Thin basement membrane disease: blood in the urine and what it means

The kidney filters blood through tiny units called glomeruli, whose filtering layer rests on a basement membrane made largely of type IV collagen. In thin basement membrane nephropathy that membrane is thin. The NHS England Genomics Education Programme (GeNotes) describes TBMN as a biopsy appearance, coupled with a mild clinical presentation, that is often associated with heterozygosity for Alport variants.

A research article explains TBMN as characterised by microscopic haematuria and a thin glomerular basement membrane on biopsy specimens, with minimal proteinuria under 500 mg a day and normal kidney function, defined as a membrane thickness of under 265 nm in adults, and thought to be present in 1% of the adult population.

Most people have no symptoms. The condition is usually found when a urine test done for another reason shows microscopic blood. GeNotes says that people with heterozygous pathogenic variants usually have only microscopic haematuria without extra-renal features, though a minority develop significant renal disease in their lifetime.

Visible blood in the urine is less usual. The NHS says you need to get any blood in your pee checked, even if there is only a small amount or you are not sure it is blood, because it can be a sign of other conditions including cancer: ask for an urgent GP appointment or get help from NHS 111. A diagnosis of TBMN should therefore only be made after other causes have been excluded.

Diagnosis in practice begins with persistent microscopic haematuria, urine protein tests, kidney function tests and imaging to exclude stones, infection or tumours. GeNotes explains that TBMN is diagnosed by microscopy when there is a thin basement membrane in the absence of other pathology, and that it is commonly familial. It also says that genomic testing is the gold standard for diagnosing Alport syndrome and that a positive result may avoid the need for a diagnostic biopsy if typical features are present.

Genetic testing may find a COL4A3 or COL4A4 variant, but GeNotes says negative findings from genomic testing are not unusual, and that lifetime implications without a COL4 variant are presumed to be the same as for heterozygous carriers. A research article reported a diagnostic rate of 53.8% (7 of 13) for likely pathogenic or pathogenic variants among TBMN patients tested, illustrating that testing does not always find a cause.

Alport syndrome is a more severe condition from altered basement membrane collagen, in its classic X-linked or recessive forms causing kidney failure and deafness in teenage or early adult life. GeNotes notes that people with a single changed copy of COL4A3 or COL4A4, found in about 1% of the UK population, usually have only microscopic haematuria, but that the risk of chronic kidney disease and end-stage kidney disease is increased, usually signalled by proteinuria and usually in later life. If a pathogenic variant is identified without features of renal disease beyond haematuria, it estimates the lifetime risk of end-stage kidney disease increases three-fold, from a UK average of about 1%.

Terminology is in flux. GeNotes says the term benign familial haematuria became obsolete when it was recognised that it is not always benign, and that autosomal dominant Alport syndrome is used in recent literature for COL4A3/4 heterozygotes despite the low clinical impact for most individuals. Do not be alarmed if you see different labels in letters; ask your kidney team what applies to you.

There is no disease-specific therapy. GeNotes says there is good evidence that early treatment slows progression of kidney disease in any form of Alport syndrome, including for people with heterozygous variants who develop proteinuria or reduced kidney filtration, and that ACE inhibitors are proven to slow progression, with SGLT2 inhibitors and other measures for proteinuric chronic kidney disease possibly helping further. It recommends long-term follow-up to monitor for complications.

In practice follow-up usually means regular checks of blood pressure, urine protein and kidney function, tailored to your risk, and prompt review if protein appears. Keeping blood pressure well controlled and avoiding unnecessary kidney-toxic medicines is sensible. GeNotes also says people with TBMN should be registered on the National Registry of Rare Kidney Diseases (RaDaR), which supports research.

Because TBMN is commonly familial, relatives may also have microscopic haematuria. GeNotes says that individuals with a chance of having a child with Alport syndrome should be offered genomic counselling including discussion of prenatal and preimplantation genetic testing. If both parents carry a COL4A3 or COL4A4 variant, a child can inherit two copies and have more severe disease, so family history of kidney failure or deafness is important to mention to your kidney team.

On the NHS, haematuria is assessed by the GP with urine and blood tests, urgent referral where cancer is suspected, and nephrology referral for persistent glomerular haematuria. Genetic testing is available through the NHS Genomic Medicine Service where criteria are met.

Private nephrology consultations and genetic panels are available, but results should be shared with your GP and NHS kidney team so that monitoring is consistent and registry enrolment can be considered.