Introduction:
Cystic kidney diseases are diverse disorders affecting children, contributing significantly to chronic kidney disease. Autosomal recessive polycystic kidney disease (ARPKD) alone affects up to 5% of children with end-stage renal disease. In 2020, cystic kidney diseases accounted for 6% of pediatric chronic kidney disease cases in India, highlighting their impact. Early detection is crucial for implementing kidney-protective measures. This multicentre project was conducted with the objective of understanding the disease etiology in India, the genetic spectrum and to identify the at risk population. We hereby present an interim analysis of the same project.
Methods:
This was a multicentre cross sectional study conducted across 19 centres initiated from January 2022. Any child (≤ 18 years) with observation of two or more kidney cysts in ultrasound scans with unknown origin, or one kidney cyst measuring ≥ 1 cm and with a family h/o cystic kidney disorder, or a proven genetic diagnosis of cystic kidney disorder, or a typical presentation of Polycystic kidney disease, or a Prenatal diagnosis of large hyperechogenic kidneys and/or renal cysts and/or oligohydramnios was included in the study. Children with single cyst without extra-renal manifestation without familial renal / liver cysts, or cystic tumoral process: nephroblastoma, etc, or multicystic dysplastic kidneys were excluded. Subjects were enrolled after taking informed consent. Detailed demographic and clinical data along with relevant lab parameters and imaging parameters noted. 5 ml blood collected and stored in EDTA vials. Temp maintained between 2-8 C during storage and shipping. DNA extraction done till analysis and analysis done by Whole Exome Sequencing. LP/P/VUS reports were followed by establishing genotype-phenotype correlation and parental segregation.
Results:
Among 104 patients screened from 2022 January to 2024 January, a genetic etiology was identified in 40% of cases. In our cohort more male were affected than females. Average age of presentation was 7.5 yrs, hwoever, the age of presentation was lower for ARPKD as a subset. However, over 60% of variants were classified as variants of uncertain significance (VUS), underscoring diagnostic challenges. Notably, mutations in TSC2 and NPHP1 genes had a higher diagnostic yield ( about 60 %) while PKHD1 and PKD1 had lower yield ( about 40 % ) . The study emphasized the importance of family studies and clinical correlation to interpret genetic findings accurately.
Conclusions:
Understanding these genetic underpinnings is crucial for improving quality of life and tailoring management strategies for affected children. The high prevalence of VUS highlights the need for ongoing research and refined diagnostic approaches in diverse populations.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.