The Recruitment Sites recruit adult men and women with either AKI or CKD for longitudinal cohort studies that include a research kidney biopsy. The Recruitment Sites work collaboratively to capture demographic information, conduct longitudinal clinical phenotyping, and collect biological samples in a standardized manner.
Tissue Interrogation Sites
Tissue Interrogation Sites receive kidney biopsy tissue collected from participants at the Recruitment Sites. They use this tissue to:
- Investigate kidney cell and disease heterogeneity in tissue sections and/or dissociated cells.
- Generate high-quality data and images for the Kidney Tissue Atlas.
- Facilitate the structural, histologic, and molecular assessment of cellular “states” associated with healthy function, activation, injury, recovery, and adaptive and maladaptive repair.
- Develop novel methods to distinguish diseased from non-diseased areas of kidney.
- Identify robust structural, histologic, and molecular signatures and pathways that can be used to accurately phenotype individuals with AKI or CKD to inform future diagnostic, prognostic, or therapeutic selection schemes (subgroups).
Our site will initially integrate large-scale 3D tissue imaging for quantitative supervised and unsupervised analysis/cytometry with sub-segmental “omics” data on the same kidney biopsy specimen. The sub-segmental “omics” pipeline will isolate specific kidney nephron segments and interstitial/other targeted areas for downstream analysis with transcriptomics and proteomics.
The omics analysis will be eventually expanded to include epigenetics. This approach will complement other interrogation techniques within KPMP by providing tissue context and increasing spatial resolution for molecular signatures that arise in heterogeneous areas during kidney disease.
We are seeking to interrogate gene expression in the kidney at the single cell level, defining cell-type and disease-state-specific gene expression profiles, with accompanying two and three-dimensional spatial characterization (cell-cell and cell-matrix relationships).
This approach allows us to understand the roles of the individual renal cell types in their cellular and disease context, which is critical to developing novel targeted therapies.
Our labs have developed two multiplex assays (multiplex Immunofluorescence and In Situ Hybridization (mIFISH) and CODEX) that visualize multiple mRNAs and proteins at single cell resolution level.
These assays, coupled with advanced high resolution whole slide imaging and sophisticated computer-assisted image analysis, can assess not only the quantitative aspects but also the spatial organizational aspects of the analytes.
The in situ assays will be supplemented by additional ancillary tissue-based assays of near single cell proteomics and multiplexed single-cell RNA-Seq (mdrosc RNA-Seq).
With our combined expertise we have developed a spatial metabolomics approach to identify metabolites in human kidneys, employing ultra-high mass resolution MS imaging for tissue analysis and a bioinformatics resource (METASPACE) to annotate metabolites for anatomical localization and 3-D reconstruction.
This allows us to understand the major metabolic pathways that initiate and cause progression of disease in patients with AKI and CKD.
We are applying and integrating several complementary technologies to create a complete catalog of molecular signatures of all kidney cell types in 3D space: two novel single-cell technologies to mature archived (frozen) human kidney specimens; a single-nucleus (sn) transcriptomic profiling method (snRNA-seq); and a 3D in situ RNA mapping method (DART-FISH).
Central hub (CH)
The purpose of the Central Hub to support the KPMP cohort, collect and de-identify all existing and new clinical data and samples, and provide scientific, infrastructure, quality control, project management, and administrative support.
The Central Hub is overseen by co-PIs, Drs Jonathan Himmelfarb and Matthias Kretzler and comprised of researchers and staff from the following institutions:
- University of Washington
- University of Michigan
- Providence Medical Center
- Mount Sinai
- Duke University
- Develop and support KPMP-wide governance, goal setting, and milestones.
- Coordinate interactions of the KPMP investigators with oversight bodies (i.e., DSMB and CMB).
- Establish necessary working groups (including a Community Engagement Committee).
- Represent the KPMP to external partners and develop a process to formalize external partnerships.
