Congenital Anomalies of the Kidney and Urinary Tract

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a spectrum of developmental disorders that affect the structure and function of the kidneys, ureters, bladder and urethra. Occurring in approximately 0.5–1 per 1 000 births, CAKUT represent a leading cause of paediatric chronic kidney disease and predispose individuals to hypertension, cardiovascular complications and, in severe cases, end-stage renal failure. Phenotypes range from mild vesicoureteric reflux and hydronephrosis to severe malformations such as renal agenesis, hypoplasia and dysplasia. Pathogenesis centres on disruption of reciprocal interactions between the ureteric bud and the metanephric mesenchyme, with both genetic and environmental factors contributing. To date, over 50 genes have been implicated in monogenic forms, yet these explain only a minority of cases, underscoring the multifactorial aetiology that includes copy-number variations, epigenetic modifications and in utero exposures. Advances in molecular diagnostics, imaging and animal models have refined phenotypic classification and informed personalised management, from prenatal detection to surgical and medical interventions. Global collaborative efforts now aim to integrate genomic data with clinical registries to improve prognostic stratification and develop targeted therapies.

Research from Nature Portfolio

Recent research has uncovered that noncoding RNAs embedded within copy-number variants can modulate gene networks critical for nephrogenesis. By analysing developmental transcriptomes, investigators identified long noncoding RNAs in key genomic intervals that interact with known CAKUT genes and, when experimentally reduced, downregulate pathways governing ureteric bud branching and renal differentiation. These findings illuminate how perturbations in the noncoding genome contribute to CAKUT pathogenesis and suggest novel regulatory targets for diagnostic and therapeutic strategies.

Congenital Anomalies of the Kidney and Urinary Tract publication trend

The graph below shows the total number of articles in congenital anomalies of the kidney and urinary tract across all publications each year (not limited to Nature Index journals).

Technical terms

Nephrogenesis: The embryonic process by which the kidney forms and matures.

Copy-number variation (CNV): A structural alteration in the genome involving deletion or duplication of DNA segments.

Long noncoding RNA (lncRNA): RNA molecules longer than 200 nucleotides that do not code for protein but regulate gene expression.

Exome sequencing: A genomic technique for sequencing all protein-coding regions in the genome.

CRISPR/Cas9: A genome-editing tool used to introduce targeted modifications in DNA.

Ureteric bud: An embryonic outgrowth from the Wolffian duct that gives rise to the collecting duct system of the kidney.

Hydronephrosis: The swelling of a kidney due to a build-up of urine from urinary tract obstruction.

References

1. Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT). Kidney International (2023).
2. Ahnak is required to balance calcium ion homeostasis and smooth muscle development in the urinary system. Cell & Bioscience (2023).
3. Integrated analysis of copy number variation-associated lncRNAs identifies candidates contributing to the etiologies of congenital kidney anomalies. Communications Biology (2023).
4. Prevalence, types, and malformations in congenital anomalies of the kidney and urinary tract in newborns: a retrospective hospital-based study. Italian Journal of Pediatrics (2019).
5. Factors Associated With the Development of Chronic Kidney Disease in Children With Congenital Anomalies of the Kidney and Urinary Tract. Frontiers in Pediatrics (2020).
6. Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT). Molecular and Cellular Pediatrics (2021).