Renal Tissue Oxygenation in Essential Hypertension

7/30/2019 Renal Tissue Oxygenation in Essential Hypertension

1/8

Hndw Pshn CopotonIntnton Jon o HyptnsonVom 2013, Atc ID 696598, 7 pshttp://dx.do.o/10.1155/2013/696598

Review ArticleRenal Tissue Oxygenation in Essential Hypertension andChronic Kidney Disease

Menno Pruijm,1 Lucie Hofmann,1 Bruno Vogt,1 Marie-Eve Muller,1

Maciej Piskunowicz,1,2 Matthias Stuber,3 and Michel Burnier1

1 Department of Nephrology and Hypertension, CHUV, Rue du Bugnon 17, 1011 Lausanne, Switzerland2 Department of Radiology, Medical University of Gdansk, Gdansk, Poland3

Department of Radiology, CHUV, Lausanne, Switzerland

Cospondnc shod ddssd to Mnno Pjm; [email protected]

Rcvd 25 Ast 2012; Accptd 9 Jny 2013

Acdmc Edto: Cdo Boh

Copyht 2013 Mnno Pjm t . Ts s n opn ccss tc dsttd nd th Ctv Commons Attton Lcns,whch pmts nstctd s, dstton, nd podcton n ny mdm, povdd th on wok s popy ctd.

Anm stds sst tht n tss hypox pys n mpotnt o n th dvopmnt o n dm n hyptnson ndn dsss, yt hmn dt w scc d to th ck o nonnvsv mthods. Ov th st dcd, ood oxynton v-dpndnt mntc sonnc mn (BOLD-MRI), dtctn doxyhmoon n hypoxc n tss, hs com powtoo to ssss kdny oxynton nonnvsvy n hmns. Ts pp povds n ovvw o BOLD-MRI stds pomd

n ptnts sfn om ssnt hyptnson o chonc kdny dss (CKD). In n wth nm stds, ct chns ncotc nd mdy oxynton hv n osvd th dmnstton o mdcton (osmd, ocks o th nn-notnsn systm) o ttons n sodm ntk n thsptntops, ndnn th mpotnt oo n sodm hndnn kdny oxynton. In contst, no BOLD-MRI stds hv convncny dmonsttd tht n oxynton s choncydcd n ssnt hyptnson o n CKD o choncy td on-tm mdcton ntk. Mo stds qdto cy ths dscpncy nd to th nv th o o n oxynton n th dvopmnt nd posson o ssnthyptnson nd CKD n hmns.

1. Introduction

Hyptnson s mjo pc hth dn nd fctsot 1 on pop wodwd. Hyptnson ncss thsk o coony ht dss nd covsc ccdnts

[1, 2]. Hyptnson s so thty ntnd wth chonckdny dss (CKD) [3, 4], dnd s vdnc o stc-t o ncton kdny nomts tht pssts o tst th months, o om tton t (GFR)

< 60 mL/mn/1.73 m2, wth o wthot vdnc o kdnydm, nd spctv o ts cs [5]. A mjoty o CKDptnts hyptnsv, nd hyptnson s on o thmn css o CKD, ccontn o ppoxmty 30% ocss o nd-st n dss (ESRD) [6, 7]. Hyptnsonnd CKD cst n os nd/o dtc sjcts, nd othdss stts sh common ndyn pthwys, sch schonc ow-d nmmton, ncsd sodm tn-ton, nd n ctvtd nn-notnsn systm [8, 9]. T

kdnys sn y som s th mn cpt n th dv-opmnt o hyptnson. nspntton stds hv ndddmonsttd tht hyptnson oows th kdnys [10, 11],nd n xtm css movn oth kdnys n tnspntdptnts cn c sstnt hyptnson [12].

Anm stds hv sstd tht n tss hypoxmht noth common mchnsm o n dmn hyptnson nd n dsss [13]. Indd, cotcnd mdy tss hypox hs n docmntd noth dss stts [14, 15]. Howv, tnston o n-m stds to hmns shod md ctosy nds hmpd y th snc o non-nvsv tchnqsown th msmnt o n tss oxynton nhmns. Ts pp ocss on th dtmnnts o ntss oxynton n hmns nd on th ct vdncpontn towds o o n tss hypox n thdvopmnt nd posson o hyptnson nd CKD nhmns.


