U.S. Department of Health and Human Services
Kidney Precision Medicine Meeting 2016

Kidney Precision Medicine Meeting

5/23/2016 8:00 AM
5/25/2016 5:00 PM
No
No
(301) 652-2000

For questions concerning meeting logistics, contact:
Rob Watson, CMP
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD 20878
Phone: 301-670-4990
Fax: 301-670-3815
Email: rwatson@scgcorp.com

For questions concerning program content, contact:
Chris Ketchum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-402-1411
Email: chrisketchum@nih.gov

Michael Flessner, M.D., Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-451-4901
Email: flessnermf@mail.nih.gov

Paul L. Kimmel, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-594-7717
Email: kimmelp@mail.nih.gov

Krystyna Rys-Sikora, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-451-4770
Email: ryssikok@niddk.nih.gov​​​

Yining Xie, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-594-7713
Email: yining.xie@nih.gov

Bethesda
Double Tree Hotel

Event Details

Purpose

Despite many academic and industry efforts to treat acute and chronic kidney disease, therapies remain limited. This conference aims to bring together basic, clinical, and translational scientists, health care professionals, industry and government representatives, and patients – all of whom are interested in the treatment of acute and chronic kidney disease:

  1. To recognize the heterogeneity of acute and chronic kidney disease and the importance in differentiating such heterogeneity so that precise treatments can be developed and provided to individual patients.
  2. To determine the quantity and usability of currently available kidney tissues obtained from patients with acute and chronic kidney disease (including transplant donors, partial nephrectomy for renal cell carcinoma).
  3. To discuss the need, challenges, and barriers in obtaining research biopsies from patients with acute and chronic kidney disease, as well as the negative consequence of not obtaining kidney tissues in the current and future treatment of those patients.
  4. To establish the scientific and clinical quality control/assurance metrics and training needed for setting up a network to obtain kidney research biopsies.
  5. To discuss the phasing and priority needed to move the field forward.
​​​​​​​​​​​​

Information regarding Hotel reservations at the Doubletree by Hilton Bethesda can be found under the Directions/Travel tab. The last day to reserve a room at the group rate is Friday, April 29.​​​

Agenda

 

Day 1: May 23

 
8:00 a.m. Goals and expectations (Robert Star)
 
Session 1: Success Stories—How has the study of human tissue significantly advanced other fields? Lessons learned (15 min. talk + 15 min. discussion for each speaker) Moderator: Stephen Hewitt
 
8:20 a.m. Gliomas in children: Why did the field need tissue and how was it obtained? What value was added? What steps were taken to gain patient acceptance? (Kathy Warren)
 
8:50 a.m. Lessons from liver biopsies in viral hepatitis and NASH (David Kleiner)
 
9:20 a.m. Monitoring health and disease with big data and omics profiling (Mike Snyder)
 
9:50 a.m. Break
 
Session 2: AKI and CKDs—What are the major unsolved clinical questions? (10 min. talk + 10 min. discussion for each speaker) Moderator: Matt Breyer
 
10:10 a.m. Major unsolved clinical questions in AKI (Joe Bonventre)
  • What is human AKI?
  • Lack of specific therapies; difficulties with animal models
  • Many targets in animals, but translation has been unsuccessful
 
10:30 a.m. Major unsolved clinical questions in CKDs (Jonathan Himmelfarb)
  • CKDs rather than CKD; no single common pathway, lessons from FIND
  • Why do we need earlier samples? Can a defining pattern of injury up front drive later treatment?
  • Biopsy for stage?
 
