Publications

Sara Denicolò,Viji Nair, Johannes Leierer, Michael Rudnicki, Matthias Kretzler, Gert Mayer, Wenjun Ju, Paul Perco
Biomolecules
(
13(1): 89
)
,
December 31, 2022
DOI:
10.3390/biom13010089
|
PMID:
36671474
|
PMCID:
PMC9855364
Summary
Jiahao Liu, Viji Nair, Yi-yang Zhao, Dong-yuan Chang, Felix Eichinger, Emily C. Tanner, Damian Fermin, Keith A. Bellovich, Susan Steigerwalt, Zeenat Bhat, Jennifer J. Hawkins, Lalita Subramanian, Sylvia E. Rosas, John R. Sedor, Miguel A. Vasquez, Sushrut S. Waikar, Markus Bitzer, Subramaniam Pennathur, Frank Brosius, Min Chen, Matthias Kretzler, Wenjun Ju, for the Kidney Precision Medicine Project and Michigan Translational Core C-PROBE Investigator Group
Diabetes
(
71(12):2664-2676
)
,
December 1, 2022
DOI:
10.2337/db22-0169
|
PMID:
36331122
|
PMCID:
PMC9750948
Summary
Brendon Lutnick, David Manthey, Jan U. Becker, Brandon Ginley, Katharina Moos, Jonathan E. Zuckerman, Luis Rodrigues, Alexander J. Gallan, Laura Barisoni, Charles E. Alpers, Xiaoxin X. Wang, Komuraiah Myakala, Bryce A. Jones. Moshe Levi, Jeffrey B. Kopp, Teruhiko Yoshida, Seung Seok Han, Sanjay Jain, Avi Z. Rosenberg, Kuang Yu. Jen, Pinaki Sarder, the Kidney Precision Medicine Project
Communications Medicine
(
)
,
August 19, 2022
DOI:
https://doi.org/10.1038/s43856-022-00138-z
|
PMID:
|
PMCID:
Summary

Goal: Artificial intelligence (AI) is the ability of a computer to conduct complex tasks that humans are capable of performing. AI is useful in the field of pathology, which involves analyzing images of the microscopic structure of different tissues. However, AI can be difficult to setup and apply to the task. One specific task, segmentation, involves picking specific structures out of tissue images and is a prime candidate for automation with AI.

Results: In our study, we have created a tool for pathology image segmentation which runs in the cloud (is accessible over the web). We demonstrate the tool by using it to segment various structures from kidney tissue.

Implication for Patients: Our experiments show that the tool is easy to use, accurate, and can estimate the presence of one type of scarring as reliably as human experts. Doctors will be able to use our tool to consult patient diagnosis over the web with other colleagues, and offer objective diagnosis with the help of AI.

 

Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Dejan Dobi, Samir Parikh, Tara K. Sigdel, Guanshi Zhang, Dusan Velickovic, Daria Barwinska, Theodore Alexandrov, Priyanka Rashmi, Edgar A. Otto, Michael P. Rose, Christopher R. Anderton, John P. Shapiro, Annapurna Pamreddy, Seth Winfree, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Laura Barisoni, Abhijit S. Naik, Kumar Sharma, Minnie M. Sarwal, Kun Zhang, Jonathan Himmelfarb, Brad Rovin, Tarek M. El-Achkar, Zoltan Laszik, John Cijiang He, Pierre C. Dagher, M. Todd Valerius, Sanjay Jain, Lisa Satlin, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, for the Kidney Precision Medicine Project
Science Advances
(
Vol 8, Issue 23
)
,
June 10, 2022
DOI:
10.1126/sciadv.abn4965
|
PMID:
35675394
|
PMCID:
PMC9176741
Summary

Kidney Precision Medicine Project (KPMP) is building a spatially-specified human tissue atlas at the single-cell resolution with molecular details of the kidney in health and disease. Here, we describe the construction of an integrated reference tissue map of cells, pathways and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 55 subjects. We use single-cell and -nucleus transcriptomics, subsegmental laser microdissection bulk transcriptomics and proteomics, near-single-cell proteomics, 3-D nondestructive and CODEX imaging, and spatial metabolomics data to hierarchically identify genes, pathways and cells. Integrated data from these different technologies coherently describe cell types/subtypes within different nephron segments and interstitium. These spatial profiles identify cell-level functional organization of the kidney tissue as indicative of their physiological functions and map different cell subtypes to genes, proteins, metabolites and pathways. Comparison of transcellular sodium reabsorption along the nephron to levels of mRNAs encoding the different sodium transporter genes indicate that mRNA levels are largely congruent with physiological activity.This reference atlas provides an initial framework for molecular classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

Jiten Patel, Jose R. Torrealba, Emilio D. Poggio, Jack Bebiak, Charles E. Alpers, Stephanie M. Grewenow, Robert D. Toto and Michael T. Eadon; for the Kidney Precision Medicine Project
Clinical Journal of the American Society of Neprhology
(
17 (4) 594-601
)
,
April 17, 2022
DOI:
https://doi.org/10.2215/CJN.10350721
|
PMID:
34911732
|
PMCID:
PMC8993486
Summary

Goal: The goal of this study was to link the KPMP's molecular data to established clinical and pathologic assessments, providing a complete and individualized interpretation of a subject's kidney biopsy specimen.

