APSGN Diagnosis: A Comprehensive Guide to Acute Post-Streptococcal Glomerulonephritis

Acute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease that emerges following an infection with Streptococcus pyogenes, commonly known as group A streptococcus (GAS). This condition typically arises after a skin infection, such as impetigo or cellulitis, or a throat infection like pharyngitis. While GAS is the most frequent culprit, groups C or G streptococci can also occasionally trigger APSGN. Prompt and accurate diagnosis is crucial for effective management and preventing potential complications, especially in vulnerable populations. This guide provides an in-depth look into Apsgn Diagnosis, drawing upon established guidelines and research to offer a comprehensive understanding for healthcare professionals and those seeking detailed information.

Understanding APSGN and Its Diagnostic Approach

Diagnosing APSGN involves a multifaceted approach, combining clinical evaluation with laboratory investigations. Due to the varied presentation of APSGN, ranging from asymptomatic cases to severe acute nephritis syndrome, a structured diagnostic process is essential. The diagnostic criteria, as outlined by health organizations, categorize cases into confirmed, probable, and possible, reflecting the level of evidence supporting the diagnosis.

Case Definitions: Confirmed, Probable, and Possible APSGN

To standardize reporting and management, APSGN cases are classified based on the strength of diagnostic evidence. These classifications are crucial for public health surveillance and ensuring appropriate clinical responses.

Confirmed APSGN Diagnosis

A confirmed diagnosis of APSGN requires either laboratory definitive evidence or a combination of laboratory suggestive evidence and clinical evidence.

• Laboratory Definitive Evidence: This is unequivocally established through a renal biopsy that is histologically suggestive of APSGN. Renal biopsy, while invasive, provides the most direct confirmation by examining kidney tissue for characteristic APSGN-related changes.

• Laboratory Suggestive Evidence AND Clinical Evidence: In the absence of a renal biopsy, a confirmed diagnosis can be made when laboratory findings suggestive of APSGN are coupled with relevant clinical signs.

  • Laboratory Suggestive Evidence includes a combination of:

    1. Microscopic Haematuria: The presence of red blood cells in the urine, specifically more than 10 red blood cells per microliter (RBC > 10/µL), detected through microscopic examination.

    2. Evidence of Recent Streptococcal Infection: This is a cornerstone of APSGN diagnosis. It is established by identifying a recent GAS infection through one or more of the following methods:

       • Isolation or Detection of GAS: Culturing Streptococcus pyogenes from skin or throat swabs. Nucleic acid amplification tests (NAAT) and rapid antigen detection tests can also be used to detect GAS.
       • Elevated or Rising Streptococcal Antibody Titres: Measuring serum antibody levels, specifically Antistreptolysin O (ASO) and Anti-DNase B titres. Elevated levels, or a rise in titre over time, indicate a recent streptococcal infection. Table 1 provides age-adjusted upper limits for normal antibody titres in populations where Strep A is endemic.

    3. Reduced C3 Complement Level: A blood test showing a decreased level of C3 complement, a protein in the immune system. This test should ideally be conducted within 4 weeks of APSGN symptom onset, as C3 levels may normalize thereafter.

  • Clinical Evidence: To complement laboratory findings, at least two of the following clinical manifestations must be present:

    • Facial and/or Peripheral Oedema: Swelling in the face and/or extremities.
    • Macroscopic and/or Moderate Haematuria: Visibly bloody urine or moderate haematuria detected on urine dipstick (≥ 2+ red blood cells).
    • Hypertension: Elevated blood pressure, adjusted for age, sex, and height percentiles. Standardized growth charts and blood pressure percentiles should be used to define hypertension in children and adolescents.

Probable APSGN Diagnosis

A probable case of APSGN is diagnosed when clinical evidence is present, and a treating clinician, ideally in consultation with a paediatrician or nephrologist, considers APSGN to be the most likely diagnosis. In these cases, while laboratory confirmation may be lacking, the clinical picture strongly suggests APSGN.

Possible (Subclinical) APSGN Diagnosis

A possible case, often referred to as subclinical APSGN, is defined by laboratory suggestive evidence alone, in the absence of overt clinical symptoms like oedema or hypertension. These cases might be identified during outbreak investigations or screening. The clinical significance and long-term implications of subclinical APSGN are still being researched.

Diagnostic Procedures and Laboratory Tests

Effective APSGN diagnosis relies on a series of clinical assessments and laboratory investigations. These procedures help confirm the diagnosis, assess the severity of the condition, and rule out other potential kidney diseases.

Initial Clinical Assessment

The diagnostic process begins with a thorough clinical evaluation, focusing on:

• Medical History: Detailed history taking should explore recent illnesses, particularly sore throat or skin infections (impetigo, cellulitis), typically within the preceding 1-6 weeks. Enquire about symptoms such as changes in urine colour, decreased urine output, swelling (especially facial or leg swelling), and high blood pressure.
• Physical Examination: A comprehensive physical exam should include:
  • Blood Pressure Measurement: Accurate blood pressure measurement is critical. Use appropriately sized cuffs and ensure correct patient positioning. Compare measurements against age, sex, and height-specific percentiles to identify hypertension.
  • Assessment for Oedema: Check for facial and peripheral oedema.
  • Urine Examination: Observe urine for macroscopic haematuria (visible blood). Perform a urine dipstick test to detect haematuria and proteinuria.

