Autosomal Dominant Polycystic Kidney Disease (ADPKD)

•    Genetics:

o    AD inheritance; mutations in PKD1 (85%) or PKD2 (15%)

o    PKD1 associated with earlier onset and faster progression to ESRD

•    Clinical Features:

o    Bilateral renal cysts (from cortex and medulla) → progressive renal enlargement and CKD

o    Hypertension (often early finding)

o    Haematuria, flank pain, recurrent UTIs or nephrolithiasis

o    Berry aneurysms → risk of subarachnoid haemorrhage (screen if FHx)

o    Hepatic cysts (common), also pancreatic/splenic cysts

o    Mitral valve prolapse, aortic root dilatation

•    Diagnosis:

o    Renal USS: ≥3 cysts bilaterally in age >40 is diagnostic with +FHx

o    MRI for detailed assessment or screening relatives

•    Management:

o    Blood pressure control: ACEi/ARB preferred

o    Tolvaptan (vasopressin V2 antagonist): slows cyst growth and CKD progression in selected patients

o    Monitor for complications (e.g. haematuria, infection, ESRD)

o    Dialysis/transplant if ESRD develops

Alport Syndrome

•    Genetics:

o    X-linked (most common), also autosomal dominant/recessive variants

o    Defect in type IV collagen

•    Clinical Features:

o    Persistent microscopic haematuria ± proteinuria

o    Progresses to CKD/ESRD in adolescence/young adulthood

o    Sensorineural deafness (bilateral, progressive)

o    Ocular abnormalities: anterior lenticonus, retinal flecks

o    Family history of haematuria and deafness often present

•    Diagnosis:

o    Electron microscopy: basket-weave appearance of GBM

o    Genetic testing may confirm diagnosis

•    Management:

o    ACE inhibitors to slow progression

o    Regular monitoring of renal function and hearing

o    Consider transplant in ESRD

Thin Basement Membrane Nephropathy (Benign Familial Haematuria)

•    Cause: Thinning of glomerular basement membrane; often familial

•    Clinical Features:

o    Isolated microscopic haematuria

o    Normal renal function; no proteinuria or hypertension

o    Excellent long-term prognosis

•    Diagnosis:

o    EM: thinned GBM

o    Often diagnosed after exclusion of other causes

•    Management:

o    Reassurance; no treatment needed

Medullary Sponge Kidney

•    Cause: Congenital dilation of collecting ducts in renal medulla

•    Clinical Features:

o    Often asymptomatic and discovered incidentally on imaging

o    May present with nephrocalcinosis, haematuria, recurrent UTIs or stones

•    Diagnosis:

o    CT or IVU: characteristic ‘brush-like’ appearance in renal medulla

•    Management:

o    Conservative; hydration to reduce stone risk

o    Treat complications (e.g. stones, infection)

Fabry Disease

•    Genetics:

o    X-linked lysosomal storage disorder

o    Deficiency of α-galactosidase A → accumulation of globotriaosylceramide

•    Renal Features:

o    Proteinuria, progressive CKD

o    May resemble FSGS histologically

•    Extra-renal Features:

o    Peripheral neuropathy (burning pain)

o    Angiokeratomas, hypohidrosis

o    Corneal verticillata, cardiac hypertrophy, stroke in young

•    Diagnosis:

o    α-gal A activity (low in males), genetic testing

o    Renal biopsy if diagnosis unclear

•    Management:

o    Enzyme replacement therapy

o    Supportive care (ACEi for proteinuria, pain management)