Correlation of UA Nephrolithiasis and Metabolic Syndrom in Obesity

8/12/2019 Correlation of UA Nephrolithiasis and Metabolic Syndrom in Obesity

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CORRELATION OF URIC ACID NEPHROLITHIASIS AND METABOLIC

SYNDROME IN PATIENTS WITH OBESITY

MUHAMAD ROSALDY

030.09.158

Trisakti University Fac!ty "# Me$icine

%A&ARTA

'01'

0


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(ORR)LAT*O+ OF UR*( A(*D +),HROL*TH*AS*S A+D M)TA-OL*(

SY+DROM) *+ ,AT*)+TS *TH O-)S*TY

Abstract. T/e ai "# t/e revie is t" #in$ t/e c"rre!ati"n "# ric aci$ ne2/r"!it/iasis #"rati"n "r

2rinci2a! 2at/"enesis an$ eta4"!ic syn$r"e in "4esity. ,atients it/ "4esity sa!!y an$

2re$"inant!y ten$ t" /ave eta4"!ic syn$r"e as t/e "r4i$ity. Once "4esity initiates

eta4"!ic syn$r"e is ettin /i/er t" $eve!"2. *t eans t/ere "!$ 4e c"2!icate$ a$verse

risk /ea!t/. St$ies n"a$ays ere cri"s t" $isc"ver t/e !ti$iensi"na! e##ects "# eta4"!ic

syn$r"e. +e2/r"!iti/iasis is t/e ain #"cs t" #in$ "t /et/er is re!ate$ t" eta4"!ic

syn$r"e. -asica!!y ne2/r"!it/iasis is t/e c"nse6ences "# inera! $e2"siti"n in t/e ki$ney an$

t/e ric aci$ ty2e "# ne2/r"!it/iasis /as a reat re!ati"ns/i2 it/ c"2"nents "# eta4"!ic

syn$r"e inc!$in "4esity. -asic ec/anis c"nsi$ere$ str"n!y is t/e !" rinary 2H t/at

i!! increase t/e rate "# ric aci$ st"ne #"rati"n. T/e !" rinary 2H is t/e c"nse6ences "#

4##erin i2airent in ki$ney t4!e ce!!s. Da! $e#ects 7$e#ect "# secreti"n "# a"ni an$

increase$ aci$ 2r"$cti"n are n"t sti!! e!!e:2!aine$ 4t t/ey are c!ear en"/ evi$ence "# t/e

2at/"enesis "# ric aci$ ne2/r"!it/iasis in eta4"!ic syn$r"ein$ce$ "4esity 4ecase t/e

2/en"en"n i!! re$ce 2H rine !eve!. Li2"t":icity is t/e ;4ri$e< "# eta4"!ic syn$r"e t"

initiate t/e 2r"ress t" ric aci$ ne2/r"!it/iasis.

Keywr!s= ric aci$ ne2/r"!it/iasis eta4"!ic syn$r"e "4esity !" rinary 2H.

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*+TRODU(T*O+

T" a22r"ac/ t/e "4vi"s re!evance "# t/e t"2ic "4esity 4asic i$enti#icati"n s/"!$ 4e "re

e:2!aina4!e. O4esity can increase s"e seri"s /ea!t/ risks t/at are re!ate$ t" eta4"!ic

syn$r"e as t/e "st c""n "r4i$ity. Meta4"!ic syn$r"e is c"4ine$ $is"r$ers "# $ia4etes

e!!its ty2e' /i/ 4!""$ 2ressre /i/ 4!""$ c/"!ester"! an$ /i/ !eve! "# tri!yceri$es. S"

t/e ain 4ackr"n$ "# eta4"!ic syn$r"e is 2re$"inant!y "riinate$ #r" a4$"ina! "4esity

an$ ins!inresistance 4esi$es ain 2/ysica! inactivity an$ /"r"na! i4a!ance. 71

&i$ney st"nes /ic/ e$ica!!y ca!!e$ as ne2/r"!it/iasis is "ne "# t/e "st c""n $iseases

/ic/ 2r"$ces /i/ e$ica! c"st in "st c"ntries "r!$i$e s" $"es t/e 2reva!ence.

