Lub raum Pathology ntawm Obesity: Structure-Function Correlations
Mar 22, 2022
Xyoo 1974, Weisinger et al1 tau tshaj tawm plaub qhov xwm txheej uas qhia tias muaj proteinuria hnyav uas yog qhov teeb meem ntawm kev rog rog loj. Txij thaum ntawd los, cov xwm txheej zoo sib xws ntawm cov neeg mob rog rog ntau nrog cov proteinuric glomerulopathy tau piav qhia.2-8 Hauv xyoo 2001, Kambham li al9 tau tshaj tawm 71 cov neeg mob rog rog nrog cov proteinuria raws li kev tshuaj xyuas ntawm qhov loj.raumbiopsy archive thiab tau tshaj tawm tias qhov tshwm sim ntawm cov neeg mob rog rog uas muaj cov yam ntxwv zoo sib xws hauv clinicopathologic tau nce ntau xyoo dhau los, thiab lub tswv yim ntawm tus kab mob ywj pheej ntawm kev rog-txog glomerulopathy (ORG) tau tsim. Tom qab ntawd, ORG cov xwm txheej tau muab faib los ntawm cov qauv kev rog sib txawv, raws li txhua haiv neeg, tau tshaj tawm los ntawm Tuam Tshoj xyoo 200810 thiab los ntawm Nyij Pooj, xyoo 2013.11 Nws tau raug tsim los hais tias qhov kev nthuav qhia zoo sib xws ntawm cov kws kho mob thib ob rau kev rog tuaj yeem tshwm sim tsis hais thaj chaw lossis haiv neeg.12,13 Muab tias kev rog rog tau dhau los ua ntau dua nyob rau xyoo tas los no, qhov muaj ntau ntxiv ntawm cov mob ntevmob raum(CKD) tej zaum yuav raug ntaus nqi los ntawm kev sib kis ntawm kev rog rog hauv cov pej xeem thoob plaws ntiaj teb.14 Qhov tseeb, ntawm ntau yam keeb kwm yav dhau los uas yuav cuam tshuam nrog kev txhim kho CKD tshiab hauv cov pej xeem, kev rog tau raug txheeb xyuas tas li. ib qho kev pheej hmoo ntawm kev ywj pheej ntawm lwm cov kev sib txawv, suav nrog kev kub siab lossis ntshav qab zib, uas feem ntau tshwm sim raws li cov teeb meem ntawm kev rog rog.15,16 Qhov xwm txheej no tau cuam tshuam los ntawm kev hloov pauv txhua xyoo hauv kev faib cov kev kuaj mob ntawm cov neeg mob uas raug mob.raumbiopsy. Ib tsab ntawv ceeb toom los ntawm Kambham et al9 tau pom tias muaj qhov tshwm sim ntau ntxiv ntawm ORG ntawmraumCov kab mob biopsy tau soj ntsuam ntawm Columbia University hauv Tebchaws Meskas, thiab tus nqi uas ORG tau kuaj pom hauv cov qauv kuaj ntshav tau nce los ntawm {{0}}.2 feem pua hauv xyoo 1986 txog 1990 txog 2.0 feem pua hauv xyoo 1996 txog 2000. ceeb toom los ntawm Hu et al,17 uas txheeb xyuas cov 34,630 haiv neegraumCov mob biopsy ntawm Zhengzhou University hauv Suav teb, qhia tias qhov xwm txheej txhua xyoo ntawm ORG tau nce los ntawm 0.86 feem pua hauv xyoo 2009 txog 1.65 feem pua hauv 2018. Qhov kev tshuaj xyuas no qhia txog kev nkag siab tam sim no ntawmlub raumpathology ntawm kev rog rog, nrog rau kev tsom mus rau cov txheej txheem thiab kev ua haujlwm sib raug zoo ntawm kev rog rograumteeb meem.
Ntsiab lus:Kev rog rog, proteinuria, raum biopsy, ib leeg-nephron GFR, glomerular hyperfiltration; raum; lub raum
CISTANCHE yuav txhim kho lub raum / raum ua haujlwm
CLINICAL NTAUB NTAWV THIAB KEV KHO MOB
Kev rog thiab ProteinuriaHauv kev tshuaj xyuas ntawm cov neeg laus uas tsis muaj ntshav qab zib hauv 34 thoob ntiaj teb pawg (n=4, 441,084), ob qho tib si nce lub cev qhov ntsuas (BMI) thiab muaj cov albuminuria yog tus kws tshaj lij kev pheej hmoo rau glomerular filtration rate (GFR) txo qis (kwv yees GFR,<60 ml/min="" per="" 1.73="" m2="" ).18="" another="" meta-analysis="" of="" 39="" cohorts="" (n="630,677)" showed="" that="" obesity="" was="" an="" independent="" predictor="" of="" new-onset="" albuminuria="" without="" a="" gfr="" decrease="" in="" the="" general="" population.16="" in="" obese="" adult="" participants="" (n="12,000;" median="" bmi,="" 35="" kg/m2="" )="" enrolled="" in="" a="" randomized="" controlled="" trial="" of="" selective="" serotonin="" 2creceptor="" agonist="" treatment="" for="" weight="" loss,="" the="" prevalence="" of="" low="" gfr="" and="" albuminuria="" was="" 20%="" and="" 19%,="" respectively.19="" these="" rates="" were="" much="" higher="" than="" the="" rates="" of="" 3.8%="" and="" 2.9%="" that="" were="" identified="" in="" the="" general="" adult="" population.20="" in="" severely="" obese="" cohorts="" subjected="" to="" bariatric="" surgery="" (mean="" bmi,="">50 kg/m2), tus nqi ntawm microalbuminuria thiab macroalbuminuria yog 14 feem pua thiab 4 feem pua ntawm cov hluas (n=230) 21 thiab 41 feem pua thiab 4 feem pua ntawm cov neeg laus (n=95), 22 feem. Ib qho ntawm cov kev tshawb fawb epidemiological thiab clincopathologic yav dhau los tau qhia tias microalbuminuria lossis qib qis-qib cais proteinuria yog qhov tseem ceeb thawj zaug kho mob phenotype hauv cov neeg mob rog.mob raum.