Result: Despite a lack of overt pathologic evidence of diabetic kidney disease, early molecular features of diabetes were found within the kidney, consistent with the subject's clinical diagnosis.

 Implication for patients: This is the first published example of the KPMP integrating molecular information into the clinical and pathologic evaluation of an individual patient's kidney disease.

Christine P. Limonte, Erkka Valo, Viktor Drel, Loki Natarajan, Manjula Darshi, Carol Forsblom, Clark M. Henderson, Andrew N. Hoofnagle, Wenjun Ju, Matthias Kretzler, Daniel Montemayor, Viji Nair, Robert G. Nelson, John F. O’Toole, Robert D. Toto, Sylvia E. Rosas, John Ruzinski, Niina Sandholm, Insa M. Schmidt, Tomas Vaisar, Sushrut S. Waikar, Jing Zhang, Peter Rossing, Tarunveer S. Ahluwalia, Per-Henrik Groop, Subramaniam Pennathur, Janet K. Snell-Bergeon, Tina Costacou, Trevor J. Orchard, Kumar Sharma, Ian H. de Boer
Diabetes Care
(
)
,
April 2, 2022
DOI:
https://doi.org/10.2337/dc21-2204
|
PMID:
35377940
|
PMCID:
PMC9210873
Summary
Rajasree Menon, Edgar A. Otto, Celine C. Berthier, Viji Nair, Evan A. Farkash, Jeffrey B. Hodgin, Yingbao Yang, Jinghui Luo, Kenneth J. Woodside, Haniyeh Zamani, Silas P. Norman, Roger C. Wiggins, Matthias Kretzler, and Abhijit S. Naik
Kidney International
(
VOLUME 101, ISSUE 4, P779-792
)
,
April 1, 2022
DOI:
https://doi.org/10.1016/j.kint.2021.11.031
|
PMID:
34952098
|
PMCID:
PMC9067613
Summary

Rajasree Menon, Andrew S. Bomback, Blue B. Lake, Christy Stutzke, Stephanie M. Grewenow, Steven Menez, Vivette D. D’Agati, Sanjay Jain, for the Kidney Precision Medicine Project
Kidney International
(
)
,
March 8, 2022
DOI:
https:// doi.org/10.1016/j.kint.2022.03.011
|
PMID:
35339536
|
PMCID:
Summary

Goal:  To definemolecular and cellular features in a biopsy from an AKI patient using singlenucleus / cell RNA sequencing methods in conjunction with detailed histopathologicalanalysis and clinical course in order to gain mechanistic insights intocellular diversity, injury states, and clinical outcome.

Results: The molecular studies reveal remarkable cellularheterogeneity  and presence of alteredcell states reflecting cellular injury and repair in a  number of proximal and distal nephron celltypes, blood vessels, fibroblasts and immune cell.  Correlates of the injured and regeneratingcells were identified by histopathology including features of regeneration, tubularinjury and remodeling in this patient. By leveraging the KPPMP+HuBMAP master kidney atlas, the molecularanalysis further permitted identification of genes and pathways associated withadaptive / maladaptive repair. Signatures associated with NSAID use were detected in altered tubuleseven after discontinuation of these medicines.

Implication for Patients: The molecular and pathologicalanalysis enables assessment of injury and repair processes and etiology of AKIat the time of the biopsy.  Identificationof pathways that may be predictive of recovery or worsening kidney function canbe useful in assessing prognosis.  Asmore of these datasets are obtained, we may be able to have a knowledge base torelate these pathways with clinical outcomes and potentially use therapeuticdrugs to inhibit those related to worsening kidney function.

Catherine R. Butler, Paul S. Appelbaum, Heather Ascani, Mark Aulisio, Catherine E. Campbell, Ian H. de Boer, Ashveena L. Dighe, Daniel E. Hall, Jonathan Himmelfarb, Richard Knight, Karla Mehl, Raghavan Murugan,Sylvia E. Rosas, John R. Sedor, John F. O’Toole, Katherine R. Tuttle, Sushrut S. Waikar, and Michael Freeman, for the Kidney Precision Medicine Project
American Journal of Kidney Diseases
(
)
,
December 3, 2021
DOI:
https://doi.org/10.1053/j.ajkd.2021.10.006
|
PMID:
34871700
|
PMCID:
PMC9166631
Summary

Goal: Participation in the Kidney Precision Medicine Project(KPMP) means undergoing kidney biopsy and while the KPMP safety protocols are intended to minimize risk of this procedure, participants nonetheless accept some personal risk.

