糖尿病肾病病理特点

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1、美国肾脏基金会肾脏病预后质量倡议(NKFKDOQI)指南标准Sl i de 3 N orm al gl om erul us:Hem atoxyl i n andeosi n st ai n of a norm al gl om erul us sect i onedt hrough the vascul ar pol e.N ot e the w i de-opencapi l l ary l um i na and the l arge percent age of thecross-secti onal area of the gl om erul us devot ed t ot he

2、 capi l l ary ci rcul at i on.The m esangi al cel l ul ari t yand m at ri x are norm al.Sl i de 1 N orm al gl om erul us:Schem at i zeddraw i ng of a norm al gl om erul us show i ng epi t hel i alcel l s i n green,endot hel i al cel l s i n yel l ow andm esangi al cel l s i n red.N ot e t hat t he g

3、l om erul arbasem ent m em branes(i n bl ack)do notcom pl et el y surround capi l l ary l oops,and t hatendot hel i al cel l s are i n di rect cont act w i t hm esangi al m at ri x(bl ue)at t he m esangi al pol esof capi l l ari es.Sl i de 165 Di abet i c nephropat hy:Thi sschem at i zed draw i ng s

4、how s t he m arkedl yt hi ckened l am i na densa of t he GBM andi ncreased m esangi al m at ri x m at eri alw hi ch are t he si ne qua non of di abet i c renaldi sease.The subsequent sl i des(166-202)dem onst rat e t he spect rum of di abet i c renaldi sease(st art i ng w i t h a revi ew of norm alg

5、l om erul ar hi st ol ogy),and i l l ust rat e di st i ngui shi ngpoi nt s bet w een ot her t ypes of gl om erul opat hi esw hi ch m ay m i m i c di abet i c nephropat hy.Sl i de 167 M oderat e di f f use di abet i cgl om erul oscl erosi s i n an i nsul i n-dependentdi abet i c(I DDM)pat i ent w i t

6、 h 16 years durat i on.N ot e t he w i deni ng of t he gl om erul ar m esangi um,t he rest ri ct i on of t he gl om erul ar capi l l aryci rcul at i on,t he t hi ckeni ng of t he gl om erul arbasem ent m em brane com pared t o sl i de 1,and t hehyal i nosi s of t he art eri ol ar w al l at t he vasc

7、ul arpol e(PAS).Sl i de 168 M arked di f f use di abet i cgl om erul oscl erosi s.There i s ext rem e expansi onof t he m esangi um w i t h bot h m at ri x and cel l ul arm at eri al.The capi l l ary l um enal ci rcul at i on i sm arkedl y const ri ct ed(PAS).W hereas t hepat i ent i n sl i de 2 had

8、 norm al renal f unct i on,t hi spat i ent had overt nephropat hy w i t h prot ei nuri a,hypert ensi on,and a 50%reduct i on i n GFR.S lid e 1 7 1 N o d u la r d ia b e tic g lo m e ru lo scle ro sis(K im m e lstie l-W ilso n le sio n s)in a p a tie n t w itho ve rt d ia b e tic n e p h ro p a th y

9、a n d p ro te in u ria,h yp e rte n sio n,a n d re d u ce d G FR.N o te th ep a lisa d in g o f m e sa n g ia l n u cle i a ro u n d th ep e rip h e ry o f th e n o d u le a n d th e fib rilla r n a tu reo f th e n o d u la r m a trix m a te ria l.N o te a lso th ere strictio n o f g lo m e ru la r

10、ca p illa ry lu m e n a l sp a ce(P A S).Sl i de 178 A capsul ar drop consi st i ng of hyal i nePAS posi t i ve m at eri al deposi t ed on t he pari et alsurf ace of Bowm ans m em brane(9 ocl ock).Sl i de 179 Form at i on of a capsul ar drop byadhesi on of gl om erul ar capi l l ary l oops cont ai n

