obtained

under

in

studies

staining using appropriate to be 32m. Serum (32m level

40 yr at the outset of dialysis Length of time on renal replacement Bioincompatibility

of dialysis

membrane

therapy

for more biointhe

and

DRA

patient (Table

should

with 2).

CTS, CTS

by /32m-amyboid

j32M Amyloidosis

Table

2. Clinical

presentations

development

of dialysis-related

of iodine’

amyboid

amyboidosis

tunnel

Large

syndrome

joint

Cystic

bone

Rarely

systemic

of DRA

of the

arthropathy/spondyboarthropathy disease

amyloid

extent

body

disease

25-babeled

P component

diagnosis

Carpal

scans

(7). These of various

ible

versus

2m,

and

stage,

with

improved

enable

interventions

at the wrist,

manifestations

of DRA.

symptom

complex

other

and

forms

with

tion

of the more

secondary

of CTS.

referred

between

to DRA

The

and

patient

complains loss

over

of the digital

muscles

to as “amyboid

hand.”

arthropathy

secondary

may

the or

patients

at risk

e.g.

occur,

The joint

usual presenting mobility. A joint

effusion

fluid

is serous,

be present.

the fluid

The

synovial

Amyloid

sediment

is stained

material

with

initially occurs as a unilateral will almost inevitably become typically amyboid discs

involving deposits and

mild, may

the have

Congo

bones

on

ligaments.

the

in proximity x-rays

of

patients

deposits,

and

do not regress

bone may

weakening play a role

Systemic fortunately renal

function described,

after

DRA.

These

transplantation

intestinal

(4).

at a later stage rise to major

joint

of /32m

secondary to 2m-amyboid emphasizing that DRA

contain with

time,

lead

joint, fractures.

tendon myocardiab

deposition can potentially

be

chain.

antigen

(HLA)

rotator-cuff

method bone

to select

lesions

occur

found

in

ecube, occur

of 2m

unlike

is an

highest

forms.

and

the

The

and T cells

and major

malignant elimination

the accumulation of /32m of uremia and dialysis.

forms

of amyboidosis,

very

cannot

be

precipitation

in

released

predominantly in the plasma proteins. In-

to

similar

the

fully

explained

of intact

f32m

mob-

fibrils may the patho-

solely

in body

in

substance

to the circulating

and spontaneous generation of J32m amyloid in salt-free solution in vitro (10). However, of DRA

body

serum

Once

occurs in inflammatory is the only known

other

amino

normal

of synthesis.

2m circulates is not bound

is biochemically

100

part of the complex, but

integral

Lymphocytes,

rate

f32m

of

1 antigen

daily,

is 0.5 to 2.0 mgIL.

cell surface, form and

of simple other been tected

It

non-HLA-associated

mg

the

formation. consisting

Class

for j32m, which explains with increased duration

on

the

tissues.

basis

Many

pobypeptides, all of which originate from j32m, have also isolated from affected tissue samples. Linke et al. de2m that had been cleaved at lysine residues, from

dys-

serum,

amyboid and amyboid urinary stones (5). a “novel” f32m isolated from amyboid which

molecular

had

weight

for asparagine advanced

a more

usually

end

isoebectric

residue

and

to be

(12).

acellubar,

and lower et al.

fibrils

Amyboid

but

acid

Miyata

of f32m in amyloid (AGE)

et al.

of aspartic

(1 1). In 1993,

products

considered

Ogawa deposits

point

of the substitution

17th

the modification glycation

its are

acidic

because

at the

demonstrated Findings

a single

creased /32m synthesis conditions. The kidney

synoviab described

(6).

Radiological

polypeptide

have

from the monomeric

rup-

have all been become life-

of 2m-amyloid

for f32m

particular,

genesis

to

of the disease and clinical problems.

and

(5),

of the

before

glycosylated in

In DRA,

seen

may

spontaneous

DRA

mechanisms

50 to 200

deposited

near a weightbearing of pathological

obstruction,

composed

They

also

compression barge bones

size

of developing

leukocyte

pathway patients

cysts

and

aligned

level if

it often

commonly

are

in number

and, if situated in the development

stones

threatening

joints,

with

increase

involvement occurs only rarely gives

Nevertheless, ture,

to synovial

acids

frequently

it is

spinal cord affecting

1 1 .8-kd

may

sterile,

Although

Proposed is an

produces

observed

the contralateral Spondyboarthropathy,

Although

thickness

noninvasive

etc.,

the formuUltrasound

Pat hogenesis

human

cervical spine, may also occur. j32mbeen found both in the intervertebral

paravertebral

f32m-amyloid

be

red.

problem, involved.

cervical spine instability and occur. Bone cysts, predominantly

and

may

allow (8).

