Rationale and design of the Kidney Precision Medicine Project

doi:10.1016/j.kint.2020.08.039

Editorial

. 2021 Mar;99(3):498-510.

doi: 10.1016/j.kint.2020.08.039.

Rationale and design of the Kidney Precision Medicine Project

Ian H de Boer¹, Charles E Alpers², Evren U Azeloglu³, Ulysses G J Balis⁴, Jonathan M Barasch⁵, Laura Barisoni⁶, Kristina N Blank⁷, Andrew S Bomback⁸, Keith Brown⁹, Pierre C Dagher¹⁰, Ashveena L Dighe¹¹, Michael T Eadon¹⁰, Tarek M El-Achkar¹⁰, Joseph P Gaut¹², Nir Hacohen¹³, Yongqun He¹⁴, Jeffrey B Hodgin⁴, Sanjay Jain¹⁵, John A Kellum¹⁶, Krzysztof Kiryluk⁸, Richard Knight¹⁷, Zoltan G Laszik¹⁸, Chrysta Lienczewski¹⁹, Laura H Mariani¹⁹, Robyn L McClelland⁷, Steven Menez²⁰, Dennis G Moledina²¹, Sean D Mooney²², John F O'Toole²³, Paul M Palevsky²⁴, Chirag R Parikh²⁰, Emilio D Poggio²³, Sylvia E Rosas²⁵, Matthew R Rosengart²⁶, Minnie M Sarwal²⁷, Jennifer A Schaub¹⁹, John R Sedor²³, Kumar Sharma²⁸, Becky Steck¹⁹, Robert D Toto²⁹, Olga G Troyanskaya³⁰, Katherine R Tuttle¹¹, Miguel A Vazquez²⁹, Sushrut S Waikar³¹, Kayleen Williams⁷, Francis Perry Wilson²¹, Kun Zhang³², Ravi Iyengar³³, Matthias Kretzler³⁴, Jonathan Himmelfarb¹¹; Kidney Precision Medicine Project

Collaborators, Affiliations

Collaborators

Kidney Precision Medicine Project:
Richard Knight, Stewart Lecker, Isaac Stillman, Sushrut Waikar, Gearoid Mcmahon, Astrid Weins, Samuel Short, Nir Hacohen, Paul Hoover, Mark Aulisio, Leslie Cooperman, Leal Herlitz, John O'Toole, Emilio Poggio, John Sedor, Stacey Jolly, Paul Appelbaum, Olivia Balderes, Jonathan Barasch, Andrew Bomback, Pietro A Canetta, Vivette D d'Agati, Krzysztof Kiryluk, Satoru Kudose, Karla Mehl, Jai Radhakrishnan, Chenhua Weng, Laura Barisoni, Theodore Alexandrov, Tarek Ashkar, Daria Barwinska, Pierre Dagher, Kenneth Dunn, Michael Eadon, Michael Ferkowicz, Katherine Kelly, Timothy Sutton, Seth Winfree, Steven Menez, Chirag Parikh, Avi Rosenberg, Pam Villalobos, Rubab Malik, Derek Fine, Mohammed Atta, Jose Manuel Monroy Trujillo, Alison Slack, Sylvia Rosas, Mark Williams, Evren Azeloglu, Cijang John He, Ravi Iyengar, Jens Hansen, Samir Parikh, Brad Rovin, Chris Anderton, Ljiljana Pasa-Tolic, Dusan Velickovic, Jessica Lukowski, George Holt Oliver, Joseph Ardayfio, Jack Bebiak, Keith Brown, Taneisha Campbell, Catherine Campbell, Lynda Hayashi, Nichole Jefferson, Robert Koewler, Glenda Roberts, John Saul, Anna Shpigel, Edith Christine Stutzke, Lorenda Wright, Leslie Miegs, Roy Pinkeney, Rachel Sealfon, Olga Troyanskaya, Katherine Tuttle, Dejan Dobi, Yury Goltsev, Blue Lake, Kun Zhang, Maria Joanes, Zoltan Laszik, Andrew Schroeder, Minnie Sarwal, Tara Sigdel, Ulysses Balis, Victoria Blanc, Oliver He, Jeffrey Hodgin, Matthias Kretzler, Laura Mariani, Rajasree Menon, Edgar Otto, Jennifer Schaub, Becky Steck, Chrysta Lienczewski, Sean Eddy, Michele Elder, Daniel Hall, John Kellum, Mary Kruth, Raghav Murugan, Paul Palevsky, Parmjeet Randhawa, Matthew Rosengart, Sunny Sims-Lucas, Mary Stefanick, Stacy Stull, Mitchell Tublin, Charles Alpers, Ian de Boer, Ashveena Dighe, Jonathan Himmelfarb, Robyn Mcclelland, Sean Mooney, Stuart Shankland, Kayleen Williams, Kristina Blank, Jonas Carson, Frederick Dowd, Zach Drager, Christopher Park, Kumar Sharma, Guanshi Zhang, Shweta Bansal, Manjeri Venkatachalam, Asra Kermani, Simon Lee, Christopher Lu, Tyler Miller, Orson Moe, Harold Park, Kamalanathan Sambandam, Francisco Sanchez, Jose Torrealba, Toto Robert, Miguel Vazquez, Nancy Wang, Joe Gaut, Sanjay Jain, Anitha Vijayan, Randy Luciano, Dennis Moledina, Ugwuowo Ugochukwu, Francis Perry Wilson, Sandy Alfano