- Communicate KPMP goals and achievements to appropriate stakeholders in the community. Solicit their input and feedback to inform KPMP efforts.
- Create and administer an Opportunity Pool to address gaps or form new partnerships.
- Oversee the renewal of the KPMP common research kidney biopsy protocols and the retention of currently enrolled KPMP participants.
- Monitor and report on study progress to ensure optimal and diverse enrollment, participant safety and retention, rigorous execution of the study protocol, and exceptional data quality.
- Train and monitor performance of KPMP study personnel.
- Manage the KPMP repository of protected health information (PHI). Develop plans for secure capture of PHI, to be controlled by a dedicated Honest Broker, and processes to minimize risks of PHI disclosures and participant re-identification.
- Manage the KPMP central laboratory and repository of biosamples.
- Ensure QA/QC of all data, workflows, and biosamples across the entire KPMP.
- Arrange for whole genome sequencing.
Kidney Tissue Atlas Coordinating center (KMAP)
The purpose of the Kidney Tissue Atlas Coordinating Center, a.k.a. Kidney Mapping Atlas Project (KMAP), is to clean, harmonize, store, and curate all de-identified KPMP data, perform integrative analyses, and create an interactive Kidney Tissue Atlas.
The KMAP is overseen by co-PIs, Drs Matthias Kretzler and Jonathan Himmelfarb. It is comprised of researchers and staff from the following institutions:
- University of Michigan
- University of Washington
- University of Florida
- Brigham & Womens
- Mount Sinai
- Duke University
- Develop computational and modeling strategies to integrate clinical phenotypic, physiologic, digital histopathologic and molecular data.
- Harmonize with complementary datasets to maximize discovery (e.g., Human BioMolecular Atlas Program (HuBMAP), Human Cell Atlas (HCA), GenitoUrinary Development Molecular Anatomy Project (GUDMAP), ReBuilding a Kidney (RBK)).
- Execute a comprehensive systems-level and integrative analysis to uncover novel molecular pathways and define new sub-phenotypes of AKI and CKD. These analyses may include efforts to:
- Find key molecular pathways, regulatory networks, marker genes, and/or gene targets to redefine AKI and CKD and its subgroups.
- Identify cellular molecular pathways to understand healthy and disease pathways that are activated in a particular cell type in a particular disease subgroup.
- Predict targets for future biomarker development from plasma or urine protein/antibody pairs, urinary exosomes, miRNA, epigenetic marks, etc. for diagnostic tool development.
- Leverage various -omic data sets (e.g., scRNA-seq, scATAC-seq, DNA methylation etc.) and participant DNA sequencing to implement functional genomic approaches to identify disease-driving variants.
- Develop quantitative, systems-level biology and computational approaches to build models for biological processes, cell-state, cell-to-cell communication, or ligand-receptor interactions.
- Annotate, analyze, and interpret multi-cellular and non-cellular neighborhoods based upon identification of cell-type, state, and spatial interactions between cells and/or interstitial components.
- Apply systems-level biological approaches to identify gene regulatory networks, and spatial and environmental determinants of cellular state, as well as to identify relationships between anatomical features, cellular and molecular states, and the role that spatial position and cell-cell interactions play in establishing cellular states in AKI and CKD.
- Define a set of state/transition markers from cellular and molecular data that classify cells as healthy, injured, activated, or undergoing recovery via adaptive or maladaptive repair.
- Ingest, clean, harmonize, store, and archive all de-identified KPMP data and metadata with FAIR principles.
- Optimize platforms for data integrity, dimensionality reduction, harmonization, scalability, security, accessibility, re-use, and potential migration to a cloud-based environment.
- Actively biocurate data to ensure analytic pipelines produce biologically plausible results and that molecular, pathological, and clinical findings can be harmonized.
- Use and enhance existing KPMP and other developed ontologies, controlled vocabularies and semantically indexed data across individuals, technologies, and disease, to develop a computational framework for the exploration of data and enable discovery.
