Introduction: Nephrotic syndrome (NS) is one of the major causes of end-stage renal disease (ESRD) in children. This study aims to analyze the genotype distribution of kidney transplant recipients with primary NS and its impact on post-transplant prognosis, providing a reference for the clinical management of such patients.
Methods: This study recruited children diagnosed with primary NS and who underwent kidney transplantation between January 2013 and December 2022 at our hospital. Whole exome sequencing (WES) and genotype-phenotype analysis were performed. Pre-transplant clinical data and post-transplant follow-up information were collected to assess the impact of genetic factors on kidney disease recurrence, infections, rejection reactions, and other complications after kidney transplantation.
Results: A total of 76 children with primary NS who underwent kidney transplantation were included in this study.


WES analysis revealed a definitive genetic diagnosis in 40 cases (52.6%), with COQ8B being the most common mutated gene (15/40, 37.5%), followed by WT1 (7/40, 17.5%), TRPC6 (4/40, 10.0%), PAX2 (4/40, 10.0%), and others.

 In 36 cases (47.4%), no definitive pathogenic gene was identified. The median follow-up time after transplantation was 1.25 years (0.80, 4.14). Compared with patients with undefined pathogenic genes, those with definitive pathogenic genes progressed to ESRD more quickly after the onset of NS, with a statistically significant difference [0.8 (0, 4.0) years vs 3.0 (1.0, 5.0) years, P = 0.01]. During the follow-up period, 6 cases (16.7%) in the undefined pathogenic gene group experienced relapse of the primary disease, while none in the definitive pathogenic gene group had a relapse. Genetic factors had no significant impact on the occurrence of infections (20 vs 18 times, P = 0.88) or rejection reactions (5 vs 8 times, P = 0.36). Additionally, 3 children with definitive genetic mutations developed symptoms of night blindness, photophobia, and other ocular discomfort during the follow-up period, all of whom carried COQ8B mutations. No such symptoms were observed in patients without a defined genetic diagnosis.
Conclusion: Genetic factors are the primary cause of primary NS in children and are an important factor influencing the recurrence rate after kidney transplantation. However, they are not significantly associated with the occurrence of post-transplant infections or rejection reactions. COQ8B gene mutation is the most common pathogenic factor and may increase the risk of ocular complications after kidney transplantation. This study provides a systematic description of the genomic features and post-transplant prognosis of children with primary NS, offering important insights for clinical decision-making.