Affiliations

¹ Department of Medicine, University of Washington, Seattle, Washington, USA. Electronic address: deboer@u.washington.edu.
² Department of Pathology, University of Washington, Seattle, Washington, USA.
³ Department of Medicine, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
⁴ Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Pathology, Columbia University, New York, New York, USA.
⁶ Department of Pathology, Duke University, Durham, North Carolina, USA.
⁷ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁸ Department of Medicine, Columbia University, New York, New York, USA.
⁹ Patient Representative, Kidney Precision Medicine Project Steering Committee Member.
¹⁰ Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
¹¹ Department of Medicine, University of Washington, Seattle, Washington, USA.
¹² Department of Pathology, Washington University School of Medicine, St. Louis, St. Louis, Missouri, USA.
¹³ Broad Institute, Cambridge, Massachusetts, USA.
¹⁴ Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, Missouri, USA.
¹⁶ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁷ American Association of Kidney Patients, Kidney Precision Medicine Project Patient Partner.
¹⁸ Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
¹⁹ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
²⁰ Department of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, USA.
²¹ Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
²² Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, USA.
²³ Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio, USA.
²⁴ Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Renal Section, Veterans Administration Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
²⁵ Joslin Diabetes Center, Boston, Massachusetts, USA.
²⁶ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁷ Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
²⁸ Department of Medicine, UT Health San Antonio, San Antonio, Texas, USA.
²⁹ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
³⁰ Department of Computer Science, Princeton University, Princeton, New Jersey, USA.
³¹ Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
³² Institute for Genomic Sciences, University of California, San Diego, California, USA.
³³ Mount Sinai Institute for Systems Biomedicine, Mount Sinai, New York, New York, USA.
³⁴ Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

PMID: 33637194
PMCID: PMC8330551
DOI: 10.1016/j.kint.2020.08.039

Editorial

Rationale and design of the Kidney Precision Medicine Project

Ian H de Boer et al. Kidney Int. 2021 Mar.

. 2021 Mar;99(3):498-510.

doi: 10.1016/j.kint.2020.08.039.

