Focal segmental glomerulosclerosis (FSGS) yog qhov ua rau mob raum thoob ntiaj teb. Lub putative etiology ntawm thawj FSGS yog plasma yam nrog reactivity rau immunosuppressive therapy thiab kev pheej hmoo ntawm rov tshwm sim tom qab hloov raum. Adaptive FSGS yog txuam nrog ntau dhau nephron loading vim lub cev loj, txo nephron muaj peev xwm, los yog ib leeg glomerular hyperfiltration txuam nrog tej yam kab mob.
Introduction
Focal segmental glomerulosclerosis yog qhov ua rau glomerular ua rau lub raum tsis ua haujlwm. Nws hais txog cov duab histological uas qhia txog 6 qhov ua tau hauv qab etiologies, sib qhia cov ntsiab lus ntawm contusion thiab podocyte depletion.
Kev kuaj mob ntawm focal segmental glomerulosclerosis yog nyob ntawm kev kho mob keeb kwm kev koom ua ke(Cov kab mob hauv tsev neeg, keeb kwm ntawm kev yug me nyuam, qhov hnyav tshaj plaws thiab lub cev hnyav, kev siv tshuaj), kev soj ntsuam kuaj pom (serum albumin, zis protein, thiab viral serologies) thiab lub raum histopathology. Proteinuria tej zaum yuav nyob rau hauv nephrotic los yog subnephrotic ntau yam. Kev tshem tawm lwm cov kab mob hauv lub cev lossis thawj lub raum pathologies uas tuaj yeem ua rau muaj qhov kev nthuav qhia zoo sib xws yog qhov tseem ceeb.
Kev kis mob thiab lub nra thoob ntiaj teb
Qhov kev nthuav dav ntawm focal segmental glomerulosclerosis, piv nrog rau lwm qhov kev kuaj mob ntawm cov kab mob zoo sib xws, tau nce thoob ntiaj teb. Txawm li cas los xij, qhov tshwm sim tiag tiag thiab qhov tshwm sim yog qhov nyuaj rau kev txheeb xyuas tau muab qhov kev hloov pauv loj thoob ntiaj teb hauv kev qhia, muaj, thiab kev txhawb nqa pathologic rau lub raum biopsy.
Kev tshuaj xyuas cov ntaub ntawv luam tawm thoob ntiaj teb tau ua tiav, uas qhia tau tias qhov xwm txheej txhua xyoo yog nyob nruab nrab ntawm 0.2 txog 1.8 rau 100,000 tus neeg nyob hauv ib xyoos. Qhov nruab nrab qhov tshwm sim yog 2.7 tus neeg mob ib lab. Muaj ib qho tseem ceeb ntawm haiv neeg thiab haiv neeg predisposition. Tsis tas li ntawd, cov tsos mob ntawm lub raum tsis ua haujlwm hauv cov poj niam tsis tshua muaj suab ntau dua li cov txiv neej.
Typology
Kev faib tawm ntawm focal segmental glomerulosclerosis yog ntau yam. Nws suav nrog pathophysiological, histological thiab caj ces yam. Thaum pib, FSGS tau muab faib ua thawj (idiopathic) thiab cov ntawv thib ob. Cov tom kawg suav nrog tsev neeg (genetic), kab mob sib txuas, ntsig txog tshuajinduced forms.
Cov lus qhia kho mob rau focal segmental glomerulosclerosis tuaj yeem xa mus rau qhov sib txawv ntawm histological, feem ntau yog cov glucocorticoid reactivity ntawm lub taub qhov txhab thiab qhov hnyav, inexorable xwm ntawm kev sib tsoo variants.
6 daim ntawv kho mob
Kev sib txuas cov noob caj noob ces, cov kab mob pathophysiological, keeb kwm kho mob, thiab cov lus teb rau kev kho mob, nws tsim nyog rau pab pawg FSGS ua rau rau daim ntawv kho mob. Lawv suav nrog:
- primary;
- adaptive;
- siab genetic;
- viral-mediated;
- drug-related;
- APOL1-related.
Histopathology ntawm tus kab mob
Cov tsos mob tsawg kawg ntawm glomerulonephritis hauv cov neeg laus yog tshwm sim los ntawm qhov tsis muaj qhov caws pliav tubulointersittal. Cov kab mob taub hau yog focal adhesion ntawm glomerular fascicle mus rau Bowman's capsule nyob ze ntawm qhov sib thooj tubule take-off.
Qhov kev hloov pauv feem ntau yog tsoo. Ib qho piv txwv tshwj xeeb tuaj yeem raug soj ntsuam nyob rau hauv qhov chaw ntawm endothelial tubulo-reticular inclusions pom ntawm kev tsom xam ultrastructural. Lawv tuaj yeem pom hauv cov xeev siab ntawm interferons, suav nrog kev kis kab mob. Kev hloov pauv tus kab mob tsawg kawg nkaus thiab kev koom tes nrog cov lus qhia yog qhov ua tau zoo tshaj plaws thiab tsis tshua muaj kev vam meej, thiab glomerulopathies ploj mus uas tiv taus kev kho mob thiab kev loj hlob sai.
