Post-Infectious Glomerulonephritis

  1. sudden onset of gross hematuria, edema, hypertension, and renal insufficiency; degree of involvement varies
  2. rare before 3 years of age
  3. develops after infection with nephritogenic strains of group A beta-hemolytic strept
    1. approx 2 weeks after throat infection
    2. skin infection may occur as far as 6 weeks in advance with (vs Rheumatic fever, caused only by resp infxns, NOT skin)
  4. ASO titer not always elevated with skin infections so may need anti-DNaseB antigen titers or Streptozyme test
  5. C3 level is usually reduced (but for only 2-3 months)
  6. Treatment in the acute phase may consist of salt restriction, diuretics, and antihypertensives
  7. acute phase generally resolves within 2 months, but urinary abnormalities may persist for more than one year
  8. early antibiotic therapy of infections does not eliminate the risk of glomerulonephritis (it prevents rheumatic fever)
  9. Note: membranoproliferative glomerulonephritis may be indistinguishable from post-strept glomerulonephritis, since both may have gross hematuria, low C3, and elevated ASO titers (which may be coincidental), but PSGN improves dramatically within 2 months of onset, whereas MPGN persists

Discussion

Acute postinfectious glomerulonephritis (PIAGN) is the current term used to describe any acute inflammation of the kidney caused by an infectious agent that results in gross hematuria, edema, and hypertension. Historically, the most common pathogen causing PIAGN was  group A beta-hemolytic Streptococcus. It is the most common cause of PIAGN in children. Other infectious agents include Staphylococcus aureus, S epidermidis, echovirus, human immunodeficiency virus, adenovirus, influenza A virus, and Epstein-Barr virus.

PIAGN can occur in children of any age, but most typically affects those younger than 12 years. Pharyngitis and pyoderma are the most likely antecedent infections associated with PIAGN. Throat infection usually precedes the onset of hematuria, edema, and hypertension by about 2 weeks; pyoderma may precede the renal manifestations by as many as 6 weeks.

Because the symptoms of PIAGN may mimic any acute glomerulonephritis, it is essential to obtain appropriate laboratory tests to confirm the diagnosis. Urinalysis typically reveals red blood cells and red blood cell casts. Serum electrolyte concentrations are generally normal in PIAGN, although some patients may experience a decline in renal function. Those who have elevated serum creatinine levels should have the creatinine measurement repeated. In patients in whom the creatinine levels continue to rise after several days, one must entertain the possibility that the patient may have rapidly progressive glomerulonephritis, requiring immediate consultation with a nephrologist.

Because the complement system is involved in the pathogenesis of PIAGN, serum complement 3 (C3) levels are reduced. Low C3 and C4 levels must raise the suspicion of other causes of AGN, such as membranoproliferative GN or lupus nephritis. One additional test that can be performed is evaluation of anti-DNAse B, which is almost uniformly abnormal in PIAGN.

Although not all patients who have PIAGN require hospitalization, those who have moderate-to-severe hypertension or decreased urinary output need to be hospitalized. The etiology of hypertension is salt and water retention; accordingly, salt restriction is essential to control blood pressure. Initial treatment with diuretics may be necessary in patients who have hypertension. Other antihypertensive medications may be necessary in unresponsive patients. There is no treatment available for the intrarenal inflammation in routine cases of PIAGN. If the blood pressure is normal or mildly elevated, the patient should be followed up the next day with the pediatrician to monitor blood pressure and urine output. In addition, the parents should monitor the urine output at home.

The follow-up of patients who have suspected PIAGN includes biweekly (qow) blood pressure determinations until the blood pressure returns to  normal. The vast majority of patients will experience a normalization of serum C3 levels within 6 weeks. (At six weeks, expect C3: Normal; Hematuria: Microscopic; Protein: Negative)  Those whose C3 levels remain low at 6 weeks may require up to 4 more weeks for normalization. If complement levels remain low and the proteinuria persists, a renal biopsy is indicated. The most likely causes, if this occurs, are membranoproliferative GN or lupus nephritis. 

References:
Bernstein J, Edelmann CM Jr. Glomerular diseases: introduction and
classification. In: Edelmann CM Jr, ed. Pediatric Kidney Disease. 2nd
ed. Boston, Mass: Little, Brown; 1992:1181-1188
Nissenson AR, Baraff LJ, Fine RN, Knutson DW. Poststreptococcal acute
glomerulonephritis: fact and controversy. Ann Intern Med.
1979;91:76-86
Wyatt RJ, Forristal J, West CD, Sugimoto S, Curd JG. Complement
profiles in acute post-streptococcal glomerulonephritis. Pediatr
Nephrol. 1988;2:219-223