Post-streptococcal glomerulonephritis

Background

• Post-streptococcal glomerulonephritis (PSGN) is an immune complex-mediated glomerulonephritis that occurs after infection with nephritogenic strains of group A beta-hemolytic streptococci (GAS), typically presenting as acute nephritic syndrome (hematuria, edema, hypertension, oliguria) after a latent period following pharyngitis or skin infection.
• PSGN is the most common cause of acute glomerulonephritis in children and is generally self-limited with excellent prognosis in pediatric patients (>95% complete recovery).
• The emergency physician's key tasks are to recognize the clinical pattern, manage acute complications (hypertensive emergency, pulmonary edema, hyperkalemia), confirm preceding streptococcal infection, and identify atypical features that suggest an alternative diagnosis.
• Most common cause of acute GN in children worldwide, especially in low- and middle-income countries
• Incidence is declining in developed countries due to improved sanitation and antibiotic use
• Bimodal age distribution: most common in children aged 3-12 years; a second peak occurs in adults >60 years (especially with diabetes, malignancy, or alcohol use disorder)
• Male predominance (~2:1)
• Pharyngitis-associated PSGN: more common in temperate/cold climates; latent period 1-2 weeks
• Skin infection (impetigo/pyoderma)-associated PSGN: more common in tropical/warm climates; latent period 3-6 weeks
• Caused by nephritogenic strains of GAS (specific M protein types); not all strep infections cause PSGN

Mechanism

• Nephritogenic GAS antigens (nephritis-associated plasmin receptor [NAPlr], streptococcal pyrogenic exotoxin B [SPeB]) → immune complex formation
• Immune complexes deposit in glomerular basement membrane → complement activation (alternative pathway) → C3 consumption → glomerular inflammation
• Result: diffuse endocapillary proliferative GN with neutrophil infiltration
• Type III hypersensitivity reaction — the latent period reflects time needed for immune complex formation
• PSGN is NOT an active kidney infection — it is a post-infectious immune reaction; the streptococcal infection has typically resolved by the time GN appears

Clinical features

Classic presentation

• School-age child (5-12 years) who had a sore throat 1-2 weeks ago OR impetigo/skin infection 3-6 weeks ago
• Cola-colored ("smoky", "tea-colored") urine — gross hematuria; the presenting complaint in >50% of cases
• Periorbital/facial edema — especially noticeable on waking; often the first sign parents notice
• Hypertension — from sodium and water retention; may be severe
• Oliguria — decreased urine output
• Malaise, fatigue, anorexia, nausea
• Abdominal or flank pain (especially in children)
• Weight gain (fluid retention; may precede visible edema)

Subclinical PSGN

• Microscopic hematuria and low complement only — no overt symptoms
• May be 4-10 times more common than clinical PSGN
• Typically discovered incidentally during screening of contacts during outbreaks

Time course of resolution (important for follow-up counseling)

• Edema: resolves within 5-10 days
• Hypertension: resolves within 2-3 weeks (may take up to 6 weeks)
• Gross hematuria: resolves within 1-3 weeks
• Low C3: normalizes by 6-8 weeks (failure to normalize by 8-12 weeks suggests alternative diagnosis — MPGN, C3 glomerulopathy, or lupus nephritis)
• Microscopic hematuria: may persist for up to 1-2 years (this alone does not indicate ongoing disease)
• Proteinuria: resolves within weeks to months

Complications (the reasons for ED presentation)

• Hypertensive emergency/encephalopathy: headache, altered mental status, visual changes, seizures — from severe volume-mediated hypertension
• Pulmonary edema/congestive heart failure: from volume overload; dyspnea, orthopnea, crackles, hypoxia
• Hyperkalemia: from decreased GFR; potentially life-threatening
• Acute kidney injury: usually mild and transient; severe AKI requiring dialysis is uncommon in children (<5%)
• Rapidly progressive GN (RPGN): rare but serious; crescent formation on biopsy; suspect if renal function rapidly deteriorates rather than improving

Differential diagnosis

The critical timing distinction

Feature	PSGN	IgA nephropathy
Timing relative to infection	1-3 weeks AFTER infection (post-infectious; latent period)	Within 1-2 DAYS of infection (synpharyngitic)
Complement C3	Low (normalizes by 6-8 weeks)	Normal
Typical age	Children 5-12	Adolescents/young adults
Course	Usually self-limited	Chronic/relapsing
Recurrence	Rare (lifelong immunity to specific strain)	Common

