What is the Kidney Precision Medicine Project (KPMP)?

The Kidney Precision Medicine Project is an ambitious, multi-year project funded by the NIDDK with the purpose of understanding chronic kidney disease (CKD) and acute kidney injury (AKI).

A number of research centers across the United States are collaborating to bring state-of-the-art and next-generation technologies together to:

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Obtain and evaluate kidney biopsies from participants with AKI or CKD
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Create a kidney tissue atlas
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Define disease subgroups
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Identify critical cells, pathways, and targets for novel therapies

Background

Acute kidney injury (AKI) and chronic kidney disease (CKD) impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. Community feedback indicates that—despite significant effort from industry and academia—development of pharmacologic therapies for AKI and CKD has been hampered by non-predictive animal models, the inability to identify and prioritize human targets, the limited availability of human kidney biopsy tissue, and a poor understanding of AKI and CKD heterogeneity [Kidney Research National Dialogue 2014; AKI Outcomes Meeting 2015; Kidney Precision Medicine Meeting 2016].

Historically, AKI and CKD have been described as single, uniform diseases; however, growing consensus suggests that different disease pathways lead to different subgroups of AKI and CKD (AKIs and CKDs). Access to human kidney biopsy tissue is a critical first step to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with AKI and CKD.

Approach

Recent advances in the multi-scale interrogation of human tissue and single cells have set the stage for precision medicine to be applied to AKI and CKD. The objectives of the KPMP are to ethically obtain and evaluate human kidney biopsies from participants with AKI or CKD, create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies.

The KPMP will be made up of three distinct, but highly interactive, activities:

Recruitment Sites

Recruit people with AKI or CKD for longitudinal cohort studies that include a kidney biopsy

Tissue Interrogation Sites

Develop and use innovative technologies to analyze human kidney disease

Central Hub

Aggregate, analyze, and visualize all of the samples and data and provide scientific, infrastructure, and administrative support for the entire project

Patient Involvement

One unique aspect of the KPMP is our commitment to patient involvement. The KPMP consortium involves patients in every facet of the project.

Our patient advocates are active participants in working groups, face-to-face meetings, and ad hoc teams, tackling issues ranging from ethics to data analysis strategies.

Timeline

It is anticipated that the KPMP will be conducted in stages:

STAGE 1

  • Optimize and validate tissue processing and interrogation methods
  • Establish common clinical protocols and cohort studies enrolling a small number of AKI or CKD patients
  • Assess the quality of phenotype data and biopsy protocols at each site
  • Begin work on the kidney tissue atlas
  • Optimize next-generation assays

STAGE 2

  • Small-scale proof of concept studies to determine if clinical and analytic pipelines are robust
  • Enrich the kidney tissue atlas
  • Implement next-generation tissue interrogation assays
  • Expand longitudinal cohort studies in initial AKI or CKD populations

STAGE 3

  • Expand to larger cohort studies (expected to occur in next project period)

Governance

To provide a community resource for advancing research in this area, all KPMP activities must meet rigorous sharing and quality control standards. Given the risk of complications from a biopsy, the KPMP will hold ethical and participant safety considerations paramount. The KPMP will work closely with participants to ensure that their viewpoints, priorities, and preferences inform all aspects of the project.

All of the KPMP activities will be overseen by a Data and Safety Monitoring Board (DSMB) constituted by the NIDDK that will focus on participant safety, study burden, and scientific validity of the clinical data; and an External Expert Panel (EEP) constituted by the NIDDK that will focus on the overall scientific progress and direction of the KPMP.

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