Acute post streptococcal glomerulonephritis 

Pathophysiology

• Prototype for Acute Glomerulonephritis
• Most common cause of kidney injury in children in the Middle East, Africa, Australia, and worldwide.
  • 97% of PSGN cases are in underprivileged countries.
• Follows Group A Beta Hemolytic Streptococcus Infection

Pathophysiology

• Immunological disease: Type III hypersensitivity reaction.
• Formation of immune complexes containing streptococcal antigen and human antibody.
• Deposition of immune complexes in kidney glomeruli or in situ formation within the kidney glomeruli.
• Activation of the alternate complement pathway, infiltration of leukocytes, and proliferation of mesangial cells.
• Impaired capillary perfusion and glomerular filtration rate (GFR), leading to renal failure, acid-base imbalance, electrolyte abnormalities, volume overload, edema, and hypertension.
• 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 higher frequency of APSGN in children than in adults

Mortality/Morbidity

• Early death is extremely rare in children (< 1%) ( 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.

Prognosis

• Most cases are self limited (95%) – Resolve within 4 weeks without residua
• Adults do worse then children – Higher risk of Chronic Glomerulonephritis

Risks 

• Anyone can get PSGN after having
  • strep throat
  • scarlet fever
  •  impetigo. 
• ATSI
• children > 5 years
  • Developing PSGN after strep throat or scarlet fever is most common in young, school-age children.
  • Developing PSGN after impetigo is most common in preschool-age children.
• adults > 60

History

• Streptococcal Pharyngitis
  • Onset 10-14 days after infection
• Scarlet Fever
  • Onset 3-6 weeks after infection
• The onset of signs and symptoms at the same time as pharyngitis (also called synpharyngitic nephritis) is more likely to be immunoglobulin A (IgA) nephropathy rather than APSGN.

Symptoms

• Nonspecific symptoms 
  • general malaise
  • weakness
  • anorexia 
  • Irritable
  • lethargic
• Weight gain from oedema
• CLassic triad
  • hematuria
  • edema
  • hypertension.
• Acute nephritic syndrome
  • is the most frequent presentation of APSGN
  • Edema : Periorbital edema 
  • Hematuria
    • Gross hematuria in 30-50% of acute PSGN cases (smoky, tea-colored, cola-colored, or rusty urine).
  • Hypertension
    1. thought to be the result of excessive salt and water retention. 
    2. 60-80% of cases, typically resolving in 10 days.
    3. Hypertensive encephalopathy occurs in 5-10% of patients
  • Oliguria
    1. urine output is less than 200 mL
    2. Less than half experience oliguria.
    3. Severe cases may show signs of anuric renal failure, life-threatening acid-base imbalance, electrolyte abnormalities, and fluid overload requiring RRT.
  • Left ventricular dysfunction

Differentials

• Anaphylaxis
  • Angioedema
• Cardiac
  • CCF
  • Myocarditis
  • CMO
  • Dysrhythmia
  • SBE
  • anaemia
• Kidney disease
  • PSGN
  • Nephrotic syndrome
  • Other types of GN
  • IgA nephropathy
  • Good Pastures Syndrome
• Liver disease with hypoalbuminaemia: Cirrhosis
• Protein losing enteropathy: CF , coeliac disease, IBD
• Infection
  • Sepsis,Cellulitis ,EBV, Mumps
• Lymphoedema
  • Burns , congenital/obstructive
• Vitamin E deficiency  (uncommon)
• Vasculitides
  • Kawasaki’s  disease
  • HSP

Medical Hx

• preceding streptococcal infection 
• pharyngitis
• tonsillitis
• pyoderma
• skin infections
• sick contacts
• recent treatments
• Dark urine (brown-, tea-, or cola-colored) 
• Odema Symptoms
  • Periorbital edema –  prominent upon awakening and, if the patient is active, tends to subside at the end of the day
  • generalized edema
• SSx of circulatory congestion – dyspnea
• Family Hx
• Meds
• Allergies and immunisations
• Social situation
  • ?main carer
  • Schooling

Examination

• Basic vitals
• Focus on
  • Cardiovascular
• BP/HTN
• HR
• ?murmur
• JVP

Signs of LV dysfunction

• Temperature
• Joint pain//swelling
• weight ?change
• skin check
  • rash
  • purpura
• oedma
• Renal

Investigations

• Evidence of preceding streptococcal infection:
  1. ASOT (Antistreptolysin O titer) + anti-DNase B titres
     • if available (repeat 10–14 days later if first test not confirmatory)
     • The false negatives rate is 20-30%, reduce false negative with anti-DNase B titre 
     • False positives can result from liver disease and tuberculosis.

Rapid antigen test

• Turnaround time of 1-3 hours
• sensitivity of 86% and specificity of 96%
•  cost only $5-$10 compared with $30 for throat cultures
• But unfortunately DOES NOT attract an MBS rebate.

