nefrozuli sindromi

(minimaluri morfologiuri

cvlilebebi) bavSvTa asakSi

klinikuri praqtikis erovnuli rekomendacia

(gaidlaini)

2

klinikuri praqtikis erovnuli rekomendacia (gaidlaini)

`nefrozuli sindromi (minimaluri morfologiuri cvlilebebi)

bavSvTa asakSi~ miRebulia klinikuri praqtikis erovnuli

rekomendaciebis (gaidlainebi) da daavadebaTa marTvis

saxelmwifo standartebis (protokolebi) SemuSavebis, Sefasebis

da danergvis erovnuli sabWos 2008 wlis 5 noembris #1 sxdomaze

da damtkicebulia saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis ministris 2009 wlis 14 aprilis # 150/o

brZanebiT.

3

nefrozuli sindromi (minimaluri morfologiuri cvlilebebi) bavSvTa asakSi

1. daavadebis definicia, sinonimebi, klasifikacia da terminologia

definicia - nefrozuli sindromi warmoadgens kliniko-laboratoriul

simptomokompleqs, romlisTvisac damaxasiaTebelia gamoxatuli, stabiluri

SeSupeba, zogjer anasarkamdec, proteinuria, romelic aRemateba 40

mg/kv.m/sT-Si an 50mg/kg/w./24sT-Si, dilis SardSi kreatininisa da cilis

Sefardebis indeqsi >200mg/mmol-ze, hipoalbuminemia (<25gr/l),

hiperlipidemia.

bavSvTa asakSi nefrozuli sindromis 85-90% Seadgens e.w. nefrozuli

sindromi minimaluri morfologiuri cvlilebebiT (1,34).

klasifikacia da sinonimebi

nefrozuli sindromi minimaluri morfologiuri cvlilebebiT (nsmc) - daavadebaTa saerTaSoriso klasifikaciis X gadaxedvis mixedviT kodi -

N04.0

sinonimebia: lipoiduri nefrozi, minimaluri cvlilebebis daavadeba,

hormonomgrZnobiare nefrozuli sindromi, nefropaTia minimaluri

cvlilebebiT. D

daavadebis morfologiur substrats warmoadgens imunohistologiurad

imunonegatiuri nefropaTia, podocitebis pedikulebisa da trabekulebis

gasadavebiT. aRniSnuli cvlilebebi vlindeba mxolod eleqtronuli

mikroskopiiT. sinaTlis mikroskopiiT paTologia ar aRiniSneba.A daavadeba

xasiaTderba kortikosteroiduli Terapiisadmi maRali mgrZnobelobiTa da

miuxedavad xangrZlivi mimdinareobisa, keTilsaimedo gamosavliT (1).

terminologia

nefrozuli sindromis remisia: mdgomareoba rodesac 3 dRis ganmavlobaSi

cilis eqskrecia SardTan erTad ar aRemateba 4mg/kv.m/sT-Si.

nefrozuli sindromis Ggamwvaveba: mdgomareoba rodesac cilis eqskrecia

SardTan erTad aRemateba 40mg/kv.m/sT-Si minimum 3 dRis ganmavlobaSi.

xSiradmorecidive nefrozuli sindromi: 2 an meti recidivi 6 Tvis, an 4 da

meti recidivi 1 wlis ganmavlobaSi.

steroidmgrZnobiare nefrozuli sindromi: remisiis

ganviTarebaEkortikosteroiduli Terapiis fonze da misi SenarCuneba

mkurnalobis moxsnidan minimum 2 kviris ganmavlobaSi.

4

steroiddamokidebuli nefrozuli sindromi: recidivis (minimum 2)

ganviTareba kortikosteroidebis mkurnalobis fonze an misi moxsnidan 2

kviris ganmavlobaSi.

steroidrezistentuli nefrozuli sindromi: remisiis miRwevis

SeuZlebloba 8 kviris ganmavlobaSi, miuxedavad adeqvaturi

kortikosteroiduli Terapiisa (prednizoloni 2mg/kg/24sT. an 60mg/m2/24sT)

(5,22).

2. epidemiologia

gavrceleba - saqarTveloSi Seswavlili araa.

SeerTebul StatebSi daavadebis gavrcelebis sixSire meryeobs 14-17

SemTxvevamde 100000 mosaxleze, amasTan daavadebis axali SemTxveva

weliwadSi 3-7 100000 mosaxleze (35).

vaJebi 2-jer ufro xSirad avaddebian vidre qalebi. daavadebulTa 80% 6

wlamde asakisaa. daavadebis piki modis 2-4 welze, xolo 10 wlis Semdeg

misi sixSire klebulobs (27).

gamosavali - nefrozuli sindromi minimaluri morfologiuri cvlilebebiT

xasiaTdeba keTilsaimedo gamosavliT da miuxedavad xangrZlivi, morecidive

mimdinareobisa SemTxvevaTa 95%-Si Tavdeba sruli gajansaRebiT 18 wlis

asakamde. 5% aReniSnebaT daavadebis recidivebi momdevno wlebSic. Tirkmlis

Tirkmlis qronikuli ukmarisoba praqtikulad ar viTardeba (2).

3. etiopaTogenezi

etiologia - dReisaTvis daavadebis gamomwvevi raime konkretuli agentisa

Tu faqtoris dadgena sakmaod rTulia da SemTxvevaTa mxolod 10% aris

SesaZlebeli. saxeldeba ramodenime mizezi romlebsac SeiZleba kavSiri

hqondeT daavadebis ganviTarebasTan.

yvelaze xSirad am mizezTagan saxeldeba alergia, romelic ama Tu im saxiT

gvxvdeba SemTxvevaTa 30%-Si. AaRwerilia daavadebis ganviTareba an

gamwvaveba iseT alergenebTan kontaqtisas rogorebicaa - ambrozia, oTaxis

mtveri, meduzas da futkris toqsini, soko, rZe, kvercxi (27,30).

literaturaSi gvxvdeba cnobebi hipoalergiuli dietis dadebiT efeqtze da

rig SemTxvevebSi daavadebis remisiis ganviTarebis SesaZleblobaze (26).

