14.11 ).Smallernumbersofothertypesofleukocytesalsomaybepresent.Inadditiontocrescents,cellularproliferationalsoisseenwithinthecapillaryloopsand/orinthemesangialareasincaseswithimmunecomplex-mediatedpathogenesis,suchaspostinfectiousGN,lupusnephritis,orIgAnephropathy.Incontrast,incaseswithanti-GBMantibody–mediatedorpauciimmunecrescenticGN,thereisnoendocapillaryhypercellularity.Immunofluorescencestudiesrevealthecharacteristicstronglinear staining withIgGandC3alongtheGBMinanti-GBMantibody-mediateddisease,agranular pattern ofglomerularstaininginimmunecomplex-mediatedGN,whileinpauci-immuneGNthestainsarenegative.Electronmicroscopyshowselectron-denseimmunecomplexdepositswithintheglomeruliinimmunecomplex–mediatedGN,butnotinbiopsiesfromthosewithanti-GBMandpauci-immunecrescenticGN.Electronmicroscopymayshowdistinctruptures in the GBM, signifyingsevereglomerularinjurythatischaracteristicofthisformofGN.ThecrescentseventuallyobliterateBowman’sspaceandcompresstheglomeruli.Intime,crescentsmayundergoscarring,andglomerulosclerosisdevelops.
The onset of RPGN is much like that of the nephritic syndrome, except that the oliguria and azotemia are more pronounced. Proteinuria sometimes approaching the nephrotic range may occur. Some affected individuals become anuric and require long-term dialysis or transplantation. The prognosis is roughly predicted by the fraction of involved glomeruli, as patients in whom crescents are present in less than 80% of the glomeruli have a more favorable prognosis than those in whom the percentage of crescents is higher. Plasma exchange may be of benefit in those with anti-GBM antibody GN and in some cases of ANCA-related pauciimmune crescentic GN.
Minimal-change disease isthemostfrequentcauseofnephroticsyndromeinchildren.Itismanifestedbyproteinuriaandeffacementofglomerularfootprocesseswithoutantibodydeposits.
Focal segmental glomerulosclerosis (FSGS)maybeprimaryorsecondary(e.g.,asaconsequenceofpreviousglomerulonephritis,hypertension,orinfectionsuchasHIV).Glomerulishowfocalandsegmentalobliterationofcapillaryluminaandlossoffootprocesses.
Membranous nephropathy iscausedbyanautoimmuneresponse,mostoftendirectedagainstthePLA2Ronpodocytes.ItischaracterizedbygranularsubepithelialdepositsofantibodieswithGBM“spike”formation,thickeningandlossoffootprocessesbutlittleornoinflammation.
Membranoproliferative glomerulonephritis type 1 isanimmunecomplex–mediateddiseasewithimmunedepositsinthesub-endotheliallocation.
Fig. 14.11 Crescenticglomerulonephritis(silverstain).Arrowsindicateareasofnecrosisandcrescentformation.ThesegmentaldistributioninthiscaseistypicalofANCA(anti-neutrophilcytoplasmicantibody)–associatedcrescenticglomerulonephritis.
http://ebooksmedicine.net •Dense deposit disease andC3 glomerulonephritis arecausedbyunregulatedactivationofthealternativecomplementpathway.ImmunofluorescenceispositiveforC3inbothconditions.