Key Laboratory Investigations

Laboratory tests are indispensable for confirming APSGN and assessing its impact on kidney function.

1. Urine Tests:

   • Urinalysis: A urine dipstick test can quickly detect haematuria (blood in urine) and proteinuria (protein in urine). Microscopic examination of urine sediment is essential to quantify red blood cells (microscopic haematuria) and identify red blood cell casts, which are suggestive of glomerular disease.
   • Urine Culture and Sensitivity (MCS) and Albumin/Creatinine Ratio: Urine MCS is performed to rule out urinary tract infection. Albumin/creatinine ratio quantifies proteinuria, helping to assess the extent of kidney damage.

2. Blood Tests:

   • Streptococcal Antibody Titres (ASO and Anti-DNase B): These blood tests detect antibodies produced by the body in response to streptococcal infection. Elevated or rising titres provide evidence of a recent GAS infection, supporting the diagnosis of APSGN. It’s important to note that ASO titres are typically elevated after pharyngitis, while Anti-DNase B titres are often more elevated after skin infections.
   • Complement Levels (C3, C4): Measuring complement levels, particularly C3, is crucial. Reduced C3 levels are a hallmark of APSGN, usually returning to normal within 6-8 weeks. C4 levels are typically normal.
   • Full Blood Count (FBC) and Film: To assess overall health and rule out other conditions.
   • CHEM20 (Electrolytes, Renal Function): This panel assesses kidney function (serum creatinine, blood urea nitrogen), electrolyte balance, and helps detect complications like hyperkalaemia or hyponatremia.

3. Throat and Skin Swabs:

   • Throat Swab: If a recent history of sore throat is present, a throat swab for GAS culture, rapid antigen detection test, or NAAT should be performed to confirm streptococcal pharyngitis.
   • Skin Swabs: If skin sores (impetigo) are present, swabs from these lesions should be taken for GAS culture and emm typing, particularly in outbreak settings or for epidemiological purposes. Request ‘APSGN case’ on the pathology form to ensure appropriate processing.

4. Renal Biopsy:

   • Renal biopsy is the definitive diagnostic test for APSGN. However, it is not routinely performed in typical cases, especially in children with classic presentations. Biopsy is usually reserved for atypical presentations, diagnostic uncertainty, rapidly progressive renal failure, or when considering alternative diagnoses. Histopathological findings in APSGN typically include diffuse proliferative glomerulonephritis with characteristic immune complex deposition (“humps”) seen on electron microscopy and immunofluorescence showing IgG and C3 deposits in a “starry sky” or “garland” pattern.

Differential Diagnosis

It is important to consider other conditions that may mimic APSGN. Differential diagnoses include:

• IgA Nephropathy (Berger’s Disease): This is the most common cause of glomerulonephritis worldwide. While it can present with haematuria following an upper respiratory infection, it typically occurs concurrently or within a few days of the infection, unlike the latent period in APSGN. IgA nephropathy is characterized by IgA deposits in the glomeruli on renal biopsy.
• Post-infectious Glomerulonephritis from other pathogens: Glomerulonephritis can also occur after infections with bacteria other than streptococcus, as well as viral or parasitic infections. Thorough history and appropriate serology are important.
• Membranoproliferative Glomerulonephritis (MPGN): MPGN is another type of glomerulonephritis that can present with persistent low C3 levels. Renal biopsy is crucial to differentiate MPGN from APSGN.
• Lupus Nephritis: Systemic lupus erythematosus (SLE) can cause glomerulonephritis. SLE is more common in females and may present with other systemic symptoms and positive serological markers for lupus (e.g., ANA, anti-dsDNA).
• Henoch-Schönlein Purpura (HSP) Nephritis: HSP is a systemic vasculitis that can affect the kidneys, causing glomerulonephritis. HSP typically presents with a characteristic purpuric rash, abdominal pain, and joint pain. Renal biopsy shows IgA deposition, similar to IgA nephropathy, but HSP is a systemic disease.

Importance of Early and Accurate APSGN Diagnosis

Timely and accurate diagnosis of APSGN is critical for several reasons:

• Prompt Management: Early diagnosis facilitates timely initiation of supportive management, including blood pressure control, fluid management, and dietary adjustments, to minimize complications and support renal recovery.
• Prevention of Complications: Appropriate management reduces the risk of severe complications such as hypertensive encephalopathy, acute kidney injury, and fluid overload, which can be life-threatening.
• Public Health Measures: Confirmed APSGN cases trigger public health responses, including contact tracing and community-level interventions, especially in outbreak settings, to prevent further transmission of nephritogenic streptococci and subsequent APSGN cases.
• Monitoring and Prognosis: Accurate diagnosis allows for appropriate monitoring of renal function and blood pressure, ensuring early detection of any progression to chronic kidney disease and guiding long-term follow-up.
• Reducing Morbidity: Effective diagnosis and management contribute to reducing the overall morbidity associated with APSGN, particularly in high-risk populations.

Conclusion

Diagnosing APSGN requires a systematic approach that integrates clinical findings with laboratory evidence. Understanding the case definitions, utilizing appropriate diagnostic tests, and considering differential diagnoses are essential steps for healthcare professionals. Emphasis on early detection and accurate diagnosis not only improves individual patient outcomes but also supports broader public health efforts to control and prevent APSGN, especially in communities with higher prevalence. Continued vigilance and adherence to diagnostic guidelines are paramount in mitigating the impact of this significant post-infectious kidney disease.

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