(9).

a condi-

affects barge- and medium-sized joints. symptoms are arthralgia and decreased may

the

be a useful,

biocompat-

,

transplantation,

palmar

predominantly

noninflammatory.

to measure

also

in the

thenar

the

to DRA

and

shoulder

may

of hand with

of the

tendons

idiopathic

associated

tests

initial

index, and middle fingers. The condition and in severe cases, contraction of the

atrophy

Destructive

common

is no difference

nocturnal or during dialysis) muscle wasting, and sensory

surfaces of the thumb, is frequently bilateral, hands

There

of CTS

secondary

pain (often weakness,

is one

estimation

the effective-

accurately,

membranes,

allowing

present

on the development and course of DRA, and lation of more efficient preventive measures deposition

by

us to evaluate

more

bioincompatible

serum

23

useful

of amyboidosis

may

511

Patients

prove

distribution

scans

Dialysis

may

at an earlier

and

ness

in Chronic

with depos-

histologically,

bone

f32m amyboid fibrils are often surrounded by macrophages. It is known that AGE-modified proteins are chemotactic for mono-

DRA

cytes,

and

scans

cytic

uptake

magnetic resonance imaging scans of bone will provide additional information to assist in the differentiation of amybid bone cysts from other cystic bone diseases encountered in

these usual

AGE-modified inflammatory

(14).

Although

hemodialysis space with

modified possibility

Because

of difficulties

topathobogical cysts

may

in

in obtaining

examination,

a patient

be helpful.

with

radiographic clinical

In certain

involved

cases,

tissue

evidence

symptoms

that

computed

suggest

tomographic

for hisof

and

bodies

may

patients. destructive be seen

Narrowing of changes involving in patients

with

the intervertebral disc the adjacent vertebral spinal

involvement.

The

amyboid

that

macrophages

of these

modified

possess

receptors

proteins

proteins may therefore nature of the amyboid this

evidence

for

(1 3).

strongly

The

the

explain deposits

suggests

endo-

presence

of

the unin DRA that

AGE-

j32m is a major constituent of DRA (12,14), another that needs to be ruled out is that the deposited j32m undergoes

secondary

AGE

modification.

512

Journal

Direct inantly

Society

of Nephrology

osteoarticular

structures,

tumor

necrosis

(IL-la) elevated

(14). in

to cause

factor-alpha

predom-

DRA

including

There are probably several reasons 2m has been shown to stimulate

secrete

shown

American

effects of 32m on bone resorption. affects

synovium. modified beta also

of the

lead to renal tissues, with

and

for this. AGEmacrophages to

(TNF-a)

and

Both of these cytokines, chronic hemodialysis

bone

interleukin-

levels patients,

1

synthesis lead

may

lead

to exposure

one

in cultured

synovial

cells

structures,

and

affinity

Homma

for 2m

et al. found

injected

evidence mineral

of bone dissolution

that

32m-induced

this

substance

multifactorial

removal

of 2m

serum

bevels

further

f32m show

calcium

efflux

is dependent

on IL-i,

(Figure

2). Chronic

by current

dialysis

which

amyboidogenic

and collagen. of DRA has study.

Patients

perparathyroidism

uremia

upon

further

substance

has

of other determined

often

DRA

to high

have

and iron or aluminum

serum

As

stated

above,

These

hy-

may

Renal

/\N

t IL-i

modified

-/

fI 2

\_

Exposure

Figure 2. Proposed patients.

reported

sofion

bevels

not useful

are

should

been

there

birefnngent

_

mechanism

Amyloid

tissue

formation

nature

for 32m-amyboid

in dialysis

a serum above

be useful

test. for con-

a definite diagthe presence

in Congo

of the

in bony

red stain-

amyboid

cysts,

treatment on occur

deposit

The

clearance

of 2m

during

hemodiabysis

ume loss. important

Two with

meability

of the

membrane

(PAN),

are

bind

2m,

not

membrane.

