Urinary heparan sulfate excretion depending on microalbuminuria in

Transkrypt

Urinary heparan sulfate excretion depending on microalbuminuria in
ANNALES
2010
17
!"#$%" $&'(&$&)* &+$,+
"#$%" $&' !&, &-&*)"!,- ."+$)&'/(-
1
2
3
441
5
1
3316
31
36
2
Urinary heparan sulfate excretion depending on microalbuminuria
in patients with diabetes
)!- "+,8 /"# /8%&,8"%8-"9 "&!%:&-(/% //#,;" $<=8,/:8),>
"&'$"?+$+* +&'!("$, "#&#$)+!+,"$" ,"+" / )"@,"$& &'-(/% ,--"! %,&-(/% / ,&-(/% / + #"!,$." &' " - -"+& + ! $+ !"$"% $& + /+"'/- %: * !",+& + & $" $$& &' !/* $"$%" $ '& ,#" $ "#&#$)
" %,&-(/% / ##"+ *-&%"/- ." -"!) !"%& +$$"! +$&-&*,- !. ,"!
*-&%"/-&#$)BCD$+%#&$ $$&"+$(-+#"!,$."%:"+"-"$ %,&-(/% /
$&+$&#$"#&,"++&"." $&"."+"$
""# +/-'$"FGH, +",&%#&+"!&'-$" $ **-/,&+% " !*-/,/& ,I
!/& ,,!"+!/"+=," "*$."-),*"!+"+/-$&'$"#"+" ,"&'%/-$#-",(&@)-,
*&/#+ !+/-'$"*&/#+"G+%;&*-),&+% &*-), FJ
JH=,+,&%#& " $&'
#"-", !* $"%&+$%#&$ $#&$"&*-), +&'$"*-&%"/-%"%( "FJH=,
%)% $ $"J,*"("""'&"G $"J+++/%"!$&"#"- "*$."-)
,*"!#&$" + ,-/! *-(/% !#"." $$"?-$$& G+"++" $-'&$"% $" ,"
&'#&#"*-&%"/-?-$$& BKMD
$ + ("" #&."! $ , *"+ $" ,& ," $$& ! O/ $$) &' +/-'$"+ *&/#+ &' G
",& ",$"!=$$"##" ,"&'" -#$&-&*"+ ,-/! *!("$, "#&#$)BPKKD
!","+"! J G "@#"++& ,&"-$"+ =$ ,"+" $" -"."- &' #&$" /" G +
%"$(&-8"!()"# +"F" !&Q*-/,/& !+"H=,+ !/,"!()$"#"+" ,"&'*-/,&+"
$"" .& %" $$+("" +&= $$"%&.-&'G'&%$"Jin vivo $+()!*"+$& =$"#$ +"-"!+$& ,"+"!/ )+","$& &'(&$'"$ !-(/% BRTD"-,:&'
+) $"++&%#"!+) $"++&'G&'J-"!+$&$"!"."-&#%" $&'%,&-(/% / !
