eMedicine Specialties > Nephrology > Glomerular Diseases

Glomerulonephritis, Poststreptococcal

Author: Duvuru Geetha, MD, MRCP, Assistant Professor of Medicine, Department of Renal Medicine, Bayview Medical Center, Johns Hopkins University
Contributor Information and Disclosures

Updated: Sep 22, 2009

Introduction

Background

Acute glomerulonephritis is characterized by the sudden appearance of hematuria, proteinuria and 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. A link between hemolytic streptococci and acute glomerulonephritis was recognized in the 20th century. (See image below and Image 1.)

Pathophysiology

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).³ 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.⁴

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.⁵

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%.^1,2

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.

Clinical

History

A history suggestive of preceding streptococcal infection may include a preceding infective episode such as pharyngitis, tonsillitis, or pyoderma. This is the sine qua non for the diagnosis of APSGN.

• Latent period
  • A latent period always occurs between the streptococcal infection and the onset of signs and symptoms of acute glomerulonephritis.
  • In general, the latent period is 1-2 weeks after a throat infection and 3-6 weeks after a skin infection.
  • The onset of signs and symptoms at the same time as pharyngitis (also called synpharyngitic nephritis) is more likely to be immunoglobulin A (IgA) nephropathy rather than APSGN.
• Dark urine (brown-, tea-, or cola-colored)
  • This is often the first clinical symptom.
  • Dark urine is caused by hemolysis of red blood cells that have penetrated the glomerular basement membrane and have passed into the tubular system.
• Periorbital edema
  • The onset of puffiness of the face or eyelids is sudden. It is usually prominent upon awakening and, if the patient is active, tends to subside at the end of the day.
  • In some cases, generalized edema and other features of circulatory congestion, such as dyspnea, may be present.
  • Edema is a result of a defect in renal excretion of salt and water.
  • The severity of edema is often disproportionate to the degree of renal impairment.
• Nonspecific symptoms
  • These can include general malaise, weakness, and anorexia and are present in 50% of patients.
  • Approximately 15% of patients complain of nausea and vomiting.

Physical

• Acute nephritic syndrome
  • Acute nephritic syndrome presenting as edema, hematuria, and hypertension with or without oliguria is the most frequent presentation of APSGN.
  • Approximately 95% of clinical cases have at least 2 manifestations, and 40% have the full-blown acute nephritic syndrome.
• Edema
  • Edema is present in 80-90% of cases, and it is the presenting complaint in 60% of cases.
  • Compromised intraglomerular blood flow due to glomerular hypercellularity results in progressive encroachment on the cross-sectional area of the glomerular capillaries.
  • This leads to reduced blood flow that manifests as low fractional excretion of sodium and concentrated urine. This salt and water retention leads to edema.
• Hypertension
  • Hypertension occurs in 60-80% of cases and is more common among elderly individuals.
  • In 50% of cases, the hypertension can be severe; however, more often it is transient, with normalization of blood pressure upon restoration of the glomerular filtration rate, loss of edema, and normalization of plasma volume.
  • If hypertension persists, it is more indicative of the progression to a more chronic stage or that the disease is not poststreptococcal glomerulonephritis.
  • Hypertension is thought to be the result of excessive salt and water retention.
  • Despite excessive sodium retention, the plasma levels of atrial natriuretic peptide are increased. In this condition, this suggests that the kidneys are unresponsive to atrial natriuretic peptide.
  • Plasma renin activity is usually low, and studies by Parra et al have shown that an inhibition of angiotensin-converting enzyme could be an effective short-term treatment for this low-renin hypertension.⁶
  • Hypertensive encephalopathy occurs in no more than 5-10% of patients. Usually, clinical improvement occurs without any neurological sequelae.
• Oliguria
  • This is present in 10-50% of cases, and, in 15%, urine output is less than 200 mL.
  • Oliguria is indicative of the severe crescentic form of the disease.
  • It is often transient, with diuresis occurring within 1-2 weeks.
• Hematuria
  • This is present universally.
  • In 30% of cases, gross hematuria is present.
• Left ventricular dysfunction
  • Left ventricular dysfunction with or without hypertension or pericardial effusion may be present during the acute congestive and convalescent phases.
  • In rare cases, persons with APSGN can show signs of pulmonary hemorrhage.
  • In a study of 28 pediatric patients with APSGN, Taskesen et al found that on clinic admission, the plasma levels of NT-proBNP (an N-terminal peptide left over when the prohormone for brain natriuretic peptide [proBNP] is cleaved to produce active BNP) were higher in these patients than in the 26 healthy children making up the control group.⁷ Moreover, the NT-proBNP levels were significantly higher in 6 patients with APSGN who were found to have left ventricular dysfunction than they were in the patients with APSGN in whom no ventricular dysfunction was diagnosed. The authors suggested that in some patients with APSGN, determination of NT-proBNP levels may prove helpful in the assessment of left ventricular volume overload and cardiac function.

Causes

• Poststreptococcal glomerulonephritis follows infection with only certain strains of streptococci designated as nephritogenic.
• The offending organisms are virtually always group A streptococci.
• 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.

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