NIDDK and ISAC Kidney Engineering Workshop

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is planning a workshop series, in collaboration with the Innovative Science Accelerator Program (ISAC), on groundbreaking approaches to engineer replacement kidneys.

The goals for these virtual workshops are to spotlight emerging research, spark innovative ideas, identify synergies between approaches and foster interdisciplinary collaborations, engage in meaningful discussions between researchers and the community and identify tools that can catalyze research and development in this area. Across the sessions, we anticipate speakers will highlight opportunities to draw inspiration from other species, leverage advances made in engineering other tissues, and discuss novel approaches to replace lost kidney functions.

The dates, timing, and other logistical information for each session can be found on the session pages.

It is anticipated that executive summaries of breakout group discussions and recordings of the presentations will be made available through this site shortly after each session.
  • Contacts
  • Related Programs
  • Session 1
  • Session 2
  • Session 3

ISAC Contacts:

Richard McIndoe, Ph.D., Augusta University
Christine Maric-Bilkan, Ph.D.: https://www.niddk.nih.gov/about-niddk/staff-directory/biography/maric-bilkan-christine
Chris Ketchum, Ph.D.: https://www.niddk.nih.gov/about-niddk/staff-directory/biography/ketchum-chris

NIDDK Workshop Contacts:

Eric Brunskill, Ph.D.: https://www.niddk.nih.gov/about-niddk/staff-directory/biography/brunskill-eric
Danny Gossett, Ph.D.: https://www.niddk.nih.gov/about-niddk/staff-directory/biography/gossett-daniel

Related programs:

Organizers:

  • Stephen R. Ash, MD, FACP, HemoCleanse Technologies, LLC and Ash Access Technology,
  • Hatim Hassan, MD, PhD, Mayo Clinic
  • Jamie Hestekin, PhD, University of Arkansas
  • Alex Hughes, PhD, University of Pennsylvania
  • Rachel Lennon, BMedSci, BMBS, PhD, University of Manchester
  • Celeste M. Nelson, PhD, Princeton University
  • Mari Winkler, PhD, University of Washington
 

Session 1) "Engineering and Biology Solutions to Achieve Tubular Functions"

May 10th, 2024, from 1:00 PM to 4:00 PM ET

This session will examine the use of a variety of means (e.g., mechanical, physiochemical, acellular, and cellular) to replicate homeostasis by engineering kidney tubules.
Webinar Registration: https://forms.gle/7EXLwYVxCHbJK6VA6

Organizers:

  • Celeste M. Nelson, PhD, Princeton University
  • Alex Hughes, PhD, University of Pennsylvania

Purpose

  1. To assemble a group of creative individuals from diverse scientific backgrounds to address the growing problem of kidney failure by replacing kidney functions.
  2. To promote the cross-fertilization of ideas of researchers and engineers from disparate scientific fields with unique perspectives and insights to develop transformative solutions and ideas to replace kidney functions beyond dialysis.

Agenda:

1:00 - 1:10 Introduction (Eric Brunskill, Danny Gossett, Alex Hughes, and Celeste Nelson)
1:10 - 1:30 Plenary Speaker #1
Juan Alvarez, PhD, University of Pennsylvania: Lessons from Translation:
Perspectives from Pancreas Engineering (15 minute presentation & 5 minute Q/A)
1:30 - 1:50 Plenary Speaker #2
Nuria Montserrat, PhD, Institute for Bioengineering of Catalonia: Where
organoids are stuck? (15 minute presentation & 5 minute Q/A)
Brief Talks. (7 minute presentations & 3 minute Q/A)
The objectives for the brief talks are to introduce novel concepts, highlight recent technological or research advances, or harness lessons learned from other fields, toward the session goals. The presentations are not exhaustive reviews but are meant to offer a snapshot of the concepts, perhaps through a few illustrative slides. Attendees are encouraged to take a deeper diver into these and other concepts in the breakout discussions.
1:50 - 2:00 Scott Wiener, MD, SUNY Upstate Medical University: From Ancient Blueprint to Modern Marvel: Evolutionary Insights into Engineering an Artificial Kidney
2:00 - 2:10 Zhongwei Li, PhD, University of Southern California: Leveraging on self-organization of kidney progenitor cells to achieve functional maturation of synthetic kidneys.
2:10 - 2:20 Quinton Smith, PhD, UC Irvine: Constructing epithelial trees, lessons from the biliary tree and liver tissue.
2:20 - 2:30 Kayla Wolf, PhD, Harvard University: Measuring tubular functions in a 3D kidney tubule model.
2:30 - 2:40 Arohan R. Subramanya, MD, FASN, University of Pittsburgh: A nephrologist's/renal physiologist's perspective on what we need to build.
2:40 - 3:10 Breakout Group Discussions (30 minutes)
3:10 - 3:20 Break
3:20 - 3:50 Breakout Group Summaries (30 minutes)
3:50 - 3:55 Closing (5 minutes)

