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Poststreptococcal Glomerulonephritis

  • Author: Duvuru Geetha, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: May 25, 2016
 

Background

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.

Diagram of a nephron. Diagram of a nephron.

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]

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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 two 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.[14]

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]

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Epidemiology

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. The 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.

A systematic review by Jackson et al demonstrated significant variation in the global incidence of APSGN, with the highest incidence of 239 per 10,000 in Australian Aborigines and lowest incidence of 0.04 in 100,000 in an Italian study of people younger than 60 years.[8]

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 also more common in adults (20%) than in children (4-10%). Approximately 83% of adults have azotemia, compared with 25-40% of children.

Six cohort studies report case fatality rates from APSGN, with three revealing a case fatality rate of 0%, two studies from India reporting a case fatality rate of 1.4% and 2%, and one study from Turkey reporting a case fatality rate of 0.08%.[8]

The long-term prognosis of children with APSGN has been the subject of several studies. Pooled data of studies published prior to 2000 with 5- to 18-year follow-up indicate abnormal urinalysis in 17.4%, proteinuria in 13.8%, hypertension in 13.8%, and azotemia in 1.3%.[9] A study from Australia demonstrated that APSGN can add to the burden of chronic kidney disease.[10]

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.

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Contributor Information and Disclosures
Author

Duvuru Geetha, MD, MRCP Assistant Professor of Medicine, Department of Renal Medicine, Bayview Medical Center, Johns Hopkins University School of Medicine

Duvuru Geetha, MD, MRCP is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation

Disclosure: previously served as consultant for Genetech but none in the past one year.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Chike Magnus Nzerue, MD, FACP Professor of Medicine, Associate Dean for Clinical Affairs, Meharry Medical College

Chike Magnus Nzerue, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

References
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  3. Ahn SY, Ingulli E. Acute poststreptococcal glomerulonephritis: an update. Curr Opin Pediatr. 2008 Apr. 20(2):157-62. [Medline].

  4. Wu SH, Liao PY, Yin PL, Zhang YM, Dong L. Elevated expressions of 15-lipoxygenase and lipoxin A4 in children with acute poststreptococcal glomerulonephritis. Am J Pathol. 2009 Jan. 174(1):115-22. [Medline]. [Full Text].

  5. Oda T, Tamura K, Yoshizawa N, et al. Elevated urinary plasmin activity resistant to alpha2-antiplasmin in acute poststreptococcal glomerulonephritis. Nephrol Dial Transplant. 2008 Jul. 23(7):2254-9. [Medline].

  6. Bakr A, Mahmoud LA, Al-Chenawi F, et al. HLA-DRB1* alleles in Egyptian children with post-streptococcal acute glomerulonephritis. Pediatr Nephrol. 2007 Mar. 22(3):376-9. [Medline].

  7. Ilyas M, Tolaymat A. Changing epidemiology of acute post-streptococcal glomerulonephritis in Northeast Florida: a comparative study. Pediatr Nephrol. 2008 Jul. 23(7):1101-6. [Medline].

  8. Jackson SJ, Steer AC, Campbell H. Systematic Review: Estimation of global burden of non-suppurative sequelae of upper respiratory tract infection: rheumatic fever and post-streptococcal glomerulonephritis. Trop Med Int Health. 2011 Jan. 16(1):2-11. [Medline].

  9. Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol. 2008 Oct. 19(10):1855-64. [Medline].

  10. Hoy WE, White AV, Dowling A, Sharma SK, Bloomfield H, Tipiloura BT, et al. Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life. Kidney International. May 2012. 81(10):1026-32. [Medline].

  11. Parra G, Rodriguez-Iturbe B, Batsford S, et al. Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: a multicentric study. Kidney Int. 1998 Aug. 54(2):509-17. [Medline].

  12. Taskesen M, Taskesen T, Katar S, et al. Elevated plasma levels of N-terminal pro-brain natriuretic peptide in children with acute poststreptococcal glomerulonephritis. Tohoku J Exp Med. 2009 Apr. 217(4):295-8. [Medline]. [Full Text].

  13. Sorger K, Gessler U, Hubner FK, et al. Subtypes of acute postinfectious glomerulonephritis. Synopsis of clinical and pathological features. Clin Nephrol. 1982 Mar. 17(3):114-28. [Medline].

  14. Batsford SR, Mezzano S, Mihatsch M, et al. Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?. Kidney Int. 2005 Sep. 68(3):1120-9. [Medline].

  15. Glassock RJ, Alvarado A, Prosek J, Hebert C, Parikh S, Satoskar A, et al. Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining "post" is important in understanding and treating infection-related glomerulonephritis. Am J Kidney Dis. 2015 Jun. 65 (6):826-32. [Medline].

  16. Nadasdy T, Hebert LA. Infection-related glomerulonephritis: understanding mechanisms. Semin Nephrol. 2011 Jul. 31 (4):369-75. [Medline].

  17. VanDeVoorde RG 3rd. Acute poststreptococcal glomerulonephritis: the most common acute glomerulonephritis. Pediatr Rev. 2015 Jan. 36 (1):3-12; quiz 13. [Medline].

 
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