+e2/r"!it/iasis c"2rises 810> "# a!! ki$ney $iseases in t/e Unite$ States.7'

+"a$ays "st st$ies investiate eac/ c"2"nents "# eta4"!ic syn$r"e in t/e "ccrrence "#

ne2/r"!it/iasis. T/is 4ene#it "# t/e st$ies 2er#"re$ as t" $isc"ver eta4"!ic syn$r"e


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D*S(USS*O+S

Discssi"n 1= Re!ati"ns/i2 -asis "# Meta4"!ic Syn$r"e an$ O4esity

O4esity $e#ines as a e$ica! c"n$iti"n c/aracteri?e$ 4y #at acc!ati"n t" t/e e:tent in 4"$y. *t

ay /ave an a$verse e##ect "n /ea!t/ an$ 4rins a4"t increase$ /ea!t/ 2r"4!es. O4esity is

"st!y case$ 4y /i/ ca!"ric intake 7/ic/ n"ra!!y t/e ty2e "# #""$ i!! 4i!$ enery #"r $ai!y

activities an$ !ack "# 2/ysica! activity.71S"e st$ies a!s" s/" t/at enetic 2re$is2"siti"n is

a!s" c""2erate$ t" raise "4esity. *n t/e US /i/ n4er "# "4esity is acc"2anie$ it/ /i/

2reva!ence "# eta4"!ic syn$r"e. Ae 2"2!ati"n "# eta4"!ic syn$r"e ten$ency is '5> in

"re t/an '0 years "!$ an$ @5> in 2e"2!e ae$ "re t/an 50 years "!$. Mean/i!e in *n$"nesia

a st$y $"ne 4y S"e"n$" in '00@

re2"rte$ t/at 2reva!ence "# eta4"!ic

syn$r"e is 13.13> an$ a!s" s/"e$

t/at criteri"ns "# "4esity 4y sin 4"$y

ass in$e: is "re t/an '5 k'. A

st$y in %akarta a!s" in '00B a!s" s/"e$

t/e eta4"!ic syn$r"e s##erers

increase$ t" 4e 'B.3> it/ centra!

"4esity 4ecae t/e /i/est c"2"nent

759.@>.7@ *n '005 International Diabetes Federation 7*DF c"nsi$ere$ "4esity centra! is t/e

ain criteri"n "# eta4"!ic syn$r"e. -asica!!y "4esity in a$!ts is $e#ine$ 4y 4"$y ass in$e:

7-M* an$ #rt/er eva!ati"n 4y $eterinin #at $istri4ti"n via /i2aist rati". -M* is

ca!c!ate$ 4y $ivi$in t/e s4Cects ass 4y t/e s6are "# /is "r /er /ei/t t/en inter2retati"n "#

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severe "4esity is any -M* E 35 "r @0 k'. Mean/i!e *DF criteri"ns "# eta4"!ic syn$r"e

s/"s in Ta4!e 1.

T/e e:act ec/anis "# eta4"!ic syn$r"e as sti!! nc!ear 4t t/ere are sti!! i2"rtant

#act"rs sc/ as 2atients< 4"$y ei/t enetics 2re$is2"siti"n en$"crine $is"r$ers ain an$

se$entary !i#esty!e 7i.e. !" 2/ysica! activity an$ e:cess ca!"rie intake. A n4er "# arkers "#

systeic in#!aati"n inc!$in (reactive 2r"tein are "#ten increase$ as are #i4rin"en

inter!ekin B7*LB T"r necr"sis #act"ra!2/a7T+FG an$ "t/ers. +"t intriin t/in is t/at

t/ere is sti!! $e4ate rear$in /et/er "4esity "r ins!in resistance is t/e case "# eta4"!ic

syn$r"e.7@

As e:2!aine$ a4"ve i2"rtant c"ntri4tin #act"rs "# syn$r"e eta4"!ic inc!$e= 71 #acin

stress#! !i#e can case a4n"ra!ity "# /"r"na! re!ati"n 7' centra! "4esity in /ic/

eta4"!ic syn$r"e is t/e key "# t/e $ian"sis 73 se$entary !i#e sc/ as 2/ysica! inactivity an$

e:cess ca!"ric intake 7@ "en /" /ave reater risk t/an en 75 c"r"nary /eart $isease 7B

2syc/iatry i!!ness sc/ as sc/i?"2/renia an$ 7B $ia4etes e!!its."#$%&

Discssi"n '= A22r"ac/in Uric Aci$ +e2r"!it/iasis

&i$ney st"nes 7ca!c!i are /ar$ene$ inera! $e2"sits t/at #"r in t/e ki$ney. T/ey "riinate as

icr"sc"2ic 2artic!es an$ crysta!s an$ $eve!"2 int" st"nes "ver tie. T/e e$ica! ter #"r t/is

c"n$iti"n is 'e()r*+t)+as+s "r rena! st"ne $isease. *t is "ne "# t/e "st c""n $isease /ic/

2r"$ces /i/ e$ica! c"st in t/e Unite$ States. T/e "vera!! 2r"4a4i!ity "# #"rin st"nes $i##ers

in vari"s 2arts "# t/e "r!$= 15> in Asia 59> in )r"2e 13> in +"rt/ Aerica '0> in

Sa$i Ara4ia.