Kim qhia tias muaj mob
Cov tsos mob thiab cov tsos mobglomerulonephritis nyob rau hauv cov neeg laus nyob ntawm seb muaj ib tug mob los yog mob ntev. Lawv suav nrog:
- cov zis liab lossis xim av xim vim muaj cov qe ntshav liab ntau ntxiv (hematuria).
- tso zis ntau dhau vim muaj protein ntau (proteinuria).
- ntshav siab (hypertension).
- Kev tuav kua dej (edema). tshwm rau ntawm lub ntsej muag, caj npab, ceg thiab plab.
cais cov tsos mob ntawm lub raum tsis ua haujlwm hauv cov poj niam:
- Txo cov zis tso zis.
- dej tuav ua rau ceg o.
- ua tsis taus pa.
- Nyob.
- Nkauj siab.
- Ntaus.
- Tsis muaj zog.
- lub plawv dhia tsis xwm yeem.
- mob raum thaj chaw.
- Fooning lossis coma thaum mob hnyav.
Txoj hauv kev kom paub meej FSGS
thawj zaug yog kuaj zis rau lub raum. Nws suav nrog ob qhov kev xeem:
- Ratio ntawm albumin rau creatinine. albumin ntau dhau hauv cov zis yog ib qho cim ntxov ntawm lub raum puas. Peb qhov txiaj ntsig zoo hauv peb lub hlis lossis ntau dua yog qhov qhia tias muaj mob.
- Globular pom tus nqi. Cov ntshav raug kuaj rau cov khoom pov tseg hu ua creatinine. Nws los ntawm cov leeg nqaij. Thaum lub raum puas lawm, muaj teeb meem tshem creatinine los ntawm cov ntshav. Cov txiaj ntsig kev xeem no yog siv rau hauv cov qauv lej nrog hnub nyoog, haiv neeg thiab poj niam txiv neej kom paub qhov glomerular filtration rate.
Qhov laj thawj tseem ceeb
Cov xwm txheej uas tuaj yeem ua rau moblub raum glomerulus yog:
- Kab mob sib kis. Glomerulonephritis tuaj yeem tsim 7-14 hnub tom qab kab mob ntawm daim tawv nqaij (impetigo) lossis kab mob streptococcal ntawm caj pas. Txhawm rau tawm tsam lawv, lub cev raug yuam kom tsim ntau cov tshuaj tiv thaiv kab mob ntxiv uas tuaj yeem nyob rau hauv lub glomeruli thaum kawg, ua rau mob.
- Kab mob endocarditis. Cov kab mob tuaj yeem kis tau los ntawm cov hlab ntsha thiab nkag mus nyob hauv lub plawv, ua rau muaj kab mob ntawm ib lossis ntau lub plawv li qub. Cov kab mob endocarditis yog txuam nrog cov kab mob glomerular, tab sis kev sib raug zoo ntawm ob yog tsis meej.
- kis kab mob. Human immunodeficiency virus (HIV), kab mob siab B thiab C tuaj yeem ua rau mob.
- Lupus. Tej zaum yuav cuam tshuam rau ntau lub cev thiab qhov chaw ntawm lub cev, suav nrog cov qe ntshav, tawv nqaij, ob lub raum, lub plawv, pob qij txha, thiab lub ntsws.
- Goodpasture's syndrome. Qhov no yog ib hom kab mob ntsws tsawg uas ua rau mob ntsws. Nws tuaj yeem ua rau glomerulonephritis thiab los ntshav hauv lub ntsws.
- Nephropathy. Tus kab mob glomerular tseem ceeb no tshwm sim los ntawm cov deposits ntawm immunoglobulin nyob rau hauv lub glomeruli. Tej zaum yuav vam meej mus ntau xyoo yam tsis muaj tsos mob tshwm sim.
xov xwm ntxiv
Cov kab mob ntxiv muaj xws li:
- polyarteritis. Daim ntawv no ntawm vasculitis cuam tshuam rau cov hlab ntsha me thiab nruab nrab. Paub tias Wegener's granulomatosis.
- ntshav siab. Lub raum ua haujlwm raug txo. Lawv ua cov sodium zuj zus.
- Focal segmental glomerulosclerosis. Nws yog tus cwj pwm los ntawm diffuse caws pliav ntawm qee qhov glomeruli. Tus mob no tej zaum yuav tshwm sim los ntawm lwm tus kab mob los yog tej zaum yuav tshwm sim vim tsis paub.
- mob raum mob raum (diabetic nephropathy).
- Alport Syndrome. keeb kwm daim ntawv. Nws kuj tseem yuav ua rau tsis hnov lus lossis tsis pom kev.
- Multiple myeloma, ntsws cancer thiab chronic lymphocytic leukemia.
Mechanism of disease
Focal segmental glomerulosclerosis yog ib hom mob sib txawv uas tshwm sim tom qab raug mob podocyte rau ntau yam laj thawj. Qhov chaw ntawm kev puas tsuaj txawv:
- ncig yam khoom;
- genetic anomalies;
- kis kab mob;
- tshuaj kho mob.
