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Definition and EtiologyTop
Thin basement membrane disease (TBMD) (also called benign familial hematuria) is a congenital glomerulopathy characterized by thinning of the glomerular basement membrane (150-250 nm; normal thickness in adult men is 370±50 nm and in adult women, 320±50 nm).
Patients with familial TBMD have autosomal dominant inheritance, although they may not have a known family history, due to the asymptomatic nature of the condition. The prevalence of this condition has been estimated to be 1%. The etiology of TBMD is probably due to a heterozygous mutation of type IV collagen genes, specifically the alpha 3 and alpha 4 genes. The identified genes, present in some families, include COL4A3 and COL4A4.
Patients develop microscopic hematuria, which is frequently detectable as early as in childhood. Mild proteinuria may develop in adulthood. Hypertension is not considered a feature of TBMD, and patients do not develop renal failure. Patients may have episodes of gross hematuria, which can occur following an upper respiratory tract infection (simulating IgA nephropathy) and may be associated with flank (loin) pain. Of note, hematuria is not aggravated by comorbidities and extrarenal symptoms do not occur.
Definitive diagnosis is based on electron microscopy examination demonstrating thin basement membranes without other abnormalities. Of note, people with microscopic hematuria and stable normal renal function usually require follow-up without biopsy (consider malignancy of the urinary tract in patients at high risk [advanced age, smoker, etc]). Referral to nephrology care may be triggered by deteriorating renal function or new-onset proteinuria.
Differential diagnosis includes IgA nephropathy (associated with proteinuria and chronic renal failure) and Alport Syndrome, which is related to TBMD, as it is also an inherited disease involving mutations in type IV collagen genes but with a markedly different clinical picture including hearing loss, ocular manifestations, proteinuria, and renal failure.
Treatment and follow-upTop
Specific treatment is neither available nor necessary, however, patients with TBMD should be reassured but not lost to follow-up. The risk of renal impairment is small (<5%). Urinalysis and measurement of blood pressure and renal function are recommended every 1 to 2 years.