New Insights into Congenital Kidney Disease

Event Details

Meeting Summary (PDF, 455.33 KB)

Background

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.

Meeting Objectives

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

Registration Deadline

September 20, 2022

Abstract Submission Deadline

September 9, 2022

Agenda

September 28, 2022

10:00 a.m. – 10:10 a.m.

Welcome
Robert Star, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

10:10 a.m. – 10:20 a.m.

Introduction
Susan Mendley, M.D., NIDDK
Eric Brunskill, Ph.D., NIDDK

Session One

Moderators:
Craig Peters, M.D., The University of Texas (UT) Southwestern Medical Center
Lori O’Brien, Ph.D., University of North Carolina at Chapel Hill

10:20 a.m. – 10:35 a.m.

A Nephrologist’s View of Congenital Kidney Disease and Nephron Endowment
Jacqueline Ho, M.D., UPMC Children’s Hospital of Pittsburgh/University of Pittsburgh School of Medicine

10:35 a.m. – 10:50 a.m.

A Urologist’s View of Congenital Kidney Disease
Linda Baker, M.D., The University of Texas (UT) Southwestern Medical Center

10:50 a.m. – 11:05 a.m.

The Role of Low Nephron Endowment in Disparities in Kidney Disease
Jennifer Charlton, M.D., University of Virginia School of Medicine

11:05 a.m. – 11:20 a.m.

Overview of Human Kidney Development
Nils Lindstrom, Ph.D., University of Southern California

11:20 a.m. – 11:35 a.m.

The Role of Stroma in Renal and Ureteral Development
Thomas Carroll, Ph.D., UT Southwestern Medical Center

11:35 a.m. – 12:15 p.m.

Discussion with Speakers’ Panel

Session Two

Moderators:
Brian Becknell, M.D., Ph.D., Abigail Wexner Research Institute at Nationwide Children’s Hospital
Deb Gipson, M.D., University of Michigan

12:15 p.m. – 12:45 p.m.

Parents’ Perspective on Congenital Kidney Disease
Panel Discussion

12:45 p.m. – 1:15 p.m.

Break

Session Three

Moderators:
Nora Franceschini, M.D., University of North Carolina at Chapel Hill
Benjamin King, Ph.D., University of Maine

1:15 p.m. – 1:30 p.m.

What Can We Learn from the Experience with Congenital Heart Disease? The National Heart, Lung, and Blood Institute Bench to Bassinet Study
Bruce Gelb, M.D., Icahn School of Medicine at Mount Sinai

1:30 p.m. – 1:45 p.m.

Whole-genome Sequencing (WGS) of Patient Cohorts — The Gabriella Miller Kids First Model
David Higgins, Ph.D., Children’s Hospital of Philadelphia

1:45 p.m. – 2:00 p.m.

The Value of WGS of Cohorts in Congenital Kidney Disease
Ali Gharavi, M.D., Columbia University

2:00 p.m. – 2:15 p.m.

Lessons from Discovery of a Genetic Cause of Disease in ~20% of CAKUT
Friedhelm Hildebrandt, M.D., Boston Children’s Hospital/Harvard Medical School

2:15 p.m. – 2:30 p.m.

Computational Tools Needed to Understand WGS Heterogeneity and Combinations of Single-nucleotide Polymorphisms in Patients and Translate That to Testable Hypotheses
Dana Crawford, Ph.D., Case Western Reserve University

2:30 p.m. – 3:05 p.m.

Discussion with Speakers’ Panel

3:05 p.m. – 3:30 p.m.

Lightning Talks

3:30 p.m. – 3:50 p.m.

Poster Viewing and Discussion

3:50 p.m. – 4:00 p.m.

Break

Session Four

Moderators:
Samir El-Dahr, M.D., Tulane University School of Medicine
Ben Fogelgren, Ph.D., University of Hawaii

4:00 p.m. – 4:15 p.m.

Using Model Systems to Test Findings from Whole-exome Sequencing 
Kameswaran Surendran, Ph.D., Sanford Research

4:15 p.m. – 4:30 p.m.

Using Model Systems to Test Findings from WGS
Kristen Brennand, Ph.D., Yale School of Medicine

4:30 p.m. – 4:45 p.m.

Using Xenopus (frog) Embryos to Model Human Variants
Rachel Miller, Ph.D., UTHealth McGovern Medical School

4:45 p.m. – 5:15 p.m.

Discussion with Speakers’ Panel

5:15 p.m.

Adjournment

September 29, 2022

10:00 a.m. – 10:10 a.m.

Overview of Day 1
Eric Brunskill, Ph.D., NIDDK

Session Five

Moderators:
Carolyn Abitbol, M.D., University of Miami
Lorraine Gudas, Ph.D., Weill Cornell Medicine of Cornell University

10:10 a.m. – 10:25 a.m.

Current Approaches to Phenotyping the Intrauterine Environment and Their Limitations
Maisa Feghali, M.D., University of Pittsburgh, Magee Women’s Research Institute

10:25 a.m. – 10:40 a.m.

