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Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology
Published on: March 27, 2018
Rationale and design of the Kidney Precision Medicine Project
Ian H de Boer1, Charles E Alpers2, Evren U Azeloglu3
1Department of Medicine, University of Washington, Seattle, Washington, USA.
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.
Insights
The Kidney Precision Medicine Project collects kidney biopsies to create a molecular atlas for stratifying patients with chronic or acute kidney injury. This research aims to identify new therapeutic targets for improved kidney disease treatment.
Area of Science:
- Nephrology
- Genomics
- Precision Medicine
Background:
- Chronic kidney disease (CKD) and acute kidney injury (AKI) represent significant global health burdens.
- Current understanding of CKD and AKI heterogeneity limits precision-based prevention and treatment strategies.
- The Kidney Precision Medicine Project (KPMP) addresses this by investigating kidney diseases.
Discussion:
- KPMP employs a multicenter prospective cohort design, ethically obtaining kidney biopsies from CKD and AKI patients.
- Integrative multi-omics (transcriptomics, proteomics, metabolomics) and deep clinical phenotyping are utilized.
- Analysis includes traditional and digital pathology for comprehensive characterization.
Key Insights:
- The project aims to establish a reference kidney atlas, detailing cell types, locations, and functions in health and disease.
- Identification of disease subgroups based on molecular and clinical features is a primary objective.
- Discovery of critical cells, pathways, and targets for novel therapeutic interventions is a key goal.
Outlook:
- Long-term prospective follow-up (10 years) will ascertain clinical outcomes.
- The creation of an open, searchable online kidney tissue atlas will facilitate broad scientific and clinical access.
- Findings are expected to advance a precision-medicine approach to kidney disease management.
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