Clinical Features ntawm ORGORG feem ntau tshwm sim nyob rau hauv cov tub ntxhais hluas mus rau cov neeg laus hnub nyoog nruab nrab, nrog rau txiv neej predominance; Txawm li cas los xij, nws tuaj yeem tshwm sim hauv txhua pab pawg hnub nyoog, suav nrog cov menyuam yaus thiab cov neeg laus.17,23,24 Cov neeg mob ORG nquag nquag muaj xws li mob ntshav siab thiab dyslipidemia.6-11 Feem ntau, thawj zaug kev rog rog.raumphenotype yog tus cwj pwm raws li cov proteinuria cais tawm (tsis muaj hematuria) nrog lossis tsis muaj GFR txo.6-11 Cov yam ntxwv kho mob hauv ORG cov neeg mob uas tau tshaj tawm hauv cov kev tshawb fawb yav dhau los tau teev nyob rau hauv Table 1. ORG feem ntau qhia tias muaj qhov tshwm sim tsis zoo nrog ntau qib ntawm cov proteinuria, uas tsis tshua muaj nrog qhov pom tseeb txo qis hauv cov ntshav albumin concentration.6-11 Yog li, qhov muaj cov kab mob nephrotic tag nrho yog qhov txawv txav thiab cov neeg mob ORG tsis tshua pom cov tsos mob pom tseeb, xws li cov kab mob edema. Cov yam ntxwv kho mob no muaj txiaj ntsig zoo rau kev paub qhov txawv ntawm cov neeg mob no los ntawm cov neeg uas muaj lwm hom kab mob glomerulopathic, tshwj xeeb tshaj yog idiopathic focal segmental glomerulosclerosis (FSGS), uas ua tiav nephritic syndrome nrog qhov pom tseeb albumin txo qis feem ntau nrog rau kev mob tshwm sim, nephritic-rangeuria, thiab systemic edema.9,12 Txawm hais tias qhov tsis muaj qhov txo qis hauv cov ntshav hauv cov ntshav, txawm tias muaj cov zis muaj protein ntau hauv cov zis, yog tus yam ntxwv ntawm ORG, cov txheej txheem hauv qab no tseem tsis meej.
Lub ntsiab lus ntawm Obesity hauv ORGTxawm hais tias kev rog rog feem ntau txhais tau tias yog BMI tus nqi ntawm 30 kg / m2 lossis ntau dua, qee qhov kev tshawb fawb los ntawm Asia siv qhov pib ntawm BMI qhov tseem ceeb ntawm 28 kg / m2 lossis ntau dua hauv Suav cov neeg mob 10 lossis 25 kg / m2 lossis ntau dua hauv cov neeg mob Nyij Pooj 25,26 rau kev kuaj mob ntawm ORG. Hauv Columbia University txoj kev tshawb fawb, qhov nruab nrab BMI ntawm cov neeg mob ORG yog 41.7 kg / m2; 46 feem pua ntawm chav kawm 1 lossis 2 rog (BMI, Ntau dua lossis sib npaug li 30 rau<40 kg/="" m2="" )="" and="" 54%="" in="" patients="" with="" class="" 3="" obesity="" (bmi,="" ≥40="" kg/m2="" ).9="" the="" findings="" of="" systematic="" biopsies="" performed="" during="" bariatric="" surgery="" for="" long-lasting="" morbid="" obesity="" (mean="" bmi,="" 53.6="" kg/m2="" )="" showed="" that="" subclinical="" renal="" structural="" changes="" already="" exist,="" but="" that="" the="" extent="" was="" much="" less="" than="" that="" in="" org="" patients="" with="" overt="" glomerulopathy.22,27="" these="" findings="" suggest="" that="" the="" development="" of="" org="" is="" not="" restricted="" to="" patients="" with="" morbid="" obesity="" and="" that="" the="" severity="" of="" renal="" lesions="" and="" clinical="" symptoms="" does="" not="" simply="" depend="" on="" the="" severity="" of="">
CISTANCHE yuav txhim kho lub raum / raum kab mob
Cov txiaj ntsig rau lub raum thiab cov ntsuas ntsuas ntsuas hauv ORGTsuas yog ob peb txoj kev tshawb fawb tau tshuaj xyuas cov txiaj ntsig ntev ntawm cov neeg mob biopsy-pov thawj ORG.8,9,11 Cov chav kho mob ib txwm muaj qhov ruaj khov lossis maj mam nce proteinuric.raumkev puas tsuaj; Txawm li cas los xij, qhov txiaj ntsig mus ntev suav nrog kev nce mus rau theem kawg ntawm cov kab mob raum (ESKD) hauv 10 feem pua rau 33 feem pua ntawm cov neeg mob. Cov hnub nyoog laus dua, lub raum tsis ua haujlwm, thiab ntau dua cov proteinuria ntawm kev nthuav qhia, nrog rau ntau dua lub sijhawm nruab nrab ntawm cov proteinuria thaum kev soj ntsuam xyuas, tau txheeb xyuas tias yog cov neeg tsis zoo.raumCov txiaj ntsig hauv kev txheeb xyuas ntau yam sib txawv.8,9,11 Ntawm kev ceeb toom, BMI tsis yog qhov kwv yees ntawmraumCov txiaj ntsig ntawm cov neeg mob kuaj mob ORG.9,11