atopiis garkveul rolze metyvelebs IgE-s donis mateba nsmc dros, Tumca

misi korelacia daavadebis mimdinareobisa da gamosavalis TaviseburebebTan

ar dasturdeba.

sxva faqtorebidan romlebsac SeuZliaT ganaviTaron nefrozuli sindromi

gamohyofen rig medikamentebs. maT Soris saxeldeba - mesalazini, d-

penicilinamini, liTiumi, rifampicini, mZime metalebi. aRwerilia daavadebis

5

asociacia hojkinis limfomasTan da sxva limfoproliferaciul

daavadebebTan.

infeqciuri faqtorebidan sayuradReboa adamianis imunodeficitis virusis

kavSiri daavadebasTan. aRmoCenilia epStein baris virusis

antigeniETirkmlis bioptatSi. gamoTqmulia mosazreba imis Sesaxeb, rom

adreul asakSi gadatanili parvovirusuli infeqcia azianebs podocitebs,

rac SemdgomSi ganapirobebs daavadebis ganviTarebas (27).

nefrozuli sindromi minimaluri morfologiuri cvlilebebiT SeiZleba

CaiTvalos polietiologiur daavadebad, Tumca gaurkvevelia ras

warmoadgens is saerTo meqanizmi, romelsac sabolood mivyevarT daavadebis

ganviTarebamde (27).

paTogenezi – miuxedavad imisa, rom paTogenezis garkveuli sakiTxebi

kvlavac diskusiis sagans warmoadgenen, mkvlevarTa umravlesoba Tanxmdeba

imaSi, rom daavadebis rogorc klinikuri gamovlinobis, ise garTulebebisa

da organizmSi mimdinare bioqimiuri Zvrebis ZiriTad safuZvels maRali

proteinuria warmoadgens (29) (ix. diagrama 1.).

diagrama 1. nefrozuli sindromis ganviTarebis paTofiziologiuri meqanizmebi

proteinuria(>40mg/kv/m/sT) cilis sinTezi RviZlSi hipoproteinemia cilis rabsorbcia

hiperlipidemia Sededebis faqtorebi plazmis onkozuri wneva nawlavis SeSupeba

plazmis moculoba

antiTrombin III mineralokortikoidebis NNa milakovani

sekrecia reabsorbcia

NadaH20Sekaveba

intersticiuli

SeSupeba

aTerosklerozis

ganviTarebis daCqareba

hiperkoagulacia

Tirkmlebis funqcia

6

pirvel rigSi cilis dakargva ganapirobebs hipoproteinemiisa da

gansakuTrebiT hipoalbuminemiis ganviTarebas, rac iwvevs onkozuri wnevis

daqveiTebas da siTxis gadasvlas sisxlZarRvis sanaTuridan qsovilebSi.

aRniSnuls mohyveba hipovolemia rasac mosdevs aldosteronisa da renin-

angiotenzuri sistemis gaaqtiveba, izrdeba antidiurezuli hormonis

sekrecia, xolo winagulovani natriurezuli hormonis done qveiTdeba. amis

Sedegad organizmSi iwyeba natriumisa da wylis Sekaveba. es procesi

klinikurad masiuri da stabiluri SeSupebis saxiT vlindeba. amave dros

unda aRiniSnos isic, rom sruli koreqcia proteinuriis xarisxsa da

SeSupebis intensivobas Soris ar arsebobs.

aris monacemebi imis Sesaxeb, rom hiperlipidemiac dakavSirebuli unda iyos

onkozuri wnevis daqveiTebasTan da hipoalbuminemiasTan. aRniSnuls Tavis

mxriv mosdevs albuminisa da lipidebis gaZlierebulii sinTezi RviZlSi.

Aamave dros qveiTdeba endoTeliaruli lipoproteinuli lipazis aqtivoba

da viTardeba hiperlipidemia. proteinuriis Semcirebisa an alagebis

SemTxvevaSi lipidebis done sisxlSi qveiTdeba an ubrundeba normas.

nefrozuli sindromisaTvis damaxasiaTebeli hiperkoagulaciis erT-erT

mizezad saxeldeba SardTan erTad antiTrombin III, C da S proteinebis

dakargva. aseve matulobs fibrinogenis sinTezi RviZlSi da Trombocitebis

agregacia.

aRsaniSnavia isic, rom maRal proteinurias, sxva faqtorebisagan

damoukideblad, SeuZlia nefronis dazianeba.

miuxedavad imisa, rom imunomorfologiurad nsmc imunonegatiur

nefropaTias warmoadgens, daavadebis ganviTarebas dReisaTvis mainc imunur

meqanizmebs ukavSireben. Ppirvel rigSi aRniSnulis sasargeblod metyvelebs

imunosupresiuli Terapiis maRali efeqturoba, daavadebis kavSiri

atopiasTan, hojkinis daavadebasTan da iseTi leikocitarul antigenebTan,

rogorebicaa DRw7, B12. aRniSnul imunur daRvevaTa ZiriTad mizezad

miCneulia T limfocitebis disfunqcia romelic vlindeba iseTi citokinebis

gamomuSavebaSi, romlebic azianeben gorglis epiTelialur ujredebs

(trabekulebsa da pedikulebs) riTac Trgunaven polianionebis sinTezs.

polianionebi ki warmoadgenen fiziologiur bariers iseTi uaryobiTad

damuxtuli makromolekulebisaTvis rogoricaa albumini. aRniSnuli

ganapirobebs albuminis ganvladobis momatebas glomerularul filtrSi.

citokinebidan daavadebis ganviTarebaSi monawileobs interleikin-12,

interleikin-2, romelTa done periferiul monocitebSi momatebulia

daavadebis gamwvavebisas, xolo remisiis dros ubrundeba normas.

interleikin-18 amJRavnebs sinergizms interleikin-12-Tan sisxlZarRvTa

ganvladobis faqtoris gamomuSavebis stimulaciaSi. Mmomatebulia agreTve

interleikin-4 da CDD23 (IgE receptori) done periferiuli sisxlis

limfocitebSi.

