Nephropathy of the thin basal membrane type N02.9

Thin basement membrane type nephropathy (TBMN), often referred to as benign familial hematuria, is characterized by diffuse thinning of the glomerular basement membrane to approximately 150-225 nm (normal value: 300-400 nm), persistent glomerular hematuria , and minimal proteinuria with otherwise normal renal function (Hashimoto H et al. 2019).

The prevalence is high and is about 1% (?) of the population. A high prevalence can be assumed, especially in familial haematuria (Santos S et al. 2017).

Children whose parents both suffer from TBMN and each carry a heterozygous change in COL4A3 or COL4A4 can inherit both variants with a probability of 25% and therefore develop Alport syndrome . For this reason, heterozygosity can be assumed for the autosomal recessive form of Alport syndrome in the presence of a TBMN.

TBMN is inherited in an autosomal dominant manner. Mutations in the COL4A3 and COL4A4 genes are detectable.

Most patients remain asymptomatic. Microscopic hematuria tends to be discovered incidentally during routine urinalysis; occasionally, low proteinuria and intermittent severe hematuria occur. Renal function is typically normal. However, some patients develop progressive renal failure for unknown reasons. Recurrent flank pain, similar to that seen in IgA nephropathy, is a rather rare clinical symptom.

The kidney biopsy is only of great importance for differentiating it from Alport syndrome. However, in the early stages of Alport syndrome a histological differentiation from TBMN is often not possible (Hashimoto H et al. 2019).

Electron microscopy can detect a diluted basement membrane on the glomerula (<265nm).

Other sources of bleeding from the urinary tract, especially tumours and urinary stones, can be excluded urologically.

A specific therapy is not known and not necessary. Patients with frequent macrohaematuria, with flank pain or proteinuria (e.g. protein/creatinine ratio in urine > 0.2) may benefit from ACE inhibitors or angiotensin receptor II blockers, which can reduce intraglomerular pressure.

Good prognosis. Patients with TBMN are considered carriers of autosomal recessive ATS. However, some patients develop hypertension and progressive renal failure.

Alport syndrome (ATS), which is characterized by glomerular hematuria and progressive proteinuria and leads to terminal renal failure, may also be associated with extrarenal changes such as inner ear hearing loss and ocular changes (lenticonus anterior). It is also caused by changes in the genes COL4A3 and COL4A4 (autosomal recessive and autosomal dominant inheritance) and COL4A5 (X-linked chromosomal inheritance). However, polymorphic COL4A5 variants could also be detected, which in some cases can cause the phenotype of a TBMN instead of an ATS.

1. Hashimoto H et al (2019) A case report of thin basement membrane nephropathy accompanied by sporadic glomerulocystic kidney disease. BMC Nephrol 20:248.
2. Hopfer H et al (2010) Hereditary nephropathies thin basement membrane, Alport glomerulopathy, Alport conduits. Nephrologist 5:508-516Kajimoto Y et al (2019) Pathologic glomerular characteristics and glomerular basement membrane alterations in biopsy-proven thin basement membrane nephropathy. Clin Exp Nephrol 23:638-649.
3. Santos S et al. (2017) Thin glomerular basement membrane in a kidney transplant of an Alport's syndrome patient: A Case Report.Transplant Proc 49:2384-2387.
4. Savige J et al. (2013) Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 24:364-375.