New Insights into Congenital Kidney Disease
Congenital diseases of the urinary tract can lead to a range of devastating conditions, including fetal loss or childhood or later-life kidney failure. Furthermore, interrupted kidney development leading to low nephron endowment may have implications for a lifelong risk of kidney failure. Although the combination of genetic studies in humans and developmental studies in model organisms has provided tremendous opportunities to understand the formation of normal and diseased kidneys, the causes of most congenital renal anomalies—such as renal dysplasia, hypoplasia, and aplasia—remain unknown. As a community of clinicians and researchers, we are unable to provide the parents of children with congenital renal anomalies an explanation of the cause of their child’s disease, and we can offer little hope for a different future for other children.
During the past decade, advances in next-generation sequencing platforms have allowed crucial discoveries of the biology and pathophysiology of disrupted renal development, including the identification of many associated genes and copy number variants. Investigations using model organisms have provided foundational insights into key genetic factors and molecular pathways that regulate the earliest stages of kidney development. However, important potential areas remain unexplored, including the control of lateral arcading in the late stages of human nephrogenesis, the role of gene-exposure interactions, the effects of variations in the intrauterine environment, maternal and infant nutrition, and the impact of social and health disparities on kidney development and nephron endowment.
The National Institute of Diabetes and Digestive and Kidney Diseases is planning a public workshop to discuss the challenges in moving beyond the current research state to an understanding of the mechanisms associated with congenital renal anomalies and low nephron endowment. The workshop seeks to engage leaders in the field to foster cross-disciplinary discussions among clinicians, computational geneticists, developmental biologists, perinatologists, environmental scientists, health disparities researchers, and investigators who work with a range of renal model systems, including organoids, to identify common scientific intersections and natural collaborations among disciplines.
The goal of the workshop is to broaden the current research field and promote multidisciplinary approaches among individuals with expertise in genetics, epigenetics, developmental biology, multi-omics, clinical phenotyping, the intrauterine environment, environmental exposures, and health disparities.
The workshop seeks to address and identify potential key needs of the community, including—
- to determine the utility of assembling a well-phenotyped patient cohort and trios and using whole-genome sequencing to identify mutations in genes, noncoding regions, and regulatory enhancers
- to determine the contribution of sequence heterogeneity in the patient population and model mechanisms using appropriate systems
- to determine how the intrauterine environment, preterm delivery, and maternal nutrition affect renal development and nephron endowment
- to consider what bioinformatic tools would be needed to interpret the data
- to identify environmental exposures that could affect renal development and nephron endowment and determine whether racial disparities in exposures associate with an increased risk of kidney failure in childhood and adulthood
May 29, 2022