7

zemoaRniSnuli kidev erTxel xazs usvams imunuri faqtorebis rols

mimnimaluri cvlilebebiT mimdinare nefrozuli sindromis ganviTarebasa da

mimdinareoba (27,28).

amave dros ukanasknel wlebSi, mkvlevarTa sul ufro mzard interess

iwvevs araimunuri faqtorebisa da maT Soris Tirkmlis gorglovani

aparatis iseT umniSvnelovanesi da natifi nawilis ultrastruqturul

cvlilebebi, rogoricaa podociti da subpodocitaluri diafragma.

proteinuriis erT-erT mizezad miCneulia swored podocitebze arsebuli

cilis – podocinis sinTezis darRveva, romlis uxSires mizezs mis

sinTezze pasuxismgebeli genis NPS2 mutacia warmoadgens. am genis

mutaciasTanaa dakavSirebuli autosomur-recesiuli ojaxuri nefrozuli

sindromis ganviTareba, Tumca aRweril iqna am genis sporadiuli mutaciis

SemTxvevebic. dReisaTvis aRmoCenilia 30-mde sxvadasxva mutacia romelsac

ZiriTadad ukavSireben idiopaTiuri nefrozuli sindromis hormono-

rezistentul variantebs, Tumca gavxvdeba hormonomgrZnobiare formebic

(31,32,33).

.

4. klinikuri simptomatika

klinika – daavadeba umetes SemTxvevebSi 6 wlamde asakis bavSvebs

unviTardebaT. mis ZiriTad da xSirad erTaderT klinikur gamovlinebas

SeSupaba warmoadgens. klinikuri manifestacia iwyba maSin, rodesac

avadmyofiis wonis mateba siTxis Sekavebis gamo miaRwevs 5-7%-s. SeSupebis

intensivoba sakmaod variabiluria, Cveulebriv asimetriulia da

damokidebulia avadmyofis sxeulis mdebareobaze. SeiZleba daiwyos

periorbitaluri SeSupebiT, SemdgomSi gavrceldes mTel sxeulze da

ganviTardes anasarka, asciti da hidroToraqsi. vaJebSi xSiria saTesle

parkis SeSupeba, romelic zogjer imdenadaa gamoxatuli, rom siarulis

problemasac qmnis. Zlieri SeSupebisas SeiZleba dairRves kanis mTlianoba,

rac inficirebis saSiSroebas qmnis, ganviTardes striebi. SeSupebis

intensioba damokidebulia proteinuriis xarisxze, Tumca sruli koreqcia

daavadebis am or gamovlinebas Soris ar aRiniSneba. arteriuli wneva

Cveulebriv normaluria, zogjer tendenciaa hipotoniisken (hipovolemiis

gamo). hipertenzia TiTqmis ar gvxvdeba da prognozulad arasasurvel niSans

warmoadgens. amave periodSi vlindeba muclis tkivili, diarea, sunTqvis

ukmarisoba (hidroToraqsis gamo). SeiZleba ganviTardes iseTi garTulebebi

rogoricaa – peritoniti, celuliti, hipovolemia da da sx. Sinagani

organoebis mxriv yuradRebas ipyrobs hepatomegalia.

daavadeba xasiaTdeba morecidive mimdinareobiT. remisia rogorc wesi

viTardeba kortikosteroiduli Terapiis Semdeg, amave dros gvxvdeba misi

spontanurad ganviTarebis (10-12%) SemTxvevebic. gamwvavebebi uxSiresad

dakavSirebulia interkurentul, ZiriTadad ki mwvave respiraciul

daaavadebebTan, Tumca rig SemTxvevebSi gamwvavebis mizezi ucnobi rCeba.

sabolood, 18 wlis asakamde avadmyofTa 95% jansaRdeba. 5%-s SemdgomSic

8

aReniSneba daavadebis recidivebi, Tumca Tirkmlis qronikuli ukmarisobis

ganviTareba praqtikulad ar xdeba (2,5,27,30).

garTulebebi – dakavSirebulia rogorc uSualod nefrozul sindromTan,

ise im mZlavr imunosupresiul TerapiasTan romelic am dros tardeba.

gamohyofen 5 ZiriTad garTulebas (22,34):

1. infeqcia;

2. Tromboembolizmi;

3. hipovolemia;

4. Tirkmlis ukmarisoba (prerenuli);

5. anasarka.

infeqcia nefrozuli sindromis dros antibiotikebisa da

kortikosteroidebis gamoyenebamde sikvdilobis umTavres mizezs

warmoadgenda. igi amJamadac sakmaod xSir da seriozul garTulebad

iTvleba.

infeqciur garTulebebisadmi midrekilebas ganapirobeben Semdegi faqtorebi:

1. IgG dabali done sisxliSi

2. T limfocitaruli sistemis depresia

3. fagocitaruli sistemis depresia

4. transferinis donis Semcireba SratSi

5. imunosupresiuli Terapia.

erT-erT yvelaze xSir infeqciur garTulebas warmoadgens pnevmokokuri

peritoniti, Tumca ar aris gamoricxuli peritoniotis sxva gamomwvevebic

(hemolizuri streptokoki, gramuaryofiTi flora). Dam garTulebaze

yovelTvis unda mivitanoT eWvi, rodesac nefrozuli sindromis

gamwvavebisas aRiniSneba muclis tkivili, cxeleba, defansi. diagnozis

dadastureba xdeba ascituri siTxis baqteriologiuri kvleviT. sxva

garTulebebidan aRsaniSnavia celuliti (wiTeli qari), sefsisi, xangrZlivi

imunosupresiuli Terapiis fonze SeiZleba ganviTardes tuberkulozi.

virusuli infeqciebidan metad mZime mimdinareobiT xasiaTdeba

kortikosteroidebisa da citostatikuri Terapiis fonze ganviTarebuli

Cutyvavila. amave dros aRwerilia daavadebis remisia wiTuras gadatanisas,

rasac endogenuri interferonis gaZlierebuli produqciiT xsnian.

