OVERVIEW: What every practitioner needs to know
Are you sure your patient has poststreptococcal acute glomerulonephritis? What are the typical findings for this disease?
Poststreptococcal acute glomerulonephritis (PSAGN) is a common cause of acute glomerulonephritis in children. It is a self-limited disease typically characterized by gross hematuria with red blood cell casts, hypertension, edema and acute kidney injury (nephritic syndrome) with evidence of previous streptococcal infection.
PSAGN is an immune complex-mediated glomerular disease with activation of the alternative complement pathway caused by an antecedent pharyngeal or skin infection by group A ß-hemolytic streptococcus. The latency period between the infection and onset of PSAGN is 7-14 days for pharyngitis and 14-21 days for pyoderma. Treatment is supportive and the prognosis is generally good, with recovery in 6-8 weeks.
History usually reveals an antecedent group A β-hemolytic streptococcus skin (2-3 weeks) or throat (1-2 weeks) infection. The clinical presentation varies from asymptomatic to microscopic hematuria to nephritic syndrome to nephritic-nephrotic syndrome. Rarely, PSAGN can present with severe acute kidney injury with rapidly progressive glomerulonephritis.
The most common symptoms include:
Gross hematuria, tea colored or cola colored
Edema due to fluid overload; in severe cases, pulmonary edema may develop
Hypertension due to fluid overload; hypertensive encephalopathy is a serious complication
What are the diagnostic criteria for PSAGN?
Clinical features of acute nephritis (gross hematuria, edema, hypertension)
Red blood cell casts or dysmorphic red blood cells on microscopic analysis of urine
Evidence of recent group A β-hemolytic streptococcal infection: positive throat culture or wound culture, increased antistreptolysin (ASO) or antideoxyribonuclease-B (anti-DNase B titers)
Decreased serum complement C3
Normalization of C3 in 6-8 weeks
What are findings on physical examination?
What other disease/condition shares some of these symptoms?
Postinfectious glomerulonephritis has a presentation and clinical course that is similar to PSAGN. The infectious cause may be from other bacterial, viral, or parasitic agents.
The differential diagnosis includes:
Henoch-Schönlein purpura (HSP)
Antineutrophilic cytoplasmic antibodies (ANCA) vasculitis
Systemic lupus erythermatosus (SLE) nephritis
Conditions associated with low complement C3 levels include PSAGN, membranoproliferative glomerulonephritis (MPGN), SLE nephritis, shunt/endocarditis nephritis. Gross hematuria concurrent with an illness (including strepococcal infections) is indicative of IgA nephropathy or Alport syndrome.
What caused this disease to develop at this time?
PSAGN is caused by an immune reaction to infection by group A β-hemolytic streptococcus. There are pharyngitis-associated, pyoderma-associated, and rheumatogenic strains of strepococcus that are defined by their surface M protein. Immune complex formation results in glomerular disease, alternative complement pathway activation, and glomerular infiltration of polymorphonuclear cells.
The exact mechanism of immune complex formation is debated; theories propose in situ immune complex formation resulting from strepococcal antigen deposition in the glomerulus, in situ cross-reaction with glomerular components (molecular mimicry), or deposition of circulating immune complexes. Nephritogenic antigen candidates include nephritis-associated plasmin receptor (NAPIr) and strepococcal pyrogenic exotoxin B (SPE B).
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Urinalysis: microscopic evaluation for dysmorphic red blood cells and red blood cell casts should be carried out.
Urinary protein to creatinine ratio in a first-morning sample: proteinuria may reach the nephrotic range.
Comprehensive metabolic panel: patient may present with elevated serum creatinine and blood urea nitrogen (BUN) levels, hyperkalemia, hyponatremia, and hypoalbuminemia.
Complement (C3) level: It is low but should return to normal in 6-8 weeks.
ASO titers: These are elevated, but titers may be affected by antibiotic treatment. Anti-DNase B and antihyaluronidase titers are more specific for pyoderma-associated PSAGN. The streptozyme panel measures five streptococcal antibodies.
Complete blood count (CBC): anemia, thrombocytosis, and leukocytosis are found in one third of cases.
Would imaging studies be helpful? If so, which ones?
In general, imaging studies are not required for the diagnosis of PSAGN. Renal ultrasonography may show enlarged, echogenic kidneys. Chest radiography may be needed to assess for pulmonary edema.
Confirming the diagnosis
Renal biopsy is not needed in most cases to make the diagnosis of PSAGN; however, biopsy may be indicated if the diagnosis is unclear.
Indications for renal biopsy include:
No laboratory evidence of previous streptococcal infection.
Significant renal insufficiency is present (to rule out crescentic glomerulonephritis).
C3 does not normalize after 6-8 weeks (to rule out MPGN).
Persistent significant proteinuria.
On histologic examination, light microscopy shows diffuse mesangial hypercellularity and inflammatory infiltrate of the glomerular tuft with polymorphonuclear cells. Immunofluoresence studies show deposits of C3 and IgG. Subepithelial humps are found on examination with electron microscopy.