@
http://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/C-reactive_proteinhttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Interleukin_6http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alphahttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/C-reactive_proteinhttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Interleukin_6http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha


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-asic ec/anis "# ki$ney st"nes #"rati"n varies t/ey are= 71 /i/ !eve! "# t/e inera!

$e2"sits t/at i!! 4e 4r$ens"e t" t/e ki$ney #ncti"ns an$ 7' ins##icient ater intake t"

$iss"!ve aste 2r"$cts. +e2/r"!it/iasis /as reaine$ a 2r"inent isse t/at i2"ses a

sini#icant 4r$en "n /an /ea!t/ an$ is a c"nsi$era4!e #inancia! e:2en$itre #"r t/e nati"n. T/e

#"r "st c""n ty2es "# st"nes are c"2rise$ "# ca!ci ric aci$ strvite an$ cystine.

*n /ans an$ /i/er 2riates ric aci$ is an en$ 2r"$ct "# 2rine eta4"!is. Oin t" t/eir

!ack "# t/e /e2atic en?ye ricase /ic/ c"nverts ric aci$ t" s"!4!e a!!ant"in t/eir ser an$

rinary !eve!s "# ric aci$ are c"nsi$era4!y /i/er t/an

in "t/er aa!s. +"ra!!y rinary ric aci$ s"!4i!ity

is !iite$ t" 9B !. *n /ans it/ a rinary ric aci$

e:creti"n "# B00 $ay t/is s/"!$ enera!!y e:cee$

t/e !iit "# s"!4i!ity an$ ssce2ti4i!ity t" 2reci2itati"n.

M"re"ver rine 2H is an"t/er i2"rtant #act"r in ric

aci$ s"!4i!ity. Uric aci$ is a eak "ranic aci$ it/ an

i"ni?ati"n c"nstant7'72&a "# 5.5.T/ere#"re at a rine

2H !ess t/an 5.5 t/e rinary envir"nent 4ec"es s2ersatrate$ it/ s2arin!y s"!4!e

n$iss"ciate$ ric aci$ t/at 2reci2itates t" #"r ric aci$ st"nes 7Fire 1.

Discssi"n 3= ("rre!ati"n "# Uric Aci$ +e2/r"!it/iasis an$ Meta4"!ic Syn$r"e in

O4esity

Meta4"!ic syn$r"e an$ ne2/r"!it/iasis 2resent sii!ar e2i$ei"!"ica! c/aracteristics. -"t/ are

case$ 4y t/e interacti"n "# enetic envir"nenta! an$ /"r"na! #act"rs 2resent a /i/

5

Fire 1= ric aci$ s"!4i!ity an$ its st"ne #"rati"n


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inci$ence an$ 2reva!ence in t/e a$!t 2"2!ati"n "# in$stria!i?e$ c"ntries an$ are c/aracteri?e$

4y a /i/ !eve! "# "r4i$ity an$ "rta!ity i# n"t a$e6ate!y i$enti#ie$ an$ treate$.

Normal Circumstances of Ammoniac Buffering System

Urinary aci$ity in #"rati"n "# ric aci$

st"nes res2ective!y "riinates #r" t/e

4"$y 2/ysi"!"ic 4asis t/at is t/e c"ntr"!

"# aci$4ase 4a!ance. T/e ki$ney is t/e

t/ir$ $e#ense !ine "ran aainst c/anes "#

i"n H in 4"$y #!i$s an$ nee$s 6ite

!"ner tie t" c"2ensate 2H c/ane.