Tromboembolizmi - am garTulebis ganviTareba dakavSirebulia Semdeg

faqtorebTan:

1. hemokoncentracia;

2. xangrZlivi da mkacri woliTi reJimi, gansakuTrebiT anasarkis

pirobebSi;

3. infeqcia;

9

4. antiTronbin III, Tavisufali S proteinis, plazminogenis dakargva

SardTan erTad;

5. hiperfibrinogenemia;

6. Trombocitebis agregaciis momateba.

miuxedavad imisa, rom Tromboemboliuri garTulebebi 2-3%-s ar aRemateba,

isini mainc seriozul problemad rCeba.

am mxriv sayuradReboa Tirkmlis venis embolia romlic klinikurad

vlindeba nefrozuli sindromis fonze ganviTarebuli makrohematuriiT,

welis an muclis tkiviliT. Tu procesi ormxrivia viTardeba Tirkmlis

mwvave ukmarisoba. diagnozis dadastureba xdeba ultrasonografiiT -

Tirkmeli zomaSi matulobs, doplerografiiT ki vlindeba sisxlis nakadis

blokireba Tirkmlis venaSi.

gxvdeba msxvil sisxlZarRvTa, maT Soris – filtvis arteriisa da qveda

kidurebis Rrma venebis Trombozebi. metad iSviaT, magram umZimes

gaTulebebs warmoadgens meningialuri da jorjlis arteriebis Trombozi.

hipovolemia – hipoproteinemiisa da onkozuri wnevis daqveiTebis Sedegia.

igi vlindeba taqikardiiT, periferiuli spazmiT, oliguriiT, gorglovani

filtraciis daqveiTebiT. diaream an diuretikebis gamoyenebam volemiis

aRdgenis gareSe, SeiZleba ganaviTaros arteriuli wnevis vardna da

hipovolemiur Soki.

Tirkmlis ukmarisoba – ar aris dakavSirebuli gorglis dazianebasTan

(daavadebis morfologiuri safuZveli mxolod pedikulebisa da

trabekulebis gasadavebaa), aramed hipovolemiis Sedegad hidrostatiuli

wnevis daqveTebidan gamomdinare, efeqtoruli filtraciuli wnevis

daqveiTebis Sedegia. gorglovani filtraciis daqveiTeba warmavalia da

hipovolemiis koreqciis Semdeg aRdgeba. Aamave dros unda gamoiricxos

Tirkmlis funqciis darRvevis sxva mizezebic, rogorebicaa Tirkmlis

venebis Trombozi, sefsisi, nefrozuli sindromis sxva morfologiuri

variantebi.

anasarka – sakmaod xSirad gvxvdeba. iwvevs respiratorul distress rac

hidroToraqsisa da filtvis SeSupebiT SeiZleba aixsnas. Kkanis mTlianobis

darRveva misi inficirebis risks aZlierebs, xolo sasqeso organoebis

(saTesle parki, sasircxo bageebi) SeSupeba siarulis problemas qmnis. yvela

CamoTvlili problemis koreqcia proteinuriis Semcirebisa

(kortikosteroiduli Terapia) da diuretikebis gamoyenebiT xorcieldeba.

10

5. daavadebis diagnozi

diagnostikuri kriteriumi - nefrozuli sindromi minimaluri

morfologiuri cvlilebebiT aRmoCnda erTaderTi qronikulad mimdinare

glomerulopaTia, romlis diagnoscireba da Sesabamisad mkurnalobis

daniSvna SesaZlebelia Tirkmlis biofsiuri masalis Seswavlis gareSe.

aRniSnulis safuZvels warmoadgens bavSvebSi Tirkmlis daavadebaTa

Seswavlis internacionaluri jgufis monacemebi, romelTa daskvniTac,

hormonomgrZnobiare avadmyofTa 97%-s morfologiurad aReniSnebodaT

minimaluri cvlilebebi (1). Semdgomma kvlevebma daadastura, rom

avadmyofTa es jgufi ZiriTadad warmoadgenda 1-dan 6 wlamde asakis

avadmyofebs, maT ar aReniSnebodaT makrohematuria, hipertenzia da

hipokomplementemia.

zemoaRniSnulidan gamomdinare dReisTvis daavadebis sadiagnozo

kriteriumad iTvleba -

nefrozuli sindromi (proteinuria 40mg/kvm/sT>, hipoalbuminemia- 25g/l,

hiperlipidemia) ganviTarebuli:

1. 1 dan 6 wlamde asakis bavSvebSi;

2. ar aris makrohematuria;

3. ar aris hipertenzia;

4. komplementis C3 da C4 komponentebis done normaluria;

5. Tirkmlis funqcia Senaxulia;

6. remisia viTardeba adeqvaturi kortikosteroiduli Terapiis fonze

(1,27).

diferencialuri diagnozis CamonaTvali:

fokalur-segmenturi glomerulosklerozi, IgM nefropaTia, C1q nefropaTia,

membranuli nefropaTia.

simZimis xarisxi – daavadeba iTvleba mZimed da moiTxovs gadaudebel

hospitalizacias nebismieri, Tundac erTi, zemoaRniSnuli garTulebis

SemTxvevaSi.

6. gamokvlevis sqema

Ppirvel 24 saaTSi:

1. Sardis saerTo analizi;

2. sisxlis saerTo analizi;

3. sisxlis plazmaSi: kreatinini, Sardovana, saerTo cila, albumini,

qolesterini;

11

4. gulmkerdis R-grafia(hidroToraqsze saeWvo SemTxvevebSi);

5. sisxlisa da Sardis baqteriologiuri analizi (cxelebis SemTxvevaSi);

6. sisxlSi eleqtrolitebi;

7. saSarde sistemis ultrasonografia.

pirvel 3 dReSi:

1. cilis 24 saaTiani eqskrecia;

2. komplementis C3 da C4 komponentebis gansazRvra; 3. HBs antigenigeni.

