Nucleoporin-associated steroid-resistant nephrotic syndrome

Area of Science:

• Genetics and Molecular Biology
• Nephrology
• Cell Biology

Background:

• Nucleoporins (Nups) are essential proteins forming nuclear pore complexes, regulating transport, gene expression, and cell cycle.
• Pathogenic variants in six NUP genes (NUP85, NUP93, NUP107, NUP133, NUP160, NUP205) cause monogenic steroid-resistant nephrotic syndrome (SRNS).

Purpose of the Study:

• To review the epidemiology, structure-function, pathogenesis, phenotypes, genotypes, and management of nucleoporin-associated SRNS.
• To discuss implications for genetic counseling and future research directions.

Main Methods:

• Literature review of nucleoporin-associated SRNS.
• Analysis of clinical data including age of onset, kidney biopsy findings, and treatment outcomes.

Main Results:

• Nucleoporin-associated SRNS presents as isolated or syndromic, with extrarenal manifestations including neurological and developmental disorders.
• Focal segmental glomerulosclerosis is found in 89% of patients, who are largely resistant to immunosuppressants.
• Progression to kidney failure varies by NUP gene, with kidney transplantation being a preferred treatment.

Conclusions:

• Next-generation sequencing is recommended for genetic diagnosis of suspected nucleoporin-associated SRNS.
• Renin-angiotensin-aldosterone system inhibitors are advised, and immunosuppressants may be discontinued post-diagnosis.
• Genetic counseling is crucial for affected families, and further research is needed for novel therapeutics.