- Build and incorporate QA/QC tools that can determine missing, incomplete, and erroneous data and sources of technical noise to ensure that only high-quality is released and displayed to the public.
- Support and enhance a collaborative informatics community across the KPMP.
- Establish and/or maintain a Digital Pathology Bank of existing KPMP and new biopsy whole slide images and develop tools for accessing and analyzing image data, including the ability to perform comparisons and searches, and curation or quality control tasks such as de-identification and artifact detection.
- Create and manage an interactive Kidney Tissue Atlas with FAIR principles representing health, disease, sex, age, race, and ethnicity. Populate the Atlas with annotated 2D and 3D tissue maps that integrate high-quality clinical phenotypic, physiologic, imaging, digital histopathologic, cellular, molecular and tissue-level spatial, functional information and relationships that are searchable and scalable.
- Lead and coordinate KPMP efforts to develop potential user personas for the Kidney Tissue Atlas and Digital Pathology Bank. These may include, but are not limited to: a bioinformatic super-user familiar with large and complex datasets; a basic scientist seeking discovery data to generate or support a hypothesis; a clinical researcher trying to link histopathologic structures to disease pathways; a student trying to visualize renal physiology; a KPMP patient participant hoping to better understand kidney disease.
- Build and manage a suite of visualization and analysis tools to facilitate computational access, navigation and downloading data to maximize broad usability and incentivize public interrogation and discovery of the KPMP Digital Pathology Bank and Kidney Tissue Atlas. These tools should allow various user personas to perform several diverse tasks, including but not limited to:
- Visualize key molecular pathways, regulatory networks, marker genes, and/or gene targets that define AKI and CKD and its subgroups.
- Identify molecular and cellular composition, cell-cell interactions, tissue organization, and anatomical structures.
- Determine tissue-level and cell-level, spatial, functional, and/or temporal relationships, including mechanisms for identifying novel cell types, cell-states and subtypes, molecular or cellular marks (e.g., anchor genes), and anatomic relationships of each cell type relative to its neighbors.
- Explore and query datasets and analyses across clinical or pathological diagnoses to identify novel clinical phenotypes that track with molecular and cellular features of the KPMP cohort.
- Visualize healthy renal physiology and disease pathophysiology.
Opportunity Pool Awardees
Our KPMP partners awarded Opportunity Pool funding collaborate with us to help achieve our study goals.
Steve Bogen, MD, PhD (Boston Cell Standards)
Analytic Calibrators and Controls Core Resource for Protein Biomarker Testing
Hongping Ye, PhD (UTHSA)
Human Kidney Mimetic Tissue Using Endogenous Lips and Metabolites as Secondary Standards
Sushrut Waikar, MD, MPH (Boston University), Anand Srivastava, MD, MPH (Northwestern University), Pottumarthi Prasad, PhD (Northshore)
Advancing Multiparametric Kidney Functional MRI to Phenotype Individuals with CKD
Sushrut Waikar, MD, MPH (Boston University), Petter Bjornstad, MD (University of Colorado)
Kidney Physiology Phenotyping in the Kidney Precision Medicine Project
Ian de Boer, MD (University of Washington), Sylvia Rosas, MD (Joslin Diabetes Center)
Advanced retinal phenotyping to identify mechanistic pathways in chronic kidney disease
October, 2019: Petter Bjornstad, MD (Colorado Children’s)
Tissue based integrative biology of early diabetic kidney disease in youth-onset type 2 diabetes
January, 2020: Jeffrey Spraggins, PhD & Richard Caprioli, PhD (Vanderbilt University)
Integrating the VU Biomolecular Multimodal Imaging Center of HuBMAP with the Kidney Precision Medicine Project
January, 2020: Katy Borner, PhD (Indiana University)
Harmonizing KPMP/HuBMAP Data: Developing Common Coordinate Framework UI