Tirkmlis biofsia (tipiur SemTxvevebSi ar tardeba)

biofsiis Cvenebebia:

1. avadmyofebi 1 wlamde da 10 wlis zeviT

2. makrohematuria

3. persistirebadi hipertenzia

4. Tirkmlis ukmarisoba (garda warmavali, prerenuli, hipovolemiuri

genezis ukmarisobisa)

5. hipokomplementemia

6. steroidrezistentoba (22,27)

7. mkurnalobis sqema

daavadebis mkurnalobis mizans warmoadgens:

1. remisiis miRweva da misi maqsimaluri gaxangrZliveba;

2. rogorc daavadebis, ise mkurnalobis Sedegad ganviTarebuli

garTulebebis Tavidan acileba.

reJimi – woliTi reJimi ar aris naCvenebi, Tu is ar aris nakarnaxevi raime

garTulebiT. unda gvaxsovdes, rom xangrZlivi wola da moZraobis SezRudva

zrdis Tromboemboliuri garTulebebis risks.

dieta - SeSupebis periodSi izRudeba mxolod sufris marili (1 gramamde

dReSi). cilis SezRudva an Warbi miReba ar aris rekomendirebuli. remisiis

perioodSi dieta ar iniSneba. gamonakliss warmoadgens romelime

konkretuli produqtis SezRudva, romlisadmi avadmyofs aReniSneba

alergiuli reaqcia (30).

12

kortikosteroiduli Terapia

ukve naxevar saukuneze metia, rac kortikosteroiduli Terapia warmoadgens

daavadebis bazisur mkurnalobas. miuxedavad imisa, rom mkurnalobis am

meTods xangrZlivi istoria aqvs, optimaluri sqemis Zieba dResac

grZeldeba. amasTan isic unda aRiniSnos, rom kortikosteroidebi sakmaod

efeqturia daavadebis remisiis misaRwevad, Tumca ar hkurnaven mas.

nefrozuli sindromis pirveli epizodi:

standartuli mkurnaloba (1,2):

prednizoloni

60mg/m2/dReSi (absoluturi maqsimumi 80mg) 1 an 3 miRebaze - 6 kvira

40mg/m2/dRegamoSvebiT 1 miRebaze diliT - 6 “__”

am sqemis gamoyenebiT avadmyofTa 90% gadis remisiaSi, Tumca SemdgomSi maT

60%-s aReniSnebaT recidivebi pirveli 10 Tvis ganmavlobaSi. SemdgomSi

daxlovebiT 20%-s aReniSnebaT iSviaTi recidivebi, xolo 40%-ze mets

unviTardebaT xSiradmorecidive an hormonodamokidebuli nefrozuli

sindromi (3).

davadebis Semdgomi recidivebis Semcirebis mizniT mowodebulia

kortikosteroiduli Terapiis ufro xangrZlivi kursi, romelic avtorTa

gadmocemiT ar zrdis mkurnalobis gverdiT efeqts (4):

prednizoloni

2mg/kg/dReSi 4 kvira

1.5mg /kg/dRegamoSvebiT 8 “__”

1mg/kg/dRegamoSvebiT 8 “__”

0.5mg/kg/dRegamoSvebiT 8 “__”

Tu pirveli 4 kviris ganmavlobaSi ar ganviTarda remisia mowodebulia

meTilprednizolonis gamoyenaba 20-30mg/kg (maqsimum 1000mg) 3 dRis

ganmavlobaSi an dRegamoSvebiT (21).

daavadebis recidivis mkurnaloba

recidivis SemTxvevaSi avadmyofTa 10-20% gadis spontanur remisiaSi (5).

amitom ar unda viCqaroT kortikosteroidebis daniSvna. Aavadmyofi unda

gvyavdes mxolod dakvirvebis qveS raTa ar gamogveparos raime garTuleba.

am periodSi SesaZlebelia CavataroT mxolod siptomuri Terapia (umarilo

dieta, diuretikebi).

13

raime garTulebis SemTxvevaSi an 2-3 kviriani uSedego simptomuri

mkurnalobis Semdeg iniSneba:

I -sqema

prednizoloni

60mg/kv/m an 2mg/kg yoveldRe remisiamde + 3 dRe

40mg/kvm an 1,5mg/kg dRegamoSvebiT, 1 miRebaze – 4 kvira.

aRniSnuli sqema sakmaod efeqturia iSviaTi recidivebis SemTxvevaSi (6).

xSiradmorecidive da gansakuTrebiT hormonodamokidebul variantebSi

mowodebulia Semdegi sqema.

II-sqema

prednizoloni:

40-60mg/kvm yoveldRe remisiamde + 5 dRe

15-20mg/kvm dRegamoSvebiT – 12-18 Tve

am SemTxvevaSi SemanarCunebel dozad SeiZleba gamoviyenoT prednizolonis

is minimaluri doza romlis dros xdeboda gamwvaveba .(7,8).

xangrZlivi kortikosteroiduli Terapiis ZiriTadi garTulebebia:

1. zrdaSi CamorCena – vlindeba ZiriTadad yoveldRiuri miRebis reJimisas.

preperatis dRegamoSvebiT miReba praqtikulad ar iwvevs am garTulebas

(9);

2. kataraqta – moiTxovs ofaTalmologis periodul kontrols;

3. Warbi wona – steroiduli Terapiis moxsnis Semdeg xSirad ubrundeba

normas, Tumca SeiZleba mozrdil asakSic gahyves;

4. Zvlebis demineralizacia, romelic ase xSiria mozrdilebSi, bavSvebSi

TiTqmis ar gvxvdeba (10).

citotoqsiuri Terapia

citostotoqsiuri Terapia iniSneba xSiradmorecidive da hormonodamo-

kidebuli nefrozuli sindromis dros, rodesac gamoxatulia

steroidtoqsiuroba. preparatebi mniSvnelovad zrdian remisiis

xangrZlivobas (11), Tumca axasiaTebT seriozuli gverdiTi movlenebi da

maTi daniSvna unda moxdes avadmyofis individualuri TaviseburebaTa

gaTvaliswinebiTa da mSoblebTan SeTanxmebiT.