'/$"$&"@,"++."/ )#&$" +"@,"$& BKUD
+", &' "-) !,$& &' *-&%"/- !%*"+ $ =+ !",!"! $& ".-/$" , *"+ / )G"@,"$& +#&++(-"/+"'/-%:"&'$"!"."-&#%" $&'!("$, "#&#$)"
116
8 &=+:)+$):" $#c+:8"!8,6&-+:
&=:&=+:
%&'$"+$/!)=+W+", *!''"" ,"+ / )G"@,"$& #$" $+=$!("$"+ ,&%#+& $&$",& $&-*&/#W".-/$& &'#&++(-""-$& +#+("$="" $"%,&-(/% /
!/ )G"@,"$& W".-/$& &'#&++(-"/+"'/- "++&'/ )G"@,"$& +-(&$&)
$"+$'&!("$, "#&#$)
G
""+",=+,& !/,$"!& M#$" $+=$$)#"!("$"+%"--$/+=&%" !U%" *"!KX$&T)"+&+#$-8"!$$" !"#$%" $&' !&, &-&*)"!,- ."+$)
&'/(- & $&-*&/#,& ++$"!&'P"-$) !.!/-+KM=&%" !KK%" *"!M$&RC
)"+=$ &:! ")&(& "-- "++"++$&)
(&$&)$"+$+=""#"'&%"! '+$ *+"/% ! M&// ",&--",$& Y/ $?,$& -
!"$"% $& &'G / "=+#"'&%"!=$$"/+"&'G"# /-'$"
:$F":*:/
&#&$& H G "@,"$& =+ "@#"++"! +Z $&$- G "@,"$& M +#",%" $+ F[*IMH
,& ," $$& F[*I%-&'/ "H !,& ," $$& ,-,/-$"!#"/ ","$ "F[*I%*,"$ "H
& ," $$& + &' ,"$ " ! %,&-(/% / ="" %"+/"! =$ $" /+" &'
!. K\PU
-)+"F"%" +H+$%$"!*-&%"/-?-$$& $"F"J]H=+,-,/-$"!/+ *$"&!?,$& &'"$ " -+"+"FH'&%/-+/,+Z
"J]^KT\@+"/%,"$ "KKPM@
*"UUC@BURM']"%-"D
"+/-$+&'$",& !/,$"!+$/!"+=""+$$+$,- -)+"!/+ *(+,#%"$"+&'!"+,#$."
+$$+$,+F%" %"! O/$-"H$-#"% ,&"-$& ,&"'?," $=+/+"!$&"+$(-+
$"++&,$& ("$="" / )G"@,"$& !%,&-(/% /"J]$$+$,- -)+"+=""
,& !/,$"!/+ *$"$$+$,#&*%%"F$$&'$&-+:H
--)#&$"+"+=""."?"!$$"+* ?, ,"-"."-&'#_UUP
RESULTS
,$"+$,+&'+"-",$"!,- ,- !-(&$&)#%"$"+&'$"+$/!) !,& $&-*&/#"
#"+" $"! (-"K"%" "J].&-/%"=+XMKF%-I% IKRC%2H !%" -(/% /
=+ KRR%*IM $" !("$, *&/# ) G "@,"$& M&/ / " ,&--",$& $"
"@% "! *&/# &' #$" $+ =$ !("$"+ =+ +* ?, $-) -&=" ,&%#+& =$ $" ,& $&-
*&/# * ?, $ !''"" ,"+ ("$="" +$/!) *&/#+ ="" &(+"."! "*!+ $& / ) G
"@,"$& "@#"++"!+,& ," $$& F#^UUUUUKH+="--+$&$-G"@,"$& M&/+#",%" F#^UUUURH !+G,& ," $$& ,-,/-$"!#"/ ","$ "F#^UUUTTH )G"@,"$& #$" $+=$!("$"+ ! $",& $&-*&/#++&= (-"
)"# +/-'$""@,"$& !"#" ! *& %,&-(/% / #$" $+=$!("$"+ 117
(-"K,$"+$,+&',& $&-*&/# !#$" $+=$!("$"+
("$,*&/#
%"$"
& $&-*&/#
n
%"
n
%"
*"F)"+H
M
PUM
KPT
P
PUP
KPC
F:%I%2H
M
28.9
7.1
P
PK
12.2
/"++F%-H
M
KTCT
XPXC
P
KK\UM
M\P
Urine creatinine concentration
F%*I%-H
M
UPC
UC
P
0.87
UCC
/$& &'!("$"+F)"+H
M
9.2
7.1
-
-
-
(-""+/-$+&'M&/G/ ""@,"$& ,& $&-*&/# !#$" $+=$!("$"+
& $&-*&/#
%"$"
("$,J&/#
#^
n
%"!
O/$-"
n
%"!