Secreti"n "# H in ki$ney t4!e is t/e key

r"!e "# rine aci$ity. T/e ki$ney c"ntr"! "#

t/e 4"$y #!i$s 2H is 4y a$Cstin t/ese !inke$ #act"rs= 71 e:creti"n "# H 7' e:creti"n "#

H(O374icar4"nate an$ 73 secreti"n "# +H37a"nia. ,r":ia! $ista! an$ c"!!ective t4!es

"# t/e ki$ney n"ra!!y secrete H as t/e c"nse6ences "# eta4"!ic activity s" t/e averae 2H

rine is ar"n$ B.0. A"nia secreti"n is t/e !ast 4##er ec/anis 4e#"re t/e 2r"t"n 7H is

#ina!!y e:crete$ in rine 7see Fire 1. -ecase "# t/e e:creti"n "# t/e a"nia is re!ate$ t" t/e

2at/"enesis "# ric aci$ st"ne #"rati"n t/e revie i!! n"t e:2!ain a4"t t/e t" ec/aniss

2ri"r t" t/e a"nia secreti"n.

As enti"ne$ a4"ve a"nia e:creti"n is t/e !ast 4##er ec/anis. T4!e ce!!s i!! a!ays

secrete Han$ t/ere st 4e a s4stance as a 4##er s" t/at t/e rine aci$ity i!! n"t 4e "re t/an

@.5. Un#"rtnate!y H(O3is n"t si!tane"s!y e:crete$ it/ H s" it ay n"t 4e as 4##er a!!

B

Fire ' -##erin syste = a"ni e:creti"n int" t4!e!en


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a!"n. ,/"s2/ates an$ a"nia are "# i2"rtant 4##er #"r t/is case. ,/"s2/ates #irst!y act as

4##er #"r H. ,/"s2/ates !"cate in t4!e !en case$ 4y e:cess intake "# it n"t a 2/ysica!

c"2ensati"n "# increase "# H secreti"n #r" t4!e ce!!s int" t/e !en. ("nse6ent!y

2/"s2/ates can #a!! int" satrati"n an$ t/e rine 2H kee2s $ecreasin 7increase$ aci$ity. *nstea$

a"nia 7+H3 i!! take "ver as t/e 4##er !ast!y. A"nia is synt/esi?e$ #r" !taine

ain" aci$ in t4!e ce!!s. T/s it i!! 2ass $i##se!y t/r"/ t4!e e4rane t" t/e !en.

A#ter e:crete$ Hi!! 4in$ t" +H3an$ #"r a"ni i"n 7+H@. T4!e e4rane is n"t t""

2erea4!e t" a"ni s" t/at a"ni i!! ;acc"2any< Ht" 4e e:crete$. *# +H3secreti"n

is $ecrease$ Hsecreti"n rate i!! 4e !iite$ 4y 2/"s2/ates /ic/ 2r"4a4!y an$ c"inci$enta!!y

e:ist 7case$ 4y inesti"n. *n a$$iti"n rate "# +H 3 is c"ntr"!!e$ 4y $irect e##ect "# e:cess

n4er "# H. S"e"ne /" n$er"es aci$"sis #"r ' 3 $ays +H32r"$cti"n rate i!! 4e

sini#icant!y increase$. T/is ;a$$iti"na!< +H3i!! raise t/e 4##erin ca2acity a#ter 2/"s2/ates

are satrate$.75

Role of Metabolic Syndrome and Obesity in Uric Acid Neprolitiasis

Meta4"!ic syn$r"e is c"4ine$ $is"r$ers "# $ia4etes e!!its ty2e' /i/ 4!""$ 2ressre /i/

4!""$ c/"!ester"! an$ /i/ !eve! "# tri!yceri$es. Dia4etes e!!its ty2e' /i/ 4!""$ c/"!ester"!

an$ /i/ !eve! "# tri!yceri$es "!$ 4e sc/ initiate$ #act"rs "# t/e ec/anis "# ric aci$

ne2/r"!it/iasis71. A center #irst re2"rte$ t/e /i/ 2reva!ence "# ric aci$ st"nes as t/e ain st"ne

c"nstitte #"n$ in $ia4etes e!!its ty2e'. Hi/er 4"$y ass in$e: an$ ins!in resistance 7i.e.

eta4"!ic syn$r"e ay 4e eti"!"ic in ric aci$ ne2/r"!it/iasis as increasin 4"$y ei/t is

ass"ciate$ it/ $ecreasin rinary 2H. Mec/anistic st$ies /ave s/"n t/at t/e t" aC"r