14

ciklofosfamidi – iniSneba 2-2,5 mg/kg 8 kvira xSiradmorecidive da 12

kvira hormonodamokidebul variantebSi (mkurnalobis dawyebamde sasurvelia

Tirkmlis biofsia). aRniSnuli mkurnaloba iZleva remisiis gaxangrZlivebas

1 wlamde avadmyofTa 69%-Si da 5 wlian remisias (12). Uunda vecadoT, rom

preparatis sumaruli doza ar aRematebodes 200mg/kg. am SemTxvevaSi

ciklofosfamidis toqsiuri moqmedeba umniSvneloa (13).

preparatis daniSvnamde tardeba prednizoloniT mkurnaloba – 60mg/kvm

remisiamde +3 dRe. Semdeg iniSneba ciklofosfamidi 2-2,5mg/kg. 2-3 Tve.

prednizoloniT mkurnaloba grZeldeba Semdegi sqemis mixedviT:

I-IVkvira – 60mg/kvm dRegamoSvebiT

V kvira – 40mg/kvm “----------------------“

VI kvira – 30mg/kvm “---------------------“

VII kvira – 20mg/kvm “----------------------“

VIII kvira – 10mg/kvm “----------------------“

ciklofosfamidiT mkurnalobis gagrZelebis SemTxvevaSi, grZeldeba

prednizoloniT mkurnalobac (10mg/kvm.). aqve unda aRiniSnos isic, rom aris

monacemebi mkurnalobis 8 da 12 kviriani kursis msgasi efeqturobis Sesaxeb

(14).

qlorambucili iniSneba 0,2 mg/kg 8 kvira prednizolonTan erTad da misi

efeqturoba utoldeba ciklofosfamidisas (15), Tumca am SemTxvevaSi

garTulebebis riski metia (16).

citotoqsiuri Terapiis garTulebebia (9):

1. leikopenia da masTan dakavSirebuli infeqciebi – leikocitebis donis

Semcireba 3000 mm3–mde da limfocitebisa 1000 mm3-mde moiTxovs

mkurnalobis Sewyvetas am parametrebis gamosworebamde.

zemoaRniSnuli moiTxovs sisxlis saerTo analizis kontrols kviraSi

erTxel;

2. gonadotoqsiuroba – iwvevs uSvilobas Tu ciklofosfamidisa da

qlorambucilis sumarulma dozam gadaaWarba Sesabamisad 168 mg/kg da 8

mg/kg (17);

3. alopecia – swordeba mkurnalobis CaTavebis Semdeg;

4. krunCxva – metad iSviaTi garTulebaa;

5. hemoragiuli cistiti – rekomendirebulia siTxiT datvirTva.

15

imunomodulaciuri Terapia

levamizoli _ iniSneba xSiradmorecidive da hormonodamokidebul

variantebis dros remisiis gaxangrZlivebis mzniT, 2,5 mg/kg (maqsimum 150mg)

dRegamoSvebiT 12 Tvis ganmavlobaSi. Ppreparati prednizolonis TandaTan

moxsnis saSualebas iZleva. Tumca levamizolis moxsnas xSirad Tan sdevs

daavadebis gamwvaveba (18).

mkurnalobis metad iSviaT, magram seriozul garTulebad SeiZleba

CaiTvalos neitropenia. aRniSnuli moiTxovs sisxlis saerTo analizis

mudmiv kontrols.

seleqtiuri imunosupresantebi

ciklosporini _ efeqturia xSiradmorecidive an hormonodamono-

damokidebuli formebis dris. axangrZlivebs remisias. iniSneba 5-6 mg/kg an

150mg/kvm prednizolonis SemanarCunebel dozasTan (0,25mg/kg) erTad an mis

gareSe (prednizolonis moxsna SesaZlebelia mkurnalobis dawyebida 3 Tvis

Semdeg.). mkurnalobis dros preparatis koncentracia sixlSi unda

meryeobdes 100-200 nanogr/ml. mkurnalobis xangrZlivobaa 6-dan 18 Tvemde.

amave dros preparatis moxsnis Semdeg daavadeba sakmaod mokle periodSi

mwvavdeba (19).

preparati gamoirCeva nefrotoqsiurobiTa da hepatotoqsiurobiT, rac

moiTxovs periodulad kreatininisa da RviZlis izofermentebis kvlevas.

mkurnalobis dawyebidan 1-1,5 wlis Semdeg mowodebulia Tirkmlis biofsia.

aqve unda aRiniSnos, rom multicentrulma, randomizebulma kvlevam aCvena

ciklofosfamidis upiratesoba, xSiradmorecidive da hormonodamokidebul

bavSvebSi (20).

simptomuri Terapia

dehidrataciuli Terapia (5,22) – aucilebelia wonis yoveldRiuri

kontroli. Tu avadmyofis wonis namati ar aRemateba 5%-s, izRudeba mxolod

sufris marili. miRebuli siTxis raodenoba ar unda aRematebodes 1

l/kvm/24sT., an gamoyofili Sardis raodenobas damatebuli siTxis

eqxtrarenuli danakargi (300-400ml.).

Tu avdmyofis wonis namati aRemateba 5%-s, iwyeba medikamenturi

dehidratacia., romelic moiTxovs garkveul sifrTxiles hipovolemiis

SesaZlo gaZlierebis TvalsazrisiT.

diuretikebidan SeiZleba dainiSnos:

1. furosemidi 1-2mg/kg dReSi 2 miRebad;

2. spirolaqtoni 5-10mg/kg (maqsimum 200mg) dReSi 2 miRebad;

3. hidroqlorTiazidi 2mg/kg (maqsimum 100mg).

16

albuminis ifuzia - ar iniSneba hipoalbuminebmiis koreqciisaTvis.

misi daniSvnis Cvenebebia:

1. .hipovolemia cirkulatoruli darRvevis niSnebiT – 4,5% albumini

20ml/kg 30-60 wuTis ganmavlobaSi. saWiroebis SemTxvevaSi manipulacia

SeiZleba ganmeordes;

2. diuretikrezistentuli SeSupeba – intravenurad 20% albumini 5ml/kg 4

saaTis ganmavlobaSi. gadasxmidan 2 da 4 saaTis Semdeg emateba

furosemidi 1mg/kg.

mikrobuli infeqcia - profolaqticuri antimikrobuli Terapia ar aris

miRebuli. Pperitonitis, kanis an saSarde gzebis infeqciisas saWiroa

dauyovnebliv gamoviyenoT penicilinis naxevradsinTezuri analogebi an

cefalosporinebi. remisiis dros mizanSewonilia CavataroT vaqcinacia

pnevmokokis sawinaaRmdegod (PPV23

virusuli infeqcia – mniSvnelovan problemas warmoadgens Cutyvavila,

gansakuTrebiT Tu is citostatikuri Terapiis fonze ganviTarda. am

SemTxvevaSi unda Sewydes citostatikis gamoyeneba, prednizoloni

ganaxevrdes, unda gamoviyenoT Cutyvavilis imunoglobulini 3 dRis

ganmavlobaSi, an acikloviri (600mg/kvm) 10 dRis ganmavlobaSi (8,23).

antiTrombuli Terapia – profilaqtikuri mizniT ar tardeba.

antiTrombuli Terapiis Cvenebebia: albuminis done < 20g/l-ze, fibrinogenis

koncentracia > 6g/l-ze, antiTrombin III-is donis daqveiTeba 70%-iT (24).

