Poststreptococcal glomerulonephritis

Poststreptococcal glomerulonephritis (PSGN) is an acute glomerular inflammation that follows infection with nephritogenic strains of streptococci. Although most commonly seen in children following group A streptococcal tonsillopharyngitis, skin infections such as impetigo may also trigger PSGN. Individuals aged > 60 years (especially those with diabetes, malignancy, or alcohol dependency) may also be affected. Deposition of immune complexes within the glomerular basement membrane results in complement activation and subsequent damage to the glomeruli. PSGN typically manifests as nephritic syndrome with hematuria, mild proteinuria, edema, and hypertension. Evidence of recent streptococcal infection (e.g., elevated antistreptolysin O (ASO) and/or anti-DNase B titers) and low complement levels support the diagnosis. Close monitoring and supportive management of edema and hypertension are usually sufficient. Antibiotic therapy is indicated if there is evidence of active GAS infection, primarily to minimize the risk of complications and community spread. While most children recover fully, adults are more likely to develop rapidly progressive glomerulonephritis and/or end-stage kidney disease and may require long-term monitoring.

• Bimodal age distribution; mostly affects children (between the ages of 3–12 years) and patients > 60 years of age
• The incidence of PSGN has decreased in developed countries due to the systematic use of antibiotics and improved hygienic standards.

Epidemiological data refers to the US, unless otherwise specified.

• Prior infection with group A beta-hemolytic streptococci (GAS)
• Site of infection
  • In children
    • Infection of the mouth and pharynx (tonsillitis, pharyngitis): PSGN typically arises 1–2 weeks following infection.
    • Soft tissue infections (erysipelas, impetigo): PSGN typically arises 4–6 weeks following infection.
    • Osteomyelitis
  • In adults, the site of infection is usually not the respiratory tract.

Infection-associated glomerulonephritis can also occur following other bacterial infections (e.g., with Staphylococcus aureus, Staphylococcus epidermidis, gram-negative bacteria), viral infections, or malaria, and it can also manifest during an acute infection. ^[1]

Infective endocarditis is a common cause of staphylococcus infection-associated glomerulonephritis, especially amongst individuals who use intravenous drugs. ^[1][2]

Infection with nephritogenic strains of group A beta-hemolytic streptococci → immune complexes containing the streptococcal antigen deposit within the glomerular basement membrane; (likely involves molecular mimicry) → complement activation (↑ consumption of complement factors) → destruction of the glomeruli → immune complex-mediated glomerulonephritis and nephritic syndrome (see “Glomerular diseases” for more information)

Approx. 50% of patients remain asymptomatic.; Symptoms occur approximately 1–6 weeks following an acute infection.

• Nephritic syndrome
  • Hematuria: tea- or cola-colored urine
  • Hypertension: can lead to headaches
  • Edema (prominent facial edema)
  • Oliguria
• Influenza-like symptoms
• Flank pain

General principles ^[1][3]

• The diagnosis of PSGN is typically based on confirming a preceding streptococcal infection in an individual with features of acute glomerulonephritis.
• The characteristic findings in PSGN include:
  • Nephritic sediment and non-nephrotic range proteinuria on urinalysis
  • Evidence of preceding streptococcal infection:
    • Elevated antistreptococcal antibody titers (ASO, anti-DNase B antibodies)
    • Or, in patients with active infection, positive rapid strep test or cultures
  • Low C3 complement with normal C4 complement
• In case of diagnostic uncertainty, consider the following to evaluate for other causes of glomerulonephritis:
  • Renal biopsy
  • Serology (e.g., factor B antibody levels, anti-GBM antibody, ANA, ANCA)

Suspect PSGN in individuals with features of nephritic syndrome and a recent history of GAS infection. ^[1]

Initial evaluation ^[1][4][5]

The following studies are typically routinely obtained in the initial workup for glomerular disease. Findings supportive of PSGN are detailed here. ^[3]

• Urinalysis with microscopy: nephritic sediment
  • Hematuria with RBC casts
  • Proteinuria
  • Pyuria
• Quantification of proteinuria: typically shows non-nephrotic range proteinuria ^[2]
  • Urine protein/creatinine ratio: usually < 300 mg/g ^[1]
  • 24-hour urine collection (less commonly obtained): usually 0.3–3.4 g/24 hour ^[1]
• BMP may reveal: ^[6]
  • ↑ BUN, ↑ creatinine
  • Electrolyte abnormalities
• CBC: : may show normocytic, normochromic anemia ^[7]
• C3 complement, C4 complement levels: : classically shows ↓ C3 complement with normal C4 complement ^[5][8]

Evidence of preceding GAS infection ^[1]

• Antistreptococcal antibody titers
  • Indication: all patients with suspected PSGN
  • Findings: ↑ ASO; , ↑ anti-DNase B antibodies, ↑ antihyaluronidase antibodies
• Isolation of group A beta-hemolytic streptococci
  • Indication: suspected active GAS infection
  • Diagnostics
    • Pharyngitis: rapid strep test, throat culture
    • Skin lesions: wound cultures

PSGN typically occurs following a GAS infection rather than during an active infection. Obtain appropriate diagnostic studies to isolate group A beta-hemolytic streptococci only if active infection is suspected. ^[1]

Additional studies ^[1]

Consider the following studies in case of diagnostic uncertainty.

