Poststreptococcal GN is an immune complex disease in which tissue injury is primarily caused by complement activation by the classical pathway. Typical features of immune complex disease, such as hypocomplementemia and granular deposits of IgG and complement on the GBM, are seen. The relevant antigens probably are streptococcal proteins. Specific antigens implicated in pathogenesis include streptococcal exotoxin B (Spe B) and streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Both have an affinity for glomerular proteins and plasmin. It is not clear if immune complexes are formed mainly in the circulation or in situ (the latter by binding of antibodies to bacterial antigens “planted” in the GBM).
MORPHOLOGYBylightmicroscopy,themostcharacteristicchangeinpostinfectiousGNisincreased cellularity oftheglomerulartuftsthataffectsnearlyallglomeruli—hencethetermdiffuse GN (
Fig.
14.9A ).Theincreasedcellularityiscausedbothbyproliferationandswellingofendothelialandmesangialcellsandbyinfiltratingneutrophilsandmonocytes.Sometimesthereisnecrosisofthecapillarywalls.Inafewcases,“crescents”(discussedlater)maybeobservedwithintheurinaryspace,formedinresponsetothesevereinjury.Electronmicroscopyshowsdepositedimmunecomplexesarrayedassubendothelial,intramembranous,or,mostoften,subepithelial “humps” nestledagainsttheGBM(see
Fig.14.9B ).Mesangialdepositsalsoareoccasionallypresent.Immunofluorescencestudiesrevealscatteredgranular deposits of IgG and complement withinthecapillarywallsandsomemesangialareas,correspondingtothedepositsvisualizedbyelectronmicroscopy.Thesedepositsusuallyareclearedoveraperiodofabout2months.
The most common clinical presentation is acute nephritic syndrome. Edema and hypertension are common, with mild to moderate azotemia. Characteristically, there is gross hematuria, the urine appearing smoky brown rather than bright red due to oxidation of hemoglobin to methemoglobin. Some degree of proteinuria is a constant feature, and, as mentioned earlier, it occasionally may be severe enough to produce the nephrotic syndrome. Serum complement levels are low during the active phase of the disease, and serum anti–streptolysin O antibody titers are elevated in poststreptococcal cases.
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Fig. 14.9 Poststreptococcalglomerulonephritis.(A)Glomerularhypercellularityiscausedbyintracapillaryleukocytesandproliferationofintrinsicglomerularcells.Notetheredbloodcellcastsinthetubules.(B)Typicalelectron-densesubepithelial“hump”(arrow) andintramembranousdeposits.BM, Basementmembrane;CL, capillarylumen;E, endothelialcell;Ep, visceralepithelialcells(podocytes).
Recovery occurs in most children with poststreptococcal disease, but some develop rapidly progressive GN owing to severe injury with formation of crescents, or chronic renal disease from secondary scarring. The prognosis in sporadic cases is less clear. In adults, 15% to 50% of affected individuals develop end-stage renal disease over a few years or 1 to 2 decades, depending on the clinical and histologic severity. By contrast, in children with sporadic cases of acute postinfectious GN, the progression to chronicity is much lower.