HISTOPATHOLOGY OF ORGCov yam ntxwv tag nrhoCovraumhnyav nyob rau hauv autopsies ntawm cov neeg rog rog, txawm nyob rau hauv qhov tsis pom tseebmob raum, tau pom tias muaj ntau dua nyob rau hauv kev sib piv nrog cov kev tswj qhov hnyav ntawm ob tus neeg laus thiab menyuam yaus, qhia tias kev rog nws tus kheej yog cuam tshuam nrog rau lub raum o.2,28-30 Txawm hais tias cov txheej txheem hauv qab ntawm lub raum hnyav hauv cov neeg rog tsis paub. , tej zaum nws yuav muaj feem xyuam rau kev them nyiaj yug hypertrophy ntawm ib tus neeg nephrons, raws li kev ua haujlwm ntawm tubular thiab glomerular hauv kev koom nrog kev rog. Lub intracellular los yog extracellular tsub zuj zuj ntawm lipid Cheebtsam kuj yuav ua rau kom nceraumhnyav nyob rau hauv cov neeg rog. Ib txoj kev tshawb fawb tsis ntev los no tau pom tias qhov kev sib sau ntawm triglycerides nyob rau hauv tib neeg lub raum cortex muaj feem cuam tshuam nrog BMI.31 Txawm hais tias qhov tso tawm ntawm triglycerides tau pom nyob rau hauv ob lub glomerular thiab tubular hlwb, nws tau pom muaj feem ntau nyob rau hauv cov tubular cell.31.
Kev tshawb fawb ntawm morphometric ntsuas siv peb-dimensional xam tomography cov duab qhia tau hais tias qhov ntim ntawmraumparenchyma hauv Nyij Pooj ORG cov neeg mob nyob rau theem ua ntej lawv pom qhov pom tseeb ntawm GFR txo qis (CKD theem G1-G2) tau ntau dua li cov neeg uas tsis muaj rog thiab rog rog.26 Qhov nruab nrab parenchymal ntim hauv CKD theem G1 txog G2 ORG , tsis muaj mobhloov raumpub dawb, thiab roghloov raumCov neeg pub dawb yog 173 § 48, 119 § 23, thiab 138 § 22 cm3, ntsig txog, thaum lub ntsiab lus cortical ntim yog 123 § 34, 85 § 17, thiab 98 § 17 cm3. Cov kev tshawb pom no qhia tau hais tias ntau lub raum o
koom nrog hauv thawj theem ntawm ORG, uas tsis sib npaug rau qhov hloov pauv ntawm lub cev. Nyob rau hauv tib txoj kev tshawb no, lubraumParenchymal ntim thiab cortical ntim hauv ORG cov neeg mob tau pom tias txo qis raws li kev nce qib ntawm CKD theem.26 Qhov nruab nrab parenchymal ntim hauv ORG cov neeg mob uas muaj CKD theem G1, G2, G3a, G3b, thiab G4-G5 yog 184 § 65, 168 § 40, 140 § 20, 135 § 31, thiab 122 § 39 cm3, raws li, thaum lub sij hawm cortical ntim yog 131 § 46, 119 § 28, 100 § 6 § 28 thiab 9. cm3, tej zaum yuav muaj kev cuam tshuam txog kev hloov pauv atrophic ntawm ob lub raum uas tshwm sim los ntawm kev poob qis ntawm kev ua haujlwm nephrons thiab hloov nrog fibrotic caws pliav raws li CKD theem siab.
Vascular Lesions Muaj qee qhov morphologically detectable hloov nyob rau hauv me meraumcov hlab ntsha uas raug ORG. Cov no muaj xws li dilation ntawm glomerular arterioles thiab peripheral capillaries nyob ib ncig ntawm lub vascular ncej ntawm glomeruli (Fig. 1A thiab 2B), 9,12,13 yuav muaj kev cuam tshuam cov neeg mob siab intravascular npaum li cas thiab / lossis nce hauv zos plasma perfusion thiab siab hauv ORG cov neeg mob. Txawm hais tias kev tshawb pom xws li arterial intimal thickening thiab arteriolar hyalinosis tau pom nyob rau hauv cov neeg mob ORG, txog tam sim no tseem tsis tau muaj cov ntaub ntawv qhia txog cov kab mob histopathologic hauv cov hlab ntsha, arterioles, peritubular capillaries, lossis cov leeg ntawm lub raum uas tshwj xeeb rau cov neeg mob ORG.