January, 2020: Anant Madabhushi, PhD (Case Western Reserve)
HistoTools: A suite of digital pathology tools for quality control, annotation, and dataset identification
January, 2020: Pinaki Sarder, PhD (University of Buffalo)
A Computational Renal Pathology Suite for KPMP
July, 2020: Ari Pollack, MD (Seattle Children’s Hospital)
Designing a Visual Decision Aid for Shared Decision Making after Renal Biopsy
James Williams, PhD (Indiana University)
Healthy Reference Tissue for KPMP
E. Steven Woodle, MD (University of Cincinnati)
Kidney Precision Medicines Project Healthy Living Kidney Donor Tissue Repository
Minnie Sarwal, MD (UC San Francisco)
Building Health Kidney Tissue Repository for KPMP
Hamid Rabb, MD (Johns Hopkins)
Sequencing KPMP AKI stool microbiome samples
Kalani Raphael, MD (OHSU) & John Asplin, MD (Litholink)
Enhancing the phenotype of KPMP participants with measurements of urinary electrolytes and acid-base parameters
Metabolite profiling of KPMP participants
Somascan 7,000 proteomics analysis of EDTA plasma and urine samples from the KPMP cohort
Wassim Obeid, PhD & Chirag Parikh, MD (Johns Hopkins)
Measurement of blood and urinary biomarkers to enhance the KPMP tissue atlas
Jonathan Taliercio, DO (Cleveland Clinic)
Cleveland CRIC KPMP
Lloyd Cantley, MD (Yale University)
Spatially preserved cell state phenotyping using Imaging Mass Cytometry-Kidney-MAPPS
Anna Greka, MD, PhD & Jamie Marshall, PhD (Broad Institute)
Slide-seq: spatial transcriptomic technology for tissue interrogation
Michael Rauchman, MDCM (Washington University St. Louis)
Chromatin Profiling of Nephrectomy and Kidney Biopsy Tissues
KPMP Standing Committees are composed of consortium members from theKPMP (including patients, clinicians, scientists, research coordinators and junior investigators) as well as volunteers from beyond the KPMP, as needed. The nature and composition of the committees convened will change over time as the needs of the KPMP evolve.
Each Committee is encouraged to collect data or propose KPMP wide consortial experiments, surveys, usability testing, etc., to fully inform their discussions and recommendations. A major focus of these recommendations will be to establish research rigor in KPMP work plans across sites to ensure that high quality, reproducible findings are to be used in the construction of the Kidney Tissue Atlas. Committees are meant to be broad-based operational committees with specific work accomplished by smaller, task oriented subgroups. All committees report to the KPMP Steering Committee, with additional communications across groups and within the KPMP encouraged as needed to facilitate collaboration.
Committees are meant to be broad-based operational committees with specific work accomplished by smaller, task oriented subgroups. All committees report to the KPMP Steering Committee, with additional communications across groups and within the KPMP encouraged as needed to facilitate collaboration.
The Steering Committee (SC) will be the primary governing body for all KPMP scientific activities. The SC will coordinate all sites awarded under these FOAs. The voting membership of the SC will include: one PD/PI from each award made under this and the companion FOAs, the NIH PS, and a representative from the Patient Engagement Working Group of the CH.
The Chair of the SC will be assigned by NIH Program Staff, and may be chosen from outside the KPMP. Face-to-face meetings of this committee will occur at least two times a year. A portion of the SC meeting may be open to the public.
- The Program Directors/Principal Investigators (PDs/PIs) of each KPMP award
- The NIH Project Scientists (together representing a minority of voting members – not to exceed 1/3 of SC membership). Other NIH Program staff may attend the meeting as non-voting members.
The SC will be the primary governing body for all of the KPMP scientific activities. The SC will coordinate all projects awarded under the KPMP FOAs.
The role of the Steering Committee includes:
- Develop protocols and guidelines delineating the scientific and other interactions of the RS, TIS and CH.