Breakout Group Questions

Breakout Groups may choose to discuss any of the following questions, or other topics nominated by the group.
  1. How do we evaluate function of an engineered tube? Do we already have the assays, or do new ones need to be developed?
  2. What are the essential biological features required to successfully engineer a functional equivalent of a kidney tubule?
  3. What mysteries remain to be uncovered in the kidney tubules? Do we know all the cells necessary for function? Do we expect new ones to be discovered with the advent of single cell and spatial transcriptomics?
  4. Are there differences between mouse and human kidneys that we need to keep in mind?
  5. How biological (cellular) does a kidney tubule need to be?
  6. What is necessary to engineer to replace the function of a kidney tubule?
  7. Comparing fabrication approaches in tissue engineering: Contrast the predefined structural design in 3D printing and tissue engineering (top down) with the self-organizing structures in organoid-based methods (bottom up). Discuss the advantages and limitations of each approach. Can these methodologies be integrated for enhanced tissue design?
  8. How can we approach engineering when developmental pathways, like Wnt, FGF, and TGF-beta/BMP, are context-dependent and are redeployed in varying manners throughout the same developmental trajectory?
  9. Cell autonomous vs. non-autonomous drivers of development: How can we distinguish the two and make strong inferences of causation (are there new tools for predicting cell-cell interactions / modeling non-linear outcomes)?
 

Session 2) Advancing Uremic Toxin Removal - Merging chemistry and microbiology to enhance purification solutions.

June 21, 2024, from 1:00 PM to 4:05 PM ET


This session will explore opportunities to leverage chemistry, microbiology, and other approaches to enhance blood purification.
Webinar Registration: https://bit.ly/4ayLgiV

Organizers:

  • Stephen R. Ash, MD, FACP, HemoCleanse Technologies, LLC and Ash Access Technology
  • Hatim Hassan, MD, PhD, Mayo Clinic
  • Mari Winkler, PhD, University of Washington

Purpose

  1. To assemble a group of creative individuals with diverse expertise to address the growing problem of end-stage renal disease by replacing kidney functions, specifically focused on the challenge of removing uremic toxins (e.g., researchers focusing on the problem of uremic toxin removal; clinicians involved with care of patients kidney disease/failure; engineers, chemists, and microbiologists with unique tools and approaches; and people living with kidney disease/failure).
  2. To promote the cross-fertilization of ideas of researchers and engineers from disparate scientific fields with unique perspectives and insights to develop transformative solutions and ideas to replace kidney functions beyond dialysis.

Draft Agenda/Outline:

1:00 - 1:05 Introduction (Eric Brunskill, Danny Gossett, Stephen Ash, Mari Winkler, and Hatim Hassan)
1:05 - 1:25 Plenary Speaker #1
Stephen R. Ash, MD, FACP, HemoCleanse Technologies, LLC and Ash Access Technology: Introduction to uremic toxins and strategies for their removal (15/5QA)
1:25 - 1:40 Plenary Speaker #2
Mari Winkler, PhD, University of Washington: How effective the removal of uremic toxins from the gut can be (10/5QA)
1:40 - 1:55 Plenary Speaker #3
Hatim Hassan, MD, PhD, Mayo Clinic "Oxalate and other considerations" (10/5QA)
Brief Talks. (10 minute presentations & 3 minute Q/A)
The objectives for the brief talks are to introduce novel concepts, highlight recent technological or research advances, or harness lessons learned from other fields, toward the session goals. The presentations are not exhaustive reviews but are meant to offer a snapshot of the concepts, perhaps through a few illustrative slides. Attendees are encouraged to take a deeper diver into these and other concepts in the breakout discussions.
1:55 - 2:08 Christian Bluechel, Nextkidney: Novel sorbents to regenerate spent dialysate
2:08 - 2:21 Karin Gerritsen, UMC Utrecht: New strategies to remove uremic toxins
2:21 - 2:34 Tammy Sirich, MD, Stanford University: Removal of Protein-bound uremic toxins (PBUT)
2:34 - 2:47 Glenda Roberts, University of Washington, Center for Dialysis Innovation: The importance of patients on design teams
2:47 - 2:55 Break
2:55 - 3:45 Breakout Group Discussions (50 minutes)
3:45 - 4:00 Breakout Group Feedback summaries (15 minutes)
4:00 - 4:05 Closing (5 minutes)
Breakout Group Questions

