MORPHOLOGYPrimaryFSGSinitiallyaffectsonlythejuxtamedullaryglomeruli.Withprogression,eventuallyalllevelsofthecortexareaffected.Thelesionsoccurinsometuftswithinaglomeruluswhilesparingothers(
Fig.14.6 ).Theaffectedglomeruliexhibitincreased mesangial matrix, obliterated capillary lumina, deposition of hyaline (hyalinosis) and foamy (lipid-laden) macrophages. Inaffectedglomeruli,immunofluorescencemicroscopyoftenrevealsnonspecifictrappingofimmunoglobulins,usuallyIgM,andcomplementintheareasofhyalinosis.Onelectronmicroscopy,thepodocytesexhibiteffacement of foot processes, asinminimal-changedisease.
Withtime,progressionleadstoglobalsclerosisoftheglomeruli,pronouncedtubularatrophy,andinterstitialfibrosis.Thisadvancedpictureisdifficulttodifferentiatefromotherformsofchronicglomerulardisease,discussedlater.
Amorphologicvariantcalledcollapsing glomerulopathy ischaracterizedbycollapseoftheglomerulartuftandepithelialcellhyperplasia.ThismoreseveremanifestationofFSGSmaybeidiopathicormaybeassociatedwithHIVinfection,drug-inducedtoxicities,andsomemicrovascularinjuries.Itcarriesaparticularlypoorprognosis.
It is important to distinguish FSGS from minimal-change disease, because the clinical courses and responses to therapy are markedly different. Both are associated with nephrotic syndrome, but the incidence of hematuria and hypertension is higher in individuals with FSGS. Also, unlike minimal change disease, FSGS-associated proteinuria is nonselective, and in general the response to corticosteroid therapy is poor. At least 50% of patients with FSGS develop end-stage renal disease within 10 years of diagnosis.
Membranous nephropathy is characterized by subepithelial immunoglobulin-containing deposits along the GBM. Early in the disease, the glomeruli may appear normal by light microscopy, but well-developed cases show diffuse thickening of the capillary wall. It usually presents in adults between the ages of 30 and 60 years and follows an indolent and slowly progressive course.
Up to 80% of cases of membranous nephropathy are primary, caused by autoantibodies against podocyte antigens. In the remainder, it occurs secondary to other conditions, including the following:
A Podocyte with effaced foot processes Normal basement membrane B
Fig. 14.5 Minimal-changedisease.(A)Whenviewedwithalightmicroscope,thesilvermethenamine–stainedglomerulusappearsnormal,withadelicatebasementmembrane.(B)Schematicdiagramillustratingdiffuseeffacementoffootprocessesofpodocyteswithnoimmunedeposits.
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Fig. 14.6 Focalandsegmentalglomerulosclerosis(periodicacid–Schiffstain),seenasacollectionofscarred,obliteratedcapillariesandaccumula-tionsofmatrixmaterialinpartoftheaffectedglomerulus.(Courtesy of Dr.
H. Rennke, Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts.)
Infections (chronic hepatitis B, syphilis, schistosomiasis, malaria)
Malignant neoplasms, particularly carcinoma of the lung and colon and melanoma
Autoimmune diseases, particularly systemic lupus erythematosus
Exposure to inorganic salts (gold, mercury)
Drugs (penicillamine, captopril, nonsteroidal anti-inflammatory agents)