Genetic glomerular disease

Genetic glomerular disease is a broad category (Orphanet group code 183586) encompassing a heterogeneous group of inherited kidney disorders that primarily affect the glomeruli — the tiny filtering units within the kidneys responsible for removing waste and excess fluid from the blood. These conditions result from pathogenic variants in genes encoding structural or regulatory proteins essential for normal glomerular function, including components of the glomerular basement membrane, podocyte cytoskeleton, slit diaphragm, and other filtration barrier elements. This grouping includes well-characterized entities such as Alport syndrome, congenital nephrotic syndrome (Finnish type), steroid-resistant nephrotic syndrome due to mutations in genes like NPHS1, NPHS2, WT1, LAMB2, and others, as well as familial forms of focal segmental glomerulosclerosis (FSGS). Clinical features vary by specific diagnosis but commonly include proteinuria (excess protein in the urine), hematuria (blood in the urine), edema (swelling), hypertension, and progressive decline in kidney function that may ultimately lead to end-stage kidney disease (ESKD) requiring dialysis or kidney transplantation. The age of onset, severity, and rate of progression differ substantially depending on the underlying genetic cause. Some forms present in the neonatal period with massive proteinuria, while others may not manifest until adulthood. Treatment is largely supportive and may include angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to reduce proteinuria and slow disease progression, management of edema with diuretics, dietary modifications, and ultimately renal replacement therapy when kidney failure occurs. Immunosuppressive therapies, which are effective in many acquired glomerular diseases, are generally ineffective in genetically determined forms. Genetic testing plays an increasingly important role in diagnosis, guiding treatment decisions, and informing family counseling.

Common questions about Genetic glomerular disease