O/$-"
HS concentration
Fp*I%-&'/ "H
P
PPU
CTRIRUC
M
2.29
KTICUP
0.00001
G,& ," $$& #"/ ","$ "
Fp*I%*,"$ "H
P
PTR
PUMI\RP
M
MRX
RTI\PP
0.0088
G$&$-"@,"$& Fp*IMH
P
MXRT
C\TMIRRCC
M
CK\
KTRUIMXP
0.0007
+* ?, $ "*$." ,&"-$& ("$="" / ) G "@,"$& ! %,&-(/% / =+
&(+"."!G"@,"$& =+#&+$."-)++&,$"!=$"J].-/"+$"#"+" $"! (-"C
(-"C&"-$& ("$="" G"@,"$& %,&-(/% / !"J] !("$,#$" $+
n
#
#"% G,&," $$& q%:&-(/% /
M
0.021
UCP
GMq%:&-(/% /
M
UUMX
UCU
GI,"$ "q%:&-(/% /
M
0.008
UMU
G,& ," $$& q"J]
CT
0.017
UCT
GMq"J]
CT
0.0028
UMR
GI,"$ "q"J]
CT
0.000001
0.69
118
8 &=+:)+$):" $#c+:8"!8,6&-+:
&=:&=+:
#$" $+ =$ !("$"+ !("$, "#&#$) + +"&/+ ,&%#-,$& =, +* ?, $-)
!"$"&$"+O/-$)&'-'" !+& "&'$"% ,/+"+&'" - +/'?," ,)]&$$"+& $"
&##&$/ $)&'"-)++"++%" $&'$"!"*""&'!"."-&#%" $&'!("$, "#&#$)=,%)
*.", ,"'&"*"++& & ($& &'$"#$&-&*)+.")%#&$ $&=!)+!"$"% $& &'/ )-(/% "@,"$& +",&%%" !"!-(&$&)$"+$'&!* &++&'!("$, "#&#$)
G&="."$+="--: &= $$%,&-(/% /!&"+ &$'/--)"s",$$""''",$."#&$" ?-$$& *-&%"/- ]& % ) )"+ $" "+","+ ." ("" -&&: * '& %/, %&" +#",?, !
+" +$."%:"+&'!+$/( ,"+ *-&%"/-?-$$& ("=,%)(""-#'/- !* &++
!%& $& *&' "#&#$)"G+,&%#& " $&'$"*-&%"/-?-$$& ("% -)
$"'&%&'#"-", $"%&+$%#&$ $#&$"&*-, BMXD$+("" "#&$"!$$, *"+ $"%&/ $ !,& ," $$& &'+/-'$"!/ $+&'G"++&,$"!=$$"!"."-&#%" $&'!("$,
"#&#$)B\KKD"=+&(+"."!$$G+!"*!$"!()"# +"" " 8)%" !/,"!()
$"#"+" ,"&' ,"+"!*-/,&+",& ," $$& + $"" .& %" $=,-"!++,& +"O/" ,"
$&$"!% + *G,& $" $ JBXD
,,&! *$&)#&$"++ ,"+"!G#&$"&*-), %"$(&-+%=$ $"*-&%"/-/+
%)#-) %#&$ $&-" $"#$&*" "++&'!("$, "#&#$)BD"'",$+ G+) $"++
, ("%:"&'!"."-&#%" $&'#$&-&*,-, *"+ *-&%"/-BXD
]&!"$"% *&'$""-)+$*"+&'!("$,,&%#-,$& +="/+"!$"O/ $$$."++"++%" $
&'/ )G"@,"$& "+/-$+&'$",& !/,$"!"+","."-"!$$ #$" $+=$!("$"+
/ ) G "@,"$& M&/ / " ,&--",$& + -&=" ,&%#+& =$ $" ,& $&- *&/#
* ?, $!''"" ,"+=""&(+"."! "*!+$&--%"$&!+&'"@#"++& &'/ )G"@,"$& Z
+,& ," $$& M&/"@,"$& !-+&+,-,/-$& #"/ ","$ "","+"!/ )
G"@,"$& #$" $+=$!("$"+%)"+/-$'&%%#"!#&!/,$& & ,"+"!!"*!$& &'J
J *-&%"/- $",&/+"&')#"*-),"%
4&:&)% !,&=&:"+&(+"."!+%-!",$& &', *"+ G"@,"$& !("$"+
") "@% "! #$" $+ =$ $)#" !("$"+ ! "."-"! $$ / " &' #$" $+ =$ !("$,
"#&#$)G,& ," $$& =++* ?, $-)!","+"!+,&%#"!$&$",& $&-*&/#
$+%#&$ $+%--)+ &/!$G,& ," $$& =+!"$"% "!()
%"$&!
