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|Acute Kidney Injury (AKI) / Acute Renal Failure
Alport's syndrome ๐งฌ is a hereditary disorder of the glomerular basement membrane (GBM), characterized by nephritis ๐ฉธ, haematuria ๐ฝ, progressive renal failure ๐ฉบ, and high-frequency sensorineural deafness ๐. Males are more severely affected due to the typical X-linked inheritance.
About ๐
- The disease was first recognized when researchers observed that the GBM in Alportโs did not bind anti-GBM antibodies (as seen in Goodpastureโs syndrome).
- This pointed to an abnormality in Type IV collagen ๐งฉ, the key protein in basement membranes of the kidney, ear, and eye.
Aetiology ๐ฌ
- Most often X-linked recessive inheritance (โ80%), predominantly affecting males ๐ฆ.
- Also has autosomal recessive (AR) and autosomal dominant (AD) forms.
- COL4A5 mutation (X-linked), or mutations in COL4A3 / COL4A4 (AR/AD forms), โ abnormal collagen IV โ progressive GBM degeneration.
Clinical Features ๐ฉบ
- Renal: Persistent microscopic or macroscopic haematuria ๐ฝ, progressing to end-stage renal disease (ESRD) in many patients.
- Hearing loss: Bilateral high-frequency sensorineural deafness ๐, usually emerging in adolescence.
- Ocular: Anterior lenticonus ๐๏ธ (pathognomonic), retinal flecks, and recurrent corneal erosions.
- Family history: Often positive for kidney disease and deafness across generations.
- Female carriers ๐ฉ may have haematuria but slower progression (due to lyonization of X-chromosome).
Investigations ๐
- Urinalysis: Proteinuria and haematuria (dysmorphic red cells, red cell casts).
- Renal function: Rising creatinine with CKD progression.
- Renal USS: Kidneys usually normal-sized early on, later contracted.
- Genetic testing: COL4A mutations, increasingly used for diagnosis.
- Skin biopsy: May show absence of ฮฑ5(IV) collagen in epidermis.
- Renal biopsy: EM shows pathognomonic GBM thickening, splitting, and lamellation (โbasket-weave appearanceโ).
Management โ๏ธ
- Supportive CKD management: BP control, salt restriction, avoid nephrotoxins.
- ACE inhibitors / ARBs: Can reduce proteinuria and slow progression ๐งช.
- Hearing aids & ophthalmology follow-up: For non-renal manifestations ๐๐๏ธ.
- Renal replacement therapy: Dialysis or transplant when ESRD develops. Patients are often young and otherwise fit, making them good transplant candidates.
- Post-transplant risk: 3โ4% develop anti-GBM nephritis โ ๏ธ within the first year, as the immune system recognizes the โnormalโ donor GBM as foreign.
Key Clinical Pearls โจ
- Think of Alportโs in a young male with haematuria ๐ฝ + renal failure ๐ฉบ + deafness ๐ ยฑ ocular features ๐๏ธ.
- Basket-weave GBM on EM = diagnostic clue ๐ฌ.
- Unlike Goodpastureโs, antibody staining is negative ๐ซ - itโs a structural defect, not an antibody attack.
