Introduction: Approximately 25% of children with chronic kidney disease (CKD) have monogenic disorders, with a higher prevalence in pediatric end-stage renal disease (ESRD). Our center in Northern Israel serves consanguineous communities, encountering a notable rate of hereditary disorders. Advances in sequencing technology have improved detection rates, facilitating timely genetic diagnosis and optimizing treatment, especially in pediatric kidney transplant recipients.
Aim: We aim To review a decade’s experience of genetic analysis in pediatric kidney transplantat recipients with suspected monogenic kidney disorders, and explore its clinical impact.
Methods: Over the past decade, genetic analyses of pediatric renal transplant recipients with renal disorders of suspected monogenic origin was performed, using either whole-exome sequencing, targeted gene sequencing, or chromosomal microarray analysis.
Results: Between 2014-2024 we performed 68 pediatric kidney transplantations on an ethnically diverse patient population, with a consanguinity rate of 50%. Ethnical origin included Muslims, Jews, Christians, and Druze, of both Israeli and Palestinian nationalities. ESRD etiology included congenital kidney and urinary tract anomalies (33%), nephrotic syndrome (22%), cystic kidney diseases (19%), chronic glomerulonephritis (13%), and other conditions (13%). Genetic analysis was conducted in 60% of patients with suspected hereditary ESRD, revealing disease-causing variants in 63% of cases. Over the depicted period, there has been a notable increase in the prevalence and extent of genetic testing, reflecting advancements in technology and methodology accessibility. Variants of unknown significance were encountered in 31% of cases, necessitating further computational and functional analysis. Molecular diagnosis had a significant impact on clinical decision-making, affecting final diagnosis, treatment modifications, familial counseling, and living-related donor candidacy.
Conclusion: Genetic analysis in pediatric renal transplant recipients, especially in conangineous populations, may offer a high detection rate of disease-causing variants, enhancing patient management. We advocate for routine genetic analysis in cases of uncertain etiology, particularly in the context of kidney transplantation.