Robbins Essential Pathology PDF, Kidney Chapter

CHAPTER 11 Kidney 189 A...

CHAPTER 11 Kidney 189 A Deposition of circulating In situ binding of antibodies with or immune complexes without immune complex formation Subepithelial (at outer Subendothelial (at inner Antibody against Anti-glomerular surface of glomerular surface of glomerular antigen on basement membrane basement membranes; basement membranes; podocytes antibody poststreptococcal GN) MPGN type I) Mesangial Subepithelial immune Anti-glomerular complex formation basement membrane (membranous glomerulonephritis glomerulonephritis) (no immune complexes formed) Granular immunofluorescence Linear immunofluorescence B Complement- and Fc receptor-mediated inflammation Fc receptor Neutrophil Complement enzymes, by-products reactive oxygen (C5a, C3a) species Inflammation and tissue injury Complement activation Fig. 11.1 Antibody-mediated glomerular injury. (A) Injury can result either from the deposition of circulating immune complexes or from antibody binding to glomerular components followed by formation of complexes in situ. Deposition of circulating immune complexes gives a granular immunofluorescence pattern. Anti–glo- merular basement membrane (anti-GBM) antibody glomerulonephritis is characterized by a linear immunoflu- orescence pattern; there is no immune deposit formation in this disease. (B) The antibodies in these deposits activate complement, leading to recruitment of leukocytes and inflammatory damage. Growth factors pro- duced during this reaction may also stimulate proliferation of glomerular cells. Focal Segmental Glomerulosclerosis Morphology. he man soogc ndng s dfuse ckenng o e Focal segmental glomerulosclerosis (FSGS) is a common cause of GBM, caused by deposon o mmune compexes and e orma- nephrotic syndrome; it is characterized by sclerosis of a subset on o “spkes” o basemen membrane maera around e depos- and portions of glomeruli and may occur as a primary disease or s (Fg. 11.3). Podocye oo processes are dfusey efaced, as n secondary to other disorders. oer dseases w proenura. here s ypcay no nlammaon. Clncal Features. Membranous nepropay usuay presens n adus Pathogeness. Injur y o podocyes s oug o represen e na- beween e ages o 30 and 60 years and oows an ndoen and sowy ng even o prmar y FSGS, oug e mecansm o njur y s usuay progressve course. he onse s sudden and s caracerzed by neproc unknown. As n mnma cange dsease, crcuang acors a may syndrome, usuay wou aneceden ness. Unke n mnma cange damage podocyes ave been suggesed bu no dened. In mos dsease, e proenura s “nonseecve, ” meanng a arge proens aso cases, FSGS s prmar y, bu  may deveop secondar y o HIV necon, eak no e urne. he dsease does no respond we o corcoserod eron abuse, oer orms o gomeruar dsease (e.g., mmunogobun erapy, and oer mmunosuppressve drugs suc as cycopospamde A [IgA] nepropay), or nered deecs n cyoskeea or podocye and cycosporn are used. Paens wo go no remsson oowng rea- proens. FSGS may aso be seen n e conex o reduced rena mass men or sponaneousy end o do we, bu abou 20% ave a remng and (e.g., due o abaon or dsease) n wc ncreased bood low o e reapsng course and abou 10% deveop rena aure. remanng kdney causes emodynamc njur y o e gomeru. 190 CHAPTER 11 Kidney A B C Fig. 11.2 Minimal change disease. (A) Glomerulus showing normal basement membranes and absence of proliferation (PAS stain). (B) Ultrastructural characteristics of minimal change disease include effacement of foot processes (arrows) and absence of deposits; compare with the podocyte foot processes (arrow) in the normal glomerulus (C). CL, Capillary lumen; M, mesangium; P, podocyte. (C, Courtesy Dr. Vighnesh Wala- valkar, Department of Pathology, University of California San Francisco.) A B C D Fig. 11.3 Membranous nephropathy. (A and B) Diffuse thickening of the glomerular basement membrane (GBM) without proliferation of cells or inflammation (A, periodic acid–Schiff stain; B, silver stain). In (B), the arrow points to “spikes” of matrix material projecting from the GBM. (C) Granular deposits of IgG by immunofluorescence along the GBM. (D) Subepithelial deposits on the basement membrane (B) with effacement of foot processes overlying the deposits (arrow). (B, Courtesy Dr. Charles Lassman, UCLA School of Medicine, Los Angeles.)  