If you are able to confirm that the patient has poststreptococcal acute glomerulonephritis, what treatment should be initiated?
Treatment for PSAGN is generally supportive and is aimed at treating problems related to volume overload and hyperkalemia. Hospitalization is indicated in patients with hyperkalemia, hypertension, pulmonary edema/heart failure, and/or acute renal injury.
Loop diuretics (furosemide) and salt restriction are mainstays for treatment of volume overload and hypertension. In cases of severe hypertension, parenteral antihypertensive drips, vasodilators and labetalol may be used. Calcium channel blockers are first-line oral antihypertensive agents. Angiotensin-converting enzyme (ACE) Inhibitors and angiotensin-receptor blockers (ARBs) should generally be avoided in the acute period because of the risk of hyperkalemia and renal insufficiency.
Hyperkalemia is treated by restriction of potassium in the diet and medications that lower potassium, including kayexalate, furosemide, insulin/glucose, bicarbonate, and beta-agonists. Calcium gluconate is given to stabilize the cardiac membrane.
Patients who have not been previously treated for the streptococcal infection should be given a course of antibiotics. Antibiotics do not alter or attenuate the course of PSAGN but should be given to prevent rheumatic fever.
Immunosuppressive therapy is reserved for cases of rapidly progressive glomerulonephritis with crescents.
What are the adverse effects associated with each treatment option?
Furosemide: hypokalemia, metabolic alkalosis, electrolyte imbalance, dehydration, ototoxicity, weakness, muscle cramps, anemia, thrombocytopenia, rash.
Amlodipine: edema, headache, fatigue, palpitations, nausea.
Labetalol: bradycardia, bronchospasm, headache, nausea, arrhythmia.
Kayexalate: hypokalemia, intestinal obstruction/necrosis, gastrointestinal (GI) perforation, constipation, hypernatremia, nausea.
Insulin: hypoglycemia, hypokalemia, anaphylaxis.
What are the possible outcomes of poststreptococcal acute glomerulonephritis?
The prognosis is generally good for PSAGN, with recovery in 6-8 weeks. Hypertension, gross hematuria, acute kidneyinjury, and proteinuria resolve during this period. C3 levels also normalize during this period. Microscopic hematuria may be present for several years after the episode. PSAGN rarely progresses to end-stage kidney disease, although those with rapidly progressive glomerulonephritis are at higher risk for the development of proteinuria, hypertension, and end-stage kidney disease.
What will you tell the family about prognosis?
Recurrence of PSAGN is extremely uncommon because long-term antibodies to the nephritogenic strain usually develop. The prognosis is generally good, with very few cases progressing to end-stage kidney disease. Those with rapidly progressive glomerulonephritis are at increased risk for hypertension, proteinuria, and progression to end-stage kidney disease. Less than 5% of patients experience hypertension or proteinuria in the long term.
What causes this disease and how frequent is it?
PSAGN is the most common cause of acute glomerulonephritis worldwide, with the majority of cases in developing countries. There are an estimated 472,000 cases per year worldwide. The peak incidence is 5-15 years of age. PSAGN is uncommon in children younger than 2 years of age because of the low incidence of streptococcal pharyngitis in this age group.
PSAGN is diagnosed two times more often in males than in females; the cause for this is unclear. It may occur sporadically or during an epidemic. Pyoderma-associated cases occur more often in the late summer and early fall months.
There is no single etiologic locus for the occurrence of PSAGN.
Other clinical manifestations that might help with diagnosis and management
Rarely, patients may present with hypertensive crisis, seizures, and posterior reversible encephalopathy syndrome. The urinalysis results may initially be normal. There have been reported cases of PSAGN occurring concurrently with HSP, acute rheumatic fever, thrombotic cytopenic purpurea (TTP), and hemolytic-uremic syndrome (HUS).
What complications might you expect from the disease or treatment of the disease?
Congestive heart failure
Are additional laboratory studies available, even some that are not widely available?
Serum IgG levels are elevated in some patients. Some patients may have classical pathway complement activation at the onset of disease with depressed serum levels of C1q, C2, and or C4.
How can poststreptococcal acute glomerulonephritis be prevented?
There is no evidence that treating streptococcal infections early with antibiotics will prevent PSAGN in individual cases. However, in cases of epidemic, treating the community with antibiotics may reduce nephritogenic strains and thus lower the incidence of PSAGN. Ideally, the development of a vaccine against nephritogenic strains of streptococcus would eradicate PSAGN and is desirable.
What is the evidence?
Elison, T, Ault, BH, Jones, DP. “Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis”. Pediatr Nephrol. vol. 26. 2011. pp. 165-80.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has poststreptococcal acute glomerulonephritis? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has poststreptococcal acute glomerulonephritis, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of poststreptococcal acute glomerulonephritis?
- What causes this disease and how frequent is it?
- Other clinical manifestations that might help with diagnosis and management
- What complications might you expect from the disease or treatment of the disease?
- Are additional laboratory studies available, even some that are not widely available?
- How can poststreptococcal acute glomerulonephritis be prevented?
- What is the evidence?