GlomerulomegalyRaws li lub teeb pom kev zoo, qhov tseem ceeb tshaj plaws hauv ORG yog qhov loj heev glomeruli, hu ua glomerulomegaly (Figs. 1A thiab 2A). Nyob rau hauv kev sib piv nrog nonobese cov ntsiab lus, txawm nyob rau hauv tsis muaj cov tsos mob ntawm lub raum kab mob.33,34 Cov kev tshawb fawb yav dhau los tsis tu ncua tau pom tias qhov loj ntawm glomerular nyob rau hauv cov neeg mob ORG tau loj dua nyob rau hauv kev sib piv nrog rau kev tswj cov kev kawm nrog los yog tsis.kab mob raum, suav nrog cov neeg mob uas muaj idiopathic FSGS lossis cov neeg tsis noj nqaij thiab rog rog hloov pauv raum. Nyob rau hauv kev pom zoo nrog rau lub raum parenchymal thiab cortical ntim, glomerular loj yog loj dua nyob rau hauv kev sib piv nrog cov rog rog.hloov raumCov neeg pub dawb, tawm tswv yim tias cov yam ntxwv uas tsis yog kev rog rog muaj feem cuam tshuam nrog kev loj hlob ntawm glomerulomegaly hauv ORG.26 Nws tau raug tshaj tawm tias glomerular loj yog 1.35 txog 2.15 npaug ntawm txoj kab uas hla thiab 1.58 txog 2.63 npaug loj dua hauv ntim piv nrog cov kev tswj hwm ( Table 1).8,9,25,26,32,78 Txog niaj hnub no, tsis muaj kev pom zoo rau ntau lub ntsiab lus ntawm glomerulomegaly uas cuam tshuam nrog kev mob hnyav lossis tshwm sim hauv ORG. Qhov nce hauv glomerular loj pom nyob rau hauv cov neeg rog rog tuaj yeem yog vim qhov nce ntawm cov glomerular capillaries. Qhov nthuav qhia ntawm capillary kev loj hlob-txhim kho yam tseem ceeb, xws li vascular endothelial kev loj hlob zoo, hauv cov ntaub so ntswg glomerular cais los ntawm cov neeg mob ORG, txhawb qhov kev xav no.35
Focal Segmental GlomerulosclerosisLwm qhov tseem ceeb histopathologic feature hauv glomeruli ntawm cov neeg mob nrog ORG yog FSGS.6-10,25,26,32 Feem ntau, kev kuaj mob ntawm FSGS yuav ua tau thaum qee qhov, tab sis tsis yog tag nrho, glomeruli qhia segmental lesions hauv lawv cov glomerular tufts, hauv koom nrog lub cev qhuav dej ntawm thaj chaw ntawm glomerular capillary lumen.36 Tam sim no feem ntau tau lees paub tias FSGS yog ib qho qauv ntawm glomerular caws pliav ntawm qhov chaw ntawm qhov tsis zoo los yog detached podocytes. Cov kab mob Sclerotic tuaj yeem tshwm sim los ntawm qhov tsis muaj qhov loj me lossis qhov muaj peev xwm sib npaug ntawm glomerular podocytes thiab / lossis hloov pauv ntawm glomerular parietal epithelial hlwb. Qee qhov sib txawv ntawm FSGS qhov txhab yuav tshwm sim nyob ntawm qhov chaw kho mob keeb kwm yav dhau los lossis cov kab mob (Daim duab 2D thiab E). Ntawm FSGS variants, perihilar variant, ib daim ntawv paub ntawm FSGS, feem ntau yog txheeb xyuas hauv cov neeg mob ORG. Qhov no tuaj yeem txuas nrog rau glomerulomegaly, tus neeg sawv cev ntawm glomerular hyperfiltration / hypertension hauv ORG. Loj los yog vacuolated podocytes thiab proliferating parietal epithelial hlwb npog cov kab mob sclerotic raug txheeb xyuas qee zaus ntawm qhov chaw ntawm FSGS cov kab mob hauv ORG. Hauv Columbia University txoj kev tshawb fawb, 57 (80 feem pua) ntawm 71 tus neeg mob tau pom FSGS qhov mob, thiab kev faib tawm ntawm cov kab mob segmental tau txheeb pom tias yog perihilar hauv 11 tus neeg mob (19 feem pua) thiab sib xyaw perihilar thiab peripheral hauv qhov seem 46 (81 feem pua) .9 Nyob rau hauv ib daim ntawv qhia uas soj ntsuam 48 Japanese ORG cov neeg mob, 20 (42 feem pua) cov neeg mob muaj FSGS lesions.26 ntawm tag nrho cov FSGS cov kab mob pom nyob rau hauv cov neeg mob, 13 (42 feem pua) yog perihilar thiab 18 (58 feem pua) tau pom ntawm qhov chaw. lwm yam tshaj qhov chaw perihilar. Cov kev tshawb pom feem ntau tau txheeb xyuas lwm qhov etiologic hauv paus ntawm FSGS, suav nrog intracranial lossis endocapillary tsim cov hlwb thiab hyalinosis, hauv FSGS cov kab mob yuav raug txheeb xyuas hauv cov neeg mob ORG.
