Rationale and design of the Kidney Precision Medicine Project

Boer, Ian H. de; El‐Achkar, Tarek M.; Gaut, Joseph P.; He, Yongqun; Toto, Robert D.; Knight, Richard; Lecker, Stewart H.; Stillman, Isaac E.; Waikar, Sushrut S.; McMahon, Gearoid M.; Weins, Astrid; Short, Samuel A.P.; Hacohen, Nir; Hoover, Paul; Aulisio, Mark P.; Cooperman, Leslie; Herlitz, Leal; O’Toole, John F.; Poggio, Emilio D.; Sedor, John R.; Jolly, Stacey E.; Appelbaum, Paul S.; Balderes, Olivia; Barasch, Jonathan; Bomback, Andrew S.; Canetta, Pietro A.; D’Agati, Vivette D.; Kiryluk, Krzysztof; Kudose, Satoru; Mehl, Karla; Radhakrishnan, Jai; Weng, Chen-hua; Barisoni, Laura; Alexandrov, Theodore; Ashkar, Tarek; Barwinska, Daria; Dagher, Pierre C.; Dunn, Kenneth W.; Eadon, Michael T.; Ferkowicz, Michael J.; Kelly, Katherine J.; Sutton, Timothy A.; Winfree, Seth; Menez, Steven; Parikh, Chirag R.; Rosenberg, Avi Z.; Villalobos, Pam; Malik, Rubab; Fine, Derek M.; Atta, Mohammed; Trujillo, Jose Manuel Monroy; Slack, Alison; Rosas, Sylvia E.; Williams, Mark; Azeloglu, Evren U.; He, Cijang; Iyengar, Ravi; Hansen, Jens; Parikh, Samir; Rovin, Brad H.; Anderton, Chris; Paša‐Tolić, Ljiljana; Veličković, Dušan; Lukowski, Jessica; Oliver, George; Ardayfio, Joseph; Bebiak, Jack; Brown, Keith; Campbell, Taneisha; Campbell, Catherine E.; Hayashi, Lynda; Jefferson, Nichole; Koewler, Robert; Roberts, Glenda V.; Saul, John; Shpigel, Anna; Stutzke, Edith Christine; Wright, Lorenda; Miegs, Leslie; Pinkeney, Roy; Sealfon, Rachel; Troyanskaya, Olga G.; Tuttle, Katherine R.; Dobi, Deján; Goltsev, Yury; Lake, Blue B.; Zhang, Kun; Joanes, Maria; Lászik, Zoltán; Schroeder, Andrew; Sarwal, Minnie M.; Sigdel, Tara K.; Balis, Ulysses; Blanc, Victoria M.; He, Oliver; Hodgin, Jeffrey B.; Kretzler, Matthias; Mariani, Laura; Menon, Rajasree; Otto, Edgar A.; Schaub, Jennifer A.; Steck, Becky; Lienczewski, Chrysta; Eddy, Sean; Elder, Michele; Hall, Daniel E.; Kellum, John A.; Kruth, Mary; Murugan, Raghav; Palevsky, Paul M.; Randhawa, Parmjeet; Rosengart, Matthew R.; Sims-Lucas, Sunny; Stefanick, Mary; Stull, Stacy; Tublin, Mitchell; Alpers, Charles E.; Boer, Ian de; Dighe, Ashveena; Himmelfarb, Jonathan; McClelland, Robyn L.; Mooney, Sean D.; Shankland, Stuart J.; Williams, Kayleen; Blank, Kristina N.; Carson, Jonas; Dowd, Frederick; Drager, Zach; Park, Chris; Sharma, Kumar; Zhang, Guanshi; Bansal, Shweta; Venkatachalam, Manjeri A.; Kermani, Asra; Lee, Simon; Lu, Christopher Y.; Miller, Tyler; Moe, Orson W.; Park, Harold S.; Sambandam, Kamalanathan K.; Sánchez, Francisco Javier Carrasco; Torrealba, José; Toto, Robert; Vázquez, Miguel A.; Wang, Nancy; Gaut, Joe; Jain, Sanjay; Vijayan, Anitha; Luciano, Randy L.; Moledina, Dennis G.; Ugwuowo, Ugochukwu; Wilson, F. Perry; Alfano, Sandy

doi:10.1016/j.kint.2020.08.039

Cited by 105 publications

(79 citation statements)

