Thedominantfeatureofnephroticsyndromeissignificant(i.e.,“nephroticrange”)proteinuria,whilenephriticsyndromeischaracterizedbyproteinuriaandhematuriaofteninassociationwithfunctionalimpairment.
Glomerularinjuryismostoftencausedbydepositonofantibodiesorimmunecomplexes,activationofcomplementandleukocyterecruitmentandactivation.
Themostcommonformsofglomerulonephritis(GN)arecausedbytheformationofimmunecomplexes,whichmaybedepositedfromthecirculationorforminsitu.Immunecomplexesshowagranularpatternofdeposition.
AutoantibodiesagainstcomponentsoftheGBMarethecauseofanti-GBM-antibody–mediateddisease,oftenassociatedwithsevereinjury.Thepatternofantibodydepositionislinear.
Lessfrequently,complementmaybeactivatedintheabsenceofantibody,becauseofacquiredorhereditarydefectsinitsregulation.
We now turn to a consideration of specific types of GN and the syndromes they produce (
Table 14.2 ). Many primary glomerular disease cause the nephrotic syndrome, but in adults this syndrome is most often secondary to diabetes, amyloidosis, and systemic lupus erythematosus (
Table 14.3 ). The renal lesions produced by lupus and amyloidosis are discussed in Chapter 5, and those caused by diabetes in Chapter 20.
Minimal-change disease, a relatively benign disorder, is the most frequent cause of the nephrotic syndrome in children and is characterized by glomeruli that have a normal appearance by light microscopy. Diffuse effacement of podocyte foot processes is seen with electron microscopy. It may develop at any age, but is most common between 1 and 7 years of age.
A popular hypothesis for the pathogenesis of minimal-change disease is that some circulating molecules injure podocytes and cause proteinuria with effacement of foot processes. Although there are numerous reports of candidate serum “factors” produced by lymphocytes and other cells, none has been characterized biochemically or definitively established as being causative in the disease. Thus, the pathogenesis of minimal-change disease remains unknown.
MORPHOLOGYUnderthelightmicroscope,theglomeruliappearnormal,thusgivingrisetothename(
Fig.14.5A ).Thecellsoftheproximalconvolutedtubulesoftenareheavilyladenwithproteindropletsandlipidsduetotubularreabsorptionofthelipoproteinspassingthroughthediseasedglomeruli.Theonlyobviousglomerularabnormalityisthediffuse effacement of the foot processes of the podocytes (see
Fig.14.5B ).ThecytoplasmofthepodocytesappearsflattenedovertheexternalaspectoftheGBM,obliteratingthenetworkofarcadesbetweenthepodocytesandtheGBM.Otherchangesinpodocytesincludevacuolization,microvillusformation,andoccasionalfocaldetachments,suggestingsomeformofpodocyteinjury.Withreversalofthechangesinthepodocytesinresponsetocorticosteroids,theproteinuriaremits.