2/8

2 Intnton Jon o Hyptnson

2. Determinants of Renal Tissue Oxygenation

Fy ys o, Aknd nd Ko w th st to pot thnq oxynton pttn o kdnyssn mcoctodssnstv to oxyn n dos nd ts. Ty msd vs otsspt pss o oxyn (pO

2) sow s1020mmH

n th md nd 50 mmH n th n cotx [16], dsptth ct tht n ood ow, nd ths oxyn dvy, s thhhst n th ody n ton to on wht. Snc thn,mch hs n nd on th mchnsms nvovd n thton o n mdy tss oxynton. As n nyon, th oc tss pO

2s dtmnd y th oxyn dv-

y ( ncton o n pson nd ood oxyn contnt)nd y th O

2consmpton, whch s dvn ssnty y

th om tton t nd th ctv t tnspot.Rn kdny pson s chctzd y pomoxyn dfson shntn, pty xpnn th ow tsspO

2vs [17]. In th kdnys, ov 90% o oxyn con-

smpton s sd o t sodm tnspot, whch dfstwn cotx nd md. T w-psd poxmts mny octd n th n cotx. Poxmt sodm sopton s pty sd on ny-consmn ctv tnspot v sot N+, K+-APsndptyon pssv tnspotv pc pthwys [18].Hnc, dspt th ct tht th poxm ts so67% o td sodm, thy consm ony 27% o totO2, stn n cotc pO

2ond 50 mmH [1921]. In

contst, Hns oops n th md cv 10% o RBFnd so 30% o sodm t tvy hh-ny cost.Ty s 67% o O

2, nd oc pO

2s s ow s 10

15 mmH nd nom ccmstncs, whch nds thmhhy sscpt to schmc njy [19, 20].

Totcy, wosnn o n tss oxynton s th

consqnc o dcd oxyn dvy o o ncsd oxy-n consmpton. Exmps o th st ctoy svn ty stnoss, n hypopson d to sptc ocdonc shock, o sv nm. Exmps o th scondctoy ny-consmn om hyptton ssn n osty nd th y sts o dts, ponmm-toy pthwys, nd/o nhncd n sodm sopton,s psnt n ssnt hyptnson.

Whtv th cs, th consqnc o n tsshypox s dntc, tht s, ctvton o hypox-ndcdctos (HIF-1) nd HIF-1 td ns. T ctvtono ths ns w not ony d to n ncsd ytho-poss nd to nononss thoh ctvton o vsc

ndoth owth cto nd ndcntc oxd synths,t so to th stmton o owth ctos tht csndoth dysncton, ctvton o nmmtoy cs,nd oxdtv stss, whch w d to tss njy ndntstt oss [22, 23]. Whs th s ccmtdvdnc o o o hypox n th dvopmnt o ctnd chonc n dm n nms, th s dntvy ssnomton on th pthophysooc o o n hypoxn hmns. Ts s d ssnty to mthodooc sons.Indd, mny tchnqs n nms ow msmnt oon n oxyn contnt, sch s th nston o oxynmcoctods nd th potopophyn phosphoscncmthod [24]. Bsds, hypox cn msd on dssctd

kdny tss sn pmondzo, moc hypoxpo whch, oown njcton, nds to tsss wth oxy-n tnson ow 10mm H [15] o y tss dosn o HIF-1o hypox-sponsv ns. Unotnty, ths tchnqs too nvsv o not dptd to sd n hmns.

3. Measurement of Renal Tissue Oxygenationin Humans with BOLD-MRI

A tvy nw tchnooycd BoodOxyntonLv-Dpndnt Mntc Rsonnc Imn (BOLD-MRI),ofs now possts to ssss n tss oxyntonnon-nvsvy n hmns [25, 26]. T BOLD fct ssd pon th dfnt mntc ttts o hmoon.Oxy-hmoon s dmntc, whs doxyhmoons pmntc. T mntc d dstncs y p-mntc mocs st n oss o phs cohnc,dn to sn ttnton on 2-whtd MR ms.Doxyntd hmoon cn tho sd s nndonos contst nt. T to o doxyhmoon tooxyhmoon con-cnttons s popoton to th pO

2

o ood, nd ood pO2

s spposd to n qmwth th sondn tss. Hnc, BOLD sn stmtdy tnsvs xton t R2 (=1/2) cn consdds snstv ndcto o tss pO

2[26]. T fct o th

mnpton o th oxy- to doxyhmoon to stsn contst chns n nms [27] nd n hmns [28]. R2

s msd y BOLD-MRI hs n shown to cotw wth tss pO

2[25, 29]. An xmp o MR ms

s otnd sn th BOLD-MRI tchnq n hthyvont s shown n F 1().

Snc 1996, BOLD-MRI hs n sd n hmns to v-t, monst oths, th fct o wt dss on nmdnd cotx n hthy vonts [34, 35] nddtcptnts [30] nd to monto chns n n oxynton dmnstton o dfnt ds [36, 37] nd ctn schm [38, 39].