Serology

• C3
  1. marked depression of C3, and some have depression fo C2, and C4
  2. indicative of an antigen-antibody interaction 
  3. The decrease in C3 concentration typically occurs before the increase in ASO titers
  4. In most uncomplicated cases, the complement levels return to normal in 6-8 weeks. 
  5. Prolonged hypocomplementemia suggests an alternative diagnosis
• Renal Function Tests:
  • Elevated blood urea nitrogen (BUN) and serum creatinine during the acute phase.
  • Values return to normal late

Urine analysis

• Hematuria
  • Macroscopic or microscopic hematuria.
  • resolves within 3-6 months but may persist as long as 18 months
  • Microscopic hematuria may be present in patients in whom the disease has otherwise clinically resolved
• Proteinuria
  • May be mild or so severe that it causes nephrotic syndrome
    • Approximately 5-10% of patients with APSGN have nephrotic-range proteinuria
    • Patients with nephrotic-range proteinuria in the acute phase or persistent heavy proteinuria have a worse prognosis. 
  • Proteinuria usually disappears in 6 months. 
• Renal Biopsy if:
  1. Absence of the latent period between streptococcal infection and acute glomerulonephritis
  2. Anuria
  3. Rapidly progressive renal failure.
  4. Normal serum complement levels
  5. No rise in antistreptococcal antibodies
  6. Extrarenal manifestations of systemic disease
  7. No improvement or continued decrease in the glomerular filtration rate at 2 weeks
  8. Persistence of hypertension beyond 2 weeks

• Atypical features in the recovery phase that mandate a renal biopsy include the following:
• Failure of glomerular filtration rate to normalize by 4 weeks
• Persistent hypocomplementemia beyond 6 weeks
• Persistent microscopic hematuria beyond 18 months
• Persistent proteinuria beyond 6 months

Imaging Studies

• Ultrasonography: Kidneys are enlarged only in a few patients.
• The chest x-ray may show pulmonary congestion in patients with symptoms consistent with volume overload or heart failure. 

Treatment / Management

PSGN is a self-limiting condition in most cases, and thus only symptomatic treatment is needed. Supportive treatment aims at controlling the complications of volume overload such as hypertension and edema, which are prominent during the acute phase of the disease

General measures

• Strict fluid balance = Salt and water restriction to treat the edema.
• Bed rest and immobilization are recommendations in the first few days of the disease. 
• Throat cultures on the patient and family members are important.
• All affected members need to be treated with penicillin or erythromycin.
• Daily weight

Symptomatic therapy

• Acute phase of the disease
  • control edema & blood pressure
  • Low-salt diet – Two grams of sodium per day
  • fluid restricit (1L/day)

• Antihypertensive medications: 
  • Blood pressure can be managed by restricting salt and fluid intake along with diuretics are needed.
  • In cases with uncontrolled blood pressure, the use of calcium channel blockers is recommended.
  • The use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) is recommended in patients with stable GFR and with near-normal potassium levels.
• diuretics
  • Loop diuretics increase urinary output and consequently improve cardiovascular congestion and hypertension.
  • Loop diuretics (furosemide) are preferred over thiazides (hydrochlorothiazide or chlorthalidone).
  • The efficacy of thiazide diuretics is very minimal when GFR < 30 ml/min.
• Dialysis if:
  • life-threatening hyperkalemia
  • clinical manifestations of uremia

• Steroids, immunosuppressive agents, and plasmapheresis are not generally indicated

• Steroids
  • MethylPred Pulse If the biopsy findings show evidence of crescentic glomerulonephritis with more than 30% of the glomeruli involved, 
• Manage streptococcal infection
  • Throat cultures should be performed on
    • APSGN Patients
    • family members
    • close personal contacts
    • children who have been staying in the household 2 weeks prior to the onset of APSGN
  • All clinical cases of APSGN should be given IM benzathine penicillin regardless of whether skin sores/pharyngitis are present at the time of presentation or not
    • Penicillin G (250 mg qid for 7-10 d) or 
    • Erythromycin (250 mg qid for 7-10 d) for patients allergic to penicillin. 
    • prevent nephritis in carriers and helps prevent the spread of nephritogenic strains to others.

Follow up

• All cases should be medically reviewed no later than 6-8 weeks after discharge.
• seen twice weekly for BP measurement, weight, dipstick urinary monitoring and physical examination until
• paediatrician or senior doctor review at 6-8 weeks. For this medical follow-up,
• please collect urine for microscopy if you are within 24 hours of laboratory
• processing (or urinary dipstick if not) and blood for complement (C3 & C4) levels

Reporting

• Cases of PSGN classified  as
  • Confirmed: Lab definitive evidence, OR Lab suggestive AND Clinical Evidence
  • Probable: Clinical evidence only
  • Possible: Lab suggestive evidence only

• Both Confirmed cases and Probable cases should be notified. 
• Possible cases should be reported to Centre for Disease Control (CDC) but not notified to NTNDS.

