genitourinary disorders
Postinfectious Glomerulonephritis (PIGN)
Diagnosis of Postinfectious Glomerulonephritis
Clinical evidence of recent infection Urinalysis typically showing dysmorphic red blood cells (RBCs), RBC casts, proteinuria, white blood cells (WBCs), and renal tubular cells Often hypocomplementemia Streptococcal postinfectious glomerulonephritis (PIGN) is suggested by history of Tonsillopharyngitis or Tests done to confirm the diagnosis depend on clinical findings. Antistreptolysin O, antihyaluronidase, and antideoxyribonuclease (anti-DNAase) antibodies are commonly measured. Serum creatinine and complement levels (C3 and CH50 [total hemolytic complement activity]) are also usually measured; however, in patients with typical clinical findings, some tests can be omitted. Sometimes other tests are done. Biopsy confirms the diagnosis but is rarely necessary. Antistreptolysin Olevel, the most common laboratory evidence of recent streptococcal infection, increases and remains elevated for several months in about 75% of patients with pharyngitis and in about 50% of patients with impetigo, but it is not specific. The streptozyme test, which additionally measures antihyaluronidase, antideoxyribonuclease, and other titers detects 95% of recent streptococcal pharyngitis and 80% of skin infections. Urinalysistypically shows proteinuria (0.5 to 2 g/m2/day); dysmorphic RBCs; WBCs; renal tubular cells; and possibly RBC, WBC, and granular casts. Random (spot) urinary protein/creatinine ratio is usually between 0.2 and 2 (normal,<0.2) but may occasionally be in the nephrotic range (≥3). may rise rapidly but usually peaks below a level requiring Hemodialysis . C3andCH50levels fall during active disease and return to normal within 6 to 8 weeks in 80% of PIGN cases; C1q, C2, and C4 levels are only minimally decreased or remain normal. Cryoglobulinemia may appear and persist for several months, whereas circulating immune complexes are detectable for only a few weeks. Biopsy specimensshow enlarged and hypercellular glomeruli, initially with neutrophilic infiltration and later with mononuclear infiltration. Epithelial cell hyperplasia is a common early, transient feature. Microthrombosis may occur; if damage is severe, hemodynamic changes due to cellular proliferation and edema of the glomerulus cause oliguria, occasionally accompanied by epithelial crescents (formed within Bowman space from epithelial cell hyperplasia). Endothelial and mesangial cells multiply, and the mesangial regions often are greatly expanded by edema and contain neutrophils, dead cells, cellular debris, and subepithelial deposits of electron-dense material. Endothelial and mesangial hypercellularity with neutrophilic infiltration (Jones silver stain,×400). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Epithelial crescents are especially common when biopsy occurs late, after a failed response to treatment. The crescent has ruptured Bowman capsule (Jones silver stain,×200). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). In the left image, immunofluorescent staining with anti-IgG demonstrates irregular IgG deposition in capillary loops (×400). In the right image, immunofluorescent staining with anti-C3 demonstrates scattered granular C3 deposition in capillary walls (×400). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Hump-shaped immune complex deposits (dark gray) with extensive foot process effacement and endocapillary proliferation are seen on transmission electron micrograph (×11,250). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Immunofluorescence microscopyusually shows immune complex deposition with IgG and complement in a granular pattern. On electron microscopy, these deposits are semilunar or hump-shaped and are located in the subepithelial area. The presence of these deposits and of small subendothelial and mesangial deposits initiates a complement-mediated inflammatory reaction that leads to glomerular damage. The major antigen is probably Zymogencysteineproteinase exotoxin B (Zymogen/SPE B). 