T BOLD-MRI tchnq ts hs n ctczd ysom [40, 41], n tht t s dct to cq th smntomc scs n ch ptcpnt whn ptn thBOLD-MRI xms. Howv, th ntosv vty oth cotc nd mdyR2vs s ow whn pomdy n xpncd nvstto nd whn sn stndd-zd th-hod tchnq [42]. An dntc phydtonpotoco nd ssssmnt o dty sodm ntk t st

s mpotnt, snc oth ctos hv n shown to nncth R2 sn (s ow).

4. Renal Tissue Oxygenation inEssential Hypertension

Essnt hyptnson s on chctzd y n ncsdsodm tnton, th n th poxm o dst nphonsmnts, pocss qn ctv sodm tnspot whchmht d to ncsd t oxyn consmpton [43, 44].Bsds, th nn-notnsn systm s n n ctvtdn hyptnsv ptnts, whch my fct n pson


3/8

Intnton Jon o Hyptnson 3

()

()

Figure 1: Exmp o ood oxynton v-dpndnt MRI (BOLD-MRI) n hthy vont () ndn ptnt sfn om chonckdny dss (). T ntomc tmpts shown on th sd, th R2 mps n th mdd, nd th cospondn coo mps onth ht; owR2 vs (nd spposd hh tss oxynton) n d nd hh R2 vs n yow.

nd oxyn consmpton [45]. To, ssnt hyp-tnson cod thotcy d to cotc nd mdyhypox.

Indd, stds n hyptnsv ts sn oxyn mco-ctods ond pononcd mdy nd cotc hypoxn spontnosy hyptnsv nms s compd to no-motnsv contos [14]. Most stds pomd n hmnsso hv ocsd on n ty stnoss, s dscssd nmo dt n noth tc o ths nm. Assssmnto n tss oxynton n ptnts wth ssnt hyp-tnson hs ony n pomd n w stds. In thst stdy, xto t . potd hh mdy R2 vsn 20 Acn-Amcn hyptnsv sjcts, s compdto 20 Ccsns sstn ow mdy oxynton

n hyptnsvs [46]. Ts osvton ws xpnd y nncsd n mdy vom (msd y contst-nhncd mtdtcto C) p ody sc (BSA),copd wth ncsd sodm sopton nd nypostndn F2 xcton n Acn Amcns [47]. How-v, dfncs n , ody mss ndx (BMI), nd st-mtd GFR (GFR) hmpd th ty to nz thssts. Bsds, th stdy dd not ncd nomotnsvconto op.

Schchn t . showd tht ntvnos nson onotnsn II to sx hthy vonts ds to n cts n ood pss (BP) nd smtnos dcs ocotc 2, sstn dcs n cotc oxynton.

Unotnty, mdy oxynton ws not ssssd nths stdy, nd snchyptnson ws tcy ndcd, thsts cnnot tnstd to th hyptnsv popton[48].

Fny, n o sch nt, w hv nvsttdtn yon nomotnsv nd ht nttd hyptnsvmn wth BOLD-MRI on wk o hh sodm(>200 mmo/dy) nd n on wk o ow sodmdt (


4/8


able 1: Cs conto stds tht hv ssssd n oxynton n dtcs.

Stdy Ptnt A (y)GFR

(mL/mn/1.73m2)MRI

(s)Mdy2

(1/sc)Cotc 2

(1/sc)

Epstn t . (2002) [30]DM2 9 48 3 119 6 1.5 17 0.5 13 0.2

Conto 9 51 2 133 7 1.5 17 0.8 13 0.2

Yn t . (2012) [31] DM2 48 3870 8110 3 Hh HhConto 67 51 14 n.m. 3 Low Low

Wn t . (2011) [32]DM2 20 65 (4977) 47 (1471) 1.5 14 2 11 1

Conto 7 35 (3045) n.m. 1.5 19 1 12 1

Ino t . (2011) [33]DM2 43 59 11 44 28 1.5 n.m. 74 8

Conto 10 36 n.m. 1.5 59 5 74 5

2

v nstd o2 v potd; n.m.: not mntond.

ndoth ow- nd hh-st condtons, possy xpnnths ck o coton nd hnc th conmn th oo th nom poxm sopton o sodm n hyp-tnson [44].

Intstny, t ny sodm ntk, hyptnsv ptntshd shty ow mdy R2 vs thn nomotnsvsjcts, sstn n ncsd th thn dcsdmdy oxynton n yon hyptnsv mn, npossy d to dcd mdy oxyn consmpton s st o ncsd poxm sodm sopton.

It s mpotnt to not tht ths stdy ws pomd nyon hyptnsv mn, nd xtmy ow o hh sod-m-ntk condtons, nd th oxynton pttn mht dfnt n od ptnts wth hyptnson-ndcd ondm.