• Lab definitive evidence = Renal Biopy
• Lab suggestive evidence
  • Haematuria on microscopy
  • Evidence of recent streptococcal infection (positive Group A Streptococcal culture from skin or throat, or elevated ASO titre or Anti-DNase B)
  • Reduced C3 level
• Clinical evidence: At least 2 of the following:
  • facial oedema
  • >= moderate haematuria on dipstick
  • hypertension
  • peripheral oedema

Secondary prophylaxis

is not required for Acute Post-Streptococcal Glomerulonephritis (APSGN) because it is a self-limited immune response to a preceding Group A Streptococcal (GAS) infection (usually of the throat or skin), and recurrence of APSGN is extremely rare.

Key reasons include:

1. Pathophysiology: APSGN results from immune complex deposition in the glomeruli following a specific immune response to a GAS infection. The renal manifestations occur due to immune system activation, not from ongoing or recurrent streptococcal infections.
2. Recurrence Risk: Unlike Acute Rheumatic Fever (ARF), which has a significant risk of recurrence and cumulative damage to cardiac tissue with subsequent streptococcal infections, APSGN typically does not recur after an initial episode, even if there is subsequent GAS exposure.
3. Duration of Disease: APSGN usually resolves spontaneously with supportive care and does not lead to chronic kidney disease in most cases, especially in children. Long-term prophylaxis is unnecessary because the condition generally does not pose a significant risk of progressive or recurrent disease in response to future infections.

Therefore, secondary prophylaxis with antibiotics (e.g., penicillin prophylaxis) is reserved primarily for conditions such as ARF to prevent recurrences due to their potential for chronic complications, unlike APSGN. The focus for APSGN patients remains supportive care, monitoring for complications, and addressing any acute infections promptly to avoid complications.

Control of APSGN 

https://www.wacountry.health.wa.gov.au/~/media/WACHS/Documents/About-us/Policies/Public-Health-Management-of-Acute-Post-Streptococcal-Glomerulonephritis-Guideline.pdf?thn=0

1. Prevention

• Control of scabies and skin sores
  • In the NT, scabies infestation is the major cause of infected skin sores that carry the streptococcus.
  • To help prevent epidemics of APSGN:
    1. promote community control of scabies and skin sores
    2. promote regular washing, especially of children, to decrease spread of the bacteria
    3. treat skin sores with a single IM dose of benzathine penicillin
• Improved housing
  • Housing construction and maintenance are beyond the direct control of health centre staff. 
  • However, it is important that health staff support initiatives that improve housing, reduce overcrowding and subsequent overuse of household facilities, as these are major contributing factors in the spread of all communicable diseases.

1. Sporadic cases:

• May or may not indicate the beginning of an outbreak
• Should be managed in consultation with a paediatrician and ideally hospitalised
  • HTN and renal function may complicate the disease
• Notified by phone to CDC
• Ideally a swab should be taken from 2 different skin sores if present for identification of GAS
• Bloods taken for above pathology
• Treat scabies with 5% permethrin
• Treat skin sores with IM benzathine penicillin according to weight
• Community health measures:
  • Family, household and close contacts (those staying in the house 2 weeks preceding the onset of the illness) should be examined for PSGN
    • Examination of contacts involves:
      • inspection of the skin for sores, scabies and oedema
      • measuring the blood pressure for hypertension
      • testing urine for the presence of haematuria
  • if aged 12 months to 17 years should also be given an injection of benzathine penicillin.
  • All individuals identified as having scabies should be treated with permethrin

Outbreaks:

• Community:

2 cases, probable or confirmed

• living in the same community
• occurring within a week of each other
• at least one case has low C3
• nd not being contacts 

OR

1 confirmed case + 2 probable cases

• living in the same community 
• occurring within a month of each other
• not being contacts of each other

→ Community outbreak response by CDC including education and community wide screening

• – Territory wide alert:
  • -4 cases, probable or confirmed within 2 week
  • → Territory wide alert to all medical officers and communities to raise awareness for diagnosing and reporting cases

Community Health

• Community education should
  • target health staff
  • parents
  • teachers
• verbal discussions with prominent community members
• Screening of all children in the community
  • aged 12 months to less than 17 years for
    • oedema
    • skin sores
    • scabies
• raise community awareness of scabies control and skin sores
• promoting regular washing especially of children to reduce bacterial spread
• skin sores are present administration of
  • IM benzathene penicillin
• scabies are identified then treatment of the case and all household contacts with
  • 5% topical permethrin
• be vigilant if there is a probable or suspected case of APSGN in your community. 
• Remember to include environmental health and health promotion teams’ members to strengthen community action in these circumstances.