CHAPTER 11 Kidney 191 A B Fig. 11.4 Focal segmental glomerulosclerosis (FSGS). (A) Low-power view showing segmental sclerosis in one of three glomeruli (arrow). (B) Involvement of a segment of a glomerulus, with sclerosis and hyaline deposit (arrow). Clncal Features. he mos common presenaon s e neproc Morphology. FSGS s caracerzed by sceross o some bu no a syndrome, bu some paens sow a neprc cnca paern. he gomeru (ence oca), and n eac afeced gomeruus, ony a por- prognoss s poor : Mos paens ave varabe degrees o rena nsui- on o e gomeruus and no e enre srucure s afeced (ence cency, and many progress o end-sage rena dsease. segmena). In afeced gomeru, ere s ncreased marx proen n e mesangum a oberaes gomeruar capares and aso C3 Glomerulopathies e deposon o marx maera (wc appears pnk n emaox- C3 glomerulopathies are rare diseases caused by excessive activa- yn-and-eosn [H&E] sans and s caed yane) rougou e tion of the alternative complement pathway. abnorma segmen (Fg. 11.4). Immunoluorescence mcroscopy he wo dseases n s group, dense depost dsease (ormery sows nonspecc rappng o anbodes bu no mmune compexes. caed MPGN ype II) and C3 gomeruoneprts (C3 GN), ave a sm- Eecron mcroscopy reveas dfuse oo process efacemen. In ar paogeness bu dsnc morpoogc eaures. paens w HIV, e dsease can be very severe and s assocaed w coapse o e enre gomeruar ut and epea ce yper- Pathogenes s. C ompemen acvaon n dense depos dsease and pasa, bo manesaons o severe gomeruar njury. C3 GN s mos oten caused by an auoanbody, caed C3 neprc acor, wc bnds and sabzes e C3 conver ase enzyme (see Clncal Features. he cassc presenaon s e neproc syndrome, Caper 4 or a dscusson o compemen acvaon). Less com- somemes assocaed w mcroscopc emaura and yperenson. he mony, nered muaons a dsabe compemen reguaor y proenura s nonseecve and e response o mmunosuppressve drugs s proens ave e same boogca consequence. Aoug uncon- poor; abou a e paens deveop end-sage rena dsease wn 10 years. roed compemen acvy can njure any ce, or unknown reasons e kdney s e major arge o compemen-medaed nlammaon Membranoproliferative Glomerulonephritis n ese dseases, and nonrena sysemc esons are uncommon. Membranoproliferative glomerulonephritis is characterized by alterations in the glomerular basement membrane as well as pro- Morphology. he soogc appearance s smar o a o MPGN. liferation of glomerular cells. he dagnosc amark s brg mmunoluorescen sanng or C3 n e mesangum and gomeruar capar y was n e absence Pathogeness. Membranoproerave gomeruoneprs (MPGN) s o deposon o anbodes or eary componens o e cassca caused by mmune compex deposon, bu e ncng angen s no compemen paway (suc as C4). In dense depos dsease, e known n mos cases. Less commony, MPGN s secondar y o oer deposs o compemen proens are muc arger and e GBM s dseases, suc as SLE, vra epas, and oer cronc necons. In convered o a rbbon-ke srucure (Fg. 11.6). ese cases, e mmune compexes may be composed o anbodes bound o se nuceoproens (n SLE) or o mcroba angens (n e C ln cal Feature s. Te usu a  pres en a  on s  e nepro  c sy n- seng o necon). drome or a mxe d nepro  c - ne p r  c p aer n. Mos p a  en s prog - ress o rena  a ure, and  e ds e as e  re qu e n y re c urs o ow ng rena   ransp an a on b e c aus e un re gu  ae d comp eme n a c  v a on Morphology. Gomeru are enarged due o e proeraon o con nues. mesanga and endoea ces and nraon o eukocyes, and e obuar arcecure o e gomeruar ut appears exaggeraed (Fg. 11.5). Pars o ese ces and e mesanga marx exend no Diabetic Nephropathy e capar y wa, and ogeer w e mmune compex deposs, Dabees s a sysemc meaboc dsease caused by decency o e gu- ey creae e appearance o a sp GBM (ke a ram rack) vsbe cose-reguang ormone nsun, resung n eevaed bood gucose. w speca sans. Immunoluorescence and eecron mcroscopy he kdney s requeny nvoved, and because o e grea ncrease n revea granuar deposs o anbodes and compemen proens. e ncdence o dabees, dabec nepropay s now e commones 192 CHAPTER 11 Kidney B A M CL C D Fig. 11.5 Membranoproliferative glomerulonephritis (MPGN). (A) Mesangial cell proliferation, basement membrane thickening, leukocyte infiltration, and accentuation of lobular architecture. (B) Splitting of the GBM (arrow) seen with a silver stain. (C) Granular deposits of IgG in the GBM and mesangium. (D) Electron-dense deposits (arrows) in the glomerular capillary wall between duplicated (split) basement