Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-Alport Syndrome and the Spectrum of Type IV Collagen-Related Diseases

Video Transcription

Video Summary

Dr. Michelle Rowe reviews Alport syndrome as a spectrum of type IV collagen diseases caused by variants in COL4A5 (X-linked) and COL4A3/COL4A4 (autosomal). Variant severity affects the glomerular basement membrane: truncating variants prevent formation of the α3/α4/α5 network, while missense variants may allow a defective network, producing widely variable phenotypes from isolated microscopic hematuria to early kidney failure with hearing and eye disease. X-inactivation explains variability in females with X-linked disease. Population data show these variants are common (COL4A5 ~1/2000; COL4A3/4 ~1/100), but few carriers progress, making risk prediction difficult. She proposes “buckets”: classic severe disease (treat early with ACEi/ARB; benefit ~20 years), mild–moderate disease (screen annually; treat when proteinuria appears), nephrotic/FSGS presentations (supportive therapy; sparsentan reduces proteinuria; immunosuppression decisions remain uncertain), and nonprogressive hematuria (monitor). New nomenclature favors “Alport spectrum” and “Alport risk.”

Asset Subtitle

Michelle Rheault

Meta Tag

Module GLOM

Speaker Michelle Rheault

Keywords

Alport syndrome spectrum

Type IV collagen (COL4A5, COL4A3, COL4A4) variants

X-linked and autosomal Alport inheritance

Genotype-phenotype correlation (truncating vs missense)

ACE inhibitor/ARB early treatment and risk stratification

FSGS/nephrotic presentation and sparsentan proteinuria reduction