SeiZleba gamoyenebul iqnes varfarini, aspirinis dabali dozebi,

dipiridamoli. amave dros am preparatebis profilaqtikur efeqtze

sarwmuno, monacemebi ar arsebibs (8).

kalciumi da D vitamini - gamoiyeneba osteoporozis sawinaaRmdegod maRali

proteinuriisa da xangrZlivi kortikosteroiduli Terapiis dros

(kalciumi-500mg, D vitamini- 2000-4000 erT. dReSi), Tumca am mkurnalobis

dadebiTi efeqti ar aris dadasturebuli (8).

paTogenezuri mkurnalobis Tanamimdevrioba

britaneTis pediatr nefrologTa asociaciis mier mowodebuli,

steroidmgrZnobiare nefrozuli sindromis, paTogenezuri mkurnalobis

sqema (25).

17

paTogenezuri mkurnalobis Tanamimdevroba

1. daavadebis I epizodi prednizolonis

standartuli sqema

2. iSviaTi recidivi recidivis mkurnalobis I

sqema

3. xSiri recidivebi recidivis mkurnalobis II

sqema

4. gamwvaveba prednizoloni >0.5mg/kg

levamizoli

2.5 mg/kg/ d g12-18 Tve

5. gamwvaveba - levamizoli

an prednizoloni >1.0mg/kg/48sT erTxel

ciklofosfamidi

2.5 mg/kg/dRe 8 kvira.

6. Pciklofosfamidis

Semdeg gamwvaveba

Precidivis mkurnalobis I

an II sqema.

7. prednizolonis

gamwvaveba > 0.5 mg/kg/ 48sT OerTxel

ciklosporini 5 mg/kg 1

weli an qlorambucili 0,2mg/kg

8 kvira

.

18

8. reabilitacia/meTvalyureoba

avadmyofi moiTxovs mudmiv ambulatoriul meTvalyureobas, rogorc

remisiisas, ise imunosupresiuli Terapiis dros, SesaZlo garTulebebis

Tavidan asacileblad.

xangrZlivi kortikosteroiduli Terapiisas – arteriuli wnevis, wonisa da

simaRlis kontroli, ofTalmologis konsultacia (kataraqtis

gamosaricxad) mkurnalobis dawyebidan 1 Tvis da 1 wlis Semdeg.

citostatikebiT mkurnalobisas (ciklofosfamidi, qlorambucili) –

sisxlis saerTo analizi kviraSi erTxel.

mSobeli informirebul unda iyos daavadebis arsis, mimdinareobis

Taviseburebebisa da garTulebebis Sesaxeb. Amas unda SeeZlos SardSi

proteinuriis gansazRvra stripis meSveobiT da Sedegebis dafiqsireba

Sesabamis dRiurSi.

sayuradReboa, rom xangrZlivi kortikosteroiduli Terapia garda sufTa

somatur iatrogeniisa, qmnis kosmetikur problemebsac (simsuqne, striebi,

mTvarisebri saxe, WarbTmianoba). aRniSnuli arc Tu iSviaTad uqmnis

avadmyofs arasrulfasovnebis kompleqss da problemebs tolebTan

urTierTobisas. Ees garemoeba moiTxovs am avadmyofTa ara marto somatur

aramed fsiqologiur reabilitaciasac.

remisiis ganviTarebis Semdegac avadmyofi 5 wlis ganmavlobaSi imyofeba

ambulatoriuli meTvalyureobis qveS.

9. gaidlainis gadasinjvis da ganaxlebis vada _ 2 weli.

10. gaidlainis miRebis xerxi/wyaro

gaidlaini miRebulia sxvadasxva gaidlainebis, monografiebisa da

saerTaSoriso JurnalebSi gamoqveynebuli statiebis SejerebiT.

11. alternatiuli gaidlaini ar arsebobs

12. gamoyenebuli literatura

1. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 1981; 98:561. A I;

2. Brodehl, J. The treatment of minimal change nephrotic syndrome: lessons learned from multicentre cooperative studies. Eur J Pediatr 1991; 150:380. A I

3. Tarshish, P, Tobin, JN, Bernstein, J, Edelmann, CM Jr. Prognostic significance of the early course of minimal changes nephrotic syndrome: Report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 1997; 8:769;

19

4. Hodson, EM, Knight, JF, Willis, NS, Craig, JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2003; :CD001533. A I;

5. Scharer K; WingerA.M.Therapie des Nephrotischen Syndroms in Kindersalter. Deutsches Arztblat-Seite 835-944/Mai 1992 B II;

6. Early identification of frequent relapsers among children with minimal change nephrotic syndrome. A report of the International Study of Kidney Disease in Children. J Pediatr 1982; 101:514. A I;

7. Broyer, M, Meyrier, A, Niaudet, P, Habib R. Minimal changes and focal and segmental glomerular sclerosis. In: Oxford Textbook of Clinical Nephrology, Cameron, JS, Davison, MA, Grünfeld, JP, et al (Eds), Oxford Medical Publications, 1992, p.29 8.Patrick Niaudet, MD Treatment of idiopathic nephrotic syndrome in children. Updates The literature review for version 15.2 is current through April 2007; A I;

8. Polito, C, Oporto, MR, Totino, SF, et al. Normal growth of nephrotic children during long-term alternate-day prednisone therapy. Acta Paediatr Scand 1986; 75:245. C III 10.Leonard, MB, Feldman, HI, Shults, J, et al. Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med 2004; 351:868;