• Factor B antibody levels ^[9][10]
• Rheumatoid factor and cryoglobulin levels ^[1][3]
• ANA, ANCA, anti-GBM antibody ^[1]

In patients with decreased C3 complement levels, factor B antibody levels may help distinguish between PSGN (elevated factor B levels) and C3 glomerulopathy (normal factor B levels). A renal biopsy is indicated in individuals with low C3 levels and normal factor B antibody levels to confirm C3 glomerulopathy ^[9][10]

If both C3 and C4 complement levels are decreased in a patient with features of glomerulonephritis, consider other causes of immune-complex mediated glomerulonephritis. ^[5]

Renal ultrasound ^[11]

• Indications: may be obtained during a diagnostic workup of hematuria
• Findings: typically normal; may show nonspecific increased echogenicity of the renal cortex

Renal biopsy ^[2][12]

• Indications: (not routinely performed)
  • Signs of rapidly progressive glomerulonephritis
  • Atypical presentation
  • Persistently low complement levels > 12 weeks ^[10]
  • Persistent proteinuria and hypertension > 1 year ^[6]
• Supportive findings: proliferative glomerulopathy with immune complex deposits ^[13]
  • Light microscopy: enlarged and hypercellular glomeruli
  • Immunofluorescent microscopy: granular deposits in the glomerular mesangium and capillaries ; ^[2][4][13]
    • Consisting of IgG, IgM, C3 complement ^[13]
    • Lumpy-bumpy appearance (also called a starry sky appearance) ^[14]
  • Electron microscopy: immune complexes between the epithelial cell layer and the glomerular basement membrane ; (referred to as subepithelial humps) ^[12][13]

• See “Diseases associated with nephritic syndrome.”
• Glomerulonephritis with low serum complement levels ^[15]
  • PSGN
  • C3 glomerulopathy
  • Cryoglobulinemic glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Shunt nephritis
  • Infective endocarditis-associated glomerulonephritis
• Glomerulonephritis with normal serum complement levels ^[15]
  • IgA nephropathy ^[1][5]
  • Hemolytic uremic syndrome
  • Anti-GBM disease
  • Henoch Schonlein purpura

The differential diagnoses listed here are not exhaustive.

Most cases of PSGN are self-limiting and complications of volume overload are managed with supportive treatment.

General principles ^[1]

• Consult nephrology to develop a treatment plan.
• Admit patients with any of the following indications of severe disease: ^[2][6]
  • Indications for dialysis
  • Moderate to severe AKI or progressive renal failure
  • Hypertensive crisis (e.g., neurological symptoms of posterior reversible encephalopathy syndrome) ^[5]
• Manage associated symptoms (e.g., edema, hypertension) as needed.
• Treat current infection, if present.
• Monitor blood pressure, BMP, urinalysis, urine protein, and complement levels until they return to baseline. ^[2][4][5]

Progressive renal failure suggests rapidly progressive glomerulonephritis; obtain a renal biopsy and initiate treatment promptly to prevent end-stage renal disease. ^[5][6]

Supportive care ^[1][2]

See also “Supportive care for AKI.”

Management of edema and volume overload

• Low-sodium diet: < 2 g/day
• Fluid restriction (e.g., < 2 L per day) ^[2]
• Loop diuretics ^[1][6]

Antihypertensives ^[1][2][12]

• Indicated for hypertension refractory to management of edema and volume overload
• Preferred agents include:
  • Calcium channel blockers (e.g., nifedipine)
  • ACE inhibitors or ARBs
    • Uncertain benefit, given the self-limited nature of PSGN ^[2][6]
    • Avoid in patients with rapidly progressive renal dysfunction.
    • Consider in patients with concomitant proteinuria, unless there are contraindications for ACE inhibitors and ARBs. ^[1]
    • Requires close BMP monitoring for progressive AKI and hyperkalemia

Avoid ACE inhibitors and ARBs in patients with rapidly worsening renal function and/or sudden onset of nephrotic range proteinuria, as these medications can exacerbate AKI and hyperkalemia. ^[1][2]

Antibiotic therapy

Antibiotics do not affect the course of PSGN but should be administered in individuals with active GAS infection to prevent complications (e.g., abscess, rheumatic fever) and community outbreak of nephritogenic strains of S. pyogenes. ^[16]

• Indication: evidence of active infection (e.g., positive cultures for GAS) to prevent ^[1]
• Regimens: should be based on the site of infection; follow local protocols when available.
  • GAS tonsillopharyngitis: Initiate recommended antibiotic regimens for acute GAS pharyngitis.
  • Skin and soft tissue infections (e.g., impetigo): Begin empiric antibiotic therapy for skin and soft tissue infections.

Role of glucocorticoids ^[1][2][12]

• Glucocorticoids are not routinely indicated for PSGN (unproven benefit).
• High-dose glucocorticoids may be considered in combination with other immunosuppressants for patients with severe disease.

Complications are more common in adults:

• Acute renal failure
• Rapidly progressive glomerulonephritis
• Nephrotic syndrome later in the course of the disease

We list the most important complications. The selection is not exhaustive.

• Recovery usually occurs within 6–8 weeks.
  • In children: restitution of kidney function in > 90% of cases
  • In some cases, urinalysis may remain abnormal for extended periods.
• In adults, about 50% of patients suffer from persistently reduced renal function.