Reimagining Kidney Function Assessment Workshop

Event Details

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.

Registration Deadline

February 5, 2024

Agenda

Draft Agenda

Please note that session times are still being determined and will be added to this page once finalized.

Monday, February 5, 2024

10:00 – 10:15 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, Division of Kidney, Urologic, & Hematologic Diseases
Robert Star, M.D., NIDDK

Measuring Tubular Functions

• 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?

Measuring Glomerular Functions

• 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.
• Discuss role of renal blood flow.
• What are the key clinical and scientific gaps?

Glomerular Charge and Size Selectivity

• Discuss potential for capturing glomerular filtration barrier permeability (charge and size selectivity) 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?

Lunch

Measuring Glomerular Capacity and Reserve

• 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?

Break

New Technologies Lightning Talks

• Present novel tools and/or discovery approaches to capture traditional or novel measures of kidney function.

4:00 p.m.

Wrap up of first day

Tuesday, February 6, 2024

10:00 a.m.

Recap of day 1 and questions

Breakout Sessions (90 minutes) Potential focus questions for small groups. To be finalized with the advisory panel

• Glomerular Function
  • Identify conceptual next steps to reliably capture GFR, fit for various clinical and scientific scenarios (including drug dosing).
  • 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?

• Glomerular Permselectivity
  • 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?

• Tubular Function
  • Identify conceptual next steps to capture various tubular functions—fit for various clinical and scientific scenarios (including drug dosing).
  • 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?

• Renal Reserve
  • Identify conceptual next steps to capture various renal reserves—fit for various clinical and scientific
  • 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?

Lunch

Summary of Breakout Group Findings Led by Moderators of Breakout Sessions

Putting it all together

• 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.

2:00 p.m.

Conclusion and Adjournment