and to attempt

have

a higher

in hemodialysis

to extracellular

and

the

more

permeable

of

The

role that

vol-

which

membrane’s

bio-

occurs

membrane

with

the

and

therapeutic

options

disease development membranes, particularly

groups

therapy

Symptomatic treatment drugs for bone pain

release

older

bioincompatibil-

f32m generation is more controversial. or PAN membranes with peripheral

preventive

resection

2m

e.g. , pobyacryboto j32m, but also

membranes,

neither

in intradialytic of cellulosic

3. Potential

to f32m dialysis

only

It is there-

properties are particularly clearance on dialysis-the per-

dialysis-membrane regard to (32m High-flux

of amyare of

three-compartment rise in serum

is secondary

dep-

tunnels,

of DRA 3). Every

to identify those patients who the condition (Table 1).

levels

tunnel

carpal

for DRA.

prevention (Table

appears to follow a modified (20). In all cases, the initial apparent

shoulder pain Surgical therapy, formation

with elevated

and synovium. Unlike other types fat-pad and rectal-mucosa biopsies

Role of Dialysis.

Endoscopic IDRAI

may

patients model

in high-risk

in red

as a diagnostic

material

The

is no specific

be made

Steroid

of osteoarticular

once

studies

tissue.

intervertebral discs, loidosis, abdominal

Table

tCollagenase

in a patient

However,

Early renal transplantation before Use of biocompatible hemodiabysis

t Bone

2m

Congo

demonstrated

ity plays Incubation

osteodystrophy

for

osition

little value. To date,

be and

be confirmed by immunohistochemical appropriate antisera. j32m-amyboid fibrib

ceblulosic

m

It should

negative

10 mgfL.

radiological

involved

has

in of

amyloid,

staining with

result

acquisition

may subsequently techniques using

actively

\\orae

& TNF-cx

2m

compatibility.

clearance

.

AGE

has been than

apple-green

of the

nitrile

RD biocompatibility

collagen

risk of developing

concomitant

132 m

histochemical

factors in the and requires

1

Serum

formation. represent

a predilection

serves

IEsRDI

t

amyloid deposits

fore important to concentrate control symptoms if they

overload.

12 m renal

level,

will for

Treatment

of less

this

ing

a

inadequate

leads

modification

that

The importance not yet been with

and

techniques

level

patients

is required

and

significant

and

some

all j32m

subcutaneous

of DRA

of typical

histologic

resorption with osteoclast-mediated bone (18). Sprague et a!. further demonstrated

of 32m,

as a potential for bone etiology

with

in which

firming clinical suspicions of DRA. However, nosis of DRA can only be made by demonstrating

that is dependent

whose bevels are elevated in dialysis patients (19). appear therefore that the etiology of DRA is prob-

It would ably

subcutaneously

not

find and

case

132m a

that

may

No

present formation,

ultrastructure

Diagnosis

(14).

to collagen degradation and con/32m itself appears to have a predi-

collagen-binding

mice

fibrillar

staining.

which

on the concentration of both /32m and collagen (17). It is also likely that 2m plays an active role in bone resorption. Neo-

natal

the

to 2m (15,16). In addition, Miyata et that AGE-modified (32m caused sufof TNF-a and IL-l3 from macrophages to

for osteoarticular

preferential

sheet

tendons

resorption,

This may subsequently nective tissue breakdown. lection

factors

f3-pleated

emphasized

of which are have been

osteoarticular structures al. further demonstrated ficient secretion stimulate collagenase

systemic

of

bone

bone disease and the exposure of collagen-rich subsequent 2m deposition. Additional local and

with

nonsteroidal

of coracoacromial including

as necessary

joint

anti-inflammatory ligament

replacement

and

for carpal

32M

blood

monocytes

in vitro

synthesis

by

these

synthesis

observed

blood/dialysis

also

during

reported

patients,

who

dialysis

the

is that

is

TNF

interaction This

may

vascular

membranes,

unequivocal use of PAN

balance incidence

bed,

as

Other

groups

have

cystic

bone

Dialysis

decrease

in PAN-dialyzed

with

Association

to lym-

with

subse-

branes, branes

versus

that the positive

were

not

exclusively

(22).

(3).

study,

Many

and some had been switched from cellubosic to AN69. Despite this, there was a trend toward

memfewer

to 32m,

the

PAN

Indeed,

to 20 mgIL

in high-risk

Although

will

daily

normalize

only

hemofiltration

groups

such

should

to slow

as the elderly,

2m

PAN

mem-

be considered

f32m

high-flux

accumulation

and

therapy

disease

tion

should

development serum

and

be

steroid

considered

1.

levels

and,

DRA.

patients

It will

in patients

who

rapidly

have

been

for less than 8 yr, should prevent disease progression in patients with symptomatic DRA, transplantation

in an

3.