Immunofluorescence thiab Electron MicroscopyKev tshawb pom Immunoflfluorescence microscopy feem ntau qhia tias tsis muaj kev tshawb pom tshwj xeeb hauv ORG, qhov tsis muaj qhov tshwj xeeb focal thiab segmental lossis thoob ntiaj teb staining ntawm glomerular tuft nrog IgM thiab C3 tuaj yeem pom qee zaus, uas cuam tshuam rau thaj chaw ntawm glomerulosclerosis.9 Qhov kev tshawb pom ntawm electron microscopy. -prominent ko taw txheej txheem effacement nyob rau hauv kev sib piv nrog cov neeg mob nrog idiopathic FSGS.9,12,13 Podocyte ko taw txheej txheem effacement yog segmental thiab feem ntau npog tsawg tshaj li 50 feem pua ntawm cov glomerular capillary nto cheeb tsam; Txawm li cas los xij, nws tuaj yeem pom diffusely hauv glomeruli ntawm ORG. Me podocyte hypertrophy, intracytoplasmic protein resorption droplets, thiab me me glomerular qab daus daim nyias nyias nyias tuaj yeem pom hauv qee cov neeg mob ORG. Focal intracytoplasmic lipid vacuoles tuaj yeem txheeb xyuas qee zaus hauv cov hlwb mesangial thiab tubular epithelial hlwb; Txawm li cas los xij, cov kev tshawb pom no tsis yog tshwj xeeb rau ORG.12,13
CISTANCHE yuav txhim kho lub raum / raum mob
Tubulointerstitial Lesions Tubulointerstitial lesions tshwj xeeb rau ORG tsis tau txheeb xyuas txog tam sim no. Raws li cov cim o thiab hypertrophic hloov nyob rau hauv glomeruli, lub raum tubules yuav loj hlob nyob rau hauv loj. Kev tshawb fawb txog kev kuaj ntshav biopsy los ntawm cov neeg mob rog rog proteinuric pom tias thaj tsam ntawm cov kab mob sib kis ntawm cov kab mob hauv lub cev yog 33 feem pua loj dua, thiab cov tubular lumen nyob ze yog 54 feem pua loj dua, piv nrog cov neeg mob proteinuric nonobese.37 Lwm qhov tseem ceeb histopathologic yam ntxwv ntawm ORG uas tsis ncaj qha qhia tias tubular hypertrophy yog qhov tsawg glomerular ntom.25,26,32 Vim lub raum yog tsim los ntawm cov qauv tubular ntau, nws pom tau tias tubular hypertrophy ua rau cov txheeb ze txo qis hauv glomerular ntom hauv cov qauv kuaj ntshav. Muab hais tias lub raum cortical ntim tau nce ntau hauv ORG cov neeg mob uas muaj lub raum khaws cia ua haujlwm, yog li ntawd, nws pom tau tias tubular hypertrophy ua ntej qhov tshwm sim ntawm glomerulosclerosis siab heev thiab cov nyiaj them rov qab hypertrophy ntawm cov nephrons ntxiv.
Differential Diagnosis ORG yog txhais tau tias yog proteinuric raum kab mob hauv cov neeg mob rog rog thiab raug kuaj raws li qhov tsis muaj lwm yam kab mob hauv lub raum paub, ob qho tib si hauv kev kho mob thiab histopathologically.9,12,13 Hauv cov kab mob hauv lub raum, glomerulomegaly nrog lossis tsis muaj FSGS cov kab mob tuaj yeem kuaj pom; Txawm li cas los xij, cov kev tshawb pom no tsis yog tshwj xeeb rau ORG. Yog li ntawd, thaum kuaj xyuas qhov chaw no, nws yog ib qho tseem ceeb kom tsis txhob suav cov kab mob uas cuam tshuam nrog kev rog rog, xws li hypertensive nephrosclerosis lossis mob ntshav qab zib glomerulosclerosis. Lub xub ntiag ntawm hypertension tsis yog ib qho kev cais tawm. Cov kab mob biopsy ntawm qee cov neeg mob rog rog pom muaj qhov mob me me mus rau qhov mob vascular loj, uas yog nrog los ntawm cov tsos ntawm diffusely collapsed glomeruli. Cov neeg mob uas muaj cov yam ntxwv zoo li no tau kuaj pom tias muaj ntshav siab nephrosclerosis ntau dua li ORG. Hauv cov neeg mob rog rog uas muaj hom 2 mob ntshav qab zib mellitus, nws feem ntau nyuaj rau txiav txim siab seb puas muaj ntshav qab zib lossis rog rog muaj lub luag haujlwm tseem ceeb hauv kev tsim cov proteinuria. Hauv cov xwm txheej ORG, glomerular nodular lesions lossis glomerular microaneurysm tsim, uas feem ntau raug txheeb xyuas hauv cov ntshav qab zib nephropathy, tsis pom. Kev nce glomerular hauv qab daus daim nyias nyias nyias tsis yog qhov ntsuas rau kev cais tawm vim tias cov neeg mob rog rog tuaj yeem pom qhov nce glomerular hauv qab daus daim nyias nyias nyias thaum tsis muaj ntshav qab zib.38,39
PATHOPHYSIOLOGY INVOLVED IN OBESITY-ASSOCIATED KIDNEY IMPAIRMENT
Intrarenal Hemodynamic Hloov thiab SingleNephron Glomerular HyperfifiltrationCov kev tshawb fawb txog kev cuam tshuam yav dhau los hauv cov neeg rog rog tau pom tias tag nrho cov ntshav ntim, lub raum ntshav ntshav, thiab tag nrho GFR nce nrog kev rog.40-43 Tsis tas li ntawd, qhov nce hauv qhov pom feem (GFR / lub raum plasma khub) yog ib qho kev hloov pauv hauv kev rog. 41,42 Tag nrho cov filtration muaj nuj nqi ntawm lub raum yog cov sum ntawm cov pom muaj nuj nqi nyob rau hauv ib tug neeg nephrons, hu ua ib leeg nephron glomerular filtration rate (SNGFR). Cov SNGFR qhov tseem ceeb no tau raug qhia kom muaj txiaj ntsig tshwj xeeb rau kev nkag siab txog cov kab mob pathophysiology ntawm kev vam meejkab mob raum.43−47 Raws li qhov tshwj xeeb histopathologic nta ntawm glomerulomegaly thiab qhov chaw perihilar ntawm FSGS cov kab mob, nws tau raug kwv yees tias kev them nyiaj yug thiab / lossis decompensatory glomerular hyperfiltration muaj feem cuam tshuam rau kev txhim kho thiab kev loj hlob ntawm ORG.11,12 Txawm li cas los xij. , qhov txawv txav hauv SNGFR ntawm ORG cov neeg mob tsis tau pom vim muaj kev nyuaj rau kev ntsuas SNGFR hauv qhov chaw kho mob. Cov kev tshawb fawb tsis ntev los no tau tsim ib txoj hauv kev los kwv yees tag nrho glomerular tus lej ntawm ib lub raum hauv kev ua neejraumLos ntawm kev faib tag nrho nephron GFR los ntawm tag nrho cov nonsclerotic (functioning) glomeruli hauv ob lub raum, SNGFR tau kwv yees thiab ntau yam tau txheeb xyuas tias. Tej zaum muaj feem cuam tshuam rau SNGFR hauv cov kev noj qab haus huv, suav nrog kev rog.50 Tsis ntev los no, Sasaki et al51,52 ntxiv hloov cov qauv no thiab tsim cov qauv kev sib npaug rov qab los kwv yees lub raum cortical ntim los ntawm kev ntsuas lub raum parenchymal ntim siv cov duab CT tsis zoo hauv tib neeg. Kev ntsuam xyuas ntawm cortical ntim los ntawm txoj kev no tau tso cai kwv yees tag nrho glomerular tus lej ib lub raum hauv cov neeg mob uas muajmob raumleej twg feem ntau tsis haum cov neeg sib tw rau cov duab tsom xam siv qhov sib piv media.
