Podocyturia: why it may have added value in rare diseases

Area of Science:

• Nephrology
• Genetics
• Lysosomal Storage Diseases

Background:

• Fabry disease is an inherited condition caused by GLA gene defects, leading to alpha-galactosidase-A deficiency and glycosphingolipid accumulation.
• This accumulation, particularly lyso-Gb3, stresses podocytes, potentially causing kidney injury.
• Current therapies include enzyme replacement and migalastat, but optimal timing for treatment initiation, especially in asymptomatic patients, remains challenging.

Purpose of the Study:

• To investigate podocyturia as a non-invasive tool for monitoring subclinical kidney injury in Fabry nephropathy.
• To assess the potential of urinary podocyte markers, specifically podocalyxin and synaptopodin, for early detection of kidney damage.

Main Methods:

• Analysis of urinary podocytes in patients with Fabry nephropathy.
• Quantification of podocalyxin and synaptopodin expression in detached urinary podocytes.
• Evaluation of the podocalyxin to synaptopodin ratio as an indicator of podocyte stress and injury.

Main Results:

• A decrease in the podocalyxin to synaptopodin ratio was observed in urinary podocytes from Fabry patients.
• Podocalyxin may be lost from detached urinary podocytes, indicating podocyte injury.
• This finding suggests podocyturia assessment could be a valuable tool for monitoring kidney health.

Conclusions:

• Podocyturia assessment, particularly the podocalyxin to synaptopodin ratio, shows promise for non-invasively monitoring subclinical kidney injury in Fabry disease.
• Early detection of podocyte damage may facilitate timely therapeutic interventions, potentially preventing irreversible kidney lesions.
• Further research is warranted to validate these findings and integrate podocyturia analysis into clinical practice for Fabry nephropathy management.