=$$"/+"&' $(&!"+%
(KUM !%
(CJKU"!","+" ( ! *&'%
(KUM $""@% "!+%#-"+,& ",$"!=$$"!% +"!+/-'$"!/ $+ G#&$"&*-), =,+
'&--&="!()!","+"!/ )G"@,"$& BKKD
-+& !.- ! ,&=&:"+ =& !"$"% "! / ) $&$- J
J "@,"$& $+ =$
+$"#$&8&, !/,"! !("$"+ &($ "! +%- "+/-$+ ") &(+"."! !","+"! / ) J
J
"@,"$& !("$"+ ,&%#+& =$ $" ,& $&- *&/# $" "@% "! / " +%#-" G
,& ," $$& +="--+,& !&$ +/-'$" !!"%$ +/-'$"=""!% +"!+$/( ,"+ / )J
J,& ," $$& +=""&(+"."!-"!) $"+",& !="":&'$""@#"%" $BKD
& ' %,&-(/% / =+ !"? "! + -(&$&) %:" &' !("$, "#&#$) &." !* &+$, /+(-$) &' / ) J
J ++"++%" $ =&/-! --&= '& "-) & .+." ! #!
%"$&! '& !* &++ &' $- +$*"+ &' !("$, "#&#$) ("'&" $" %,&-(/% / =+
)"# +/-'$""@,"$& !"#" ! *& %,&-(/% / #$" $+=$!("$"+ 119
#"+" $ &/"+",="&(+"."!+* ?, $ "*$.",&"-$& ("$="" / )G"@,"$& !%,&-(/% / !#&+$."++&,$& =$J].-/"+$, ()"@#- "!()$" ,"+"
-(/% / + ,& +"O/" ," &' -$"$& &' $" #"%"(-$) &' ?-$$& (" =, +
,,&%# "! () $" !","+" / ) G "@,"$& + =+ +&= &/ !$ " &(+"."!
!","+" J] "@,-/!" $" "''",$ &' !% + * / " G ,& ," $$& !/" $& $" ,"+"!
?-$$& " #"+" $"! !$ !,$" $$ !"$"% * G , (" .-/(-" %:" !* &++ &'
!("$, "#&#$)u&="."!"$-+&'$"#" -)$, ! -)$,#+" ""!$&("#&,"++"! $",- ,-+#",$'/$" ."+$*$& +""O/"!& *"$" /%("&',+"+,& +!" *% )
',$&++/,+$"$)#"&'!("$"+!% +$""!$"$%" $ !$"!/$& &'$"!+"+"
" "+/-$+ +/**"+$ $$ !","+"! G $" / " #$" $+ =$ !("$"+ %) "s",$
+$/,$/- , *" & -$""! #&,"++ * &' G =$ $" J "$"% $& &' / " G
"@,"$& , (""*!"!+$"+$'&!("$, "#&#$) !#&$" $--)/+"'/-!* &+$,$&&-
'&--&= *%&"#",+" !"@$" !"!&(+".$& + .&-. *-*" /%("&',- ,-,+"+
REFERENCES
K!.-&-% ,"-,,4 )"@,"$& &'*-),&+% &*-), + !-(/% "@#"%" $-!("$"+%"--$/+J-),&(&-&*)KUKTPUUU
",:"$"$-Z8" !, *"+"-",$.$)&'*-&%"/-?-$$& $)#"K!("$,#$" $+=$ !