membranes (double arrows) and in mesangial regions (M). CL, capillary lumen. cause o cronc kdney dsease n e Uned Saes. I s dscussed n deposed n e gomeru, acvae compemen by e cassca paway, Caper 16, n e conex o dabees. and nduce acue nlammaon a damages e gomeru. Prevenon o s compcaon s an mporan reason or rapd anboc reamen o Acute Poststreptococcal Glomerulonephritis e necon. Suc reamen s ready avaabe n ger-ncome coun- This uncommon sequela of streptococcal infections is caused by res, so s dsease occurs prmary n ower-ncome counres. A smar the glomerular deposition of immune complexes of streptococcal dsease may occur ater necons w organsms oer an srepococc, antigen and a specic antibody. so e generc name acute postnfectous GN s somemes preerred. Pathogeness. Acue possrepococca gomeruoneprs (GN) s a cas- sc organ-specc mmune compex dsease caused by gomeruar depo- Morphology. Gomeru sow a dfuse ncrease n ceuary owng o son o mmune compexes resung n proeraon o and damage o e nlux o nlammaory ces, mosy neurops, as we as e pro- gomeruar ces and nraon o eukocyes, especay neurops. In eraon o gomeruar ces (Fg. 11.7). Immunoluorescence sows a ess an 1% o cases o roa or skn necon by group A β-emoyc granuar sanng paern or IgG and C3. Eecron mcroscopy reveas srepococc, rena esons deveop 1 o 4 weeks ater sympoms rom e arge “umps” o deposed mmune compexes, mos oten n e sub- na necon abae. In afeced paens, or unknown reasons, srepo- epea regon o e GBM, bu somemes n e subendoea and cocca proen angens perss and nduce e ormaon o IgG anbodes, nramembranous regons and n e mesangum, as we. and mmune compexes are ormed n e crcuaon. hese compexes are  CHAPTER 11 Kidney 193 O e sx casses, dfuse lupus neprts (caed cass IV) s e mos common and severe orm. he ypca morpoogc pcure s proerave GN afecng mos gomeru. he nvoved gom- eru sow proeraon o endoea, mesanga, and epea ces, somemes w crescen ormaon (descrbed aer). Exen- sve subendoea mmune compex deposon may ead o GBM ckenng, creang e appearance o “wre oops. ” Oer common rena esons n SLE are ubuonersa CL nlammaon, w or wou mmune compex deposon aong CL e ubuar basemen membrane, and vascus w mmune com- pex deposon and, somemes, romboss. he prognoss wors- ens w ncreased severy o bo o ese esons. Clncal Features. Cnca manesaons range rom md emaura and proenura o massve proenura w neproc syndrome (as n dopac membranous nepropay) and progressve rena aure. Rapidly Progressive Glomerulonephritis Fig. 11.6 Dense deposit disease. Dense homogeneous deposits in the This group of diseases shares clinical and morphologic features GBM. CL, capillary lumen. (especially the formation of crescents in glomeruli) but may have diverse etiologies. Clncal Features. Paens presen w e acue neprc syndrome, Because crescens are e sne qua non o RPGN,  s aso caed marked by emaura, varabe, ypcay md proenura, azoema, crescentc GN. edema, and yperenson. Serum compemen eves decrease durng e acue pase. Mos cdren w e dsease recover, aoug rarey Pathogeness. RPGN may be caused by dferen mmune mecansms. e dsease may evove no rapdy progressve GN (RPGN, descrbed    An-GBM auoanbodes, oten reacve w angens n e aer). he prognoss n adus s sgncany worse; abou a rd noncoagenous componen o e GBM, are deposed aong e deveop end-sage rena dsease over 10 o 20 years. GBM, acvae compemen, and nduce desrucve nlammaon. In some paens, e anbodes aso bnd o basemen membranes Lupus Nephritis o pumonar y aveoar capares, causng ung emorrages; e Renal involvement is common in lupus and usually dominated by combnaon o rena and pumonar y nvovemen s caed Good- immune complex–mediated glomerulonephritis. pasture syndrome. Sysemc upus er yemaosus (SLE) s an auommune dsease n    RPGN may be a manesaon o a known mmune compex ds- wc annucear auoanbodes are produced a orm mmune ease, suc as acue posnecous GN or upus. In some cases o compexes w se nucear angens (see Caper 4). Dsease man- RPGN, mmune compexes are deeced n e absence o anoer esaons are many due o deposon o ese compexes n vesses underyng dsease. n dferen ssues. he kdney s a major se o mmune compex    Pauc-mmune crescenc GN s dened by e presence o e car- deposon, and rena aure s one o e mos serous compcaons acersc gomeruar eson n e absence o deecabe anbodes o e dsease. Auoanbodes agans nonnucear angens aso con- or mmune compexes. An–neurop cyopasmc anbodes rbue o e