Relating Maternal Health and Nutrition during Pregnancy to Fetal Renal Development
Sunder Sims-Lucas, Ph.D., University of Pittsburgh

10:40 a.m. – 10:55 a.m.

The Effects of Preterm Delivery on Nephron Endowment
Meredith Schuh, M.D., Cincinnati Children’s Hospital Medical Center

10:55 a.m. – 11:10 a.m.

Environmental Chemical Exposures and Kidney Development
Alison Sanders, Ph.D., M.S., University of Pittsburgh

11:10 a.m. – 11:40 a.m.

Discussion with Speakers’ Panel

11:40 a.m. – 12:00 p.m.

Break

Session Six

Moderators:
Michael McMahon, Ph.D., Kennedy Krieger Institute/Johns Hopkins School of Medicine
Jennifer Charlton, M.D., University of Virginia

12:00 p.m. – 12:15 p.m.

The Potential Value of Ultrasound Microvessel Imaging in Congenital Kidney Disease
Shigao Chen, Ph.D., Mayo Clinic

12:15 p.m. – 12:30 p.m.

Radiologic Approaches to Phenotyping
Sila Kurugol, Ph.D., Boston Children’s Hospital and Harvard Medical School

12:30 p.m. – 12:45 p.m.

Developing a Cohort Study—Lessons from the Epilepsy Phenome and Genome Project and Epi4K
Heather Mefford, M.D., Ph.D., St. Jude Children’s Research Hospital
Ann Poduri, M.D., M.P.H., Boston Children’s Hospital/Harvard Medical School

12:45 p.m. – 1:15 p.m.

Discussion with Speakers’ Panel

1:15 p.m. – 2:30 p.m.

Breakout Sessions with Topic Questions

• Studying Kidney Developmental Disorders from Gestation Through Childhood
  How can we create a continuum of research that spans intrauterine development through birth and childhood?
  Could the widespread use of antenatal ultrasound be systematically harnessed to study congenital kidney disease?
  How can we discern and follow genitourinary, cardiac and neurodevelopmental anomalies that are coincident with congenital kidney disease?
  What phenotyping strategies would be needed?
  How could a cohort be identified and followed?
  How could parents contribute to this effort?
• Translating WGS to Hypotheses and Model Systems
  Whole genome sequencing is expected to find SNPs in many untranslated regions.
  What computational tools are needed to understand WGS heterogeneity and combinations of SNPs in patients and translate that to testable hypotheses?
  What are the strengths and limitations of current model systems to understand human kidney development?
  What concerns do parents and caregivers have about whole genome sequencing of children and their parents?
• Environmental Exposures and Nutrition
  How can one detect environmental exposures and their potential effects on kidney development and nephron endowment?
  How can one discern the effect of nutritional deficiencies and excesses on kidney development?
  What developmental periods might be impacted by nutrition and environmental exposures?
  How broad or how local should exposure and nutrition studies be?
  How could environment exposures and nutrition be linked to kidney disease in childhood and adulthood?
  What control groups would be appropriate?

2:30 p.m. – 2:45 p.m.

Break

2:45 p.m. – 3:45 p.m.

Report Back and Discussion

3:45 p.m. – 4:00 p.m.

Closing Remarks and Discussion

4:00 p.m.

Adjournment

Abstracts

Submission Deadline

September 9, 2022

Submitting Abstracts

All abstracts must be submitted via email to John Hare, with “Abstract-New Insights into Congenital Kidney Disease” in the subject line. The abstract submission should be a 1-page Microsoft Word document that does not exceed 250 words (not including the abstract’s title and name and affiliation of all authors).

Presenters are welcome to present abstracts previously-presented in other venues.

Download the Abstract Template (DOCX, 24.67 KB) .

Abstract Organization

Organize the body of the abstract as follows:

• Statement of the study’s purpose
• Statement of the methods used
• Summary of the results presented in sufficient detail to support the conclusion
• Statement of the conclusions reached

Formatting Requirements

Please follow the instructions below to format an abstract. (Note: Submissions will not be edited for spelling or grammar and will be accepted “as is.”)

• The abstract should be a Microsoft Word document with 1-inch margins, typed single space, using Times New Roman font; a 12-point font should be used for everything except the title.
• The abstract’s title should be Typed in Title Case using Bold 16-Point font, and it should clearly represent the nature of the investigation. Do not use subheadings (e.g., Methods, Results) in the body of the abstract.
• Skip one line after the title, and list the author’s first and last names, degree, affiliation, city, state, and country. Separate multiple authors with a semicolon, and underline the primary author’s name (one primary author per abstract).
• Use one blank line between the title and the authors, the authors and the body of the abstract, and between paragraphs.
• Please ensure that your abstract is the correct length (no longer than 250 words).
• Use standard abbreviations (e.g., RBC) and standard symbols for units of measure (e.g., kg, g, mg, mL, L, and %). Place abbreviations and acronyms in parentheses after the full word the first time that the term appears. Use numerals to indicate numbers, except as the first word of a sentence.
• Simple tables or graphs may be included; however, the abstract may not be longer than one page, including any tables or graphs

Poster Presentations

Poster presentations will be conducted virtually.

All presenters must register in advance for the conference.