Unilateral renal diseases encompass structural anomalies such as unilateral renal agenesis (complete absence of one kidney), unilateral renal hypoplasia (underdeveloped kidney), and related conditions like multicystic dysplastic kidney or significant asymmetry in kidney size. While often asymptomatic in adulthood due to compensatory function of the contralateral kidney, they increase risks of hypertension, proteinuria, chronic kidney disease (CKD) progression, and end-stage kidney disease. Current knowledge indicates genetic contributions, including mutations in developmental genes and copy number variations (CNVs), often with incomplete penetrance and variable expressivity. However, most studies focus on pediatric or severe bilateral cases, leaving adult-onset or mild unilateral presentations understudied.
Leveraging the unique resource in the UK Biobank (large-scale abdominal MRI, whole-exome/whole-genome sequencing, serum/urine biomarkers, and linked health records), we are interested in investigating the following research questions:
1. What is the prevalence and phenotypic spectrum of unilateral renal diseases (e.g., agenesis, hypoplasia, significant volume asymmetry) in the UK Biobank adult population?
2. Are there genetic variants (common GWAS loci, rare coding variants, CNVs) associated with unilateral renal anomalies, reduced unilateral kidney volume, or asymmetry?
3. How do these genetic factors interact with environmental/lifestyle variables to influence compensatory function in the contralateral kidney and risk of CKD progression?
4. Do unilateral renal diseases confer increased risk for hypertension, cardiovascular disease, or mortality, and is this genetically mediated?
This research could uncover novel genetic mechanisms linking developmental or non-developmental unilateral anomalies to adult CKD risk, inform screening for at-risk individuals, and highlight the solitary functioning kidney as a model for hyperfiltration-induced disease.