Results: Design and implementation of the KPMP has involved substantial ethical deliberation, and in this article, we use this experience as an example to understand the ethical foundation and implications of research that involves risk to participants.

Implication for Patients: Specifically, efforts to respect diverse participant values, support participants’ opportunity to act altruistically, and enhancing benefits to participants’ community are critical features of the KPMP research paradigm needed to respect and support participant in research that involves some personal risk.

 

Andreas Bueckle, Kilian Buehling, Patrick C. Shih, Katy Börner
PLoS ONE
(
PLoS ONE 16(10): e0258103.
)
,
October 27, 2021
DOI:
https://doi.org/10.1371/journal.pone.0258103
|
PMID:
34705835
|
PMCID:
PMC8550408
Summary

Goal: In our paper (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258103), we tested three implementations of a tissue registration user interface (one on a 2D screen, two in virtual reality or VR) with regards to accuracy, completion time, and satisfaction with 42 human subjects.

Results: We found that while the VR implementations allow user to be significantly faster, more satisfied, and more accurate with regards to rotation, there was no difference regarding position accuracy, once again showing the viability of 2D interfaces for registering human tissue block inside 3D reference organs.

Implications for patients: Our incremental research and development towards accurate, quick, and satisfying 2D tissue registration enables the continued improvement of the user interfaces for building a Human Reference Atlas (https://hubmapconsortium.github.io/ccf/) in HuBMAP (https://commonfund.nih.gov/hubmap) with the goal of mapping the human body at single-cell level.

Veličković D, Bečejac T, Mamedov S, Sharma K, Ambalavanan N, Alexandrov T, Anderton CR
Analytic Chemistry
(
93(40):13421-13425
)
,
October 12, 2021
DOI:
10.1021/acs.analchem.1c02347
|
PMID:
34581565
|
PMCID:
Summary
Insa M.Schmidt, Mia R.Colona, Bryan R.Kestenbaum, Leonidas G.Alexopoulos, RagnarPalsson, AnandSrivastava, JingLiu, Isaac E.Stillman, Helmut G.Rennke, Vishal S.Vaidya, Haojia Wu, Benjamin D.Humphreys, Sushrut S.Waikar, Kidney Precision Medicine Project (KPMP)
Kidney International
(
S0085-2538(21)00505-6
)
,
May 26, 2021
DOI:
https://doi.org/10.1016/j.kint.2021.04.037
|
PMID:
34051265
|
PMCID:
PMC8384690
Summary

Goal: Kidney fibrosis can result in structural damage and impairment of kidney function but non-invasive biomarkers (e.g., proteins measured in a patient’s blood or urine) to assess kidney fibrosis are currently not available.

Results: In this study, we identified SMOC2, PEDF, and CDH11 as promising new biomarker proteins that may be used to estimate the degree of fibrosis in patients with kidney disease and identify patients at high risk of kidney disease progression.

Implication for Patients: These biomarkers may be used as markers of response to treatment, for example facilitating the investigation of new therapies that are under development for the treatment of kidney fibrosis

Yi Zheng, Clarissa A Cassol, Saemi Jung, Divya Veerapaneni, Vipul C Chitalia, Kevin Y M Ren, Shubha S Bellur, Peter Boor, Laura M Barisoni, Sushrut S Waikar, Margrit Betke, Vijaya B Kolachalama
The American Journal of Pathology
(
May-2021
)
,
May 21, 2021
DOI:
https://doi.org/10.1016/j.ajpath.2021.05.005
|
PMID:
34033750
|
PMCID:
PMC8453248
Summary

Goal: To develop a widely applicable way to stratify kidney disease severity. Chronic kidney damage is assessed by scoring the amount of interstitial fibrosis and tubular atrophy (IFTA) in a renal biopsy sample.

Results: A novel Artificial Intelligence (AI) tool was developed to predict the grade of IFTA, a known structural correlate of progressive and chronic kidney disease.

Implication for Patients: Having a computer model that can mimic an expert pathologist's workflow and assess disease grade can further the potential to increase efficiency in clinical practices. AI models that can automatically score the extent of chronic damage in the kidney can serve as a second opinion tool in clinical practices.