11、i ngsubendot hel i al hyal i ne(t he so-cal l ed“exudat i vel esi on”)t o Bowm ans capsul e(9 ocl ock and11 ocl ock).I t i s l i kel y t hat t he gl om erul ar capi l l aryl oops ret ract,deposi t i ng t he hyal i ne m at eri al al ongt he Bowm ans capsul ar wal l.Sl i de 174 Earl y gl om erul ar ar

12、t eri ol ar hyal i nosi si n an af f erent art eri ol e.Not e t he sm oot h,waxy,hom ogenous PAS posi t i ve m at eri al i n t hesubendot hel i al space.Thi s I DDM pat i ent hadnorm al renal f unct i on.Sl i de 176 Art eri ol ar hyal i nosi s i n bot h af f erent(l ow er l ef t si de)and ef f erent

13、 (l ow er ri ght si de)gl om erul ar art eri ol es(PAS).N ot e t he di f f use andnodul ar di abet i c gl om erul oscl erosi s i n t hi s I DDMpat i ent w i t h earl y overt nephropat hy.Sl i de 175 Advanced arteri ol ar hyal i nosi s w i thvi rtual com pl ete repl acem ent of the vessel w al l byhy

14、al i ne w axy m ateri al (PAS).Sl i de 200 Thi s and t he subsequent t w o sl i desi l l ust rat e t he at ypi cal l esi ons com m onl y seen i nm i croal bum i nuri c N I DDM pat i ent s.Som e of t hesepat i ent s,as i l l ust rat ed i n t hi s PAS sl i de,haveest abl i shed art eri ol ar hyal i no

15、si s l esi ons w i t h l i t t l eor no gl om erul ar or t ubul oi nt erst i t i al i nj ury.S lid e 1 8 1 Mild e x p a n s io n o f th e in te rs titia ls p a c e a n d tu b u la r b a s e me n t me mb ra n eth ic k e n in g w ith o u t tu b u la r a tro p h y (P A S).T h is ID D M p a tie n t h a

16、d n o rma l re n a l fu n c tio n.T h is mild d e g re e o f in te rs titia l e x p a n s io n isc o mmo n in d ia b e tic p a tie n ts,e v e n th o s e w h o s eg lo me ru la r a n d v a s c u la r d is e a s e d o n o t p ro g re s s.Sl i de 182 M ore advanced t ubul ar i nt erst i t i aldi sease

17、w i t h t ubul ar at rophy and i nt erst i t i alf i brosi s i ndi cat ed by t he green col or on t het ri chrom e st ai ni ng.Thi s I DDM pat i ent had m i l ddi f f use di abet i c gl om erul oscl erosi s andm i croal bum i nuri a.S lid e 2 0 2 T h is N ID D M p a tie n t w ithm ic ro a lb u m in

18、u ria a n d h yp e rte n sio n sh o w s a re a so f a d va n c e d tu b u lo in te rstitia l in ju ry w ith o u tsig n ific a n t g lo m e ru lo p a th y o r va sc u lo p a th y.T h isa n d th e p re c e d in g tw o slid e s illu stra te th a tm ic ro a lb u m in u ric N ID D M p a tie n ts m a y h

19、a ve re n a lle sio n s w h ic h a re n o t typ ic a l o f th o se se e n inID D M w h e re th e g lo m e ru la r,a rte rio la r,g lo m e ru lo sc le ro tic,a n d tu b u lo in te rstitia l le sio n ste n d to a d va n c e in p a ra lle l.P a tie n ts w ith th e p a tte rn s sh o w n in th e la st th

20、 re eslid e s te n d n o t to h a ve p ro life ra tive re tin o p a th ya n d,g e n e ra lly,a re m o re o b e se th a n N ID D Mp a tie n ts w ith typ ic a l d ia b e tic n e p h ro p a th y.H o w e ve r,p a tie n ts w ith th e se a typ ic a l p a tte rn s a lsoh a ve h ig h e r le ve ls o f h e m