- Foster collaboration, synergy and sharing among the KPMP sites and investigators.
- Provide the primary mechanism for interactions with the NIH.
- Oversee the planning of the KPMP scientific activities, including dynamic adjustment as needs and opportunities arise.
- Guide the development and documentation of the KPMP standards and guidelines.
- Prioritize the use of the KPMP resources including systems biology analyses and bioinformatics.
- Evaluate progress in the KPMP sites and recommend adjustments in approaches if necessary, including implementation of new projects and changes to ongoing studies and termination of projects and sites.
- Foster partnerships and collaborations that will facilitate the extension of the approach to new technologies and their application to related kidney disease.
- Develop and approve the KPMP-wide intellectual property agreements consistent with the terms and conditions of the cooperative agreement awards, applicable regulations, and the policies and practices of the awardee institutions.
Regular meetings will be conducted by teleconference or videoconference. Prior to each meeting, teleconference or videoconference, the SC Chair will prepare an agenda for review and approval, and distribute to members of the SC. Following these meetings, a list of participants and summary of discussion, action items, and recommendations will be prepared and submitted to the PO by the SC. Part of these meetings may be open to the public. The SC Chair may convene additional teleconferences, videoconferences, or electronic reviews to avoid delays in addressing key issues that cannot be evaluated at the regularly scheduled meetings. Regularly scheduled SC meetings will be convened in order to:
- Review progress of the KPMP sites; review progress of standardization and validation studies, other performance assessments, and future plans; and take remedial actions to address delays or other problems.
- Make recommendations to the KPMP sites about informatics and data and/or information management processes.
- Awardee members of KPMP will be required to accept and implement policies approved by the SC.
- Guide the development and documentation of the KPMP standards and guidelines.
- The SC may make recommendations to the CH to establish working groups, or assign responsibility to key staff for other KPMP-related activities.
Voting may occur electronically, in-person, or via teleconferences. There are a total of 14 Steering Committee votes. Each grant is allotted one vote, regardless of the number of PIs associated with the grant. NIDDK has one vote, and the SC patient representative has one vote.
(last updated September, 2022)
Chair: Jonathan Himmelfarb (University of Washington)
The following members are allowed to vote on behalf of their grant/affiliation. Only one vote may be cast per affiliation.
- Boston University-Joslin Diabetes Center Sylvia Rosas, Sus Waikar
- Central Hub Jonathan Himmelfarb, Matthias Kretzler
- Cleveland Clinic John O'Toole, Emilio Poggio, John Sedor
- Indiana University Pierre Dagher, Michael Eadon, Tarek Ashkar
- Johns Hopkins-Yale Chirag Parikh
- Kidney Tissue Atlas Coordinating Center (KMAP) Matthias Kretzler, Jonathan Himmelfarb
- Michigan-Broad-Princeton (PREMIERE) Jeff Hodgin, Nir Hacohen, Olga Troyanskaya
- Mt. Sinai Kirk Campbell, Steven Coca, Girish Nadkarni
- NIDDK NIDDK project scientists
- Patient Partner Nichole Jefferson
- UCSD Sanjay Jain
- University of Colorado Elena Hsieh, Joshua Thurman
- University of Illinios, Chicago Ana Ricardo, James Lash
- University of Minnesota Patrick Nachman, Luiza Caramori
- University of North Carolina & University of Arizona Amy Mottl, Chip Brosius
- UT Southwestern Miguel Vazquez, Bob Toto
- UTHSA-PNNL-EMBL Kumar Sharma, Chris Anderton, Theodore Alexandov
- Vanderbilt University Jeffrey Spraggins
- Yale University Vijay Kakade, Lloyd Cantley
OBSERVATIONAL STUDY MONITORING BOARD (OSMB)
The OSMB members oversee the scientific progress and direction of the KPMP. Their expertise and advice to the investigators, as well as the NIDDK, helps hone the research design and results of the KPMP.