Thin glomerular basement membrane disease: clinical significance of a morphological diagnosis--a collaborative study of the Italian Renal Immunopathology Group

Abstract

This study confirms that a considerable proportion of patients with TBMD have a type IV collagen disorder and that this lesion is not always benign. Thus, families should be investigated carefully whenever possible and patients and affected relatives should be examined periodically for signs of disease progression.

Chronic Renal Failure and Shortened Lifespan in COL4A3+/− Mice

“…It is estimated that TBMN occurs in at least 1% of otherwise normal children and adults (25,27,28). Twenty to 50% of families with biopsy-proven TBMN have hematuria that is thought to segregate with COL4A3/4 mutations (5,7,10,20,(25)(26)(27). Our study proves the conjectural association between TBMN and the COL4A3 gene on an inductive rather than a deductive level, as done in human clinical studies before, and strengthens the above-mentioned epidemiologic figures for the incidence of TBMN.…”

“…At present, it is recommended that patients with TBMN be monitored for the development of hypertension, proteinuria, and renal impairment (20). It must be stressed how important screening and prevention strategies are for detecting those who are at risk for developing CKD (39,40).…”

“…A spate of new data have become available concerning individuals with thin basement membrane nephropathy (TBMN) showing heterozygous mutations in the COL4A3 and COL4A4 genes (4 -10). TBMN, or familial benign hematuria (11) first was described in 1926 (12) and is a very common hereditary disorder that clinically is characterized by persistent or recurrent hematuria that can be aggravated by increased BP in approximately 30% of patients (5,(13)(14)(15), proteinuria (15)(16)(17)(18)(19), hearing loss, and/or progression toward chronic renal failure (11,(13)(14)(15)17,20). The trait is inherited in an autosomal dominant pattern (8).…”

“…In 20 to 50% of families with a clinical diagnosis of TBMN, the condition co-segregates with heterozygous COL4A3/4 mutations (5,7,10,20,25,26). Therefore, it now is the general consensus that the COL4A3/4 genes are involved in both the pathogenesis of autosomal AS and TBMN.…”

Nephrotic-range proteinuria in an infant with thin basement membrane nephropathy

“…About 20 % of patients with TBMN show progressive renal impairment [8]. TBMN associated with heterozygous COL4A3/COL4A4 mutations was reported to show a causal relationship with the development of focal segmental glomerulosclerosis (FSGS) and renal failure [4,9,10].…”