Cytochrome P450 3A gene family and medication in childhood nephrotic syndrome: An update

Nephrotic syndrome (NS) is a renal disease characterized by excessive proteinuria (greater than 3.5 g/dl per 24 h), which results in hypoalbuminemia and leads to hyperlipidemia, edema, and various complications. NS patients typically respond to standard steroid treatment (prednisolone) and are classified as having steroid-sensitive nephrotic syndrome (SSNS). However, patients who do not respond to steroid therapy after 4 weeks are referred to as having steroid-resistant nephrotic syndrome (SRNS). The unequal response to steroid treatment in nephrotic syndrome involved many factors, including genetic, medication, and kidney diseases. The CYP3A gene family is predominantly involved in the metabolism of medications used in the treatment of NS.

A systematic literature review was conducted from January 2014 to June 2024 using an extensive electronic search of data related to pediatric nephrotic syndrome and the CYP gene family, including associated polymorphisms. Through this review, we systematically analyze factors that affect the metabolism of medications targeting the CYP3A gene family (including steroidal and non-steroidal drugs) commonly used in the treatment of NS and its comorbidities.

Studies have correlated the relationship between polymorphisms in the CYP3A gene family and medication in NS, with 90 % of the research focusing primarily on post-kidney transplant NS patients. Many studies have reported a correlation between CYP3A gene family polymorphisms and increased tacrolimus (TAC) dosage.