Session 3: Tissue Interrogation—What have others done with tissue? What new technologies are available to address kidney cell type and disease heterogeneity? (10 min. talk + 10 min. discussion for each speaker) Moderator: Ravi Iyengar
 
10:50 a.m. Redefining kidney disease phenotypes (Chip Brosius)
  • Multiscale description of healthy and diseased phenotypes (histology and beyond)
  • Need for “normal,” pre-dysfunction, and early dysfunction
  • Explain what is new and why it is feasible now
 
11:10 a.m. Molecular analysis and mapping of biopsied tissue (Jeremy Norris) (20 min. talk + 10 min. discussion)
  • Tissue preparation for in situ analysis
  • Molecular analysis (proteomic, lipidomics, etc.) and imaging techniques
  • Molecular mapping (linking structure to function in healthy and diseased tissues)
 
11:40 a.m. Interrogating single cells to understand tissue heterogeneity (Rahul Satija)
  • Overview of single cell analysis techniques (including RNAseq vs. whole tissue)
  • Issues with cell dissociation
  • Identify signature profiles for cell types/rare cell types/cell subpopulations
  • Identify cellular differences in different physiological and disease states
  • Map cells within a tissue to understand cell biology in normal and acute injury/disease states (bottom-up approach)
 
12:00 p.m. Lunch and posters
 
1:00 p.m. Integrative data analysis and modeling of complex human disease (Olga Troyanskaya)
  • Analysis of large omic data collections to create tissue-specific functional networks
  • Use of bioinformatics and computational modeling to identify crucial disease pathways and phenotypes (active pathways—genomics, epigenetics, and other; heterogeneity phenotype)
  • Combining information to predict function, functional units, mechanisms of disease and phenotyping
 
1:20 p.m. Six perspectives on how to analyze kidney tissue (7 min. talks followed by a panel discussion)
  1. Andy McMahon
  2. Stephen Hewitt
  3. Betty Diamond
  4. Maria Gomez
  5. Katalin Susztak
  6. Avi Rosenberg
 
Session 4: Tissue Collection (10 min. talk + 10 min. discussion for each speaker) Moderator: Katalin Susztak
 
2:10 p.m. Lessons learned about training, tissue collection, and quality control from an existing kidney cohort (Matthias Kretzler)
 
2:30 p.m. Break
 
Session 5: Bioethics—What are the ethical issues of the research renal biopsy? (10 min. talk + 10 min. discussion for each speaker) Moderator: Paul Kimmel
 
2:50 p.m. Research biopsies in patients with AKI: Changing paradigms (Steve Korbet)
  • Practices and pitfalls in doing kidney biopsies in patients with acute illness
  • How do we initiate a change in practice? What are the patient acceptance issues?
 
3:10 p.m. Research biopsies in patients with CKDs: Changing paradigms (Sus Waikar)
  • How do we get started (DN, unclear etiology, patient wants exact diagnosis)?
  • How do we obtain earlier samples (other sources)?
  • Can tissue be used for staging and prognosis?
 
3:30 p.m. Ethical and patient-centered issues in performing a renal biopsy (Robert “Skip” Nelson)
  • Usefulness of information to the individual and society; setting of unclear benefit
  • Ethical perspectives on collaborating with critically ill patients
  • Cost/benefit considerations
  • Paradigmatic changes—clinicians, patients, and researchers
  • Patient-centered issues
 
3:50 p.m. Patient perspectives (Paul Conway, Richard Knight, Sandra Palumbo)
 
4:10 p.m. Break
 
Session 6: Day 1 Breakout Groups
 
4:30 p.m. Meeting will split into three different groups to discuss specific issues related to Tissue Interrogation (Ballroom C), Tissue Collection (Harmony Room), and Bioethics (Balance Room). Each session may include short talks, tasking smaller working groups, and facilitated discussions.
  1. Tissue Interrogation (Ballroom C): How can we best obtain integrated knowledge about physiology and pathophysiology from biopsy samples? How will we integrate data from complementary technologies? Are analytic pathways different for AKI and CKDs (because the processes/cells might be different)? Are pathways sufficiently robust, scalable, and validatable? How deep should we go before diminishing returns? How do we deal with heterogeneity within kidney tissue and cells? How will we tie the data to sample site/assay noise/patient subgroups? How can we analyze and visualize results (and map back onto tissue?) Where do we start? What are the benchmarks (hierarchy)? What are the downstream studies (animals, etc.)?