Bardin

has demonstrated

pain in patients with low-dose prednisone

some

success

before

4.

(25). Transplantation in the size of bone

been

these

recovered

from

tion (4). Symptomatic treatment. nonsteroidal anti-inflammatory but does

not alter

disease

cysts

on

6.

dialysis

(4). Even will suc-

in treating

7.

an (4). bone 8.

does not appear to cysts, and 32m has

up to 10 yr after

been

pain

in

It may be necessary to conif the patient has evidence of

a result

of

erosive

spondyloar-

of

significant

and

is potentially

morbidity

described recently, much but the exact pathogenesis

has been continues

of

on

these

patients

already

Although

it

learned about to allude us.

suffer

from

it is important for nephrobogists and attempt to slow its progression

renal

to recognize in susceptible

with pain,

AA arnyloidosis,

Di,

Otieno

LS:

Carpal

hemodialysis.

tunnel

Postgrad

syndrome Med

in patients

J 5 1 : 450-452,

on 1975

F, Yamada T, Odani 5, Nakagawa YM, Arakawa M, Kunitono T, Kataoka H, Suzuki M, Hirasawa Y, Shirahama T, Cohen AS, Schmid K: A new form of amyloid protein associated with chronic hemodialysis was identified as f32-microglobulin. Biochem Biophys Res Commun 129: 701-706, 1985 Geyjo

Van

Ypersele

De

Strihou

C, Jadoul

M,

Malghem

J. Maldague

B.

L, and the Working

Party on Dialysis Amyloidosis: Effect and patient’s age on signs of dialysis-

of dialysis membrane related amyboidosis. Kidney

mt

Bardin

T, Lebail-Darne

Zingraff

Kreish

H, Kuntz

JL,

39:

1012-1019,

1991

J, Laredo

JD,

Voisin

MC,

D: Dialysis arthropathy: Outcome after renal transplantation. Am J Med 99: 243-248, 1995 Linke RP, Bommer J, Ritz E, Waldherr R, Eulitz M: Amyloid kidney stones of uraemic patients consist of /32-microglobulin fragments. Biochem Biophys Res Commun 1 1 2: 665-67 1 1986 Ogawa H, Saito A, Hirabayashi N, Hara K: Amyloid deposition in systemic organs in long term hemodialysis patients. Clin Nephrol

28:

Zingraff

J, Caillat-Vigneron

Moretti

JL,

labelled

amyloid

199-204,

Bardin

1987

N, Urena

T, Drueke

P component

TB:

P, Gagne

Plasma

in 2m

ER,

kinetics

amyloidosis:

Bererhi of

L, 1251

A possible

approach to quantitate disease activity. Nephrol Dial Transplant 10: 223-229, 1995 Tan SY, Madhoo 5, Brown E, Gower P, Irish A, Winearls C, Clutterbuck RI, Pepys MB, Hawkins PN: Effect of renal transplantation on dialysis-related amyloid deposits: Prospective evalby ‘231-SAP

scintigraphy

[Abstract].

Nephrol

Dial

Tra,is-

plant 9: 1017, 1994

9.

Unlike

Warren

uation

transpbanta-

Symptomatic treatment drugs may help to relieve progression.

has

shoulder

,

the

normalize

DRA who are on dialysis with the use of (4 to 8 mg), but further studies are needed

to confirm his findings lead to any decrease

of

dialysis.

many

Jamart

5.

transplanta-

cessfully alleviate the bone pain associated with DRA, effect that may be secondary to the use of steroid treatment Indeed,

treatment

long-term

intermittent

development

Renal

in all suitable

of established

2m

therapy.

replacement.

ligament

References

(3).

Transplantation

as

in patients

Because

biocompat-

for dialysis

is a cause

has only been the condition,

32m

to reduce with

DRA

life-threatening

permeable

serum

able

joint

infil-

Summary

2.

the cellubosic

it is more

not

et al. were

with

with

total

steroid

thropathyof DRA.

still ten times normal (24). However, in patients unsuitable for transplantation, and particularly

membranes

auempt

(23).

membrane

Canaud

branes, a value who are deemed

compared

In some cases, large-joint disease,

of

mem-

group,

local

symptoms. Severe

in patients

membranes. with

instability

in DRA. to avoid

groups.

a statistically

cysts

spine

osteodystrophy, this condition

In a European

registry

of bone dialyzed

of

AN69

cysts in the AN69 (23% versus 38%)

levels.