Hnc, cqd dt n hmns, so , not n nwth nm stds nd show no c dfnc twnnomotnsv nd hyptnsv sjcts o vn hhmdy oxynton n hyptnson s compd wthnomotnsv contos. Whth ths s d to ss ctvmd sodm tnspot, dpttons n md mco-ccton o td t vnos shntn s compd tonom sjcts mts th nvsttons. A psntddt shod ntptd wth cton, d to th smsmp sz, nd conmton n pospctv stds sndd.

5. Renal Tissue Oxygenation inChronic Kidney Disease

In cnc pctc, n schm hs com w-ccptd cs o ct n n sttons o cc-toy shock, ccontn o most 50% o css o ctn nscncy [49]. Howv, th o o n hypoxn th pthophysooy o chonc kdny dsss mndy ndpotd. Rcnty, Fn nd Nomn poposdtht kdny njy ds to vcos cc o tss oss,psnt otton o th n mcovsct, ndth hypox [50]. T sttmnt ws sd on th cttht th xtnt o n dysncton s pooy ssoctd wthchns n om mophooy s snn kdny opsso ptnts wth chonc n dss, whs t cots

w wth chonc tontstt oss, known cons-qnc o n hypox [51]. Onc nstd, th dcton oncton n mss n CKD sts n nm o commonncton, stct, nd mtoc dpttons tht d toth kdny dm, whtv th ndyn cs [52].Amonst ths mchnsms th ctvton o th nn-notnsn systm, om hyptton n sdom, th pton o nmmtoy cytokns schs GF-whch on hs tn stmts th omton o nt-stt oss, th dvopmnt o potn, nd wosnno tss hypox [52, 53].

Accmtn dt om nm stds sppots ndd, pthonc o o tss hypox n th chonc dt-oton o kdny ncton. T most convncn vdncpoy coms om Mnothm t ., who hv shown n mnnt kdny mod (whch s psnttv modo CKD) tht th nm o hypoxc ts ws mkdyncsd 4 nd 7 dys stot (5/6) nphctomy, scompd to shm-optd conto op [15]. Hypoxws msd on kdny opss sn mmnostnn opmondzo. O ntst, ths ndns occd n pwth dstd pt cpy pson nd ntdtdny hstooc vdnc o tontstt dm. Hypoxpsstd nt th dvopmnt o ntstt oss; n sop ttd wth omstn, n notnsn II typ 1cpto ock, ockd o th nn-notnsn sys-tm motd pt cpy pson nd t- hypox nd d to ss ntstt oss. Stds yJohnson t . hv so dmonsttd tht chonc systmchypox css n ntstt dm nd pdsposs

nms to psstnt hyptnsonnd tsndms [54].Mdy hypox hs n docmntd n nm stdsxmnn th dvopmnt o dtc nphopthy [55, 56].

BOLD-MRI cn so sd to stmt n tssoxynton n CKD ptnts (F 1()), nd sv std-s hv sd BOLD-MRI n hmns to nvstt noxynton n dfnt omso CKD. Dtc nphopthyhs n most qnty stdd, nd smmy o thsts s shown n 1. Ony on stdy potd owmdy oxynton n dtcs s compd wth con-tos; two ond no dfncs, whs on vn potdhh mdy oxynton n dtcs. Concnn thcotx, n ony th stdy o Yn t . potd ow


5/8


cotc oxynton (hh R2 vs) n dtcs s com-pd wth contos [31]; th oth stds ond no df-ncs. Howv, dfncs xstd n GFR o th d-tcs ncdd n ths stds. Moov, dfntstndd-zton pocds w oowd (so vss phydton,mdcton wthdw vss non), th hmpn

dct compsons. In th stdy o Yn t ., dtcs wdvdd nto o ops o ncsn kdny dm (stIIV, ccodn to Monsn). Athoh mdy oxyn-ton ws shty ow n dtc opss compd wthcontos, mdy oxynton ncsd wth wosnnkdny ncton, dspt th ct tht hmoon vsstony dcsd, nd ncsd om st I to IV. Tsnxpctd ndn ws xpnd y th thos s posssn o dcsd oxyn consmpton d to dcd GFRnd ctv t tnspot. Ts cod sst tht ndvncd CKD, dcd t oxyn consmpton ot-vs dcd mdy pson nd oxyn dfson ndtht possv ntstt oss my ncss ththn dcss mdy oxynton.