    • Technology Chairs: Andy McManon, Steve Potter, Katalin Susztak, Ravi Iyengar
    • AKI Chairs: Manjeri Venkatachalam, Charlie Alpers
    • CKD Chairs: Avi Rosenberg, Ray Harris
    • NIDDK Reps: Krystyna Rys-Sikora and Deborah Hoshizaki

    GOAL: How to best use tissue to understand the function of the kidney in healthy (normal) and disease states.

    4:30- 5:15 p.m. Bullet Presentations (order TBD, 3 slides max) (5 mins each)

    Tissue Interrogation Breakout Session SHORT TALKS

    1. SCA-disassociation and analysis to identify cell types (kidney biopsies from LN) (Nir Hacohen)
    2. Epigenetics, genetics and proteomic analyses of DKD biopsies (Katalin Susztak)
    3. Proteomics and lipidomics on whole renal tissue samples (Jeremy Norris)
    4. Multiplex expression approaches (Andy McMahon)
    5. Object oriented pathology and linking molecular pathology and physiology (Stephen Hewitt)
    6. xMD techniques on extracellular matrix (Avi Rosenberg)
    7. Deep Sequencing of microdissected tubules: omics and mapping pathways (Mark Knepper)
    8. BEAt-DKD approaches for tissue interrogation (Maria Gomez)
    9. SCA-spatial mapping (Steve Potter)

    5:15-6:00 p.m. Discuss strategies for moving forward and address the Tissue Interrogation questions above.

  2. Tissue Collection (Harmony Room): How will we collect tissue and from whom? How much tissue is needed for extensive molecular analysis? What new tools might improve collection? How will we ensure tissue quality control? What new tools might improve tissue quality and sampling variability? Which patients should be studied? Will biopsy be acceptable to the patients? Will control patients be necessary, or is normal tissue or data available? Are there specific issues for AKI? Are there specific issues for CKDs?

    • Technology Chairs: Stephen Hewitt, Matthias Kretzler
    • AKI Chairs: Lloyd Cantley, Joe Bonventre
    • CKD Chairs: John Sedor, David Salant, Amy Mottl, Mike Mauer
    • NIDDK Reps: Mike Flessner and Danny Gossett

  3. Bioethics (Balance Room): What are the risks? What are the benefits? How do we adequately communicate with patients? What will be required to change the existing culture? How will patients be selected and recruited? Are there specific issues for AKI? Are there specific issues for CKDs?

    • AKI Chairs: Chirag Parikh, Steven Korbet
    • AKI Patient: Sandra Palumbo
    • CKD Chairs: William Knowler, Kathy Tuttle
    • CKD Patients: Richard Knight, Paul Conway
    • NIDDK Reps: Paul Kimmel, Andy Narva, and Kevin Abbott
6:00 p.m. Adjournment
 

Day 2: May 24

 
8:00 a.m. Welcome (Robert Star)
 
8:10 a.m. KEYNOTE: Lessons from big data (Nancy Cox - webinar) (20 min. talk + 20 min. discussion) Moderator: Rebekah Rasooly
 
Session 7: Breakout Group Reports (20 min. presentation + 30 min. discussion for each group) Moderator: Chris Ketchum
 
8:50 a.m. Tissue Interrogation
 
9:40 a.m. Tissue Collection
 
10:30 a.m. Break
 
10:50 a.m. Bioethics
 
Session 8: Moving Forward—What have others done? (20 min. talk + 20 min. discussion for each speaker) Moderator: Joe Bonventre
 
11:40 a.m. Lessons from AMP (Accelerating Medicines Partnerships), a public/private partnership on rheumatoid arthritis and lupus (Bob Carter)
 
12:20 p.m. Lunch and posters
 
1:20 p.m. Lessons from NCI tissue collections (Stephen Hewitt)
 