9. Immunosuppressive agents in childhood nephrotic syndrome: A meta-analysis of randomized controlled trials. Anne M Durkan, Elisabeth M Hodson, Narelle S Willis and Jonathan C Craig. Kidney Int 59: 1919-1927; doi:10.1046/j.1523-1755.2001. A I;

10. Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome in childhood. Lancet 1970; 2: 479-482. C III;

11. Trompeter, R. S., Hicks, J., Lloyd, B. W., White, R. H. R., and Cameron, J. S. (1985). Long term outcome for children with minimal change nephrotic syndrome. Lancet i ,368–370;

12. Ueda, N., Kuno, K., and Ito, S. (1990). Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Archives of Disease in Childhood 65 , 1147–1150 C III;

13. Baluarte, HJ, Hiner, L, Gruskin, AB. Chlorambucil dosage in frequently relapsing nephrotic syndrome: A controlled trial. J Pediatr 1978; 92:295 B II;

14. Müller, W. and Brandis, M. (1981). Acute leukemia after cytotoxic treatment for non malignant disease in childhood. European Journal of Pediatrics 136 , 105–108.C III;

15. Watson, AR, Rance, CP, Bain, J. Long-term effects of cyclophosphamide on testicular function. Br Med J 1985; 291:1457 C III;

16. Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology. Lancet 1991; 337:1555. C III;

17. Niaudet, P, Habib, R. Cyclosporine in the treatment of idiopathic nephrosis. J Am Soc Nephrol 1994; 5:1049;

18. Ponticelli, C. et al . (1993a). Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrology, Dialysis, Transplantation 8 , 1326–1332. A I;

19. Murnaghan, W. M., Vasmant, D., and Bensman, A. (1984). Pulse methylprednisolone therapy in severe idiopathic childhood nephrotic syndrome. Acta Paediatrica Scandinavica 73 , 733–739. C III;

20. Nottingem Pediatric Guideline N6.1, Nephrotic Syndrome; 21. Goldstein, SL, Somers, MJ, Lande, MB, et al. Acyclovir prophylaxis of varicella in children with

renal disease receiving steroids. Pediatr Nephrol 2000; 14:305. C III;

20

22. McBryde, K. D., Kershaw, D. B., and Smoyer, W. E. (2001). Pediatric steroid-resistant nephrotic syndrome. Current Problems in Pediatric Adolescence Health Care 31, 280–307;

23. Report of a Workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians. Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Arch Dis. child 1994; 70: 151-157 B I;

24. Laurent, J., Rostoker, G., Robeva, R., Bruneau, C., and Martin-Govantes, J. (1987). Is adult idiopathic nephrotic syndrome food allergy? Nephron 47 , 7–11;

25. M, Meyrier, A, Niaudet, P.Minimal changes and focal and segmental glomerular sclerosis. In: Oxford Textbook of Clinical Nephrology, Cameron, JS, Davison, MA, Grünfeld, JP, et al (Eds), Oxford Medical Publications, 2005;

26. Araya CE, Wasserfall CH, Brusko TM, Mu W, Segal MS, Johnson RJ, et al. A case of unfulfilled expectations. Cytokines in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol. May 2006;21(5):603-10;

27. Holdsworld S.R., Atkins R.C. Pathogenesis of glomerulonefritis. In Textbook of Renal Disease.Edited by J.A.Whitworth.1994;

28. m.gelovani, g.megreliSvili `glomerulopaTia bavSvTa asakSi~ –

Tbilisi, 1988;

29. Antignanac C. Genetic models: clues for understanding the pathogenesis of idiopathic nephritic syndrome. J Clin Invest, February 2002,V.109,N4,447-449;

30. Garidi G., Bertlli R., Di luca M. Broadening the Spectrum of Diseases Related to Podocin Mutations. J Am Soc Nephrol 14:1278-86,2003;

31. kvirkvelia d., Citaia g., canava m., abulaZe T., Citaia n. idiopaTiuri

nefrozuli sindromis mkurnalobisa da prognosis kliniko-genetikuri

aspeqtebi. Tssu samecniero Sromebis krebuli, tomi XLI, Tbilisi,

2005/2006, 187-190; 32. Patrick Niaudet, MD. Complications of idiopathic nephrotic syndrome in children. The literature

review for version 15.2 is current through April 2007; 33. Robert C. Kelsch and Aileen B. Sedman Nephrotic Syndrome Pediatr. Rev., Jan 1993; 14: 30 –

38; 34. Karl S. Roth, Barbara H. Amaker, and James C.M. Chan Nephrotic Syndrome: Pathogenesis and

Management. Pediatr. Rev., Jul 2002; 23: 237 – 248.

12. avtorTa jgufi:

sasqarTvelos pediatr-nefrologTa asociacia

⇒ daviT kvirkvelia _ Tssu g.Jvanias saxelobis sauniversiteto

pediatriuli klinikis pediatriuli departamentis

xelmZRvaneli, medicinis doqtori;

⇒ guram Citaia – med. mecn. doqtori, profesori, g. Jvanias sax.

sauniversiteto pediatriuli klinikis nefrologiis

ganyofilebis gamge;

21

⇒ medea canava –g.Jvanias sax. sauniversiteto pediatriuli

klinikis nefrologiis ganyofilebis ordinatori; medicinis

doqtori;

⇒ Tamar abulaZe _ g.Jvanias sax. sauniversiteto pediatriuli

klinikis nefrologiis ganyofilebis ordinatori; medicinis

doqtori.

eqspertebi:

⇒ saojaxo medicinis profesionalTa kavSiri _ irina qarosaniZe;

⇒ irma WoxoneliZe _ saqarTvelos dializis, nefrologiisa da

Tirkmlis transplantaciis kavSiris Tavmjdomare; urologiis

erovnuli centris nefrologiuri ganyofilebis gamge; med.

mecn. kandidati, Tssu Sinagan sneulebaTa departamentis

asistent-profesori nefrologiaSi;

⇒ lela woworia _ saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis saministros janmrTelobis dacvis

departamenti;

⇒ Tea TavidaSvili _ saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis saministros janmrTelobis dacvis

departamenti.