Publications

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MAnuscripts

Catherine R. Butler
American Journal of Kidney Diseases
(
)
,
December 3, 2021
DOI:
https://doi.org/10.1053/j.ajkd.2021.10.006
|
PMID:
34871700
|
PMCID:
Summary

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. 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. 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
PLoS ONE
(
PLoS ONE 16(10): e0258103.
)
,
October 27, 2021
DOI:
https://doi.org/10.1371/journal.pone.0258103
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PMID:
|
PMCID:
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.

Insa M. Schmidt
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
The American Journal of Pathology
(
May-2021
)
,
May 21, 2021
DOI:
https://doi.org/10.1016/j.ajpath.2021.05.005
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PMID:
34033750
|
PMCID:
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
Journal of Clinical Investigation
(
6(11):e147464
)
,
May 11, 2021
DOI:
https://doi.org/10.1172/jci.insight.147464
|
PMID:
33974569
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PMCID:
PMC8262289
Summary
Ian H. de Boer
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.

Katherine R. Tuttle
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.

Eadon MT
Nephrol Dial Transplant
(
)
,
February 4, 2021
DOI:
10.1093/ndt/gfaa331
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PMID:
33537765
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PMCID:
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*
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
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
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, PhD
Kidney International
(
2020 Oct 07
)
,
October 7, 2020
DOI:
https://doi.org/10.1016/j.kint.2020.09.015
|
PMID:
32511461
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PMCID:
PMC7241118
Summary
Emilio D. Poggio
CJASN
(
October 2020, CJN.04710420
)
,
October 1, 2020
DOI:
https://doi.org/10.2215/CJN.04710420
|
PMID:
33060160
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PMCID:
PMC7646247
Summary
Tara K. Sigdel
Frontiers in Medicine
(
17 Sept 2020
)
,
September 17, 2020
DOI:
https://doi.org/10.3389/fmed.2020.00499
|
PMID:
33072769
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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.

Ong E
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
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
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.

Rajasree Menon
JCI Insight
(
2020 Mar 26;5(6):e133267
)
,
March 26, 2020
DOI:
10.1172/jci.insight.133267
|
PMID:
32107344
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PMCID:
PMC7213795
Summary
Dušan Veličković
J Am Soc Mass Spec
(
2020 Feb 06;31(3):508-516
)
,
February 6, 2020
DOI:
10.1021/jasms.9b00074
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PMID:
32126772
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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
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
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
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
Semin Nephrol
(
2018 Jan;38(1):40-51
)
,
January 1, 2018
DOI:
10.1016/j.semnephrol.2017.09.006
|
PMID:
29291761
|
PMCID:
PMC5753434
Summary
Blue B. Lake
bioRxiv
(
)
DOI:
10.1101/2021.07.28.454201
|
PMID:
|
PMCID:
Summary
Daria Barwinska
Science Advances
(
Vol. 7, no. 7, eabd3359
)
DOI:
10.1126/sciadv.abd3359
|
PMID:
33568476
|
PMCID:
PMC7875540
Summary
Daria Barwinska
JoVE
(
June 9, 2020
)
DOI:
10.3791/61371
|
PMID:
32597856
|
PMCID:
PMC8136155
Summary
Andrew W. Schroeder
BioRxiv 973925 [Preprint]
(
2020 Mar 04
)
DOI:
10.1101/2020.03.02.973925
|
PMID:
|
PMCID:
Summary
Tarek M. El-Achkar
BioRxiv 828665 [Preprint]
(
2019 Nov 06
)
DOI:
10.1101/828665
|
PMID:
33197228
|
PMCID:
PMC7847045
Summary

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