2:00 p.m. Industry perspective—panel discussion (Moderator: Paul Kimmel)
  • Cynthia Arbeeny [Sanofi]
  • Carine Boustany [Boehringer Ingelheim]
  • Matt Breyer [Lilly]
  • Maria Chiara Magnone [AstraZeneca]
  • Dan Levy [Pfizer]
  • Peter Linde [AbbVie]
  • Ulf Meier-Kriesche [Bristol-Myers Squibb]
 
3:00 p.m. Break
 
Session 9: Day 2 Breakout Groups
 
3:20 p.m. Meeting will split into three different groups to discuss specific issues related to AKI (Ballroom C), CKDs (Harmony room), and Data (Balance Room). Each session may include short talks, tasking smaller working groups, and facilitated discussions.
  1. AKI Session (Ballroom C):
    (Chair: Lloyd Cantley. Other discussion leaders: Joseph V. Bonventre, Stephen Korbet, Manjeri Venkatachalam, Charlie Alpers, Robert “Skip” Nelson, Sandra Palumbo, Nicholas Sadovnikoff. NIDDK Reps: Paul Kimmel and Kevin Abbott)

    Overall Goals
    • Assuming we are able to get adequate tissue from a substantial number of subjects with AKI, what would you like to do with it with what goal in mind?
    • Kidney biopsy: Will it lead to new pathways and drug targets in AKI?
    • What are the driver cells of interest? What are the driver pathways?

    Other questions for discussion (will be given to discussion leaders):
    • Discuss the variety of AKI phenotypes and potential mechanisms: What is the state of our knowledge, and what is missing?
    • Will control patients/biopsies be necessary or is normal tissue and/or data available?

    Defining the Cohort
    • Will research biopsy of patients with AKI be acceptable to patients?
    • What patient populations (questions, populations, endpoints, feasibility, safety)?
      1. Cisplatin, other nephrotoxins, delayed graft function, post cardiac surgery, contrast nephropathy, ICU without sepsis, ICU sepsis, pre-renal, ATN, other?
      2. Should populations be studied all at once, or in phases? If phases, who in Phase 1, 2, and 3?

    Other questions for discussion (will be given to discussion leaders):
    1. Will biopsy of patients with AKI require a shift in culture among nephrologists?
    2. What are patients’ perceptions of these proposals?
    3. Are there methods/techniques that can minimize the risk of collecting tissue?
    4. How do we as a community increase the value of the biopsy in identifying new therapeutic targets? How do we communicate the importance of the biopsy to local IRBs?
    5. What data should be collected in addition to tissue—longitudinal phenotypic data, environmental/work exposures, biosamples (urine, blood, stool, other)?
    6. How many patients are needed? How many centers are needed?
    7. What must be considered for Institutional Review Board (IRB) approval?

  2. CKD Session (Harmony Room) (The entire group will discuss Overall Goals, Defining the Cohort, and Phasing the Study sequentially for ~50 min each)
    (Discussion Leaders: Sus Waikar, William Knowler, Avi Rosenberg, Kathy Tuttle, Amy Mottl, Paul Conway, Maria Gomez, Ray Harris, John Sedor, Matthias Kretzler, David Salant, Jeffrey Kopp, and Brad Rovin. NIDDK Reps: Mike Flessner and Tracy Rankin)

    Overall Goals
    (Chair: Ray Harris. Other discussion leaders: Avi Rosenberg, Charles Alpers, David Salant, Jeffrey Kopp)
    • Assuming we are able to get adequate tissue from a substantial number of subjects with CKDs, what would you like to do with it and with what goal in mind?
    • Using biopsy tissue as the diagnostic platform, what cellular processes or pathways would be most informative to establish CKD phenotypes?
    • What molecular pathways in CKDs would be most amenable to a therapeutic target? Repair pathways? Transport and signaling pathways? Uremic solute pathways?