a lower PAN

membranes

to show

cellulosic

of of

to demonstrate

(EDTA)

unable

in the incidence

AN69

patients

levels

lead

benefit release

of the coracoacromial in the

513

although

require

long-term dialysis patients (26). sider cervical spine stabilization

in the incidence

patients

et a!. were

difference

dialyzed

ible

cellubosic

a similar

Brunner

significant

bone group

with

noted

Transplantation

however,

their

compared

often

complement

development with the use

difficult

will

successful

the

cervical

it has been

improve be required.

of the hips,

Patients

is of any surgical

damage,

moderately

with

benefit. Chanard et al. showed membranes reduced the annual

lesions

neurological may transiently surgery may

that

Dialysis

that colchicine usually requires

resection

of 2m in the body by 50%. They also showed of CTS in patients dialyzed with long-term

membranes,

e.g.,

in Chronic

Endoscopic

of blood

Although many studies do suggest delayed DRA and a decrease in DRA symptomatology a clear routine

has dialysis

tration repeated

DRA

to

there is no evidence Treatment of CTS

permanent

membrane.

leads

release.

f32m

a direct

peritoneal

biocompatibbe

phocyte activation in the pulmonary quent increased j32m synthesis.

biocompatible

by

Moreover,

membranes

and

any

caused

(21).

the in vivo

IL-i

not

of j32m

that

ambulatory

ultimate

cellulose with

suggest

interaction

possess

bioincompatibbe

to an inhibition

would

in continuous

possibility

activation,

lead

This

membrane

been

One

will

cells.

Amyloidosis

10.

Jadoul M, Malghem J, Van De Berg B, Van Ypersele De Strihou C: Ultrasonography of joint capsules and tendons in dialysisrelated amyboidosis. Kidney tnt 43[Suppl 41]: 5106-51 10, 1993 Connors LH, Shirahama T, Sipe JD, Skinner M, Fenves A,

5

14

Journal

Cohen

of the American

AS: Formation

globulin.

Biochem

Society

of Nephrology

of amyloid

Biophvs

Res

fibrils

from

Commun

intact

131:

f32-micro-

1063-1068,

osteoclastic

1 1 . Ogawa H, Saito A, Oda 0, Nakajima M, Chung TG: Detection of novel /32-microglobulin in the serum of hemodialysis patients and its amyloidogenic predisposition. Cli,i Nephrol 30: 158-163, I 988 12.

Miyata

T, Oda

S. Taniguchi

0, Inagi

R, lida

N, Maeda

ified with advanced

glycation

13.

N, Yamada

N. Horiuchi

T: 2-microglobulin

end products

of hemodialysis-associated 1252,

Y, Araki

K, Kinoshita

mouse 19.

92:

H, Moldawer

L, Chan

cachectin/tumor T, Inagai

R, lida

vanced

glycation

motaxis

An interleukin-

21.

17.

22.

DR,

N, Oda

GE,

with

ad-

23.

587-591,

J, Caudwell

Molina

1992

Role

of IL-lB

bone

V, Lavaud

S. Wong

turnover

mineral

T, Revillard

in dialyzed

pa-

1992

R, Rodriguez

R, Munoz-Gomez

synthesis

globulin

in lymphocyte

culture.

Nephron

Chanard

J: Prevention

of dialysis-related

AN69

SM:

1995

inhibit

of hemodiabmonocyte

of TNF

and

IL-l

membrane.

EJ,

McGuire

MKB,

stimulates 1983

bone

Russell

resorption

daily

in vitro.

and

J, Revert

release

of (32-micro-

59: 691-692,

1991

amyloidosis

Contrib

TS, Smith

DD,

Mundy

affinity

of 2

ciated

F, Isemura

M, Arakawa

microglobulin,

amyloidosis.

using

Nephrol

the

1 12:

137-

Nephrology

under faculty

program

at St. Louis

the direction of Dr. Kevin Martin, has ten full-time members with diverse interests in basic and clinical

research.