Steven Menez, Wenjun Ju, Rajasree Menon, Dennis G. Moledina, Heather Thiessen Philbrook, Eric McArthur, Yaqi Jia, Wassim Obeid, Sherry G. Mansour, Jay L. Koyner, Michael G. Shlipak, Steven G. Coca, Amit X. Garg, Andrew S. Bomback, John A. Kellum, Matthias Kretzler, Chirag R. Parikh
Journal of Clinical Investigation
(
6(11):e147464
)
,
May 11, 2021
DOI:
https://doi.org/10.1172/jci.insight.147464
|
PMID:
33974569
|
PMCID:
PMC8262289
Summary
Katherine R Tuttle, Jack Bebiak, Keith Brown, Catherine Campbell, Ashveena Dighe, Lynda Hyashi, Nichole Jefferson, Glenda V Roberts, Christy Stutzke, Richard Knight, Kidney Precision Medicine Project
Kidney International
(
VOLUME 99, ISSUE 3, P511-514
)
,
March 1, 2021
DOI:
https://doi.org/10.1016/j.kint.2020.10.036
|
PMID:
33637195
|
PMCID:
Summary

Goal: To guide scientific inquiry toward clinically meaningful benefit, patients are equal partners for priority setting, study design and conduct, and dissemination of findings.

Results: Patient partners in the Community Engagement Committee led the development of the informed consent process, the ethics statement, the return-of-results plan, a “patient primer” for scientists, and community advisory boards at the recruitment sites.

Implication for Patients: Patients’ viewpoints and priorities have been central in directing the KPMP to produce research that brings clinically meaningful benefit to them.

Ian H. de Boer, MD, MS, Charles E. Alpers, MD, Tarek M. El-Achkar, MD, Evren Azeloglu, PhD, Ulysses G. J. Balis, MD, PhD, Jonathan M. Barasch, MD, PhD, Laura Barisoni, MD, Kristina Blank, MPH, Andrew S. Bomback, MD, Keith Brown, Pierre C. Dagher, MD, Ashveena L. Dighe, MS, MPH, Michael T. Eadon, MD, Joseph P. Gaut, MD, PhD, Nir Hacohen, PhD, Yongqun He, PhD, Jeffrey B. Hodgin, MD, PhD, Sanjay Jain, MD, PhD, John A. Kellum, MD, Krzysztof Kiryluk, MD, MS, Richard Knight, and Zoltan G. Laszik, MD, PhD, Chrysta Lienczewski, Laura H. Mariani, MD, Robyn L. Mcclelland, PhD, Steven Menez, MD, Dennis Moledina, MD, PhD, Sean D. Mooney, PhD, John O’Toole, MD, Paul M. Palevsky, MD, Chirag R. Parikh, MD, PhD, Emilio Poggio, MD, Sylvia Rosas, MD, Matthew R. Rosengart, MD, MPH, Minnie Sarwal, MD, PhD, Jennifer A. Schaub, MD, John R. Sedor, MD, Kumar Sharma, MD, Becky Steck, Robert Toto, MD, Olga Troyanskaya, PhD, Katherine Tuttle, MD, Miguel Vazquez, MD, Sushrut S. Waikar, MD, Kayleen Williams, MPH, Francis Perry Wilson, MD, Kun Zhang, PhD, Srinivas Ravi Iyengar, PhD, Matthias Kretzler, MD, Jonathan Himmelfarb, and For the Kidney Precision Medicine Project
Kidney International
(
VOLUME 99, ISSUE 3, P498-510
)
,
March 1, 2021
DOI:
https://doi.org/10.1016/j.kint.2020.08.039
|
PMID:
33637194
|
PMCID:
PMC8330551
Summary

Goal: Describe the objectives and study design of the Kidney Precision Medicine Project, and the rationale for kidney precision medicine.

Results: 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.

Implication for Patients: All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Daria Barwinska, Tarek M El-Achkar, Ricardo Melo Ferreira, Farooq Syed, Ying-Hua Cheng, Seth Winfree, Michael J Ferkowicz, Takashi Hato, Kimberly S Collins, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Brad H Rovin, Samir V Parikh, Carrie L Phillips, Pierre C Dagher, Michael T Eadon, Kidney Precision Medicine Project
Science Advances
(
Vol. 7, no. 7, eabd3359
)
,
February 10, 2021
DOI:
10.1126/sciadv.abd3359
|
PMID:
33568476
|
PMCID:
PMC7875540
Summary
Michael T Eadon, Sam Lampe, Mirza M Baig, Kimberly S Collins, Ricardo Melo Ferreira, Henry Mang, Ying-Hua Cheng, Daria Barwinska, Tarek M El-Achkar, Tae-Hwi Schwantes-An, Seth Winfree, Constance J Temm, Michael J Ferkowicz, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Sharon M Moe, Ranjani N Moorthi, Carrie L Phillips, Pierre C Dagher, Kidney Precision Medicine Project
Nephrol Dial Transplant
(
)
,
February 4, 2021
DOI:
10.1093/ndt/gfaa331
|
PMID:
33537765
|
PMCID:
PMC8826640
Summary

Goal: Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis.

Results: The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes kidney disease (DKD) or other predisposing diagnoses.  

