Overcoming Barriers in Acute Kidney Injury (AKI)

Event Details

Background

AKI is a common, deadly complication of medical and surgical illnesses, which more frequently affects African Americans, those with diabetes mellitus, the elderly, and those with chronic kidney disease (CKD). Outcomes associated with AKI include progressive diminution of renal function in those with CKD, loss of renal function in those with previously normal renal function, the development and progression of cardiovascular disease, and increased disability and decreased quality of life.

Meeting Objectives

The purpose of the workshop is to facilitate the development and testing of therapies that may have a meaningful impact on clinical outcomes of AKI. This may entail the development of clinically relevant animal models that mimic Phase 2 and 3 clinical trial designs, identification of new druggable cellular and molecular targets, new pharmacological screening methodologies, and advances in clinical trials in the field. As in the past, industry participation in the workshop will be encouraged. This multidisciplinary meeting will bring together basic and clinical scientists to propose (a) pilot and feasibility projects on the development of clinically relevant animal models of AKI, and (b) clinical trials designed in specific patient populations to ameliorate short- and long-term outcomes of AKI. The long-term goal is to stimulate research using novel animal models, by developing new therapies and proposing clinically relevant, feasible clinical trials.

This workshop will review present AKI research and make recommendations regarding needed changes. The outcome of this workshop will be a report outlining the gaps in evidence that need to be filled, which will be made available to the research community. Each of the speakers or discussion group leaders will provide a summary of his/her session after the meeting so a formal report may be developed. It is envisioned that the workshop report will provide important new information for AKI research communities—especially for those within the NIDDK mission.

Agenda

February 10, 2015

Pre-Conference at Hyatt Hotel, Bethesda

7:30 p.m.

Robert Califf

8:00 p.m.

Robert Temple

February 11, 2015

Day 1 at Building 45 (Natcher) on NIH campus

7:00 a.m. – 8:00 a.m.

Registration

8:00 a.m.

Introduction: How Do We Move the Field Forward?
Robert Star

Session 1: How to Get Beyond Dark Matter—Lessons from Other Fields

Moderator: Taylor Thompson

Is it Possible to Succeed? Lessons from Other Disciplines.
(15 min. presentation, followed by 15 min. discussion)

8:15 a.m.

Lessons Learned from Subtypes in Adult Respiratory Distress Syndrome
Carolyn Caffee

Lessons from Asthma
Geoffrey Chupp

Sepsis: Differences Between Subtypes
John Marshall

9:45 a.m.

Break

Session 2: Design Feasible Phase 2 Proof-of-Concept Study

Moderator: Paul Palevsky

Early Secondary Prevention, Delayed Graft Function; Repair/Recovery; Primary Prevention
(20 min. presentation, followed by 15 min. discussion)

10:00 a.m.

"What's Feasible Now?"
Paul Palevsky

How to Design a Bad Translational Research Project
Frank Harrell

11:10 a.m.

Break

Breakout Discussion (4 Groups)—Breakout Leaders

11:30 a.m.

Breakout Group Issues:

1. Primary prevention
   Lakhmir Chawla, Mark de Caestecker, James Kaufman, Taylor Thompson
2. Secondary prevention after insult
   Anupam Agarwal, Tom Greene, Mark Okusa, Paul Palevsky
3. Hasten recovery
   Joseph Bonventre, Laura Dember, Kathleen Liu
4. Delayed transplant graft function—Phase 2 trials
   Linda Fried, Frank Harrell, Samina Khan, Diane McKay

Identify 3–4 feasible designs in humans.

1:30 p.m.

Lunch

Session 3: Build Preclinical Animal Models that Match Phase 2 Proof of Concept Studies

Moderator: Lakhmir Chawla
(15 min. presentation, followed by 15 min. discussion)

2:30 p.m.

"Animal Models and Drug Development – Where Have We Gone Wrong and How Can We Fix Things?"
Steve Perrin

3:00 p.m.

Break

Breakout Discussion (4 Groups)—Breakout Leaders

3:15 p.m.

Breakout Group Issues:

1. Primary prevention
2. Secondary prevention after insult
3. Hasten recovery
4. Delayed transplant graft function—Phase 2 trials.

How to replicate: pick 3–4 Proof of Concept designs in animals, based on human subject considerations.

5:30 p.m.

Adjourn (Day 1)

February 12, 2015

Day 2 at Building 45 (Natcher) on NIH campus

Session 4: How to Prove that Animal Models Reproduce Human Situations, and Vice Versa

Moderator: Kathleen Liu
(20 min. presentation, followed by 10 min. discussion)

7:30 a.m.

How to Detect Staging/Severity/Mechanistic Pathways
Robert Gerszten

What Can We Learn from Special Cases (Cisplatin, Aminoglycosides) that May Not Be Amenable to Industry Phase 2 studies
Frank Sistare

8:30 a.m.

Lessons from Oncology: Tissue is the Issue!
Kimryn Rathmell

Can We Use the Kidney Biopsy as a Research Tool? Practical and Ethical Aspects, Challenges, and Barriers
William Whittier

9:20 a.m.

Break

9:35 a.m.

Industry panel: Issues in Drug Development (1 hour, incl. Questions & Answers)
Moderator: Paul Kimmel
Jacques Arend, Samina Khan, Frank Sistare, Steven Textor, Anna Zuk

10:35 a.m.

Breakout Group: Finalize recommendations regarding preclinical & clinical studies.

12:30 p.m.

Lunch

Session 5: Full circle—Building a pipeline

Moderators: Paul Kimmel/Robert Star

1:15 p.m.

Reports from Breakout Groups
(20 min. presentation, followed by 10 min. discussion for each group)

3:15 p.m.

Break

Session 6: Patients, Animal Models, Linkages, Small Phase Zero Studies, Small Proof of Mechanism Studies

Moderator: Ben Humphreys

3:30 p.m.

Panel Discussion: What did we learn at this workshop? What are the challenges? What are the opportunities?
Joseph Bonventre, Kathleen Liu, Mark Okusa, Paul Palevsky, Aliza Thompson

4:30 p.m.

Putting it all together
Taylor Thompson and Robert Star

5:30 p.m.

Adjourn