Reimagining Kidney Function Assessment Workshop

Event Details

Meeting Resources

• Watch the meeting video

Purpose

This workshop aims to help delineate a path forward for a more comprehensive assessment of various kidney functions.

Meeting Objectives

The primary goal of this workshop is to critically assess the existing limitations inherent in our current estimates of kidney function. We have focused on glomerular filtration rate (GFR) and proteinuria as measures of kidney functional status and thus have ignored a wide range of important renal mechanisms that may be affected early or differentially in different disease states. This shortsightedness has limited the tools available to phenotype the full spectrum of kidney disease. The aim of this workshop is to propel a paradigm shift towards a comprehensive approach to assessing kidney function and dysfunction that can improve our ability to describe pathophysiologic mechanisms and disease subgroups. Broadening the approaches and tools we use to measure the functions of the entire nephron will allow us to refine disease classification and enable better targeting of treatments at the right time and for the right individuals.

Background

Analysis and Identified Limitations: Comprehensive Renal Function Assessment

1. Inability to Capture Specific Functions of Renal Compartments:
   • Challenge: Lack of generally accepted/standardized protocols for capturing the full range of functions of critical renal compartments (e.g., proximal tubule, thick ascending limb, collecting duct, microvasculature).
   • Impact: Hinders the ability to measure a comprehensive suite of renal functions; prevents thoughtful endophenotyping of common kidney diseases; prevents recognition of variant forms of kidney disease; prevents recognition of the earliest forms of kidney disease; prevents development of targeted interventions.
2. Difficulty in Estimating Average GFR:
   • Challenge: Prior measured GFR approaches do not account for the high biological variability in true GFR.
   • Impact: Inaccurate estimations hinder our ability to understand the average true GFR and prevent recognition of early disease essential for assessing overall kidney function.
3. Lack of a Practical Gold Standard for GFR Measurement:
   • Challenge: The absence of a practical gold standard complicates the accurate measurement of GFR.
   • Impact: Impedes the development of reliable and universally accepted benchmarks for GFR assessment and the development of robust estimating equations and biomarkers.
4. Lack of Established Methods for Assessing Renal Reserve Functions:
   • Challenge: Current methods do not adequately assess glomerular renal reserve functions, which is crucial for determining early loss of function.
   • Impact: Missed opportunities for early intervention and understanding the progression of kidney diseases.
5. Challenges in Assessing Kidney Function and Reserve during Acute Kidney Injury:
   • Challenge: Current methods are inadequate for reliably assessing kidney function and reserve during acute kidney injury.
   • Impact: Impairs timely and accurate management of acute kidney injury, a critical aspect of overall kidney health.
6. Inability to Integrate Various Kidney Function Measures:
   • Challenge: Lack of integration of diverse kidney function measures into a specific individual-level global assessment.
   • Impact: Hinders the ability to create a holistic understanding of an individual's renal health status, limiting personalized treatment strategies.

Overall Impact: The identified limitations collectively contribute to a significant gap in our ability to comprehensively and dynamically assess various renal functions. This gap impedes the accurate classification of diverse kidney diseases and the development of targeted treatments, hindering progress in the field. To overcome these challenges, it is imperative to establish reliable tools, standardized procedures, and new tailored approaches that address the multifaceted nature of renal function assessment. This workshop aims to address these issues and provide a platform for the formulation of effective solutions that advance the understanding and management of kidney diseases.

Organizing Committee

External Members

NIDDK

Registration Deadline

February 5, 2024

Agenda

Monday, February 5, 2024

10:00 a.m. – 10:20 a.m.

Opening Remarks and Objectives
Afshin Parsa, M.D., M.P.H., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• The kidneys play a pivotal role in health and homeostasis, extending beyond traditional assessments of creatinine clearance and albuminuria prevention. However, our current focus on glomerular filtration rate (GFR) and proteinuria provides a limited perspective, overlooking diverse essential physiological processes. This prompts the question: Are we adequately equipped to discern and precisely target the diverse spectrum of kidney diseases and their pathophysiologic subsets? There is a pressing need to revisit and reformulate a comprehensive, standardized battery of kidney function measures that accurately evaluate distinct functional states, reserves, and trajectories in various kidney compartments. Such an overhaul could pave the way for tailored therapeutic strategies in nephrology, aligning with the principles of precision medicine.

Message from the Director
Robert Star, M.D., NIDDK

10:20 a.m. – 11:20 a.m.

Measuring Tubular Functions
Moderators: Tim Meyer, M.D., Stanford University; and Valerie Luyckx, M.D., Ph.D., M.Sc.,
University of Zurich
Speakers: Bryan Kestenbaum, M.D., M.S., University of Washington; and Jay Koyner, M.D.,
University of Chicago

• Describe different tubular functions (including acid/base handling) and clinical relevance.
• Discuss when and why it may be beneficial to capture tubular function measures.
• Discuss measures and challenges in capturing various tubular functions.
• Discuss tubular responses to physiologic challenges and its significance.
• What are the key clinical and scientific gaps?
• Q&A

11:20 a.m. – 12:20 p.m.

Measuring Glomerular Filtration
Moderators: Chi-yuan Hsu, M.D., M.S., University of California, San Francisco; and Andrew Rule, M.D., M.S., Mayo Clinic
Speakers: Jesse Seegmiller, Ph.D., University of Minnesota; and Lesley Inker, M.D., M.S., Tufts University

• Describe current state and limitations of mGFR.
• Discuss difference in mGFR vs. true GFR – include diurnal variation.
• Discuss impact of limitations of mGFR on derivation of eGFR.
• What are the key clinical and scientific gaps?
• Q&A

12:20 p.m. – 12:50 p.m.

Lunch

12:50 p.m. – 1:40 p.m.