Implication for Patients: Despite similar clinical and histopathologic characteristics in ING and DKD, the uncovered transcriptomic signature suggests that ING has distinct molecular features from nodular DKD.

Tarek M El-Achkar, Michael T Eadon, Rajasree Menon, Blue B Lake, Tara K Sigdel, Theodore Alexandrov, Samir Parikh, Guanshi Zhang, Dejan Dobi, Kenneth W Dunn, Edgar A Otto, Christopher R Anderton, Jonas M Carson, Jinghui Luo, Chris Park, Habib Hamidi, Jian Zhou, Paul Hoover, Andrew Schroeder, Marianinha Joanes, Evren U Azeloglu, Rachel Sealfon, Seth Winfree, Becky Steck, Yongqun He, Vivette D'Agati, Ravi Iyengar, Olga G Troyanskaya, Laura Barisoni, Joseph Gaut, Kun Zhang, Zoltan Laszik, Brad H Rovin, Pierre C Dagher, Kumar Sharma, Minnie M Sarwal, Jeffrey B Hodgin, Charles E Alpers, Matthias Kretzler, Sanjay Jain
Physiological Genomics
(
2021/01/11 Vol. 53, No. 1
)
,
January 11, 2021
DOI:
https://doi.org/10.1152/physiolgenomics.00104.2020
|
PMID:
33197228
|
PMCID:
PMC7847045
Summary
Michael J Ferkowicz, Seth Winfree, Angela R Sabo, Malgorzata M Kamocka, Suraj Khochare, Daria Barwinska, Michael T Eadon, Ying-Hua Cheng, Carrie L Phillips,Timothy A Sutton, Katherine J Kelly, Pierre C Dagher, Tarek M El-Achkar, Kenneth W Dunn, Kidney Precision Medicine Project
Nature: Laboratory Investigations
(
06 January 2021
)
,
January 6, 2021
DOI:
https://doi.org/10.1038/s41374-020-00518-w
|
PMID:
33408350
|
PMCID:
PMC8363780
Summary
Katherine R Tuttle, Richard Knight, Paul S Appelbaum, Tanima Arora, Shweta Bansal, Jack Bebiak, Keith Brown, Catherine Campbell, Leslie Cooperman, Celia P Corona-Villalobos, Ashveena Dighe, Ian H de Boer, Daniel E Hall, Nichole Jefferson, Stacey Jolly, Asra Kermani, Simon C Lee, Karla Mehl, Raghavan Murugan, Glenda V Roberts, Sylvia E Rosas, Jonathan Himmelfarb, R Tyler Miller, Kidney Precision Medicine Project
CJASN
(
November 2020, CJN.10270620
)
,
November 1, 2020
DOI:
https://doi.org/10.2215/CJN.10270620
|
PMID:
33257411
|
PMCID:
PMC8092068
Summary

Goal: Describe patient and community engagement and the value they bring to the KPMP.

Results: The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians, and assures that the science is developed and conducted in a manner relevant to study participants and the clinical community.

Implications for Patients: Patients have guided the KPMP to produce research aligned with their priorities, and set new benchmarks for patient leadership in precision medicine research.

Rajasree Menon, Edgar A Otto, Rachel Sealfon, Viji Nair, Aaron K Wong, Chandra L Theesfeld, Xi Chen, Yuan Wang, Avinash S Boppana, Jinghui Luo, Yingbao Yang, Peter M Kasson, Jennifer A Schaub, Celine C Berthier, Sean Eddy, Chrysta C Lienczewski, Bradley Godfrey, Susan L Dagenais, Ryann Sohaney, John Hartman, Damian Fermin, Lalita Subramanian, Helen C Looker, Jennifer L Harder, Laura H Mariani, Jeffrey B Hodgin, Jonathan Z Sexton, Christiane E Wobus, Abhijit S Naik, Robert G Nelson, Olga G Troyanskaya, Matthias Kretzler
Kidney International
(
2020 Oct 07
)
,
October 7, 2020
DOI:
https://doi.org/10.1016/j.kint.2020.09.015
|
PMID:
32511461
|
PMCID:
PMC7241118
Summary
Emilio D Poggio, Robyn L McClelland, Kristina N Blank, Spencer Hansen, Shweta Bansal, Andrew S Bomback, Pietro A Canetta, Pascale Khairallah, Krzysztof Kiryluk, Stewart H Lecker, Gearoid M McMahon, Paul M Palevsky, Samir Parikh, Sylvia E Rosas, Katherine Tuttle, Miguel A Vazquez, Anitha Vijayan, Brad H Rovin, Kidney Precision Medicine Project
CJASN
(
October 2020, CJN.04710420
)
,
October 1, 2020
DOI:
https://doi.org/10.2215/CJN.04710420
|
PMID:
33060160
|
PMCID:
PMC7646247
Summary
Tara K. Sigdel, Paul D Piehowski, Sudeshna Roy, Juliane Liberto, Joshua R Hansen, Adam C Swensen, Rui Zhao, Ying Zhu, Priyanka Rashmi, Andrew Schroeder, Izabella Damm, Swastika Sur, Jinghui Luo, Yingbao Yang, Wei-Jun Qian, Minnie M Sarwal, Kidney Precision Medicine Project (KPMP) Consortium
Frontiers in Medicine
(
17 Sept 2020
)
,
September 17, 2020
DOI:
https://doi.org/10.3389/fmed.2020.00499
|
PMID:
33072769
|
PMCID:
PMC7533534
Summary