T st stdy so ssssn n oxynton tdfnt ds o kdny dysncton ws cnty potdy Mchy t . [57]. Ts stdy ncdd 400 ptnts whondwnt MR mn o nonspcc sons, ncdnstn o domn tmos nd MR nophs ont-domn vsss. O thm, 280 ptnts hd vsm ctnn vs, nd KDOQI sts o CKDw psntd. No coton ws ond twn R2

vs nd GFR (ccodn to th MDRD om [58]),nd R2 vs w not fctd y nd nd. Hnc,dspt som shotcomns o ths stdy (no nomtonon mdcton o dty sodm ntk, no stnddztono BOLD nd ctnn msmnt), t sms tht noxynton s kpt constnt ov od n o phys-ooc nd pthooc condtons. As sch, th ndnso Mchy t . pt nto qston whth chonc nhypox ty xsts n hmns o whth ct psodso hypox coctd y, o xmp, ttons nn mcoccton nd HIF-ndcd ntstt oss.In n wth thshypothss,Jd t . hv dscd ctncss n cotc nd mdy R2 vs th st dys stot cppn o th n ty [38]. Yt, o wks cppn, n hypox cod no on dtctd [59].

6. Antihypertensive Drugs and

Renal Oxygenation

T s o ocks o th nn-notnsn systm (RASocks) s nthyptnsv nd ntpotnc mdctonhs n ptcy fctv n sown th posson on dss n typ 2 dtcs [60], nd xstn d-ns dvs to ntodc n notnsn convtn nzymsnhto (ACEI) o n notnsn II cpto ock (ARB)n dtc ptnts wth CKD, s soon s mcomns dtctd o n cs o hyptnson [61].

Anm stds hv sstd tht dmnstton oRAS ocks ds to n ct ncs n n tssoxynton [24, 53]. In hmns, Djm t . potd

dcs n cotc R2 vs, sstn ncsd oxy-nton,n nn hthy vonts two hos th ntko 50 m o ostn [62].

W cnty pomd coss-ov pot stdy n twvptnts wth typ 2 dts nd CKD (mn 60 y, GFR

62 mL 22 mn/1.73 m2). Ptnts w th dy on

ttmnt wth n ACEI o ARB o hd om ndctonto stt on (hyptnson, (mco)mn, o oth). Inths stdy, cotc nd mdyR2 vs w not td on month o np (20 m qd) no on montho cndstn (16 m qd) s compd wth sn (dtpsntd t th 5th Intnton mtn o th FnchSocty o Hyptnson, Ps, Fnc, Dcm 2011).Act chns n R2 vs w not ssssd n ths stdy.Howv, n comnton wth th stdy o Djm t .,on mht concd tht RAS ocks ndc ct yt notchonc ncss n n oxynton.

T dmnstton o osmd hs n shown tondc n n ct dop o mdy nd to ss d

cotc R2

vs n hthy vonts, n dtcs, ndn ptnts wth n ty stnoss sstn dtc-ndcd ncs n n oxynton [21, 46]. T fct oosmd on n oxynton hs n tttd to dcton o th ctv oxyn-consmn sodm tnspotn th scndn oop o Hn [46]. o th st o oknowd, no stds hv ssssd th fct o choncosmd ntk on n oxynton.

7. Conclusions and Perspectives

kn toth, th BOLD-MRI tchnq hs opnd nxctn nw d o sch tht ows o th st tm thssssmnt o n oxynton non-nvsvy n hmns.T chns n n oxynton osvd n spons toosmd o n ssocton wth dty sodm ntksst tht n sodm hndn s on o th mn dt-mnnts o n tss oxynton.

So , no stds hv convncny dmonsttd thtn oxynton s dcd n ssnt hyptnson, d-ts, o CKD. Ts ndns n contst wth mostnm stds. Fst o , t mht tht BOLD-MRI s notsnstv noh o smpy not s ood too to ssss noxynton. Indd, th ssmpton tht tss oxynton

vs wth ood oxynton mht not wys hod nkdnys tht chctzd y poond tovnos

oxyn shntn. Nonthss, sv nm stds hvvdtd ths tchnq. Anoth possty s tht nmstds povd xcnt mods to stdy shot-tm chnsn oxynton t tht thy soptm n smtn thon-tm chns nd dpttons n th kdny tht mhthv occd sv dcds o xpos to choncdss stts sch s dts o hyptnson. Whtvth tth my , BOLD-MRI nd oth nw dooctchnqs tht stdy n nctonn non-nvsvy mtth ttnton o cncns, nd th dvopmnt wctny hp to th nv th o o n oxyntonn th dvopmnt nd posson o ssnt hyptnsonnd CKD n hmns.


6/8


References

[1] P. C. W. vn dn Hoon, E. J. M. Fskns, N. J. D. Nkkt ., T ton twn ood pss nd motty dto coony ht dss mon mn n dfnt pts o thwod, Te New England Journal of Medicine, vo.342, no. 1, pp.18, 2000.

[2] J. M. Fck, J. Nton, R. Gmm J. t ., Bood pss ndmotty mon mn wth po myocd ncton, Circu-lation, vo. 92, no. 9, pp. 24372445, 1995.

