Of Nephrology and Nephrologists Spotlighting new and provocative developments in world nephrology and featuring nephrologists who occupy leadership roles Manuel Martı´nez-Maldonado, MD Editor-at-Large Postinfectious Glomerulonephritis Bernardo Rodrı ´guez-Iturbe, MD, DSc A CUTE GLOMERULONEPHRITIS may pre- sent in association with a variety of bacte- rial and viral infections. The best known is the disease that follows streptococcal infections or poststreptococcal glomerulonephritis (PSGN). Recognized for about two centuries, it was first described as oliguria and dark urine as a compli- cation in the convalescence period of scarlet fever. Group A streptococcal infections of the skin (usually M types 47, 49, and 57) or upper respira- tory tract (usually M types 1, 2, 4, and 12) precede PSGN. In recent years, the incidence of PSGN has decreased in the United States and in central Europe, but cases continue to be reported from all over the world, and epidemics tend to recur in certain regions. Acute PSGN is twice as common in males as in females and mostly affects children from 2 to 14 years of age. A high familial incidence exists, but no genetic marker has been identified for the disease. 1 Postinfectious glomerulonephritides are immu- nologically mediated. Antigen-antibody reac- tions may occur in the circulation or in situ at glomeruli, which results in the activation of the complement cascade with the subsequent genera- tion of chemotaxis (C5a) and platelet-derived inflammatory mediators. In addition to antibody- dependent mechanisms, cellular immunity also plays an important pathogenetic role. Cytokines participate and amplify the damage. Apoptosis appears to be the major mechanism for resolu- tion of the inflammatory hypercellularity that results from this response. 2 Two antigens isolated from nephritogenic streptococci are under investigation in PSGN: zymogen, precursor of the exotoxin B, 3-5 and glyceraldehyde phosphate dehydrogenase (GAPDH), formerly described as ‘‘preabsorbing antigen.’’ 6,7 These fractions have affinity for the glomeruli and have been shown in biopsy specimens of acute PSGN patients to induce specific, long- lasting antibody response. In addition to strepto- coccal antigens, anti-immunoglobulin (Ig) G re- activity (anti-IgG deposits in biopsy specimens, IgG rheumatoid factor), and antineutrophil cyto- plasmic antibody serum antibodies are present in some of these patients. Streptococcal neuramini- dase may be responsible for anti-IgG generation and may play a role in facilitating the infiltration of the kidney by peripheral blood leukocytes. 8 The pathogenetic significance of the autoim- mune reactivity is still undefined. The diagnosis of postinfectious glomerulone- phritis requires the detection of both glomerulo- nephritis and the cause of the infection. In PSGN, the success rate in obtaining a positive culture during epidemics varies from 10% to 70%. The diagnosis usually depends on serological criteria. An increase in titers of anti-streptococcal antibod- ies indicates recent infection, but not all of these tests are equally useful. Anti-streptolysin O (ASO) titers are less frequently elevated than anti- DNAse B titers. Recent studies indicate that the relatively unavailable anti-zymogen titer test is superior to both ASO and anti-DNAse B titers. In fact, anti-zymogen titers two dilutions higher than the mean in healthy controls (1:600 in our laboratories) have a sensitivity of 88% and a specificity of 85% in the diagnosis of streptococ- cal infection in patients with glomerulonephri- tis. 4 High antibody titers to GAPDH are also characteristic of acute PSGN in patients. 7 The typical clinical presentation of acute glo- merulonephritis is the acute nephritic syndrome: hematuria, edema, and hypertension with or with- xlvi American Journal of Kidney Diseases, Vol 35, No 1 (January), 2000: pp xlvi-xlviii