Cov thev naus laus zis tshiab ntawm CT thiab biopsy-based stereology tau siv tsis ntev los no los kwv yees tag nrho glomerular tooj thiab SNGFR hauv cov neeg mob ORG. Okabayashi et al26 kwv yees tag nrho nephron tus lej thiab SNGFR hauv cov neeg mob biopsy-diag nosed ORG siv kev sib xyaw ua ke ntawm CT thiab biopsy-based stereology (Fig. 3). SNGFR qhov tseem ceeb hauv ORG cov neeg mob nrog CKD theem G1 thiab G2 yog 64 feem pua thiab 52 feem pua siab dua hauv kev tswj tsis muaj rog thiab rog (ORG, 97 § 43; nonobese tswj, 59 § 21; kev rog rog, 64 § 21 nL / min, feem. ), hos SNGFR
Cov txiaj ntsig ntawm kev rog rog thiab tsis muaj rog tsis sib txawv rau qhov tseem ceeb hauv kev txheeb cais. Cov txiaj ntsig no nthuav tawm cov pov thawj kho mob ntawm ib leeg-nephron hyperfiltration nyob rau theem pib ntawm lub raum tsis zoo hauv ORG. Tsis tas li ntawd, tib txoj kev tshawb fawb tau pom tias SNGFR tau nce siab thaum ntxov CKD theem thiab pom qhov txo qis nrog kev nce qib CKD, piv rau qhov nce ntxiv hauv ib leeg-nephron urinary protein excretion (tag nrho cov zis protein excretion ib tag nrho cov nonsclerotic glomerular tooj nyob rau hauv ob qho tib si. ob lub raum) (Fig. 4). Qhov no yuav qhia txog cov txheej txheem ntawm decompensated glomerular hyperfiltration hauv cov ncauj lus nrog ORG nrog rau qib CKD nce qib.
Nce Tubular ntsev thiab dej reabsorption hauv rogMuaj ob lub tswv yim loj los ntawm kev ua haujlwm glomerular thiab tubular kev sib txuas lus hauv nephron: glomerulotubular balance (GTB) thiab tubuloglomerular tawm tswv yim (TGF). Cov tubules teb rau glomeruli nrog GTB, qhov glomeruli teb rau tubules los ntawm TGF.53 GTB hais txog qhov tshwm sim uas ib feem ntawm cov lim dej ntawm cov nephron yog resorbed hla ntau GFRs. Cov tubule ze ze yog cov ntsiab lus tseem ceeb uas GTB ua haujlwm, thiab kwv yees li 70 feem pua ntawm cov lim dej ntawm sodium thiab dej yog reabsorbed nyob rau hauv cov tubule proximal, tsis hais tus nqi GFR.54 Tubular overload los ntawm glomerular hyperfiltration yog li ntawd tuaj yeem txhawb nqa sodium thiab dej reabsorption nyob rau hauv proximal tubules ntawm GTB. Nyob rau hauv kev teb rau kev nce sodium cov phooj ywg tus nqi, TGF, lub luag haujlwm tseem ceeb uas yog lub luag haujlwm rau kev tswj cov ntshav glomerular thiab yog li GFR, ua kom muaj zog preglomerular vascular resistance.55 Cov kev tshawb fawb yav dhau los hauv ORG cov neeg mob thiab cov neeg rog rog tau hais tias qhov nce tubular reabsorption. thiab glomerular hyperfiltration, uas yuav ua tau ib lub voj voog vicious ntawm hyperfunction ntawm tag nrho lub raum, yog qhov tseem ceeb hauv lub raum pathology ntawm kev rog (daim duab 5).12,13,56,57.