[3] M. J. K, P. K. Whton, B. L. Rnd t ., Bood pssnd nd-st n dss n mn, Te New England Journalof Medicine, vo. 334, no. 1, pp. 1318, 1996.

[4] F. L. Bnct, P. K. Whton, L. H. K, nd M. J. K, D-ts mts, c, nd sococonomc stts. A popton-sd stdy, Annals of Epidemiology, vo. 6, no. 1, pp. 6773,1996.

[5] B. Stn, S. Bon, P. C. W. vn Djk t ., nds n th nc-dnc o n pcmnt thpy o nd-st n dssn Eop, 19901999, Nephrology Dialysis ransplantation, vo.18, no. 9, pp. 18241833, 2003.

[6] R. J. Gssock, T sn td o nd-st n dss: whtcn don? Clinical and Experimental Nephrology, vo. 8, no.4, pp. 291296, 2004.

[7] J. M. Wsstch nd L. D. Dwokn, Dos ssnt hyptn-son cs nd-st n dss, Kidney International, vo.36, pp. S33S37, 1992.

[8] K. A. Jmson nd R. R. ownsnd, T ttt dno hyptnson: ocs on CKD, Advances in Chronic KidneyDisease, vo. 18, no. 1, pp. 610, 2011.

[9] R. W. Sch, A. Msom, nd E. Ehssn, Adoston: on dmtosdsods, hyptnson,choncn ,ndmtoc syndom, Clinical Journal of the American Society ofNephrology, vo. 5, no. 6, pp. 11321140, 2010.

[10] . M. Cofmn, S. Hmmstn, C. Bst, nd P. E. Kotmn,Post-tnspnt hyptnson n th t: fcts o cptop ndntv nphctomy, Kidney International, vo.36,no. 1,pp. 3540, 1989.

[11] R. Rtt, Dos th kdny py o n th tooy opmy hyptnson? Evdnc om n tnspnttonstds n ts nd hmns, Journal of Human Hypertension,vo. 7, no. 2, pp. 177180, 1993.

[12] J.J. Cts, R. G. Lk, A. G. Dthm t ., Bnts o movo ntv kdnys n hyptnson n tnspntton,Te Lancet, vo. 2, no. 8458, pp. 739742, 1985.

[13] M. Nnk, Chonc hypox nd tontstt njy: n common pthwy to nd-st n ,Journal of theAmerican Society of Nephrology, vo. 17, no. 1, pp. 1725, 2006.

[14] W. J. Wch, H. Bmt,D.Ls,nd C. S. Wcox, Nph-on pO

2ndn oxyn s n th hyptnsvt kdny,

Kidney International, vo. 59, no. 1, pp. 230237, 2001.

[15] K. Mnothm, . nk, M. Mtsmoto t ., Evdnc ot hypox n th y phs n th mnnt kdnymod, Journal of the American Society of Nephrology, vo. 15,no. 5, pp. 12771288, 2004.

[16] K. Aknd nd J. Ko, Rn oxyn tnson, Nature, vo.188, no. 4751, p. 671, 1960.

[17] H. J. Schk, U. Jost, H. Bmt, H. Btm, nd U. Hck-mnn, Evdnc o pom oxyn dfson shnt nt n cotx, American Journal of Physiology, vo. 259, no. 6,pt 2, pp. F910F915, 1990.

[18] F. K, Rn ny mtosm nd ton o sodmsopton, Kidney International, vo. 11, no. 3, pp. 153160,1977.

[19] M. Bzs, S. Rosn, P. Sv, nd F. H. Epstn, Rn schm: nw pspctv, Kidney International, vo. 26, no. 4, pp. 375383, 1984.

[20] W. J. Wch, Intn oxyn nd hyptnson, Clinical andExperimental Pharmacology and Physiology, vo. 33, no. 10, pp.10021005, 2006.

[21] S. I. Gomz, L. Wn, J. A. Hs t ., Incsd hypoxnd dcd n t spons to osmd dtctdy BOLD mntc sonnc mn n swn novschyptnson, American Journal of Physiology, vo. 297, no. 4,pp. F981F986, 2009.

[22] J. . Pch, Dvy on dmnd nw o n thpy?Te New England Journal of Medicine, vo. 348, no. 13, pp. 12821283, 2003.

[23] M. Nnk nd K. U. Eckdt, Hypox nd th HIF systmn kdny dss,Journal of Molecular Medicine, vo.85,no. 12,pp. 13251330, 2007.

[24] J..Nomn, R. Stdw, M. Sn, ndL. G. Fn, AnotnsnII ockd mnts n cotc mcovsc pO

2ndct-

n nov, potnty nopotctv cton, Nephron, vo.94,no. 2, pp. p39p46, 2003.

