Decrease of Serum Paraoxonase Activity in Chronic Renal Failure

J Am

Decrease of Serum Renal Failure

Paraoxonase

THIERRY F. DANTOINE,* LOUIS MERLE,t PIERRE CLAUDE LEROUXROBERT* *Nephrology

Unit

and

Activity

9: 2082-2088,

1998

in Chronic

JEAN DEBORD,t JEAN-PIERRE MARQUET,t GERARD LACHATRE,t

Department

Nephrol

Soc

of Pharmacology-Toxicology,

CHARMES,* and

Dupuytren

University

Hospital,

Limoges,

France.

Paraoxonase compounds.

Abstract.

phosphate and

could

protect

possible

familial

is associated

paraoxonase

Paraoxonase

with

the

main

cause

infarction,

death

three

was

synthetic

4-nitrophenyl

in

acetate)

in

305

patients

Cardiovascular

disease

is the main

failure

(CRF)

patients

(accounting

cases;

references

1 and

tion

is five times

greater

than

in the general

(3).

No clear

and

contribute

abnormalities, atherosclerosis

dyslipidemias studies

CRF against

have

shown

patients,

a higher might

processes the arterial

leading wall:

toward

of LDL

cells,

and

growth

and

factors)

(10,1

acid

against

esters

human

serum

and

shown

several

of Nephrology,

a blue ribbon. Correspondence Limoges,

to

2 Avenue

New Dr.

Orleans,

Jean-Pierre

Martin

Luther

LA,

November

Charmes, King,

3-6,

reduced

the

to

teins

against

LDL

production

gous

1), several

(1 7, 1 8).

Service

87042

Limoges

a

Copyright

of the ©

American 1998

by the

Society American

and

received

Nephrologie, Cedex,

France.

Chu

[high

Society

of Nephrology

with

activity])

age

studies

have

been

is related

variation

but

lipid

to induce

monorole

of

this

mellitus, that

in high heterozy-

myocardial

showed

hypoth-

noticed

infarction paraoxonase

(19). a triphasic

paraoxon: AB

defined

to a single

distribution

Three

[intermediate

(20-22).

two

amino

polymorphism

paraoxonase

acid

of serum

phenotypes

Genetic

studies

isozymes

(glutarnine

of the paraoxonase

and

and BB

activity],

have whose

or arginine gene

shown to affect the concentration its specific activity (24-26). Recently,

it has been

not

support

or

with

A second

54 is known;

of paraoxonase,

been

LDL significantly

was

diabetes we

toward activity],

difference

linking has

a protective

activity

with

[low

that

LDL Thus,

Other

display

activity

associated

position

of Nephrology

oxidized

study,

populations (AA

decreased paraoxonase

(16).

patients

previous

decreased

genotypes

It

hypercholesterolemia,

In

191) (23,24).

1046-6673/0901 1-2082$03.00/0 Journal

de

of the American

atherosclerosis:

a decreased

risk

familial

4-nitrophenyl

atherosclerosis has been suggested, as of the protective role of HDL lipopro-

that

cardiovascular

and

emerged

purified

oxidation.

showing

its procom-

has

paraoxonase

that

for

metabolite of parathion: several aromatic carboxacetate

to

to

paraoxonase/

known

of organophosphorus

evidence

of mildly

of

first

es-

seems

enzyme

phenyl

interactions

paraoxonase against well as an explanation by

as

and

ability

paraoxonase 1996,

some

aging,

transplantation

was

recently, purified

(15)

Caucasian

Society

with

[P < 0.05],

failure

vascular

HDL-linked

paraoxonase

cyte-endothelial

esis

Renal

the toxic to hydrolyze

(such

in vitro

that

activity

Received August 12, 1997. Accepted May 4, 1998. These data were presented in part at the 29th Annual Meeting

sub-

4-nitrophenyl

in patients renal

of premature

the toxicity

More

peroxidation in

the

hydrolyzing and its ability

trans-

a number

immunogenicity,

(by

(14).

to the formation of atherosclerotic plaques in enhancement of macrophage uptake, cytotox-

cytokines,

pounds paraoxon) acetate)

seems

promoting

studied

activity

ylic

lipoproteins

of atherosclerosis

factor

( 12, 13). Paraoxonase

arylesterase

tective

(7-9).

LDL

be an essential

have

of

to oxidation

of

with

lower

Patients

control

hemodialysis [P < b01, chronic peritoneab dialysis l0]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure

groups

of mortality,

protection

hypothesis (oxidized

endothelial

of oxysterols,

the

renal

was

(chronic

renal

factors, melbitus,

(6). Recently,

susceptibility

be impaired

established

cause

observed

that

the oxidation

(4,5). After

a major

frequently

suggesting

oxidation

Because

remains

also

are

be currently

icity

may

activity

insufficiency

when dialysis is used. paraoxonase activity.

of this

Several diabetes

patients.

Especially

peciably restore

infarctherapy

explanation

transplant of aged-matched

195).

=

paraoxonase

renal

groups

with

50%

relative risk of myocardial in patients on renal replacement has been found. of hypertension,

plantation,

in chronic

approximately

“accelerated” atherosclerosis including increased prevalence lipid

failure,

treated

of death

for

132

two

number

of renal

could

disease,

renal

22 patients

cause

usand

kidney

chronic

and with

[P