Thin Basement Membrane Nephropathy

Thin basement membrane nephropathy (TBMN, benign familial haematuria) is a common inherited cause of isolated persistent microscopic haematuria, caused by heterozygous COL4A3 or COL4A4 variants.

• Prevalence 1 to 2% of the population; autosomal dominant.
• Diffuse thinning of the GBM (under 250 nm in adults) on electron microscopy.
• Traditionally benign with preserved renal function, but 20 to 30% of those with heterozygous COL4A3/4 variants develop proteinuria and CKD (autosomal dominant Alport syndrome overlap), particularly with FSGS lesions or other risk factors.
• Distinguished from IgA nephropathy and X-linked Alport syndrome.

• Persistent glomerular microscopic haematuria, discovered incidentally, in childhood or adulthood.
• Occasional episodes of macroscopic haematuria after exercise or infection.
• Normal or minimal proteinuria, normal blood pressure and renal function in most.
• Familial haematuria with no deafness, ocular disease, or early renal failure.

• Persistent dysmorphic microscopic haematuria, red cell casts rare, normal complement, urine protein/creatinine ratio normal or under 0.5 g/g.
• Family history: haematuria in first-degree relatives with no ESKD.
• Genetic testing for COL4A3/COL4A4 confirms diagnosis and identifies risk of progression.
• Renal biopsy only if proteinuria, declining GFR, or uncertain diagnosis: GBM thickness under 250 nm (adults) or under 180 nm (young children) with preserved structure.
• Exclude IgA nephropathy, Alport syndrome (hearing, eye findings, family history of ESKD), urological causes (cystoscopy, imaging), hypercalciuria.

• Reassurance, with explanation of the generally benign course.
• Annual review: blood pressure, urinalysis, urine protein/creatinine ratio, eGFR.
• Start ACE inhibitor or ARB (ramipril 2.5 to 10 mg) if proteinuria appears or hypertension develops.
• Control cardiovascular risk (blood pressure, lipids), avoid nephrotoxins, treat other causes of CKD.
• Refer to nephrology if proteinuria over 0.5 g/day, falling eGFR, hypertension, or family history of ESKD.
• Genetic counselling; screening of relatives when needed (including potential kidney donors).
• Haematuria alone is not a contraindication to living kidney donation after careful assessment, although long-term risk should be counselled.
• Pregnancy is typically uncomplicated; monitor blood pressure and proteinuria.