1. Wasn’t this category previously called postinfectious glomerulonephritis (PIGN)?

There has been considerable effort to reclassify glomerular diseases that occur as a result of an infection. PIGN describes a unique clinical and pathogenic sequence of events that lead to an immune complex–mediated glomerulonephritis after resolution of an acute infection. Specifically, the acute glomerulonephritis develops after (post) a latent period of variable duration from the time the infection has completely cleared. Since the infection has completely resolved, antibiotic therapy is ineffective for treating the kidney disease. The only infection known to cause this scenario of events is streptococcal disease. Therefore the category of PIGN is better termed poststreptococcal glomerulonephritis (PSGN), as no other microorganism leads to this pathologic phenomenon.

Compared with PSGN, all other infections (viral, bacterial, and fungal) can be “associated” with the development of glomerulonephritis through a separate pathogenic pathway. For these infections, the onset of glomerulonephritis is almost synchronous with the presence of active infection, and the immune complexes are completely dependent on the availability of ongoing antigenemia generated from the infection. In this circumstance as opposed to PSGN, eradication of the infection through antibiotic therapy will halt the ongoing immune complex deposition in the kidney. Staphylococcal-associated acute glomerulonephritis (SAAG) is now as common as PSGN in adults and represents the classic example of this paradigm of infection-associated glomerulonephritis. It is essential to understand the differences between PSGN and SAAG not only in regard to pathophysiology but more importantly in regard to therapeutic intervention. Key points in differentiating PSGN from SAAG and other glomerular diseases are shown in Table 34.1 .

2. Does the site of infection or strain of streptococcal infection affect whether a patient will develop PSGN?

Infections at any site in the body have the potential to cause PSGN. Since the original description of this disease appeared after an episode of streptococcal pharyngitis, most physicians primarily associate this site of infection with the development of PSGN; they may not be aware that skin infections, pneumonia, visceral abscesses, urinary tract infections, periodontitis, and endocarditis as a result of streptococcal infection can also lead to the same kidney lesion. The important point to keep in mind is that it is not the location of the streptococcal infection that is important, but rather infection with a specific nephritogenic strain.

Certain nephritogenic group A beta-hemolytic streptococcal strains cause kidney disease only after an upper respiratory infection, whereas other nephritogenic strains are exclusive to the development of glomerulonephritis after skin infections.

3. What is the typical time for presentation of PSGN after an infection?

The course of PIGN has been well documented for both pharyngitis and skin infections. Typically kidney disease begins 7 to 14 days after the onset of streptococcal pharyngitis, whereas it takes about 21 days or longer for the development of glomerulonephritis after a skin infection such as impetigo. The onset of glomerulonephritis after infection in other sites of the body also follows a course of between 2 and 4 weeks postinfection. These time patterns are critical because the infection has healed and been forgotten; only later on does the patient present with kidney disease. A careful history and laboratory workup (described later) may help identify the cause of the kidney disease and the unrecognized existence of a preceding streptococcal infection. During community outbreaks of group A beta hemolytic streptococcal infection, the incidence of PSGN ranges between 5% and 10% for upper respiratory infections to 15% to 25% for skin infections.

4. How does PSGN present clinically?

A wide variety of clinical presentations can occur with PSGN, but most children with transient microhematuria (dysmorphic red cells) remain asymptomatic. However, full-blown nephritic syndrome even with nephrotic-range proteinuria can occur. Kidney function is often significantly impaired, with concomitant hypertension and peripheral/pulmonary edema. Severe, uncontrolled hypertension is a common feature in patients with acute PSGN and requires immediate control and management. Many patients with PSGN present with “dark or tea-colored” urine due to gross hematuria. The color is indicative of the effect of pH on the free hemoglobin molecule, with alkaline urine being more bright red and acidic urine being a darker brownish hue.

5. What laboratory findings are characteristic of PSGN?

The development of glomerulonephritis results from immune complex deposition in the basement membrane of the glomerulus, leading to loss of the filtration area and increased permeability to protein. These immune complexes consist of an antigen from the infection and usually an immunoglobulin G (IgG) antibody. The damage to the basement membrane from these complexes is often a result of local complement activation exclusively through the alternative pathway. This pathway leads to C3 cleavage and then the production of the membrane attack complex C5-9. Bypassed in this pathway is the activation of C4, which is used only in activation of the classic complement pathway. Therefore when PSGN is suspected, the measurement of serum complement both C3 and C4 is crucial. In PSGN, the C3 level will be low, but the C4 level will typically be normal. If both C3 and C4 are low, the diagnosis of PSGN is suspect, and another source of immune complexes—such as SAAG, cryoglobulinemia, or systemic lupus erythematosus—may be present that activates the classic complement pathway.

Microbiologic and radiologic tests for infection are frequently negative but should still be done. These studies include a chest x-ray as well as blood, sputum, pharyngeal, and urine cultures in addition to a careful examination of the skin, anogenital region, and oral cavity for signs of inflammation. If a streptococcal infection is suspected, specific serologic assays are available, such as the anti-streptolysin O (ASO) titer. However, this test may be falsely negative and lacks the sensitivity to be used as a stand-alone test for streptococcal infection. A more sensitive screen for a recent streptococcal infection is the streptozyme test, which includes five different antibodies that develop to this infection. These include ASO titer, antihyaluronidase (AHase), antistreptokinase, anti–nicotinamide adenine dinucleotidase, and anti-DNAse B antibodies. This test is important because the source of the streptococcal infection will determine what pattern of antibodies will develop; for skin infections, only the anti-DNAse and AHase are positive, whereas for a pharyngeal infection, all five antibodies are usually present in various concentrations. An ASO test alone would miss the previous presence of a streptococcal skin infection.