Glomerular Charge and Size Selectivity
Moderators: Denise Marciano, M.D, The University of Texas Southwestern Medical Center; and Petter Bjornstad, M.D., University of Colorado
Speakers: Thomas Benzing, M.D., University of Cologne; and Kevin Lemley, M.D., Ph.D., Keck School of Medicine of USC

• Discuss utility and potential for capturing glomerular filtration barrier permeability on and beyond albuminuria (e.g., dextran, Ficoll, and IgG/IgG4).
• Discuss how it may be measured.
• What are the key clinical and scientific gaps?
• Q&A

1:40 p.m. – 2:10 p.m.

Measuring Glomerular Capacity and Reserve
Moderators: Sushrut Waikar, M.D., M.P.H., Boston University; and Ragnar Palsson, M.D.,
National University Hospital of Iceland
Speaker: Dana Fuhrman, D.O., M.S., University of Pittsburgh

• Describe renal reserve capacities and clinical relevance.
• Discuss when and why it may be beneficial to capture.
• Discuss measures, challenges, and limitations to capture glomerular function reserve.
• Discuss potential new approaches/tools to capture renal reserve.
• What are the key clinical and scientific gaps?
• Q&A

2:10 p.m. – 2:20 p.m.

Break

2:20 p.m. – 3:40 p.m.

New Technologies Lightning Talks
Moderators: Lilach Lerman, M.D., Ph.D., Mayo Clinic; and Gary Friedman, M.D., Pfizer

• Detecting Spontaneous Physiological Fluctuations Associated With Kidney Autoregulation Using MRI – Kevin Bennett, Ph.D., Washington University School of Medicine in St. Louis
• Point-of-care Glomerular Filtration Rate Measurement Utilizing Transdermal Detection Methodology – Stuart Goldstein, M.D., Cincinnati Children's Hospital and MediBeacon
• Quantifying Renal Hemodynamics Using Non-Contrast, DeoxyHb Dynamics Susceptibility Contrast MRI - Adam Bush, Ph.D., The University of Texas at Austin
• Nanoparticle Tools to Elucidate Glomerular Filtration and Interactions With Nephron Segments – Jie Zheng, Ph.D. and Mengxiao Yu, Ph.D., The University of Texas at Dallas
• Urine Derived Stem Cells as Markers of Kidney Disease/State – Yuanyuan Zhang, Ph.D., Wake Forest Institute for Regenerative Medicine
• Hyperpolarized (HP) 13C Pyruvate MRI to Investigate Kidney Energy Metabolism for Noninvasive Monitoring of Human Kidney Injury – Zhen Jane Wang, M.D., UCSF

3:40 p.m. – 3:50 p.m.

Wrap up of first day.

Tuesday, February 6, 2024

10:00 a.m. – 10:20 a.m.

Recap of Day 1
Petter Bjornstad, M.D., University of Colorado; and Sushrut Waikar, M.D., M.P.H., Boston University

10:20 a.m. – 11:50 a.m.

Concurrent Breakout Sessions (Small group discussions to openly deliberate questions and topics.)

• Group 1 - Glomerular Filtration
  Moderators: Chi-yuan Hsu, M.D., M.S., UCSF; and Andrew Rule, M.D., M.S., Mayo Clinic
  • Identify conceptual next steps to reliably capture GFR, fit for various clinical and scientific scenarios.
  • Propose next steps to develop/establish new practical techniques to capture mGFR (acute and chronic).
  • Propose how to identify novel biomarkers for eGFR (acute and chronic).
  • Are there promising novel approaches or technologies that are ready for testing?
  • Are we missing anything, and if so, how might we address it?

• Group 2 - Glomerular Permselectivity
  Moderators: Denise Marciano, M.D, The University of Texas Southwestern Medical Center; and Petter Bjornstad, M.D., University of Colorado
  • Identify conceptual next steps to comprehensively assess glomerular size and charge selectivity.
  • Propose next steps to develop/establish new practical techniques to assess glomerular integrity.
  • Propose how to identify novel biomarkers for size selectivity.
  • Consideration for capturing glomerular sieving coefficient.
  • Are there promising novel approaches or technologies that are ready for testing?
  • Are we missing anything, and if so, how might we address it?

• Group 3 - Tubular Function
  Moderators: Bryan Kestenbaum, M.D., M.S., University of Washington; and TBD
  • Identify conceptual next steps to capture various tubular functions, fit for various clinical and scientific scenarios.
  • Propose next steps to develop/establish new practical techniques to capture various tubular functions.
  • Propose how to identify novel biomarkers for various tubular functions.
  • Are there promising novel approaches or technologies that are ready for testing?
  • Are we missing anything, and if so, how might we address it?

• Group 4 - Renal Reserve
  Moderators: Ragnar Palsson, M.D., National University Hospital of Iceland; and Dana Fuhrman, D.O., M.S., University of Pittsburgh
  • Identify conceptual next steps to capture various renal reserves, fit for various clinical and scientific scenarios.
  • Propose next steps to develop/establish new practical techniques to capture renal reserve.
  • Propose how to identify novel biomarkers for various renal reserves.
  • Are there promising novel approaches or technologies that are ready for testing?
  • Are we missing anything, and if so, how might we address it?

11:50 a.m. – 12:20 p.m.

Lunch

12:20 p.m. – 1:30 p.m.

Summary of individual breakout sessions and Q&A

1:30 p.m. – 1:45 p.m.

Putting it all Together
Robert Star, M.D., NIDDK

• Discuss potential approaches to integrate various renal function measures into a core measure.
• Discuss potential development of novel biomarkers.
• Describe how various measures could impact clinical practice assessment of kidney function, prognosis and pathophysiology.

1:45 p.m.

Adjournment