21、o g lo b in A 1 c th a nN ID D M p a tie n ts w ith o u t re n a l in ju ry,su g g e stin gth a t th e se “a typ ic a l”fo rm s o f in ju ry m a y a lso b ein flu e n c e d b y th e d ia b e tic sta te.Sl i de 185 El ectron photom i crograph i l l ustrati nga norm al gl om erul ar basem ent m em bra

22、ne w i dth(bottom panel)and di ffuse thi ckeni ng of thegl om erul ar basem ent m em brane consequent todi abetes(upper panel).The basem ent m em branew i dth of the di abeti c pati ent show n here i s m orethan tw i ce norm al thi ckness.Sl i de 186 El ect ron phot om i crograph of an I DDMpat i en

23、t w i t h est abl i shed renal l esi ons.Despi t e t hei ncreased GBM w i dt h and m esangi al expansi on,especi al l y w i t h i ncreased m esangi al m at ri xm at eri al,t hi s pat i ent had norm al renal f unct i on,i ncl udi ng norm al uri nary al bum i n excret i on rat es.Sl i de 187 El ect ro

24、n phot om i crographdem onst rat i ng advanced di abet i c nephropat hyw i t h m arked t hi ckeni ng of t he GBM,great l yi ncreased m esangi al m at ri x m at eri al,andconst ri ct i on of t he capi l l ary l um i na.Thi s I DDMpat i ent had overt di abet i c nephropat hy.S lid e 1 8 9 Im m u n o f

25、lu o re sc e n t m ic ro sc o p ysh o w in g th e lin e a r p a tte rn fo r Ig G sta in in g u su a llyse e n in ID D M d ia b e tic p a tie n ts.N o te th e sta in in go f th e g lo m e ru la r c a p illa ry b a se m e n t m e m b ra n e,B o w m a n s c a p su le,a n d tu b u la r b a se m e n tm e

26、 m b ra n e.In c re a se d lin e a r Ig G a n d a lb u m insta in in g o f re n a l e xtra c e llu la r b a se m e n tm e m b ra n e s is ve ry c o m m o n ly se e n in d ia b e ticp a tie n ts re g a rd le ss o f w h e th e r o r n o t th e yu ltim a te ly d e ve lo p se rio u s re n a l in ju ry.S

27、l i de 188 I m m unofl uorescent m i croscopy l i neari m m unofl uorescent stai ni ng for al bum i n al ong thegl om erul ar capi l l ary basem ent m em brane,Bow m an s capsul e,and tubul ar basem entm em brane i n an I D D M pati ent.型，肾小球基膜增厚：光镜下，活检组织仅有孤立的肾小球基膜增厚和轻度非特异性增生。无肾小球系膜增生，系膜基质无结节性增生（Kim

28、melstiel&dash；Wilson病变）或球形肾小球硬化程度不足50%型，肾小球系膜增生：又分为轻度（a）和重度（b）。肾活检发现轻至重度肾小球系膜增生，但无结节性硬化（KimmelstielWilson病变）或球形肾小球硬化程度不足50%型，结节性硬化（KimmelstielWilson病变）：至少有1个肾小球发生系膜基质结节增大（KimmelstielWilson），但球形肾小球硬化程度不足50%型，晚期糖尿病性肾病肾小球硬化：球形肾小球硬化程度超过50%，且有其他临床或病理证据支持这一病变为糖尿病肾病所致Avogaro A,Schernthaner G.Acta Diabetol.2012 Dec 2.Epub ahead of printGarber AJ,et al.Endocr Pract.2013;19(2):327-36.终末期肾病 血液透析5055604035302545eGFRmL/min 1.73 mSmPC/NICEAustralianCanadian2013 AACE.慎用禁忌症对是否应用进行评估慎用SmPC:Summary of product characteristics，药品说明书6030