Other causes of acute nephritic syndrome

• Lupus nephritis — low C3 AND C4 (PSGN: low C3, usually normal C4); other SLE features; ANA/anti-dsDNA positive
• MPGN / C3 glomerulopathy — persistently low C3 (>8-12 weeks; does not normalize like PSGN)
• ANCA-associated vasculitis — normal complement; ANCA positive; adults
• Anti-GBM disease (Goodpasture) — normal complement; anti-GBM positive; hemoptysis
• Endocarditis-associated GN — may have low C3; positive blood cultures; cardiac murmur; fever; often staphylococcal
• Henoch-Schönlein purpura (IgA vasculitis) — palpable purpura, arthritis, abdominal pain, GN; may follow strep infection (confusing overlap)
• Staphylococcal infection-associated GN — increasingly common; occurs during active infection (not post-infectious); often in older/diabetic/immunocompromised adults; MRSA; C3 may be normal; IgA dominant

Red flags suggesting NOT PSGN (trigger nephrology referral/biopsy)

• C3 not normalizing by 8 weeks
• Persistent or worsening renal function beyond 4 weeks
• Nephrotic-range proteinuria (>3.5 g/day; occurs in <5% of PSGN)
• Rapidly rising creatinine (suspect RPGN)
• Recurrent gross hematuria (suggests IgA nephropathy or Alport syndrome)
• No evidence of preceding streptococcal infection
• Systemic symptoms (rash, joint pain, hemoptysis, fever) suggesting vasculitis or lupus
• Adult with severe presentation (worse prognosis than children; lower threshold for biopsy)

Causes of Glomerulonephritis

• Poststreptococcal glomerulonephritis
• Hemolytic-uremic syndrome
• Henoch-Schonlein purpura
• IgA nephropathy
• Lupus nephritis
• Alport syndrome
• Goodpasture syndrome
• Paraneoplastic

Hyperkalemia

• Pseudohyperkalemia: hemolyzed specimen, prolonged tourniquet use prior to blood draw, thrombocytosis or leukocytosis
• Redistribution (shift from intracellular to extracellular space)
  • Acidemia (see DKA)
  • Cellular breakdown: see Rhabdomyolysis/Crush syndrome, electrical/thermal burn, hemolysis, see Tumor lysis syndrome
• Increased total body potassium
  • Inadequate excretion: Acute/chronic renal failure, Addison's disease, type 4 RTA
  • Drug-induced: potassium-sparing diuretic (spironolactone), angiotensin converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Excessive intake: diet, blood transfusion
• Other causes: succinylcholine, digitalis, beta-blockers

Evaluation

ED workup

• Urinalysis with microscopy: the most important initial test
  • Hematuria (dysmorphic RBCs, RBC casts — virtually pathognomonic for GN)
  • Proteinuria (usually 1-3+ on dipstick; subnephrotic)
  • Sterile pyuria, WBC casts (common)
• BMP/CMP:
  • Creatinine (mild elevation common; severe AKI uncommon)
  • Potassium (hyperkalemia risk from decreased GFR)
  • BUN (elevated; often disproportionately to creatinine from volume contraction)
  • Bicarbonate (metabolic acidosis if severe AKI)
• CBC: normochromic, normocytic anemia (dilutional from hypervolemia)
• Albumin: usually normal or mildly low (markedly low suggests nephrotic overlap or alternative diagnosis)
• Blood pressure: frequently elevated

Confirming preceding streptococcal infection

Test	Utility
ASO (anti-streptolysin O) titer	Elevated after pharyngitis (peaks 10-14 days; positive in ~80% of post-pharyngitis PSGN); may be normal after skin infection
Anti-DNase B titer	Elevated after skin infections (impetigo/pyoderma); more sensitive than ASO for skin-related PSGN; also elevated after pharyngitis
Streptozyme test	Measures 5 streptococcal antibodies simultaneously; positive in >95% of PSGN after pharyngitis
Throat culture / rapid strep test	May be negative by the time GN presents (infection has resolved); does not exclude prior infection

• Both ASO and anti-DNase B should be sent — using both increases sensitivity to >95% for detecting preceding streptococcal infection
• Prior antibiotic treatment may blunt the antibody rise

Complement levels

• C3: low in ~90% of PSGN during the first 2 weeks (alternative complement pathway activation)
• C4: usually normal (or only slightly low) — this distinguishes from lupus nephritis (both C3 AND C4 are low)
• C3 should normalize by 6-8 weeks — failure to normalize is a red flag for MPGN, C3 glomerulopathy, or lupus and mandates nephrology referral

When is renal biopsy needed?