=$&/$-(/% /("$&-&*C\MMKXXC
C"/&"$-Z
-& *$/! -".-/$& &'/ )*-),&+% &*-), +"@,"$& &%&-(/% /,
$)#"K!("$,+#$" $+- "%("!MMP\KUU\
MG/+$Z$/,$/"'/ ,$& !#$&-&*)&'#&$"&*-), + !*-),&+% &*-), + $"/ )
$,$&-!6&-CKKXXM
P8 &=+:)+$):"$-Z *"+ $""@,"$& &'*-),&+% &*-), +=$/ " #$" $+
=$*-&%"/-!+"+"
-"+",$UCPUUR
\ 8 &=+:)+$): " $#c+: &-+: 6 &=:&=+: Z ) G "@,"$& !("$,#$" $+
-"+",$KMPUUX
R/"G+,-- *
ZG"# +/-'$" )++'&%!("$,$*-&%"/-6&-"%
TTMCUUR
T ".!&$+ "$ -Z G"# +" + .&-."! $" #$&*" "++ &' #&$" / + "+/-$ &'
*-&%"/-& "#$+6
%&,"#&-KP\TUUM
X "=+ 6 / Z ( &%- J-&%"/- "%"(-$) ,$"+$,+ ("$, "#&#$)
("$"+"CKUUUT
KU-"$-Z$,&@!"!"*!$& &'"# !"# +/-'$"&,"%6CMMRCKXXR
KK4&:&)%G"$-Z"/% !/ ),& ," $$& +&'"# +/-'$" #$" $+=$!("$,
"#&#$)! ") $P\\PUKXXX
120
8 &=+:)+$):" $#c+:8"!8,6&-+:
&=:&=+:
4
"G+,&%#& " $&'$"*-&%"/-?-$$& ("% -) $"'&%&'#"-", !
* $+("" "#&$"!$$, *"+ $"%&/ $ !,& ," $$& &'+/-'$"!/ $+&'G"
++&,$"!=$$"!"."-&#%" $&'!("$, "#&#$)"-,:&'&%#"!+) $"++&'G J-"!+$&$"!"."-&#%" $&'%,&-(/% / !'/$""@,"++."/ )#&$" "@,"$& &!"$"% "$""-)+$*"+&'!("$,,&%#-,$& +="/+"!$"O/ $$$."++"++%" $&'/ )
G"@,"$& "%&'$"+$/!)=++", *'&!''"" ,"+ / )G"@,"$& #$" $+
=$!("$"+ ,&%#+& $&$",& $&-*&/#".-/$& &'$" s/" ,"&'%,&-(/% /& / )G"@,"$& !".-/$& &'#&++(-"/+"'/- "++&'/ )G"@,"$& +-(&$&)
$"+$'&!("$, "#&#$)"+/-$+&'$",& !/,$"!"+","."-"!$$ #$" $+=$!("$"+
/ ) G "@,"$& M&/ / " ,&--",$& + -&=" ,&%#+& =$ $" ,& $&- *&/#
* ?, $!''"" ,"+=""&(+"."! "*!+$&--%"$&!+&'"@#"++& &'/ )G"@,"$& Z
+,& ," $$& M&/"@,"$& !-+&+,-,/-$& #"/ ","$ "","+"!/ )
G"@,"$& #$" $+=$!("$"+%)"+/-$'&%%#"!#&!/,$& & ,"+"!!"*!$& &' J
J *-&%"/- $" ,&/+" &' )#"*-),"% &/ "+", =" &(+"."! +* ?, $
"*$.",&"-$& ("$="" / )G"@,"$& !%,&-(/% / !#&+$."++&,$& =$"J].-/"+"#"+" $"!!$ !,$"$$!"$"% *G, (".-/(-"%:" $"
