Classification of AKI
Clinicians categorize the causes of AKI into three distinct types based on the anatomical location of the insult:
- Pre-renal: Caused by reduced blood flow to the kidney (e.g., dehydration or hypotension).
- Intrinsic renal: Damage to the kidney tissue itself (e.g., glomerular or tubular damage).
- Post-renal: Obstruction of urine outflow (e.g., kidney stones or prostate issues).
KDIGO Staging
To standardize the assessment of severity, the KDIGO criteria are used, focusing on rises in serum creatinine and decreases in urine output:
| Stage | Serum Creatinine | Urine Output |
|---|
| Stage 1 | ↑≥26.5 μmol/L within 48h OR 1.5–1.9× baseline | <0.5 mL/kg/h for 6–12 hours |
| Stage 2 | 2.0–2.9× baseline | <0.5 mL/kg/h for ≥12 hours |
| Stage 3 | ≥3× baseline OR ≥353.6 μmol/L OR dialysis | <0.3 mL/kg/h for ≥24h OR anuria ≥12h |
Exam Tip: AKI is defined by a sudden fall in function. Early recognition of small rises in creatinine or oliguria (low urine output) is vital to prevent permanent damage.
Pathogenesis of Acute Post-Streptococcal Glomerulonephritis (APSGN)
APSGN is a specific type of intrinsic renal AKI that occurs following an infection with Group A Streptococcus (GAS), such as pharyngitis (sore throat) or skin infections.
Type III Hypersensitivity
Unlike a direct bacterial infection of the kidney, APSGN is an immune-complex-mediated disease, classified as a Type III hypersensitivity reaction. The process follows a specific sequence:
- Antigen-Antibody Formation: Following a streptococcal infection, antigen-antibody complexes form in the circulation.
- Immune Complex Deposition: These complexes deposit within the glomerular basement membrane.
- Complement Activation: The deposited complexes trigger the complement system (specifically the classical and alternative pathways). This leads to significant hypocomplementaemia (low serum C3 levels) because the complement proteins are "consumed" during the inflammatory response.
Glomerular Damage and Clinical Presentation
The resulting inflammation causes structural damage to the glomerular filtration barrier. This damage allows substances that are normally filtered out to leak into the urine:
- Haematuria: Red blood cells leak through the damaged barrier, often resulting in "cola-colored" or dark urine.
- Proteinuria: Proteins leak into the urine due to the loss of barrier integrity.
Clinically, a child may present weeks after a sore throat has resolved with a constellation of symptoms known as nephritic syndrome:
- Oliguria (reduced urine output)
- Edema (swelling around the eyes or peripheral limbs)
- Hypertension (high blood pressure)
- Fatigue, headache, or nausea.
Diagnosis and Laboratory Findings
Diagnosis relies on identifying evidence of a recent streptococcal infection and the physiological markers of glomerular inflammation.
Serology and Urinalysis
Because the initial infection may have cleared by the time renal symptoms appear, clinicians look for specific antibodies:
- Anti-streptolysin O (ASO) titres: Elevated in cases following pharyngitis.
- Anti-DNase B antibodies: Particularly useful if the preceding infection was a skin infection.
Urinalysis typically reveals haematuria, proteinuria, and the presence of RBC casts. A hallmark blood finding is low C3 complement levels.
Histopathology
If a kidney biopsy is performed (though not always necessary in typical cases), two key features are observed:
- Light Microscopy: Shows diffuse proliferative glomerulonephritis, characterized by enlarged, hypercellular glomeruli due to inflammatory cell infiltration.
- Immunofluorescence: Shows a characteristic "lumpy-bumpy" granular pattern caused by the deposition of immune complexes and complement.
Management and Prognosis
Treatment Approach
There is no specific treatment to "remove" the immune complexes once they have deposited. Therefore, management is primarily supportive:
- Fluid and Sodium Restriction: To manage edema and hypertension.
- Diuretics: To assist with fluid overload.
- Antihypertensive therapy: To control blood pressure.
- Antibiotics: Only used if the streptococcal infection is still active to prevent further transmission; they do not reverse the established kidney inflammation.
Prognosis
The prognosis for children is generally excellent, with most recovering completely as GFR restores and C3 levels normalize. However, adults may face a more complicated course with a higher risk of persistent renal impairment.