Breakout Group Questions

Breakout Groups may choose to discuss any of the following questions, or other topics nominated by the group.
  1. Innovative Technologies and Approaches:
    • What novel technologies or methodologies could be developed to enhance the removal of uremic toxins in people with chronic kidney disease or end stage kidney disease?
    • How can we leverage advances in bioengineering and nanotechnology to improve the efficacy of uremic toxin removal? What are the trade-offs to consider for these approaches?
    • How sholid we evaluate the performance of devices and/or cellliar constructs for removing uremic toxins?
    • How can we foster partnerships between academia, industry, and patients to accelerate the development of new treatments?
  2. Evaluating Effects of Therapies:
    • What are the challenges in identifying and validating novel measures (in blood, urine, fecal, effluent) of uremic toxin levels and treatment efficacy?
    • Given the myriad uremic toxins discussed today, what are the important measures/biomarkers to evaluate the efficacy of new treatments (preclinically, clinically)?
    • How can we integrate patient-centered outcomes, patient-reported outcomes, and quality of life measures into the evaluation of new treatments for uremic toxin removal?
  3. Gut Microbiome and Uremic Toxins:
    • What are the translational challenges for gut-based therapies? What are some opportunities to address these challenges through mlitidisciplinary research?
    • How colid gut-based therapies complement current treatments in CKD and ESRD?
    • What is the role of the gut microbiome in the production and removal of uremic toxins, and how can we manipliate it for therapeutic benefit?
    • What are the potential risks and benefits of long-term manipliation of the gut microbiome in people with CKD?
  4. Mechanisms of Uremic Toxin Production and Clearance:
    • What are the key biological pathways involved in the production and clearance of uremic toxins, and how can they be targeted therapeutically?
    • What are some of the challenges in targeting these biological pathways?
    • How do genetic and environmental factors influence the levels and effects of uremic toxins in people with CKD?
 

Session 3) Innovations in Designing Artificial Glomeruli and Filtration Systems for the Kidney.

July 26, 2024, from 1:00 PM to 4:00 PM ET

This session will explore opportunities to leverage chemistry, microbiology, and other approaches to enhance blood purification.

Webinar Registration: https://tinyurl.com/we3revm8

Organizer:

  • Jamie Hestekin, PhD, University of Arkansas

Purpose

  1. To assemble a group of creative individuals from diverse scientific backgrounds to address the growing problem of end-stage renal disease by replacing kidney functions, specifically focused on filtration and glomerular function.
  2. To promote the cross-fertilization of ideas of researchers and engineers from disparate scientific fields with unique perspectives and insights to develop transformative solutions and ideas to replace kidney functions beyond dialysis.

Draft Agenda/Outline:

1:00 - 1:10 Introduction (Eric Brunskill, Danny Gossett, and Jamie Hestekin)
1:10 - 1:40 Plenary Speaker (20/10QA)
Linus Butt, MD, University of Cologne, Modeling glomerular filtration
Brief Talks
1:40 - 1:50 Jamie Hestekin, PhD, University of Arkansas, Electrodeionization
Brief Talks. (10 minute presentations & 3 minute Q/A)
The objectives for the brief talks are to introduce novel concepts, highlight recent technological or research advances, or harness lessons learned from other fields, toward the session goals. The presentations are not exhaustive reviews but are meant to offer a snapshot of the concepts, perhaps through a few illustrative slides. Attendees are encouraged to take a deeper diver into these and other concepts in the breakout discussions.
1:50 - 2:00 Mira Krendel, PhD, SUNY Upstate Medical University, Focus on podocytes: specialized epithelial cells of the glomerular filter
2:00 - 2:10 Dean Johnson, PhD, University of Rochester Medical Center, Specifications for membranes
2:10 - 2:20 Nick Ferrell, PhD, Ohio State University Medical Center, In Vitro Models to Evaluate Molecular Permeability of the Kidney Filtration Barrier
2:20 - 2:30 Break
2:30 - 3:15 Breakout Group Discussions (45 minutes)
3:15 - 3:45 Reconvene for Breakout Group Feedback summaries (30 minutes)
3:45 - 4:00 Closing (15 minutes)

Breakout Group Questions

Session 3 Breakout Group Questions
Please read these questions in advance of the meeting. Consider these to be possible discussion topics for the breakout groups. All breakout groups are provided the same questions, and it is not expected that groups will cover every question.
  • Technology
    • What are some of the gaps where there is a need for fundamental enabling technologies for next generation filtration?
    • What are the current limitations of existing filter technologies and where are advances in materials science, nanotechnology, and other fields needed to achieve more efficient and biocompatible filters for kidney replacement?
    • How can new filter designs address the issue of biocompatibility and reduce the risk of immune responses, clotting?
    • What strategies can be employed to mimic the selective permeability of the glomerulus in artificial filters? How to improve filter design?
  • Modeling
    • Are there computational models and simulations that can be used to predict the performance of new filter designs and enhance their development?
    • What are the appropriate experimental systems (e.g., co-cultures, benchtop models) to validate filtration modeling?
  • Innovation, Technology Development, and Collaboration
    • How can collaborations between engineers, biologists, clinicians, and patients accelerate the development of innovative kidney replacement solutions?
    • How can we use patient-specific data to tailor kidney replacement filters and optimize their performance for individual needs?
    • How can patient feedback be incorporated into the design process for kidney replacement filters to ensure they meet the needs and preferences of end-users?

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