References 36 publications

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Section: Introductionmentioning

confidence: 99%

“…To this end, we report a next-generation multimodal single cell and 3D atlas that leverages integrated transcriptomic, epigenomic and imaging data over three major consortia: the Human Biomolecular Atlas Program (HuBMAP) 7 , the Kidney Precision Medicine Project (KPMP) 8 , and the Human Cell Atlas (HCA) 9 . To ensure robust cell state profiles, reference tissues were obtained from multiple sources, and biopsies were collected from AKI and CKD patients under rigorous quality assurance and control procedures 7,8,10 . We define micro niches for healthy and altered states across different regions of the human kidney spanning the cortex and medulla, to the papillary tip, and identify gene expression and regulatory modules in altered states associated with worsening kidney function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An atlas of healthy and injured cell states and niches in the human kidney

Lake¹,

Menon

Winfree

et al. 2021

Preprint

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114

185

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Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of ~1.2 million neighborhoods provided linkages to active immune responses. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An atlas of healthy and injured cell states and niches in the human kidney

Lake¹,

Menon

Winfree

et al. 2021

Preprint

Self Cite

114

185

View full text Add to dashboard Cite

show abstract

“…To achieve these goals and reduce the burden of CKD, researchers are dedicating efforts to the discovery of signaling pathways and molecular targets to help develop novel therapies. The development of robust research platforms and functional in vitro models could greatly benefit from the ability to recapitulate patient-specific biological responses as needed for personalized medicine and related applications [ 6 ]. There is also a need to develop in vitro models that are ethical and employ noninvasive technologies to more closely reflect a patient’s response to treatment at the kidney’s cell, tissue, and organ levels.…”

Section: Introductionmentioning

confidence: 99%

A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium

et al. 2021

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Progress in understanding kidney disease mechanisms and the development of targeted therapeutics have been limited by the lack of functional in vitro models that can closely recapitulate human physiological responses. Organ Chip (or organ-on-a-chip) microfluidic devices provide unique opportunities to overcome some of these challenges given their ability to model the structure and function of tissues and organs in vitro. Previously established organ chip models typically consist of heterogenous cell populations sourced from multiple donors, limiting their applications in patient-specific disease modeling and personalized medicine. In this study, we engineered a personalized glomerulus chip system reconstituted from human induced pluripotent stem (iPS) cell-derived vascular endothelial cells (ECs) and podocytes from a single patient. Our stem cell-derived kidney glomerulus chip successfully mimics the structure and some essential functions of the glomerular filtration barrier. We further modeled glomerular injury in our tissue chips by administering a clinically relevant dose of the chemotherapy drug Adriamycin. The drug disrupts the structural integrity of the endothelium and the podocyte tissue layers, leading to significant albuminuria as observed in patients with glomerulopathies. We anticipate that the personalized glomerulus chip model established in this report could help advance future studies of kidney disease mechanisms and the discovery of personalized therapies. Given the remarkable ability of human iPS cells to differentiate into almost any cell type, this work also provides a blueprint for the establishment of more personalized organ chip and ‘body-on-a-chip’ models in the future.

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“…Kidney biopsies are increasingly recognized as essential and safe procedures to understand heterogeneous kidney diseases and move towards personalized therapy in both the clinical and research domains. 8,9 This improved safety with use of image guidance has been demonstrated in a recent large meta-analysis. 2 The observed increasing paraprotein-related kidney disease may be due to increasing recognition of this diverse entity.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 94%

Inpatient Native Kidney Biopsies and Glomerular Disease: Utilization and Diagnostic Trends in the United States, 2006-2015

Tran

Walther

2021

Kidney Medicine

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Rationale and design of the Kidney Precision Medicine Project

Cited by 105 publications

References 36 publications

An atlas of healthy and injured cell states and niches in the human kidney

An atlas of healthy and injured cell states and niches in the human kidney

A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium

Inpatient Native Kidney Biopsies and Glomerular Disease: Utilization and Diagnostic Trends in the United States, 2006-2015

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