Lub luag hauj lwm ntawm Renin-Angiotensin-Aldosterone System Cov kev hloov hauv lub raum hemodynamics pom nyob rau hauv kev rog rog yog txuas ze rau kev nce ntsev rhiab heev.57 Qhov tseeb, piv nrog rau cov neeg mob lean, cov neeg rog rog muaj feem yuav tsim ntsev-sensitive ntshav siab thiab proteinuria raws li ib tug Qhov tshwm sim ntawm kev noj ntsev ntau dhau.58,59 Mechanisms los ntawm qhov uas ntsev rhiab heev thiab cov reabsorption kiag li tau nce ntxiv nrog rau kev rog rog suav nrog kev ua kom lub cev intrarenal renin-angiotensin-aldosterone system (RAAS) 60,61 thiabraumsympathetic nerves.62,63 Adipose cov ntaub so ntswg paub tias yog ib qho kev ywj pheej RAAS system, thiab nws paub tias kev ua kom lub RAAS system tshwm sim nyob rau hauv cov neeg rog rog.64,65 Qhov ntau lawm ntawm angiotensinogen, aldosterone, thiab aldosterone-stimulating yam yog qhia. nyob rau hauv adipocytes los ntawm cov neeg rog rog.66-68 Lub plasma aldosterone concentrations nyob rau hauv cov neeg rog rog yog correlated nrog lub visceral rog volume, uas yog txo los ntawm qhov hnyav poob.69,70
Muaj peev xwm pab tau hloov pauv lub raum Glucose MetabolismLub raum glucose reabsorption yog ib qho tseem ceeb ntawm cov piam thaj hauv cov ntshav homeostasis. Lub reabsorption ntawm qabzib nyob rau hauv cov tubules proximal yog kho los ntawm sodium-glucose co-transporters (SGLTs); Ntawm cov no, 90 feem pua ntawm tag nrho cov qabzib reabsorption tshwm sim ntawm SGLT-2.71 Hyperglycemia thiab angiotensin II paub tias yuav ua rau muaj kev nthuav qhia ntawm SGLT-2.72,73 Yog li, hauv cov neeg rog rog, uas ob leeg hyperglycemia. thiab RAAS kev ua kom muaj zog tuaj yeem tshwm sim, qhovraumtubular reabsorption ntawm qabzib tuaj yeem nce ntxiv los ntawm kev tswj hwm ntawm SGLT-2. Ib txoj kev tshawb fawb loj tsis ntev los no tau pom tias SGLT-2 inhibitor therapy ua rau qhov kev poob qis zuj zus.lub raum ua haujlwmhauv cov neeg mob proteinuric CKD yam tsis muaj ntshav qab zib, qhia txog lub luag haujlwm muaj txiaj ntsig ntawm SGLT-2 inhibitors hauv ORG cov neeg mob.74
Tag Nrho Nephron Number thiab Pathogenesis ntawm Kab Mob Raum Hauv Cov Neeg Mob Qhov Ncauj Yog vim li cas cov neeg mob feem ntau ua rau kev rog rog yam tsis muaj qhov qhia pom ntawm lub raum tsis zoo, thaum lwm tus qhia txog kev mob raum tsis ua haujlwm, tsis paub. Praga et al75 tau tshuaj xyuas cov yam ntxwv ntawm cov neeg mob uas muaj kev pheej hmoo ntawm kev tsim cov proteinuria tom qab unilateral nephrectomy thiab pom tias BMI muaj ntau dua rau cov neeg mob uas tsim cov proteinuria thiab lub raum tsis txaus, piv nrog rau cov kev soj ntsuam hauv cov neeg mob uas tsis qhia qhov txawv txav. Ib txoj kev tshawb fawb los ntawm tib pab pawg tau pom tias kev rog rog yog ib qho kev kwv yees ntawm cov proteinuria lossis lub raum tsis zoo ntawm cov neeg mob uas muaj lub raum tsis zoo thiab lub raum tsis tu ncua.76 Tsis tas li ntawd, ib qho kev tshawb fawb loj, mus sij hawm ntev, kev soj ntsuam nyob rau hauv cov neeg mob raum hloov pauv tau txheeb xyuas. Kev rog dhau los ua ib qho kev pheej hmoo ntawm kev ywj pheej rau kev nce qib ntawm ESKD.77 Cov txiaj ntsig no qhia tau tias kev rog rog koom nrog kev txhim kho ntawm lub raum raug mob hauv kev teeb tsa lub raum loj.
Txawm hais tias qhov tsawg glomerular ntom pom nyob rau hauv lub raum biopsy cov qauv ntawm cov neeg mob ORG tej zaum yuav tshwm sim los ntawm ntau yam, qhov muaj peev xwm uas cov neeg mob ORG qhia cov lej nephron tsawg tseem yuav raug tshawb xyuas. Txhawm rau tshuaj xyuas qhov muaj peev xwm no, peb nyuam qhuav kwv yees tag nrho cov glomerular tus lej hauv cov neeg mob ORG.26 Zuag qhia tag nrho, tag nrho cov naj npawb ntawm kev ua haujlwm glomeruli (tsis muaj sclerotic glomeruli thoob ntiaj teb) tau qis dua hauv pawg ORG piv nrog cov neeg rog rog lossis tsis muaj mob raum noj qab haus huv. Hauv pab pawg ORG, tus naj npawb ntawm kev ua haujlwm glomeruli poob qis heev thaum CKD theem siab. Cov txiaj ntsig no txhawb nqa qhov muaj peev xwm ua haujlwm tsawg ntawm nephrons, txawm tias yog los yog tau txais, yog ib qho ntawm cov kev pheej hmoo uas ua rau cov neeg rog rog mus rau qhov kev loj hlob ntawm ORG tau tsim. Txawm li cas los xij, tag nrho cov neeg mob uas tsis muaj tus kab mob sclerotic glomerular nyob hauv ORG cov neeg mob uas muaj lub raum tsis ua haujlwm (CKD theem G1 thiab G2; n=25), cov neeg tsis noj qab haus huv rau lub raum (n=20), thiab cov rog rog raum pub dawb (n=13) yog 0.542 § 0.227 £106 , 0.652 § 0.211 £1{{ 18}}6, thiab 0.673 § 0.217 £ 106 ib lub raum, ntsig txog, thiab tsis txawv ntawm qhov tseem ceeb ntawm kev txheeb cais. Tsis tas li ntawd, kev sib piv ntawm tag nrho cov glomerular tooj, suav nrog thoob ntiaj teb sclerotic glomeruli, kuj tsis pom qhov txawv txav. Cov naj npawb zoo sib xws ntawm nephrons hauv ORG cov neeg mob uas muaj lub raum tsis ua haujlwm thiab hauv kev noj qab haus huv tsis zoo thiab cov neeg rog rog tswj tau qhia tias nws tsis zoo li tus lej nephron tsawg yog ib qho tseem ceeb uas ua rau cov neeg rog rog rau txoj kev loj hlob ntawm ORG.