dsease, ncudng ose a bnd o and depee red ces (PR3-ANCAs) are ypcay presen n e serum, w or wou or paees (see Caper 9) and oers a afec coaguaon, caed assocaed sysemc vascus (see Caper 7). hus, pauc-mmune anpospopd anbodes (see Caper 3). Here we dscuss e rena crescenc GN may be a manesaon o a sysemc vascus or nvovemen; oer aspecs o SLE are dscussed n Caper 4 dopac (med o e kdney). Pathogeness. he gomeruar esons are caused by e deposon o Morphology. he morpoogc canges n RPGN are relecons o mmune compexes, acvaon o compemen, and subsequen recru- severe gomeruar njur y. hs s manesed n some cases w seg- men and acvaon o eukocyes va compemen producs and by e mena capar y necross, breaks n e GBM (vsbe by eecron deposed anbodes bndng o eukocye Fc recepors. hs s e yp- mcroscopy), and e deposon o brn n e Bowman space. he ca sequence o evens n a mmune compex dseases (see Caper gomeru sow proeraon ousde e capar y oops, gvng rse 4). Less commony, ere s evdence o ubuonersa neprs and o dsncve proerave esons caed crescents a oberae e vascus, aso caused many by mmune compexes. Bowman space (Fg. 11.9). Crescens conss o proerang epe- a ces nng e Bowman capsue and nrang monocyes and oer eukocyes. In addon o exracapar y proeraon, ceuar Morphology. he gomeruar dsease caused by e deposon proeraon may aso be seen n e capar y oops and mesan- o mmune compexes s dvded no sx casses a ave dsnc gum, smar o wa s seen n oer orms o mmune compex– paooges (Fg. 11.8), cnca eaures, and prognosc mpcaons. medaed njur y. Immunoluorescence mcroscopy reveas near he gomeruar esons are cassed on e bass o e se o depos- or granuar sanng or IgG and C3 aong e GBM (excep n e on o e mmune compexes (mesanga, subendoea, subepe- pauc-mmune ype). Eecron mcroscopy may sow rupures n a), e resung proerave reacon o e gomeru (mesanga, e GBM, w or wou mmune deposs. oca or dfuse), and e exen o sceross o e gomeruar uts. 194 CHAPTER 11 Kidney A B C Fig. 11.7 Acute poststreptococcal glomerulonephritis. (A) Glomerular hypercellularity is due to intracapillary leukocytes and proliferation of intrinsic glomerular cells. (B) Immunofluorescent stain demonstrates discrete, coarsely granular deposits of IgG (and C3), corresponding to deposit seen in (C). (C) Typical electron-dense subepithelial deposit and a neutrophil in the lumen. (A to C, Courtesy Dr. H. Rennke, Brigham and Women’s Hospital, Boston. B, Courtesy D. J. Kowaleska, Cedars-Sinai Medical Center, Los Angeles.) Clncal Features. RPGN, regardess o e underyng cause, presens w e caracersc IgA deposs. Paens presen w emaura w a rapdy deveopng severe neprc syndrome, ypcay w oowng a respraory or oer necon, wc usuay resoves spon- emaura, moderae proenura, ogura, and azoema. he progno- aneousy and recurs oten. Mos paens manan rena uncon or ss depends on e proporon o gomeru nvoved; more an 80% decades, bu a mnory sowy progress o end-sage rena dsease. porends a poor oucome. Remova o an-GBM anbodes by pasma excange can bene paens w suc anbodes. Hereditary Nephritis Heredtary neprts reers o a group o rare dseases caused by ner- IgA Nephropathy ed muaons n genes encodng GBM proens. In e mos severe IgA nepropay s a requen cause o recurren emaura n cdren orm, Aport syndrome, ere s accompanyng sensorneura deaness and young adus. I oten oows an upper respraory necon. Depos- and ocuar abnormaes. hn basemen membrane dsease s e cause s o IgA are deeced n e mesangum by mmunoluorescen san- o mos cases o so-caed bengn ama emaura. B o orms o ng (Suppemena eFg. 11.2). he suspeced paogeness s unusua: eredar y neprs are caused by muaons afecng ype IV (base- I s posuaed a e respraory necon nduces ncreased mucosa men membrane) coagen. Mos Apor syndrome cases are caused by IgA producon as par o e os’s mmune response and a some muaons n e α5 coagen gene, wc s ocaed on e X cromo- o s IgA s abnormay gycosyaed. hs abnorma IgA appears o some, so maes are afeced more requeny and more severey an e mmune sysem as a oregn proen, and se ecs an anbody emaes. Rare auosoma recessve and domnan cases are nked o response. he compexes o IgA and an-IgA are deposed n e kdney oer genes. Paens w e Apor syndrome presen n cdood and may acvae compemen, causng gomeruar njury. Hsoogcay, or e eenage years w emaura, somemes accompaned by pro- gomeru may be norma or sow sube nlammaory canges, aong enura, and may progress o rena aure n 2 o 3 decades.