    Other questions for discussion (will be given to discussion leaders):
    • What have the CRIC and CKiD observational studies taught us regarding CKD sub-phenotypes, beyond diabetic and non-diabetic?
    • Have biomarker studies been informative in this regard?
    • Will “molecular phenotyping” be able to override albuminuria as a marker of CKD progression?
    • Discuss the array of CKD phenotypes and potential mechanisms: What is the state of our knowledge, and what is missing?
    • What have we learned from failed or negative trials?
    • Can novel insights be gained from the study of unusual populations (e.g., Mesoamerican nephropathy)?
    • Identify observations/data from other consortia like the African American Study of Kidney Disease (AASK) or the Nephrotic Syndrome Study Network (NEPTUNE) that point to the need for tissue biopsy. Have these studies pointed to new targets in CKDs?
    • Will control patients/biopsies be necessary or is normal tissue and/or data available? What are the best sources of “normal” tissue?

    Defining the Cohort
    (Chair: Cathy Tuttle. Other discussion leaders: Amy Mottl, John Sedor, William Knowler, Richard Knight, Paul Conway)
    • Should nephrologists perform research biopsies or biopsies for indications, such as diabetes or long-term hypertension? When would it be best to biopsy during the course of “traditional” CKD for sub-type diagnosis?
    • Will research biopsy of patients in early stages of CKDs be acceptable to patients? How about repeat biopsies for research purposes?

    Other questions for discussion (will be given to discussion leaders):
    1. Will biopsy of patients with early stages of CKDs require a culture shift amongst nephrologists? What have we learned from the Pima Indian Biopsy Study?
    2. What are the patients’ perceptions of these proposals?
    3. Are there methods/techniques that can minimize the risk of collecting tissue?
    4. How do we as a community increase the value of the biopsy toward identifying new therapeutic targets? How do we communicate the importance of the biopsy to the local IRBs?
    5. Which patients should be studied? What indications warrant biopsy?
    6. Do early events predict later events or disease progression?
    7. What data should be collected in addition to tissue—longitudinal phenotypic data, environmental/work exposures, biosamples (urine, blood, stool, other)?
    8. Will we be able to use the electronic health records (EHR) to identify possible patients and to collect their data?
    9. How many patients are needed? How many centers are needed?

    Phasing the Study
    (Chair: Sus Waikar. Other discussion leaders: Mike Mauer, Brad Rovin, and Maria Gomez)
    • Introduction: KPMI Logic Model
    • Task 1: Develop/test techniques/protocols
    • Task 2: Pilot studies
    • Task 3: Phase 2 patient study?
    • Task 4: Phase 3 clinical study?

    Other questions for discussion (will be given to discussion leaders):
    1. Task 1: Develop and test techniques and protocols to collect tissue, phenotypic data, and other biosamples. Carry out preliminary studies in humans to validate these techniques and protocols
    2. Task 2: Pilot studies
      1. Defining the population: early versus later progressors; high versus low ACR; diabetics versus non-diabetics
      2. Impact of patient selection on design of study
      3. Should a trial be restricted to proteinuric disease or have a stratum with a target proportion with proteinuria and normo-albuminuria? If so, how would proteinuria be defined?
      4. Is the recruitment strategy feasible?
      5. Is it possible to link EHRs to identify possible participants?
    3. Task 3: Phase 2 patient study
      1. Broader population: non-diabetic CKD, hypertension, HIVAN
      2. Pilot treatment study to segregate patient sub-population
      3. Biomarkers for risk stratification
    4. Task 4: Phase 3 study
      1. Cohort study. How large? CRIC-CKiD sized? Length of follow-up?
      2. Discuss pathways of cooperation among industry, academia, government, and patient advocacy groups for tissue-centric studies