Lub luag hauj lwm ntawm tus txheeb ze thiab tsis txo qis hauv Podocyte NumberMuab lub luag haujlwm tseem ceeb ntawm glomerular podocytes hauv kev saib xyuas cov qauv thiab pom muaj peev xwm ntawm glomeruli, kev ntsuas xws li tag nrho cov naj npawb lossis qhov ntom ntawm glomerular podocytes tuaj yeem muab kev pom zoo rau cov txheej txheem hauv qab ntawm qhov kev poob qis ntawm kev ua haujlwm pom hauv ORG. Qhov tseeb, ib txoj kev tshawb fawb tau tshaj tawm tias qhov ntom ntom ntawm podocytes hauv cov neeg mob ORG yog 55 feem pua tsawg dua thiab qhov nruab nrab glomerular ntim yog 58 feem pua siab dua hauv cov neeg tsis muaj lub raum pub dawb, qhia txog kev hloov pauv tsis ua haujlwm ntawm podocytes hauv kev npog glomerular tufts koom nrog hauv cov kab mob ntawm cov protein. leakage.78 Qhov kev them nyiaj rov qab tsis ua haujlwm tau pom nyob rau hauv cov neeg mob ORG siab heev nrog FSGS cov kab mob yog li no yuav piav qhia los ntawm kev ua haujlwm tsis zoo ntawm cov glomerular podocytes. Zoo ib yam li qhov sib txawv ntawm tus lej nephron, cov kev tshawb fawb tsis ntev los no tau pom qhov txawv txav ntawm tus lej podocyte ib glomerulus ntawm cov tib neeg ib txwm muaj.79 Mismatch ntawm qhov txawv txav ntawm glomeruli thiab tus neeg podocyte endowment tuaj yeem ua rau lwm yam uas ua rau cov neeg mob ORG raug mob glomerular.
Obesity-Proteinuria SyndromeIb qho kev nce ntxiv ntawm cov neeg mob rog rog nrog CKD hauv cov pej xeem feem ntau qhia tias cov neeg mob biopsy-kuaj kuaj ORG sawv cev tsuas yog lub taub dej khov thiab ntau tus neeg rog rog qhia tias insidious proteinuria yuav muaj peev xwm nce mus rau overt nephropathy thiab ESKD. Qhov no yog qhov zoo sib xws rau qhov xwm txheej ntawm cov ntshav qab zib nephropathy raws li kev mob raum mob ntshav qab zib mellitus, qhov tshwm sim thawj zaug yog microalbuminuria, uas tom qab ntawd nce mus rau cov proteinuria thiab ESKD.80 Ib yam li ntawd, ORG cov neeg mob thiab cov neeg mob rog rog nrog subclinical proteinuria yuav sawv cev rau ntau theem lossis qib ntawm tib tus kab mob ntawm kev rog-proteinuria syndrome (Fig. 5). Zoo ib yam li cov kab mob raum ntawm lwm yam etiologies, lub raum tsis ua haujlwm thiab hnyav proteinuria ntawm kev nthuav qhia yog qhov kev kwv yees ntawm cov txiaj ntsig ntawm lub raum tsis zoo, qhia txog qhov xav tau kev kuaj mob ntxov thiab kev cuam tshuam ntxov hauv pawg neeg mob loj hlob no. Lub elucidation ntawm cov yam ntxwv keeb kwm yav dhau thiab biomarkers cuam tshuam nrog kev txhim kho tshiab ntawm proteinuria hauv cov neeg rog rog yuav pab kom nkag siab zoo dua cov xwm txheej cuam tshuam rau lub raum teeb meem hauv kev rog rog.
Cov lus xaus
Kev soj ntsuam kuaj mob thiab kuaj histopathologic hauv ORG cov neeg mob tau pom cov kab mob pathophysiological uas tuaj yeem txuas kev rog thiab mob raum mob. Cov qauv thiab kev ua haujlwm hloov pauv uas tshwm sim los ntawm qhov txawv txav hauv glomerulotubular thiab tubuloglomerular kev sib cuam tshuam tuaj yeem ua rau muaj kev cuam tshuam glomerular pom tsis ua haujlwm, podocyte poob, thiab tubulointerstitial caws pliav vim muaj proteinuria ntau dhau, thiab ua rau lub voj voog tsis zoo uas ua rau overt nephropathy thiab ESKD. Yam uas txiav txim siab rhiab heev rau, lossis kev ua siab ntev ntawm, kev rog rau lub raum raug mob tseem tsis to taub thiab xav tau kev tshawb fawb ntxiv.