Authors

Collaborators

Kidney Precision Medicine Project:
Richard Knight, Stewart Lecker, Isaac Stillman, Sushrut Waikar, Gearoid Mcmahon, Astrid Weins, Samuel Short, Nir Hacohen, Paul Hoover, Mark Aulisio, Leslie Cooperman, Leal Herlitz, John O'Toole, Emilio Poggio, John Sedor, Stacey Jolly, Paul Appelbaum, Olivia Balderes, Jonathan Barasch, Andrew Bomback, Pietro A Canetta, Vivette D d'Agati, Krzysztof Kiryluk, Satoru Kudose, Karla Mehl, Jai Radhakrishnan, Chenhua Weng, Laura Barisoni, Theodore Alexandrov, Tarek Ashkar, Daria Barwinska, Pierre Dagher, Kenneth Dunn, Michael Eadon, Michael Ferkowicz, Katherine Kelly, Timothy Sutton, Seth Winfree, Steven Menez, Chirag Parikh, Avi Rosenberg, Pam Villalobos, Rubab Malik, Derek Fine, Mohammed Atta, Jose Manuel Monroy Trujillo, Alison Slack, Sylvia Rosas, Mark Williams, Evren Azeloglu, Cijang John He, Ravi Iyengar, Jens Hansen, Samir Parikh, Brad Rovin, Chris Anderton, Ljiljana Pasa-Tolic, Dusan Velickovic, Jessica Lukowski, George Holt Oliver, Joseph Ardayfio, Jack Bebiak, Keith Brown, Taneisha Campbell, Catherine Campbell, Lynda Hayashi, Nichole Jefferson, Robert Koewler, Glenda Roberts, John Saul, Anna Shpigel, Edith Christine Stutzke, Lorenda Wright, Leslie Miegs, Roy Pinkeney, Rachel Sealfon, Olga Troyanskaya, Katherine Tuttle, Dejan Dobi, Yury Goltsev, Blue Lake, Kun Zhang, Maria Joanes, Zoltan Laszik, Andrew Schroeder, Minnie Sarwal, Tara Sigdel, Ulysses Balis, Victoria Blanc, Oliver He, Jeffrey Hodgin, Matthias Kretzler, Laura Mariani, Rajasree Menon, Edgar Otto, Jennifer Schaub, Becky Steck, Chrysta Lienczewski, Sean Eddy, Michele Elder, Daniel Hall, John Kellum, Mary Kruth, Raghav Murugan, Paul Palevsky, Parmjeet Randhawa, Matthew Rosengart, Sunny Sims-Lucas, Mary Stefanick, Stacy Stull, Mitchell Tublin, Charles Alpers, Ian de Boer, Ashveena Dighe, Jonathan Himmelfarb, Robyn Mcclelland, Sean Mooney, Stuart Shankland, Kayleen Williams, Kristina Blank, Jonas Carson, Frederick Dowd, Zach Drager, Christopher Park, Kumar Sharma, Guanshi Zhang, Shweta Bansal, Manjeri Venkatachalam, Asra Kermani, Simon Lee, Christopher Lu, Tyler Miller, Orson Moe, Harold Park, Kamalanathan Sambandam, Francisco Sanchez, Jose Torrealba, Toto Robert, Miguel Vazquez, Nancy Wang, Joe Gaut, Sanjay Jain, Anitha Vijayan, Randy Luciano, Dennis Moledina, Ugwuowo Ugochukwu, Francis Perry Wilson, Sandy Alfano

Affiliations

¹ Department of Medicine, University of Washington, Seattle, Washington, USA. Electronic address: deboer@u.washington.edu.
² Department of Pathology, University of Washington, Seattle, Washington, USA.
³ Department of Medicine, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
⁴ Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Pathology, Columbia University, New York, New York, USA.
⁶ Department of Pathology, Duke University, Durham, North Carolina, USA.
⁷ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁸ Department of Medicine, Columbia University, New York, New York, USA.
⁹ Patient Representative, Kidney Precision Medicine Project Steering Committee Member.
¹⁰ Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
¹¹ Department of Medicine, University of Washington, Seattle, Washington, USA.
¹² Department of Pathology, Washington University School of Medicine, St. Louis, St. Louis, Missouri, USA.
¹³ Broad Institute, Cambridge, Massachusetts, USA.
¹⁴ Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, Missouri, USA.
¹⁶ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁷ American Association of Kidney Patients, Kidney Precision Medicine Project Patient Partner.
¹⁸ Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
¹⁹ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
²⁰ Department of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, USA.
²¹ Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
²² Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, USA.
²³ Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio, USA.
²⁴ Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Renal Section, Veterans Administration Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
²⁵ Joslin Diabetes Center, Boston, Massachusetts, USA.
²⁶ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁷ Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
²⁸ Department of Medicine, UT Health San Antonio, San Antonio, Texas, USA.
²⁹ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
³⁰ Department of Computer Science, Princeton University, Princeton, New Jersey, USA.
³¹ Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
³² Institute for Genomic Sciences, University of California, San Diego, California, USA.
³³ Mount Sinai Institute for Systems Biomedicine, Mount Sinai, New York, New York, USA.
³⁴ Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