The

curriculum

ible and allows

for two

track

comprises

months

in

research

academic

devoted

the

year

to those

exclusively

nephrology

training

a 365-bed

tertiary-care

ical center

Cochran

will obtained

optional

to

laboratory

occurs

hospital

fellows management

develop of acute

and

yrs

to are

medical

area

renal

fellow

including

renal

outpatient

transplantation research

faculty. of

cluding

prostaglandin

Current

volving

the

departments

elec-

of acid-base

and physiology

material

I, Takemura

T,

of shoulder Dial

pain

Transplant

6:

several spectrum relevant

among

ancillary

chronic

hemodialysis,

Each

out under

of

acIn

services,

fellow

careful

research

regulation,

and

is also

as-

on

and

cell

cell

biology,

The

horprojects

in-

pharmacology, Nephrology designed

basic

inthe

calcium-regulating

conferences

to the practice

the

proliferation,

biochemistry,

and

by

include

Collaborative

ongoing.

clinical

supervision

projects

acids

and bone. of

weekly

is also recipients.

clinic.

fatty

are also

ambulatory

Division

services.

and

including

continuous transplant

metabolism

kidney

failure,

rotate

polyunsaturated

in the

broad

Hamanaka

of hemodialysis, and

active

mones

nephrol-

ar-

1994

University

nephrology

study

conducts

1992 amyloid

Nephrol

of renal

is carried

effects

First-year

of

mem-

in hemodial-

management

Nephrology

will

outpatient

path;

med-

Y,

histopathobogy,

the

and at the John

center.

the

Basic

C: Failure

dialysis-related

patients.

The

Clinical

as a major

Takatori

Endoscopic

in the care

analare

in

therapies

addition,

the

to normal 7: 924-930,

and all aspects

dialysis.

an

Dial

permeable

Transplant

hemodialysis

involved

signed

different

1990.

hospital,

in consultative chronic

a

of training

University

serves

St. Louis expertise

path

investigation. that

Administration

assigned

via the clinical

third

at St. Louis

in the metropolitan

Veterans

be

18 to 20 to pursue

of this

tively

of clinical

wishing

activities

and

of

S.

0:

dialytic

peritoneal

is flex-

nephrology

consisting Fellows

clinical

second

clinical

4 to 6 months

nephrology

The

in the first

however,

and

program

The

fellowship

investigation.

track.

ogous

paths.

rotations

laboratory

career

major

a 2-yr

of clinical

and/or

of the fellowship

highly

Ed Fr 61 : 975-1005,

Rhurn

disorders,

continuous

two

Nephrol

concentration

Dial

at St. Louis

trolyte

University,

of

R, Mion

using

Rev

long-term

Program

P, Angar

prednisone

I, Ninomiya

Geerlings

AJ: Case control

registry.

Low-dose

K, Otsubo

117-119,

Training

A, Kerr

Nephrol

Otsubo

W,

influence

the EDTA

programme

Okutsu

in

1989

Fassbinder

0, Wing

The

from

to (32 microglobulin T:

JHH,

1990

B, Assounga

thropathy.

of hemodialysis-asso-

53: 37-40,

training

Data

5: 432-436,

Bardin

M: Collagen-binding

a preprotein

Nephron

nephrology

arthropathy:

patients.

ysis

OR:

Ehrich

NH, Tufveson

dialysis

hemofiltration

brane

Bringman

H,

membranes.

Canaud

24.

RGG:

26.

N, Gejyo

Brynger

G, Selwood

on

dialysis

J Clin

.

FP,

study

che-

1986

Homma

Brunner

W, Rizzoni

516-518,

ogy,

Sprague

membranes

Transplant

1994 DD, Ihrie

Nedwin

Maeda

modified

of human

secretion

0,

Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature (Land) 319:

clinical

JM,

Dialysis

polyacrylnitrile

25.

The

C, Chanard

Campistol

recep-

in the pathogenesis

b-like factor 306: 378-380,

(Li’nd)

M, Yamada

Induction

macrophage

Invest 93: 521-529, Gowen M, Wood

Bertolini

products

amyloidosis.

and

Nature

Y, Sato

of f32-microglobulin

end

ysis-associated

16.

SA,

neonatal

1 1 : 302-306,

144, 1995

Miyata

K, Seo H: Involvement

15.

Kidney

Vincent

I 989 14.

Cummings

JP: Kinetics of ‘25I-32-microglobulin tients. Kidnei’ Jut 42: 1434-1443,

glycosylated proteins is upregulated by factor. J Cli,i Invest 84: 1813-1820,

necrosis

BK,

from

Metab

in /32-microglobulin-induced

20.

1243-

B: Macrophage/monocyte

Calc Reg Hor Bone

Hack

stimulates

dissolution

Jut 47:

L:

tor for nonenzymatically

mineral

and prostaglandins

1993

Vlassara

SM,

SM: 32-microglobulin

bone

dissolution.

component

J Cliz invest

SA, Sprague

mediated

calvariae.

Moe

mod-

is a major

amyloidosis.

Moe SM, Barrett

18.

1985

Division to cover

pathophysiological

of nephrobogy

a