Thin Basement Membrane: An Underrated Cause of End-Stage Renal Disease

Abstract

The term "thin basement membrane" (TBM) refers to a glomerular disorder characterized by diffuse uniform thinning of the glomerular basement membrane (GBM) on electron microscopy. Patients with TBM usually show an isolated hematuria with excellent renal prognosis. However, some patients can develop proteinuria and progressive kidney dysfunction in the long term. Most patients with TBM are heterozygous for pathogenic variants in genes encoding for both the α3 and α4 chains of collagen IV, a major constituent of GBM. Such variants are responsible for a wide range of clinical and histological phenotypes. The differential diagnosis between TBM and autosomal-dominant Alport syndrome and IgA nephritis (IGAN) may be difficult in some cases. Patients who progress to chronic kidney disease may show clinicopathologic features similar to those of primary focal and segmental glomerular sclerosis (FSGS). Without a shared classification of these patients, the risk of misdiagnosis and/or underestimation of the risk of progressive kidney disease is real. New efforts are needed to understand the determinants of renal prognosis and recognize the early signs of renal deterioration, allowing a custom-made diagnosis and therapeutic approach. For this purpose, a practical and simple clinical approach is supplied.

Keywords: Alport syndrome; COL4 nephropathies; Dysmorphic hematuria; Proteinuria; Thin basement membrane.