Goal: The goal was to study Proximal Tubular and Glomerular proteins using laser capture microdissection followed by mass spectrometry.

Results: We established near single-cell proteomics protocol kidney tissue and identified more than 2,500 human proteins of which 25 proteins) were specific to proximal tubules  and 67 were specific to glomerulus  (Glom; n = 67 proteins) regions.

Implication for Patients: This near-single-cell proteomics workflow can be extended to other kidney micro-compartments which ultimately will help understand changes in the proteomic landscape of normal kidneys as well as different etiologies of acute and chronic kidney disease.

Edison Ong, Lucy L Wang, Jennifer Schaub, John F O'Toole, Becky Steck, Avi Z Rosenberg, Frederick Dowd, Jens Hansen, Laura Barisoni, Sanjay Jain, Ian H de Boer, M Todd Valerius, Sushrut S Waikar, Christopher Park, Dana C Crawford, Theodore Alexandrov, Christopher R Anderton, Christian Stoeckert, Chunhua Weng, Alexander D Diehl, Christopher J Mungall, Melissa Haendel, Peter N Robinson, Jonathan Himmelfarb, Ravi Iyengar, Matthias Kretzler, Sean Mooney, Yongqun He, Kidney Precision Medicine Project
Nature Reviews Nephrology
(
16 September 2020
)
,
September 16, 2020
DOI:
10.1038/s41581-020-00335-w
|
PMID:
32939051
|
PMCID:
PMC8012202
Summary

Goal: To model the kidney disease using ontology.

Results: The development of two new community-based ontologies — the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation —supports the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney, leading to more advanced kidney disease modeling and analysis.

Implication for Patients: The usage of ontology supports the standard data integration and analysis of kidney precision medicine.

Jessica K. Lukowski, Annapurna Pamreddy, Dusan Velickovic, Guanshi Zhang, Ljiljana Pasa-Tolic, Theodore Alexandrov, Kumar Sharma, Christopher R. Anderton, and the Kidney Precision Medicine Project
J. Am. Soc. Mass Spectrom
(
September 8, 2020
)
,
September 8, 2020
DOI:
https://doi.org/10.1021/jasms.0c00256
|
PMID:
32897710
|
PMCID:
PMC8162764
Summary

Goal: We sought to understand the optimal storage conditions for spatial lipidomic analysis of human kidney tissue sections, as it is common practice to share tissue among the consortium and between tissue interrogation sites.

Results: Overall, we found that molecular degradation of the tissue sections was unavoidable over time, regardless of storage conditions, but storing tissue sections in an inert gas at low temperatures can curtail molecular degradation within tissue sections.

Implications for Patients: By storing kidney tissue sections under these optimal conditions we can maximize the molecular readout from the kidney biopsies.

Keith D. Brown, Catherine Campbell, Glenda V. Roberts
Nat Rev Nephr
(
2020 Aug 08
)
,
August 8, 2020
DOI:
10.1038/s41581-020-0319-0
|
PMID:
32760017
|
PMCID:
PMC7404073
Summary

Interviews with three individuals who have been affected by kidney failure for their views on the importance of understanding the drivers of kidney disease, and what they hope might be achieved with this information.

Daria Barwinska, Michael J Ferkowicz, Ying-Hua Cheng, Seth Winfree, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Brad H Rovin, Samir V Parikh, Carrie L Phillips, Pierre C Dagher, Tarek M El-Achkar, Michael T Eadon, Kidney Precision Medicine Project
JoVE
(
June 9, 2020
)
,
June 9, 2020
DOI:
10.3791/61371
|
PMID:
32597856
|
PMCID:
PMC8136155
Summary
Rajasree Menon, Edgar A Otto, Paul Hoover, Sean Eddy, Laura Mariani, Bradley Godfrey, Celine C Berthier, Felix Eichinger, Lalita Subramanian, Jennifer Harder, Wenjun Ju, Viji Nair, Maria Larkina, Abhijit S Naik, Jinghui Luo, Sanjay Jain, Rachel Sealfon, Olga Troyanskaya, Nir Hacohen, Jeffrey B Hodgin, Matthias Kretzler, Kidney Precision Medicine Project Kpmp, Nephrotic Syndrome Study Network (NEPTUNE)
JCI Insight
(
2020 Mar 26;5(6):e133267
)
,
March 26, 2020
DOI:
10.1172/jci.insight.133267
|
PMID:
32107344
|
PMCID:
PMC7213795
Summary
Dušan Veličković, Guanshi Zhang, Dejan Bezbradica, Arunima Bhattacharjee, Ljiljana Paša-Tolić, Kumar Sharma, Theodore Alexandrov, Christopher R. Anderton, and KPMP Consortium
J Am Soc Mass Spec
(
2020 Feb 06;31(3):508-516
)
,
February 6, 2020
DOI:
10.1021/jasms.9b00074
|
PMID:
32126772
|
PMCID:
PMC7293970
Summary