  3. Data Session (Balance Room):
    (Chair: Andy McMahon. Other discussion leaders: Steve Potter, Sanjay Jain, and Chirag Parikh. NIDDK Reps: Rebekah Rasooly and Deborah Hoshizaki)
    1. What types of data need to be collected or generated (clinical phenotype, cell and molecular omics, 2D histology, 3D images, super-resolution microscopy)?
    2. What types of curation and annotation are needed to make data accessible to the research community?
    3. What samples should be stored? How will they be stored?
    4. How will samples be linked to longitudinal phenotypic and physiologic data? What data needs to be collected upfront to ensure later linkage to USRDS?
    5. What are the advantages of a website versus a federated portal? Are there good examples to emulate? What are they?
    6. How will we ensure confidentiality of data? How will we preserve the participant identity so that it can be linked to other efforts (without double counting)?
    7. What should be the sharing policy?
    8. When will data and samples be shared with the broader research community? Should data be shared upon validation (and prior to publication)?
    9. Are there specific issues for AKI? CKDs?
6:00 p.m. Adjournment
 

Day 3: May 25

 
8:00 a.m. Welcome (Robert Star)
 
Session 10: Breakout Group Reports (30 min. talk + 30 min. discussion for each group) Moderator: John Sedor
 
8:10 a.m. AKI breakout report
 
9:10 a.m. CKD breakout report
 
10:10 a.m. Break
 
10:30 a.m. Data breakout report
 
11:30 a.m. Meeting summary—Where do we go from here? (Robert Star)
 
12:00 p.m. Adjournment

Directions/Travel

Meeting Location

DoubleTree Bethesda
8120 Wisconsin Avenue, Bethesda, Maryland 20814
Phone: 301-652-2000 | Fax: 301-652-4525 | Email: wasbh_dt@hilton.com

To make reservations for the May 23 – 25, 2016 Kidney Precision Medicine Meeting at the DoubleTree by Hilton in Bethesda, please call 1-800-955-7359 and request the group rate for the meeting by using Group Code: KP5. You can also go online to www.doubletreebethesda.com, click on the Reservations Tab, enter dates and on the Special Accounts Section enter KP5 for the Group/Convention Code.

The last day to reserve a room at the DoubleTree by Hilton Bethesda is Friday, April 29.

Driving Directions

From Washington National Airport (Ronald Reagan) (DCA Airport)

George Washington Pkwy North to I-495 North heading towards Maryland. From I-495 take Exit 34 South Wisconsin Ave. South (Route 355 South). The hotel is 2 miles on the right hand side. Distance from Hotel: 12 mi. Drive Time: 29 min.

From Baltimore/Washington International (BWI Airport)

I-95 South to I-495 (Capital Beltway) proceed West to Silver Spring/Bethesda. I-495-Exit 34 S. Wisconsin Ave/Rockville Pike, proceed South to Bethesda/DC. Hotel is 2 miles on the right hand side. Distance from Hotel: 35 mi. Drive Time: 42 min.

From Washington Dulles International Airport (IAD Airport)

Dulles Access Road East to I-495 (Capital Beltway) heading North to Bethesda/Baltimore. From I-495 take Exit 34 Wisconsin Ave. (Route 355 South). Hotel is 2 miles on the right hand side. Distance from Hotel: 26 mi. Drive Time: 35 min. ​

Minutes

ClickKPMP Meeting Summary.pdfKPMP Meeting Summary.pdf to download the meeting summary.

Attendees

Click Attendee.List_KPM.pdfAttendee.List_KPM.pdf to download the list of meeting attendees.

Abstracts

Clickabstract.pdfabstract.pdf to download abstracts from this meeting.
 

Location

Line
  • 8120 Wisconsin Ave
  • MD 20814
Webinar

Contacts

Line

For questions concerning meeting logistics, contact:
Rob Watson, CMP
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD 20878
Phone: 301-670-4990
Fax: 301-670-3815
Email: rwatson@scgcorp.com

For questions concerning program content, contact:
Chris Ketchum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-402-1411
Email: chrisketchum@nih.gov

Michael Flessner, M.D., Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-451-4901
Email: flessnermf@mail.nih.gov

Paul L. Kimmel, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-594-7717
Email: kimmelp@mail.nih.gov

Krystyna Rys-Sikora, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-451-4770
Email: ryssikok@niddk.nih.gov​​​

Yining Xie, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Phone: 301-594-7713
Email: yining.xie@nih.gov