Rau feem ntau, kev sib cuam tshuam ntawm cov tsav tsheb no tsis meej thiab nyuaj. Piv txwv li, adaptive FSGS suav nrog ob qho tib si podocyte kev nyuaj siab (tsis sib haum xeeb ntawm glomerular load thiab glomerular muaj peev xwm) thiab genetic susceptibility.
Podocyte kev puas tsuaj los ntawm txhua hom FSGS (lossis los ntawm lwm cov kab mob glomerular) pib cov txheej txheem ua rau mob nephritic syndrome. Muaj kev poob zuj zus ntawm cov podocytes puas rau hauv qhov chaw tso zis. Txhawm rau sib npaug qhov tsis txaus, cov hlwb no them nyiaj los ntawm hypertrophy los ntawm txheej txheej ntawm glomerular capillaries.
Hauv kev hloov pauv FSGS, glomerular hypertrophy tshwm sim thaum ntxov ntawm tus kab mob. Hauv lwm hom, glomerular hypertrophy tshwm sim nrog kev poob ntawm nephron. Qhov no ua rau muaj kev ntxhov siab ntxivthiab tam sim no nyob rau hauv qhov seem glomeruli ntawm patent.
Cov ntu hauv qab no tham txog cov txheej txheem pathological, kev kho thiab kev kho mob ntawm focal segmental glomerulosclerosis.
Primary FSGS
suav nrog cov noob caj noob ces, kab mob thiab tshuaj-txog FSGS. Cov txheej txheem ntawm kev raug mob podocyte cuam tshuam nrog kev cuam tshuam, tejzaum nws yog cytokine, uas ua rau cov neeg mob raug mob. Qhov no yog hom kab mob feem ntau hauv cov hluas thiab cov hluas. Nws feem ntau cuam tshuam nrog nephrotic-series proteinuria (qee zaum loj), txo qis ntshav albumin qib, thiab hyperlipidemia.
Tam sim no, thawj FSGS tau kho nrog cov tshuaj tiv thaiv kab mob. Cov no yog glucocorticoids thiab calcineurin inhibitors uas ncaj qha hloov kho cov phenotype ntawm podocyte. Kev rov tshwm sim FSGS tseem yog qhov teeb meem kho mob. Tsuas yog ib qho ntawm 77 thawj lub raum biopsies nyob rau hauv cov neeg mob uas tom qab relapsed pom ib tug perihilar variant. Kev kho ntshav plasma tuaj yeem ua rau muaj kev tshem tawm ib ntus.
Adaptive FSGS
tshwm sim tom qab lub sijhawm glomerular hyperfiltration ntawm qib nephron thiab post-pathophysiology kub siab. Cov xwm txheej uas cuam tshuam nrog nws txoj kev loj hlob suav nrog:
- kab mob cyanotic mob plawv;
- sickle cell anemia;
- obesity;
- androgen tsim txom;
- pw tsaug zog apnea;
- noj zaub protein ntau.
Lub sijhawm ntawm ib leeg-nephron glomerularhyperfiltration feem ntau yog ntsuas ntau xyoo ua ntej glomerulosclerosis zuj zus. Adaptive FSGS ua rau muaj kev vam meej ntawm glomerular hypertrophy, kev ntxhov siab thiab kev qaug zog, thiab kev tso tawm ntau dhau ntawm extracellular matrix hauv glomerulus. Lub raum biopsy nta txhawb kev kuaj mob muaj xws li loj glomeruli, predominance ntawm perigillar nti uas qhia txog kev hloov pauv sclerotic. Cov yam ntxwv kho mob suav nrog cov ntshav albumin ib txwm, uas tsis tshua muaj tshwm sim hauv thawj FSGS.
Genetic FSGS
Ua ob daim ntawv. Qee cov neeg mob uas muaj qee yam kev mob caj ces yuav tsim tus kab mob thaum lwm tus yuav tsis ua. Tus naj npawb ntawm cov noob cuam tshuam nrog FSGS tau nce txhua xyoo, feem ntau vim yog kev loj hlob ntawm tag nrho exome sequencing. Tsawg kawg yog 38 tau txheeb xyuas txog hnub no.
Qee cov noob muaj feem cuam tshuam nrog cov tsos mob uas suav nrog kev tshwm sim ntxiv. Qhov no tuaj yeem muab cov ntaub ntawv tshawb fawb pom tias tus neeg mob yuav muaj kev hloov pauv hauv ib qho gene. Lwm qhov cuam tshuam nrog cov yam ntxwv hloov pauv hauv qab daus membrane morphology lossis mitochondrial morphology.
Yog tias tsev neeg tsis tau raug kuaj caj ces yav dhau los, txoj hauv kev zoo tshaj plaws yog siv cov panels tsom rau thaum ntxov FSGS (me nyuam mos thiab menyuam yaus). Cov peev txheej kuaj noob caj noob ces thoob ntiaj teb muaj los ntawm National Center for Biotechnology Information thiab National Institutes of He alth.