PMID: 33637194
PMCID: PMC8330551
DOI: 10.1016/j.kint.2020.08.039

Abstract

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Keywords: acute kidney injury; chronic kidney disease; diabetes; hypertension; precision medicine.

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Figures

Figure 1.. In the Kidney Precision Medicine Project, kidney biopsy tissues will be interrogated with multiple levels of omics technologies, and results will be integrated with digital pathology, clinical characteristics and outcomes to create a reference kidney atlas, develop mechanism-based disease subtypes, and identify critical cells, pathways, and targets for novel therapies.
CKD = chronic kidney disease AKI = acute kidney injury.

**Figure 2.. Kidney Precision Medicine Project tissue triage and interrogation schematic.**
Kidney biopsy tissues will be processed for local clinical pathology review and remote research interrogation according to a detailed, standardized protocol. KPMP = Kidney Precision Medicine Project; EM = electron microscopy; IF = immunofluorescence; LM = light microscopy; OCT = optimal cutting temperature compound; N₂ = nitrogen; ISH = in-situ hybridization’ MALD-MSI = matrix-assisted laser desorption ionization mass spectrometry imaging; LC-MS/MS = liquid chromatography-mass spectrometry.

**Figure 3.. Vision for a kidney tissue atlas.**
The Kidney Precision Medicine Project will integrate digital pathology, omics data, and clinical data using common ontologies, making raw data, curated maps, and analysis and visualization tools widely available to clinical and research communities.

See this image and copyright information in PMC

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References

1. Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System website. https://nccd.cdc.gov/CKD (accessed August 26, 2019.
1. Afkarian M, Zelnick LR, Hall YN, et al. Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988–2014. JAMA 2016; 316(6): 602–10. - PMC - PubMed
1. Al-Jaghbeer M, Dealmeida D, Bilderback A, Ambrosino R, Kellum JA. Clinical Decision Support for In-Hospital AKI. J Am Soc Nephrol 2018; 29(2): 654–60. - PMC - PubMed
1. Kellum JA, Lameire N, Group KAGW. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17(1): 204. - PMC - PubMed
1. Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371(1): 58–66. - PMC - PubMed

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[1] Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System website. https://nccd.cdc.gov/CKD (accessed August 26, 2019.

[2] Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System website. https://nccd.cdc.gov/CKD (accessed August 26, 2019.

[3] Afkarian M, Zelnick LR, Hall YN, et al. Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988–2014. JAMA 2016; 316(6): 602–10. - PMC - PubMed

[4] Afkarian M, Zelnick LR, Hall YN, et al. Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988–2014. JAMA 2016; 316(6): 602–10. - PMC - PubMed

[5] Al-Jaghbeer M, Dealmeida D, Bilderback A, Ambrosino R, Kellum JA. Clinical Decision Support for In-Hospital AKI. J Am Soc Nephrol 2018; 29(2): 654–60. - PMC - PubMed

[6] Al-Jaghbeer M, Dealmeida D, Bilderback A, Ambrosino R, Kellum JA. Clinical Decision Support for In-Hospital AKI. J Am Soc Nephrol 2018; 29(2): 654–60. - PMC - PubMed

[7] Kellum JA, Lameire N, Group KAGW. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17(1): 204. - PMC - PubMed

[8] Kellum JA, Lameire N, Group KAGW. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17(1): 204. - PMC - PubMed

[9] Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371(1): 58–66. - PMC - PubMed

[10] Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371(1): 58–66. - PMC - PubMed

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Rationale and design of the Kidney Precision Medicine Project

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Rationale and design of the Kidney Precision Medicine Project

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