• NOT routinely needed for classic PSGN in children with typical presentation (self-limited; biopsy adds risk without changing management)
• Biopsy indications:
  • C3 not normalizing by 8-12 weeks
  • Persistent or worsening renal impairment beyond 4 weeks
  • Nephrotic-range proteinuria
  • Rapidly progressive course (suspect RPGN/crescentic GN)
  • Atypical features (no strep evidence, systemic symptoms, recurrent hematuria)
  • Adults with severe presentations (lower threshold for biopsy; worse prognosis)

Management

Hypertension and volume overload — the most common ED problems

• Fluid restriction: limit intake to insensible losses + urine output
• Sodium restriction
• Loop diuretics: furosemide 1-2 mg/kg IV (children) or 40-80 mg IV (adults) — first-line treatment for both hypertension and edema in PSGN
  • Hypertension in PSGN is volume-mediated — diuretics are more effective than vasodilators as initial therapy
• Antihypertensives if BP not controlled with diuretics:
  • Calcium channel blockers (nifedipine, amlodipine) — first-line add-on
  • ACE inhibitors/ARBs: useful for chronic BP control but use cautiously in acute AKI with hyperkalemia
  • IV antihypertensives (nicardipine, labetalol) for hypertensive emergency

Hyperkalemia

• Manage per standard Hyperkalemia protocols
• Calcium gluconate (membrane stabilization if ECG changes)
• Insulin + dextrose, albuterol, bicarbonate, kayexalate
• Dialysis if refractory

Pulmonary edema

• Furosemide IV (high-dose if impaired GFR)
• Oxygen, CPAP/BiPAP or intubation if severe
• Fluid restriction
• Dialysis/ultrafiltration if refractory to diuretics

Severe AKI

• Rare in children; more common in adults
• Supportive care; dialysis if indications present (refractory hyperkalemia, acidosis, volume overload, uremia)

Antibiotics

• Penicillin V (oral) or penicillin G benzathine (IM) to eradicate any residual GAS — does NOT treat the GN itself (the immune reaction has already occurred) but prevents ongoing streptococcal carriage and spread to contacts
• Alternative for penicillin allergy: erythromycin or azithromycin
• Antibiotics do not alter the course of PSGN — they are given for public health (preventing transmission) and to eradicate the organism

Immunosuppression

• NOT indicated for typical PSGN — the disease is self-limited
• Immunosuppression is reserved for RPGN with crescent formation (rare; nephrology-directed; pulse methylprednisolone ± cyclophosphamide)

Disposition

• Admit:
  • Hypertensive emergency or BP requiring IV antihypertensives
  • Pulmonary edema or respiratory distress
  • Hyperkalemia
  • Significant AKI (creatinine >2x normal, oliguria)
  • Severe edema unresponsive to oral diuretics
  • Inability to restrict fluids/sodium at home (young children)
• Consider discharge with close follow-up (within 48-72 hours):
  • Classic presentation in a child with mild-moderate hypertension responsive to oral medications
  • Stable renal function (creatinine normal or only mildly elevated)
  • No hyperkalemia
  • Reliable family able to restrict fluids/sodium and administer medications
  • Ensure pediatric nephrology follow-up
• Follow-up schedule:
  • Weekly BP and urinalysis until improving
  • Repeat C3 at 8 weeks — must normalize; if not, refer to nephrology for alternative diagnosis evaluation
  • Repeat renal function at 4-8 weeks
  • Anti-hypertensives can usually be weaned by 6 weeks
  • Microscopic hematuria may persist for 1-2 years; this alone does not require treatment
• Return precautions: decreased urine output, worsening edema, headache, visual changes, seizures, difficulty breathing, dark urine recurrence

See Also

• Nephritic syndrome
• Nephrotic syndrome
• Lupus nephritis
• IgA nephropathy
• Henoch-Schönlein purpura
• Hypertensive emergency
• Hyperkalemia
• Acute kidney injury
• Streptococcal pharyngitis

External Links

• CDC — Clinical Guidelines for Post-Streptococcal Glomerulonephritis
• CDC — About Post-Streptococcal Glomerulonephritis
• World J Nephrol — Management and outcomes of APSGN in children (2022)
• Cureus — Comprehensive Review of PSGN (2022)
• StatPearls — Infection-Related Glomerulonephritis
• Royal Children's Hospital Melbourne — PSGN Clinical Practice Guidelines