Glomerulonephritis, Poststreptococcal 

Acute glomerulonephritis is characterized by the sudden appearance of hematuria, proteinuria, red blood cell casts in the urine, edema, and hypertension with or without oliguria. It can follow streptococcal infections. This illness was first recognized as a complication of the convalescence period of scarlet fever in the 18th century.^[1] A link between hemolytic streptococci and acute glomerulonephritis was recognized in the 20th century.

Although the incidence of poststreptococcal glomerulonephritis has declined in the United States, it continues to have high incidence in other parts of the world, especially in areas with tropical climates where skin infections are common.^{[2, 3]}

Recent studies

In a study of leukocytes and glomeruli obtained from 22 pediatric patients with acute poststreptococcal glomerulonephritis (APSGN), Wu et al found evidence that in cases of nephritis, the 15-lipoxygenase derivatives lipoxin A ₄ (LXA ₄ ) and 15-S-hyroxyeicosatetraenoic acid (15-S-HETE) have anti-inflammatory effects.

The authors found up-regulation of LXA ₄ and 15-LO expression in patients' leukocytes and glomeruli during the acute phase of glomerulonephritis and for 6-8 weeks after the disease's onset. Moreover, blood and urinary concentrations of leukotriene B ₄ (LTB ₄ ) peaked during the acute phase of glomerulonephritis and fell during the disease's resolution phase, with the number of glomerular polymorphonuclear leukocytes also rising and falling during the acute and resolution phases, respectively.

In addition, the investigators found that in vitro, the introduction of 15-S-HETE and LXA ₄ inhibited LTB ₄ -induced chemotaxis of polymorphonuclear leukocytes; inhibition of LTB ₄ production from the leukocytes of patients with APSGN was also noted.^[4]

Poststreptococcal glomerulonephritis follows infection with only certain strains of streptococci, designated as nephritogenic. The offending organisms are virtually always group A streptococci. Acute poststreptococcal glomerulonephritis (APSGN) follows pyodermatitis with streptococci M types 47, 49, 55, 2, 60, and 57 and throat infection with streptococci M types 1, 2, 4, 3, 25, 49, and 12.

Although many morphologic, clinical, and serologic features suggest that APSGN is an immune complex disorder, the precise nature of the antigen-antibody interaction is undefined. APSGN is believed to be an immune-mediated disease, in which an immune complex containing a streptococcal antigen is deposited in the affected glomeruli. The size of glomerular basement membrane (GBM) pores and the molecular size of the streptococcus-Ig complex are also important determinants. The molecular size of the streptococcus-Ig complex is about 15 nm (10 nm for streptococcus group A and 5 nm for immunoglobulin). The GBM pore sizes in children and adults are 2-3 nm and 4-4.5 nm, respectively. Therefore, the immune complex molecule can be more easily rodded into the glomerulus in children than in adults and, thus, may explain the increased frequency of APSGN in children compared to that in adults.

The 2 antigens isolated from nephritogenic streptococci are under investigation in APSGN. These include the cationic cysteine protease streptococcal pyrogenic exotoxin B and nephritis-associated streptococcal plasmin receptor, which is a plasmin-binding protein with glyceraldehyde phosphate dehydrogenase (also known as presorbing antigen or PA-Ag).^[5] These fractions have an affinity for glomeruli and have been shown to induce specific, long-lasting antibody responses in biopsy specimens from patients with APSGN. The relevance of exotoxin B and glyceraldehyde phosphate dehydrogenase was evaluated in the same renal biopsy and serum samples of patients with well-defined APSGN. Glomerular deposits of and antibody response to exotoxin B were more consistently present in APSGN than were deposits of and antibody response to glyceraldehyde phosphate dehydrogenase.

Antibodies to exotoxin B and PA-Ag are elevated in the majority of patients with APSGN. Intravenous injections of PA-Ag produce acute glomerulonephritis in animals. Antibodies to PA-Ag are found in 30 of 31 patients with APSGN but are low or absent in those with uncomplicated streptococcal infection or in patients with rheumatic fever.

PA-Ag is also known to activate the alternate pathway of the complement cascade, which happens to be preferentially activated in persons with APSGN. The observation that some patients may only have C3 deposition may relate to this mechanism.

In addition to streptococcal antigens, rheumatoid factor, cryoglobulins, and antineutrophil cytoplasmic serum antibodies are present in some of these patients. The pathogenic significance of this autoimmune response is not defined.

There are also host susceptibility factors. In one study, HLA-DRB1*03011 was reported to be found at a significantly higher frequency in 32 unrelated patients with APSGN as compared to 380 healthy individuals.^[6]

Frequency

United States

The incidence of clinically detectable glomerulonephritis during an epidemic is up to 10% of children with pharyngitis and 25% of children with impetigo. One study reported a change in the epidemiology of APSGN and found that pharyngitis has replaced impetigo as the predominant cause of APSGN.^[7]

International

APSGN can occur sporadically or epidemically.

• Incidence seems to be decreasing in the United States and Europe, but sporadic cases of the disease continue to be reported from all over the world. The prevalence of nephritis varies considerably among persons with sporadic infections with nephritogenic streptococci. The reason for this variability is not known.
• Epidemic poststreptococcal glomerulonephritis occurs mainly in developing countries in areas such as Africa, the West Indies, and the Middle East. Reasons for this changing epidemiology relate to the nutritional status of the community, the more liberal use of antibiotic prophylaxis, and possibly, the change in the nephritogenic potential of streptococci. Among epidemic infections with nephritogenic streptococci, the apparent clinical attack rate is 10-12%.^{[2, 3]}

Mortality/Morbidity

Early death is extremely rare in children (< 1%) but is significantly more common in adults (25%). This is secondary to congestive heart failure and azotemia.

• Congestive heart failure is more common in adults (43%) than in children (< 5%).
• Nephrotic-range proteinuria is more common in adults (20%) than in children (4-10%).
• Approximately 83% of adults have azotemia, compared to 25-40% of children.

Race

No racial predilection is recognized.

Sex

Clinical cases of APSGN are twice as common in males than in females. If subclinical disease is considered, both sexes are affected equally. The familial incidence rate is nearly 40%, but no genetic marker has been identified.

Age

This condition typically affects children aged 2-12 years. A large series reported that 5% are younger than 2 years and 10% are older than 40 years.