#act"rs res2"nsi4!e #"r a4n"ra!!y !" rine 2H are a c"4inati"n "# !e,ect+-e NH%e/cret+'

an$ +'crease! 'etac+! e/cret+' "NAE&.7B

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1. De,ect+-e NH% e/cret+'. T/e

$e#ective +H@ e:creti"n in ric

aci$ ne2/r"!it/iasis re6ires t/e

rine t" 4e 4##ere$ ain!y 4y

titrata4!e aci$s 7#"r e:a2!e

2/"s2/ates t" aintain t/is

e6i!i4ri t/s 2r""tin an

aci$ic rinary 2H an$ 2r"vi$in an

envir"nent /i/!y c"n$cive #"r ric aci$ 2reci2itati"n 7Fire 3. *ncrease$ aci$

2r"$cti"n a!"ne ay n"t 4e s##icient in casin a4n"ra!!y aci$ic rine as t/e e:crete$

aci$ is netra!i?e$ 4y rinary 4##ers. Severa! st$ies /ave 2r"vi$e$ evi$ence s22"rtin

a re!ati"ns/i2 4eteen ric aci$ ne2/r"!it/iasis "4esity an$ ins!in resistance. T/ese

st$ies s22"rt t/e 2"tentia! r"!e "# ins!in resistance in an i2aire$ rinary +H@

e:creti"n an$ !" rinary 2H. *ns!in rece2t"rs are e:2resse$ in vari"s 2"rti"ns "# t/e

ne2/r"n. Frt/er"re in !itrost$ies /ave s/"n t/at ins!in /as a sti!at"ry #ncti"n

in rena! a"niaenesis 7a 2r"cess "# synt/esi?in +H@ in ki$ney t4!e ce!!s. *n

a$$iti"n +H@ secreti"n is re!ate$ 4y t/e s"$i/y$r"en e:c/aner +H)3. As

+H)3 /as a key #ncti"n in t/e trans2"rt "r tra22in "# +H@in t/e rena! t4!ar !en

ins!in resistance ay 2"tentia!!y !ea$ t" $e#ective rena! +H @ e:creti"n.7I One "t/er

2!asi4!e ec/anis ay 4e substrate competition4y s4stittin circ!atin #ree #atty

aci$ #"r !taine /ic/ is increase$ in t/e eta4"!ic syn$r"e t/ere4y re$cin t/e

2r":ia! rena! t4!ar ce!! ti!i?ati"n "# !taine an$ rena! a"niaenesis7B 7Fire

5.

8

Fire 3 = 4##erin syste is taken "ven 4y titrata4!e aci$s


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'. I'crease! 'et ac+! (r!0ct+' "NAE&. An e!evate$ +A) ay "ccr $e t" increase$

en$"en"s aci$ 2r"$cti"n "r 4ecase "# $ietary in#!ences sc/ as !" $ietary a!ka!i "r

t/e increase$ c"ns2ti"n "# aci$ric/ #""$s 7Fire @. Meta4"!ic st$ies c"2arin

s4Cects "n #i:e$ !"aci$ as/ $iets s/"e$ a /i/er +A) in ric aci$ ne2/r"!it/iasis

2atients c"2are$ t" c"ntr"! s4Cects sestin t/at en$"en"s aci$ 2r"$cti"n ay

increase in ric aci$ ne2/r"!it/iasis.7I*n a$$iti"n t/e rinary +A) #"r any iven rinary

s!#ate 7a srr"ate arker "# aci$ intake ten$e$ t" 4e /i/er in 2atients it/ Dia4etes

e!!its ty2e'. T/ese st$ies a!s" i2!ie$ t/at t/e 2at/"2/ysi"!"ic ec/anis

acc"ntin #"r increase$ +A) is re!ate$ t" "4esity "r ins!in resistance. S22"rtin t/is

c"rre!ati"n a$$iti"na! st$ies /ave s/"n increase$ "ranic aci$ e:creti"n it/ /i/er

4"$y ei/t an$ /i/er 4"$y sr#ace area. T/e natre "# t/ese "ranic ani"ns an$ t/eir

!ink t" "4esity an$"r ric aci$ st"nes /as n"t 4een #!!y st$ie$.7BI

Role of "idney #ipoto$icity in te Basis of #o% Urinary p&

9

Fire @ = +et aci$ e:creti"n n$er a #i:e$ eta4"!ic $iet


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M"st +H@ is 2r"$ce$ an$ secrete$ 4y t/e rena! 2r":ia! t4!ar ce!!s. +H@ is $irect!y

trans2"rte$ 4y +H)3 eit/er as +a +H@ int" t/e

2r":ia! t4!ar !en "r 4y t/e 2r"cess "# n"n

i"nic $i##si"n "# +H3 int" t/e rena! 2r":ia!

