Membranous nephropathy is a form of chronic immune complex glomerulonephritis induced by antibodies reacting in situ to endogenous or planted glomerular antigens.
Antibodies against the podocyte antigen phospholipase A2 receptor (PLA2R) are frequently present but it is not established that they are causative. Formation of subepithelial immune deposits leads to complement activation on the surface of podocytes and generates the membrane attack complex (C5-C9). This in turn causes podocyte injury and proteinuria.
MORPHOLOGYThemainhistologicfeatureofmembranousnephropathyisdiffuse thickening of the capillary wall onroutineH&Estains(
Fig.14.7A ).Electronmicroscopyrevealsthatthisapparentthickeningiscausedinpartbysubepithelial deposits, whichnestleagainsttheGBMandareseparatedfromeachotherbysmall,spikelikeprotrusionsofGBMmatrixthatforminreactiontothedeposits(spike and dome pattern) (see
Fig.14.7B ).Asthediseaseprogresses,thesespikescloseoverthedeposits,incorporatingthemintotheGBM.Inaddition,asinothercausesofnephroticsyndrome,thepodocytesshoweffacement of foot processes. Laterinthedisease,theincorporateddepositsmaybebrokendownandeventuallydisappear,leavingcavitieswithintheGBM.Continueddepositionofbasementmembranematrixleadstoprogressivethickeningofbasementmembranes.Withfurtherprogression,glomerulimaybecomesclerosed.Immunofluorescencemicroscopyshowstypicalgranular deposits ofimmunoglobulinsandcomplementalongtheGBM(see
Fig.14.4A
Most cases of membranous nephropathy are sudden in onset and present as full-blown nephrotic syndrome, usually without antecedent illness; other individuals have lesser degrees of proteinuria. In contrast to minimal-change disease, the proteinuria is nonselective, and usually fails to respond to corticosteroid therapy. Secondary causes of membranous nephropathy should be ruled out. Membranous nephropathy follows a notoriously variable and often indolent course. Overall, although proteinuria persists in greater than 60% of patients, only about 40% progress to renal failure over a period of 2 to 20 years. An additional 10% to 30% of cases have a more benign course with partial or complete remission of proteinuria.
Fig. 14.7 Membranousnephropathy.(A)Diffusethickeningoftheglomeru-larbasementmembrane(periodicacid–Schiffstain).(B)Schematicdiagramillustratingsubepithelialdeposits,effacementoffootprocesses,andthepres-enceofspikesofbasementmembranematerialbetweentheimmunedeposits.A B Podocyte with effaced foot processes Subepithelial deposits "Spikes" Thickened basement membrane http://ebooksmedicine.net