Goal: The goal of this research was to develop a reliable and robust optimization strategy for our spatial metabolomics assay’s sample preparation steps that could be utilized universally for different tissue types.

Results: Through development of a novel experimental design coupled with mathematical modeling, we can optimize sample preparation for spatial metabolomics (via matrix-assisted laser desorption/ionization mass spectrometry imaging) with minimal time and tissue utilization.

Implication for Patients: This approach will ensure that we will obtain the highest quality spatial metabolomics data from the invaluable KPMP tissue biopsies.

Beatriz Desanti De Oliveira, Katherine Xu, Tian H. Shen, Miriam Callahan, Krzysztof Kiryluk, Vivette D. D’Agati, Nicholas P. Tatonetti, Jonathan Barasch & Prasad Devarajan
Nat Rev Nephrol
(
2019 Oct;15(10):599-612
)
,
October 1, 2019
DOI:
10.1038/s41581-019-0184-x
|
PMID:
31439924
|
PMCID:
PMC7303545
Summary
Blue B Lake, Song Chen, Masato Hoshi, Nongluk Plongthongkum, Diane Salamon, Amanda Knoten, Anitha Vijayan, Ramakrishna Venkatesh, Eric H Kim, Derek Gao, Joseph Gaut, Kun Zhang, Sanjay Jain
Nat Commun
(
2019 Jun 27;10(1):2832
)
,
June 27, 2019
DOI:
10.1038/s41467-019-10861-2
|
PMID:
31249312
|
PMCID:
PMC6597610
Summary

Goal: To profile the diverse molecular cell type composition of human kidneys, we developed a reproducible method for isolating and sequencing RNA transcripts within single kidney nuclei.

Results: This enabled gene expression profiling of cell types spanning the major functional units of the kidney with minimal processing artifacts.

Implication for Patients: Using this approach, our analysis portrays remarkable cellular and molecular heterogeneity and insights into kidney organization, function and disease.

Paul L. Kimmel, Nichole Jefferson, Jenna M. Norton and Robert A. Star
Clin J Am Soc Nephrol
(
2019 May 7;14(5):768-770
)
,
May 7, 2019
DOI:
10.2215/CJN.14591218
|
PMID:
30917992
|
PMCID:
PMC6500937
Summary

Goal: To reflect on two NIDDK consortia and the benefits of community-engaged research to nephrology.

Results: Putting patients first and meaningfully involving them in nephrology research as full partners may increase research relevance and efficiency, with particular benefits for studies addressing underserved or minority populations.  

Implication for Patients: Inclusion of the patient and community perspective across the spectrum of nephrology research may benefit patients, investigators, and the nephrology field as a whole.

Brad P. Dieter, Radica Z Alicic, Katherine R. Tuttle
Am J Physiol Renal Physiol
(
2018 Dec 1;315(6):F1519-F1525
)
,
December 1, 2018
DOI:
10.1152/ajprenal.00211.2018
|
PMID:
30110568
|
PMCID:
PMC6337002
Summary

Goal: A review article covering the effects of GLP-1 receptor agonists on the diabetic kidney from clinical trial data to basic science and preclinical studies.

Results: These data set the stage for understanding mechanistic underpinnings, inclusive of tissue interrogation akin to KPMP, for kidney protection by GLP-1 receptor agonists.

Implication for Patients: Linking kidney disease mechanisms to therapeutic interventions helps to identify individuals who may benefit from a specific therapy.

Krzysztof Kiryluk, Andrew S Bomback, Yim-Ling Cheng, Katherine Xu, Pablo G Camara, Raul Rabadan, Peter A Sims, Jonathan Barasch
Semin Nephrol
(
2018 Jan;38(1):40-51
)
,
January 1, 2018
DOI:
10.1016/j.semnephrol.2017.09.006
|
PMID:
29291761
|
PMCID:
PMC5753434
Summary
Samir Parikh, Sethu Madhavan, John Shapiro, Richard Knight, Avi Z Rosenberg, Chirag R Parikh, Brad Rovin, Steven Menez, for the Kidney Precision Medicine Project
CJASN
(
18(3):p 402-410
)
,
DOI:
DOI: 10.2215/CJN.09260822
|
PMID:
|
PMCID:
Summary
Samir Parikh, Sethu Madhavan, John Shapiro, Richard Knight, Avi Rosenberg, Chirag Parikh, Brad Rovin, Steven Menez
Clinical Journal of the American Society of Nephrology
(
)
DOI:
|
PMID:
36344211
|
PMCID:
Summary

Goal: To explore a case of acute kidney injury (AKI) in a pregnant woman, presumed to be related to NSAID use, who underwent kidney biopsy, pairing standard pathological investigation with newer, molecular methods to interrogate the kidney tissue.