!* &++ &' !("$, "#&#$)u &="." !"$-+ &' $" #" -)$, ! -)$, #+" ""! $&
("#&,"++"! $",- ,-+#",$'/$" ."+$*$& +""O/"!& *"$" /%("&',+"+
,& +!" *% )',$&++/,+$"$)#"&'!("$"+!% +$""!$"$%" $ !$"!/$& &'
$"!+"+"
")=&!+Z!("$"+"# +/-#$"!("$, "#&#$)
33
,8 "# /FGH+$ &=+:x! :(")?-$,); ";:xy(/+8:<= ":&=),*x<= "
=#&+$,#"-": /*) )&="!8& &9"8% )=:& ," $,;-&z,*/#+,8 &=),
G+>#&=>8 "8=)+$>#" "% "'&#$,/:8),&=";:-/(/#&z-"!8& +) $"8G(x& )
#&!+$= "; #&=!8 !& &8=&;/ %:&-(/% / !-"; !& !%" "*& =)!- (x":
8 %&,8"% & &:"z-" #&=:xc ,/:8),) #&+x/9& & +y =y, &," > -&z,&=> =)!- G
8%&,8"%"-"%#,)()x&Z#&+8/:= "<9 ,==)!- /G8%&,8"%/#,;" $<=8,/:8),>
= #&<= / 8 */#> :& $&- > &," 8-"9 &z, #&%y!8) %:&-(/% /> =)!- "%
G 8 %&,8"% &8 &," "=" $/- "; #8)!$ &z, &8 ,8 =)!- G 8 %&,8"% ;:&
$"+$/ -(&$&); "*& = "'&#$ ,/:8),&="; ) : #8"#&=!8& ), (!c =):8x) 9"
/ &+<( ,"#>,), ,/:8),y =)!- " G 8 %&,8"% = 8(<," M*&!8 "; ;"+$ 9+8" 9
=#&!&( ";#&!=8*-y!"%#x,=":/*/#"&+<(8!&=),+$&$ &z{+$$)+$),8 >/8)+: &!-
=+8)+$:, +#&+&(<= =)9 =)!- G 8 %&,8"% $; ;:& +$y9" =)!- M #&
#8"-,8" / :"$) y( 9& "=)!- "G8%&,8"%/#,;" $<=8,/:8),>+/*"/;"9"
#=!&#&!&( )%#&=&!"%$),8% %&9"(){+#!":#&!/:,;-/(#8)+#"+8& !"*!,;
J
J = +$/:$/, (x& ) :xy(/+8: &(+"=&= #&!,8+ #"*-:"% +8), (! ,
)"# +/-'$""@,"$& !"#" ! *& %,&-(/% / #$" $+=$!("$"+ 121
/8)+:-z%) +$&$ > +$$)+$),8 " /;"% > :&"-,;y %y!8) =)!- "% G %:&-(/% />
=!&,8 > = 8:"+" =+8)+$:, +#&+&(<= =)9 =)!- G 8 %&,8"% &8 !&!$ >
:&"-,;y8=$&z,%"J]8"!+$=& "! "=+:8/;>9"&8 ,8 "G%&9"(){#8)!$ )%
%:""% = !* &+$)," "'&#$ ,/:8),&="; =)%* ;"! : &#,&= +8,8"*<x<= '8)
#8"! -$),8 "; -$),8 ";+#":,":- ,8 )%:& ",8 "+>&(+"=,;" =y:+8";-,8("
#,;" $<=8/=8*-y! " "%+8""*/,8) :<=$:,;:Z$)#,/:8),)+$&+&= "-",8" "&8
,8+$= ,&&()
x&=:-/,8&="Z,/:8),+,8 "# / "'&#$,/:8),&=