[Nephrotic syndrome in childhood]

Area of Science:

• Pediatric Nephrology
• Genetics
• Immunology

Context:

• Minimal change nephrosis is the most common pediatric nephrotic syndrome, typically steroid-sensitive.
• Relapses can lead to steroid resistance, manifesting as focal segmental glomerulosclerosis (FSGS).
• FSGS has a poor prognosis, often progressing to end-stage renal disease.

Purpose:

• To review the causes and management of steroid-resistant nephrotic syndrome (SRNS) in children.
• To highlight the role of podocyte gene mutations in SRNS and FSGS.
• To emphasize the importance of genetic evaluation for guiding treatment and predicting transplant recurrence.

Summary:

• Idiopathic nephrotic syndrome (INS) in children is usually minimal change nephrosis, but relapses can cause steroid resistance, often presenting as FSGS.
• Podocyte mutations account for about one-third of SRNS cases, significantly influencing treatment decisions.
• Genetic testing for podocyte mutations is critical before initiating aggressive immunosuppression or considering transplantation due to recurrence risks in mutation-negative patients.

Impact:

• Genetic evaluation for podocyte mutations should be integrated into the management of pediatric SRNS.
• Identifying podocyte mutations can prevent contraindicated aggressive steroid therapy and guide personalized treatment strategies.
• Understanding genetic underpinnings of FSGS improves prognostication and informs post-transplant management to reduce recurrence.