t4!ar !en tra22e$ as +H@ 4y !ina! H

secreti"n. Recent a$vances /ave 4een a$e in

$e#inin t/e ce!!!ar ec/aniss !inkin t/e MS t"

ric aci$ st"ne #"rati"n. /en t/ere is

$ise6i!i4ri 4eteen ca!"ric intake an$ ca!"ric

ti!i?ati"n as "ccrs it/ "4esity $ia4etes an$ t/e MS #at acc!ates int" n"na$i2"cyte

tisse. T/is re$istri4ti"n 2r"cess /as 4een tere$ ;*+(t/+c+ty< an$ /as 4een e!! $e"nstrate$

t" a##ect car$iac y"cytes 2ancreatic Jce!!s ske!eta! sc!e ce!!s an$ 2arenc/ya! !iver ce!!s.

Li2"t":ic e##ect is t/e res!t "# acc!ati"n "# t":ic 4y2r"$cts sc/ as #atty acy! ("A

$iacy!!ycer"! an$ cerai$e.7BIDe t" t/e increase$ #i!ter !"a$ "# #ree #atty aci$ 2r":ia!

t4!ar ce!!s are s2eci#ica!!y v!nera4!e t" !i2"t":icity.7B87Fire 5

(O+(LUS*O+

it/ t/e "r!$i$e e2i$eic "# "4esity it is e:2ecte$ t/at ric aci$ st"neric aci$

ne2/r"!it/iasis 2reva!ence i!! 2r"ressive!y increase. Uric aci$ st"nes /ave eere$ as a aC"r

/ea!t/ c"ncern iven its !inks t" t/e eta4"!ic syn$r"e "4esity an$ $ia4etes e!!its ty2e'.

Sini#icant a$vances /ave 4een a$e in "r n$erstan$in "# t/e 2at/"2/ysi"!"ica! ec/aniss

"# ric aci$ ne2/r"!it/iasis. Severa! eta4"!ic st$ies /ave $e"nstrate$ t/at a4n"ra! rine

10

Fire B= Mec/aniss n$er

Li2"t":icity

Fire 5= M"$e! "# rena! !i2"t":icityre 5 = M"$e!s "# !i2"t":icity


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aci$ity in t/is 2"2!ati"n can 4e attri4te$ t" $a! ec/aniss= $e#ective rinary +H@ e:creti"n

an$ increase$ aci$ 2r"$cti"n.

R)F)R)+()S

1. -arness LA O2it? %M Ki!4ert-arness ). O4esity= enetic "!ec!ar an$ envir"nenta!

as2ects. A. %. Me$. Kenet '00I '@= 301B3@.

'. R"er" Ak2inar H Assi"s DK. &i$ney st"nes= a !"4a! 2ictre "# 2reva!ence inci$ence

an$ ass"ciate$ risk #act"rs. Rev Ur"! '010 1'7'3= '5

3. Da$"n M Lac"r - %ners ,. *n#!ence "# 4"$y si?e "n rinary st"ne c"2"siti"n in en

an$ "en. Ur"! Res '00B 3@73= 1939.

@. S"e"n$" S ,rnaasari D. Sin$r" Meta4"!ik. *n= S$"y" Setiy"/a$i - A!i *

Sia$i4rata M Setiati S e$it"rs. -k ACar *! ,enyakit Da!a. 5 t/e$. %akarta= *nterna

,4!is/in '009.2. 18B59

5. S/er""$ L. Han ,/ysi"!"y= #r" (e!!s t" Systes. 'n$ e$. irinia= T/"s"n

,4!is/in *nc '00'.2. 5'B30.

B. Maa!"# +M (aer"n MA M"e O et a!. L" rine 2H= a n"ve! #eatre "# t/e eta4"!ic

Syn$r"e. (!in % A S"c +e2/r"! '00I'75=8838.

I. Sak/aee &. Recent a$vances in ric aci$ ne2/r"!it/isis= r"!e "# t/e eta4"!ic syn$r"e. US

+e2/r"! '011 B71= 105

8. ein4er %M. Li2"t":icity. &i$ney *nt '00B I079= 15B0B.

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