[25] P. V. Psd, R. R. Edmn, nd F. H. Epstn, Nonnvsvvton o ntn oxynton wth BOLD MRI, Circu-lation, vo. 94, no. 12, pp. 32713275, 1996.

[26] P. V. Psd, Evton o nt-n oxynton y BOLDMRI, Nephron, vo. 103, no. 2, pp. c58c65, 2006.

[27] S. Ow, . M. L, A. S. Nyk, nd P. Gynn, Oxynton-snstv contst n mntc sonnc m o odnt nt hh mntc ds, Magnetic Resonance in Medicine, vo.14, no. 1, pp. 6878, 1990.

[28] K. K. Kwon, J. W. Bv, D. A. Chs t ., Dynmcmntc sonnc mn o hmn n ctvty d-n pmy snsoy stmton, Proceedings of the NationalAcademy of Sciences of the United States of America, vo. 89, no.12, pp. 56755679, 1992.

[29] M. Pdsn, . H. Dssn, J. Mokno t ., Vdton oqntttv BOLD MRI msmnts n kdny: ppctonto nt t ostcton, Kidney International, vo. 67,no. 6, pp. 23052312, 2005.

[30] F. H. Epstn, A. Vvs, nd P. V. Psd, Efct o dts onn mdy oxynton dn wt dss, DiabetesCare, vo. 25, no. 3, pp. 575578, 2002.

[31] W. J.Yn, F. L, X. M. L t ., Nonnvsv vton onoxynton n dtc nphopthy y BOLD-MRI, European

Journal of Radiology, vo. 81, no. 7, pp. 14261431, 2012.[32] Z. J. Wn, R. Km, S. Bnj, ndC. Y. Hs, Bood oxyn

v-dpndnt (BOLD) MRI o dtc nphopthy: pm-ny xpnc, Journal of Magnetic Resonance Imaging, vo.33, no. 3, pp. 655660, 2011.

[33] . Ino, E. Kozw, H. Okd t ., Nonnvsv vtono kdny hypox nd oss sn mntc sonncmn,Journal of the American Society of Nephrology, vo.22,no. 8, pp. 14291434, 2011.

[34] P. V. Psd nd F. H. Epstn, Chns n n mdy pO2

dn wt dss s vtd y ood oxynton v-dpndnt mntc sonnc mn: fcts o n ndcycooxyns nhton, Kidney International, vo. 55, no. 1,pp. 294298, 1999.


7/8


[35] F. H. Epstn ndP. Psd, Efcts o osmd on mdyoxynton n yon nd od sjcts, Kidney Interna-tional, vo. 57, no. 5, pp. 20802083, 2000.

[36] L. Homnn, S. Smon-Zo, A. Nowk t ., BOLD-MRI oth ssssmnt o n oxynton n hmns: ct fct onphotoxc xnootcs, Kidney International, vo.70, no. 1, pp.144150, 2006.

[37] D. H. Kstnsn, M. Pdsn, M. C. Gn t ., Intnood oxynton nd n ncton msd y mntcsonnc mn dn on-tm cycospon ttmnt,ransplantation Proceedings, vo. 37, no. 8, pp. 33023304, 2005.

[38] L. Jd, L. O. Lmn, D. G. K t ., Bood oxynv-dpndnt msmnt o ct nt-n schm,Kidney International, vo. 65, no. 3, pp. 944950, 2004.

[39] S. K. Aod, E. A. Sdowsk, O. Un t ., Dtcton o ctn schm n swn sn ood oxyn v-dpndntmntc sonnc mn, Journal of Magnetic ResonanceImaging, vo. 22, no. 3, pp. 347353, 2005.

[40] P. E. Tw, R. yo, nd S. M. Msh, Non-nvsvnvstton o kdny dss n typ 1 dts y mntcsonnc mn, Diabetologia, vo. 54, no. 9, pp. 24212429,2011.

[41] C. S. Zo, N. M. Rosky, H. Mht t ., Vsztonnd qntcton o n R2 chns dn wt dss,Journal of Magnetic Resonance Imaging, vo. 17, no. 6, pp. 676682, 2003.

[42] S. C. Smon-Zo, L. Homnn, A. G t ., Non-nvsvmonton o n oxynton sn BOLD-MRI: po-dcty stdy, NMR in Biomedicine, vo. 19, no. 1, pp. 8489,2006.

[43] A. Choo, M. Md, J. Nss, H. R. Bnn, ndM. Bn, Poxm sodm sopton: n ndpndntdtmnnt o ood pss spons to st, Hypertension,vo. 36, no. 4, pp. 631637, 2000.

[44] M. Bn, M. Bochd, nd M. Md, Poxm tncton nd st snstvty, Current Hypertension Reports, vo.8, no. 1, pp. 815, 2006.