Results: the standard pathological results showed evidence of acute tubular injury, without significant scarring in other parts of the kidney. However, the molecular investigation, looking at protein signatures in the kidney tissue, showed evidence of inflammation and scarring in the kidney that was not clearly evident on pathology.

Implications for patients: This case of AKI highlights how the molecular evaluation of kidney tissue performed by investigators in the KPMP adds significant, additional information beyond standard investigation done currently in clinical practice. These new methods add further precision to the diagnosis of AKI and hold promise for future clinical use.

Blue B. Lake, Rajasree Menon, Seth Winfree, Qiwen Hu, Ricardo Melo Ferreira, Kian Kalhor, Daria Barwinska, Edgar A. Otto, Michael Ferkowicz, Dinh Diep, Nongluk Plongthongkum, Amanda Knoten, Sarah Urata, Abhijit S. Naik, Sean Eddy, Bo Zhang, Yan Wu, Diane Salamon, James C. Williams, Xin Wang, Karol S. Balderrama, Paul Hoover , Evan Murray, Anitha Vijayan, Fei Chen, Sushrut S. Waikar, Sylvia Rosas, Francis P. Wilson, Paul M. Palevsky, Krzysztof Kiryluk, John R. Sedor, Robert D. Toto, Chirag Parikh, Eric H. Kim, Evan Z. Macosko, Peter V. Kharchenko, Joseph P. Gaut, Jeffrey B. Hodgin, Michael T. Eadon, Pierre C. Dagher, Tarek M. El-Achkar, Kun Zhang, Matthias Kretzler, Sanjay Jain, for the KPMP consortium
bioRxiv
(
)
DOI:
10.1101/2021.07.28.454201
|
PMID:
|
PMCID:
Summary
Tarek M. El-Achkar, Michael T. Eadon, Rajasree Menon, Blue B. Lake, Tara K. Sigdel, Theodore Alexandrov, Samir Parikh, Guanshi Zhang, Dejan Dobi, Kenneth W. Dunn, Edgar A. Otto, Christopher R. Anderton, Jonas M. Carson, Jinghui Luo, Chris Park, Habib Hamidi, Jian Zhou, Paul Hoover, Andrew Schroeder, Marianinha Joanes, Evren U. Azeloglu, Rachel SealfonSeth Winfree, Becky Steck, Yongqun He, Vivette D’Agati, Ravi Iyengar, Olga G. Troyanskaya, Laura Barisoni, Joseph Gaut, Kun Zhang, Zoltan Laszik, Brad H. Rovin, Pierre C. Dagher, Kumar Sharma, Minnie M. Sarwal, Jeffrey B. Hodgin, Charles E. Alpers, Matthias Kretzler, andSanjay Jain; for The Kidney Precision Medicine Project
BioRxiv 828665 [Preprint]
(
2019 Nov 06
)
DOI:
10.1101/828665
|
PMID:
33197228
|
PMCID:
PMC7847045
Summary
Andrew W. Schroeder, Swastika Sur, Priyanka Rashmi, Izabella Damm, Arya Zarinsefat, Matthias Kretzler, Jeff Hodgin, George Hartoularos, Tara Sigdel, Jimmie Chun Ye, Minnie M. Sarwal, for the Kidney Precision Medicine Project
BioRxiv 973925 [Preprint]
(
2020 Mar 04
)
DOI:
10.1101/2020.03.02.973925
|
PMID:
|
PMCID:
Summary
Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Dejan Dobi, Samir Parikh, Tara K. Sidgel, Theodore Alexandrov, Andrew Schroeder, Edgar A. Otto, Christopher R. Anderton, Daria Barwinska, Guanshi Zheng, Michael P. Rose, John P. Shapiro, Dusan Velickovic, Annapurna Pamreddy, Seth Winfree, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Abhijit Nair, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Zoltan Laszik, Brad Rovin, Pierre C. Dagher, John Cijiang He, Tarek M. El-Achkar, Sanjay Jain, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, for the Kidney Precision Medicine Project Consortium
Biorxiv [Preprint]
(
2020 July 24
)
DOI:
10.1101/2020.07.23.216507
|
PMID:
|
PMCID:
Summary

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