[45] A. Dn, C. M. Mc, J. M. Sz t ., Oxyn consmp-ton n th kdny: fcts o ntc oxd synths sooms ndnotnsn II, Kidney International, vo. 68, no. 2, pp. 723730,2005.

[46] S. C. xto, J. F. Gockn, L. O. Lmn t ., T s om-ntc sonnc to vt tss oxynton n n tystnoss, Journal of the American Society of Nephrology, vo. 19,no. 4, pp. 780788, 2008.

[47] M. Pjm, L. Homnn, M. Md t ., Efct o sodmodn/dpton on n oxynton n yon nomotnsvnd hyptnsv mn, Hypertension, vo. 55, no. 5, pp. 1116

1122, 2010.[48] H. Schchn, M. Kho, L. Lnd, J. Dw, ndK. Sch-

, Anotnsn II dcss th n MRI ood oxyntonv-dpndnt sn, Hypertension, vo. 47, no. 6, pp. 10621066, 2006.

[49] R. Tdhn, M. Psc, nd J. V. Bonvnt, Act n, Te New England Journal of Medicine, vo. 334, no. 22,pp. 14481460, 1996.

[50] L. G. Fn nd J. . Nomn, Chonc hypox s mchnsmo posson o chonc kdny dsss: om hypothss tonov thptcs, Kidney International, vo. 74, no. 7, pp. 867872, 2008.

[51] A. A. Eddy, Posson n chonc kdny dss, Advancesin Chronic Kidney Disease, vo. 12, no. 4, pp. 353365, 2005.

[52] H. Aod nd W. L. Hnch, Cnc pctc. St IVchonc kdny dss, Te New England Journal of Medicine,vo. 362, no. 1, pp. 5665, 2010.

[53] A. Dn, . n, P. Snh t ., Rton o oxyn tz-ton y notnsn II n chonc kdny dss, Kidney Inter-national, vo. 75, no. 2, pp. 197204, 2009.

[54] R. J. Johnson, B. Rodz-It, . Nkw, D. H. Kn,D. I. F, nd J. H-Acost, St n njy s ky common mchnsm o st-snstv ssnt hyptnson,Hypertension, vo. 45, no. 3, pp. 326330, 2005.

[55] E. A. dos Sntos, L. P. L, L. J, nd P. V. Psd, Ey chnswth dts n n mdy hmodynmcs s vtdy optc pos nd BOLD mntc sonnc mn,Investigative Radiology, vo. 42, no. 3, pp. 157162, 2007.

[56] F. Pm, M. Fdch, P. O. Csson, P. Hns, . nk,nd P. Lss, Rdcd ntc oxd n dtc kdnys d toncsd hptc nn mtosm: mpctons o no-mdy oxyn vty, American Journal of Physiology,vo. 294, no. 1, pp. F30F37, 2008.

[57] H. J. Mchy, L. Mtz, S. Hnd, J. Hnsmnn, S. O.

Schon, nd U. I. Attn, Rn BOLD-MRI dosnot ct n ncton n chonc kdny dss, KidneyInternational, vo. 81, no. 7, pp. 684689, 2012.

[58] A. S. Lvy, J. Cosh, . Gn t ., Usn stnddzdsm ctnn vs n th modcton o dt n ndss stdy qton o stmtn omtton t,Annals of Internal Medicine, vo. 145, no. 4, pp. 247254, 2006.

[59] N. Ronnt, F. G-Ezh, J. Bcchtt t ., Evotono n oxyn contnt msd y BOLD MRI downstm chonc n ty stnoss, Nephrology Dialysis ransplan-tation, vo. 26, no. 4, pp. 12051210, 2011.

[60] M. A. Poh, S. Bmnth, D. J.Codonn t ., Indpndntndddtvmpct o oodpss contond notnsnIIcpto ockd on n otcoms n th stn dtc

nphopthy t: cnc mpctonsnd mttons,Journalof the American Society of Nephrology, vo. 16, no. 10, pp. 30273037, 2005.

[61] N. A. Khn, B. Hmmn, R. J. Hmn t ., T 2009Cndn Hyptnson Edcton Pom commndtonso th mnmnt o hyptnson: pt 2thpy, TeCanadianJournal of Cardiology, vo. 25,no. 5, pp. 287298, 2009.

[62] A. Djm, E. A. Sdowsk, R. J. Mh t ., BOLD-MRIssssmnt o ntn oxynton nd oxdtv stss nptnts wth chonc kdny o dysncton, AmericanJournal of Physiology, vo. 292, no. 2, pp. F513F522, 2007.


8/8

Submit your manuscripts at

http://www.hindawi.com

Documents

Renal Tissue Oxygenation in Essential Hypertension