Acute kidney injury (AKI) and chronic kidney disease (CKD) impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. Historically, AKI and CKD have been described as single, uniform diseases. However, growing consensus suggests that different disease pathways lead to different subgroups of AKI and CKD (AKIs and CKDs).
Access to human kidney biopsy tissue is a critical first step to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with AKI and CKD.
The KPMP is made up of four distinct, but highly interactive, activity groups:
The recruitment sites are responsible for recruiting participants with AKI or CKD into the longitudinal study and performing the kidney biopsy.
The tissue interrogation sites are responsible for developing and using innovative technologies to analyze the biopsy tissue.
The central hub is responsible for aggregating, analyzing, and visualizing the generated data and providing scientific, infrastructure, and administrative support for the KPMP consortium.
The KPMP recognizes that it must collaborate
with the broader research community to fully achieve these objectives. Thus, the KPMP Central Hub (CH) will administer an “Opportunity Pool” to facilitate the formation of new partnerships.
In collaboration with a number of research centers across the United States, we aim to accomplish the goals of the KPMP by obtaining kidney tissue from KPMP participants, analyzing it using state-of-the-art technologies, and developing next-generation software tools to visualize and share the resulting data.
This will allow us to redefine kidney disease in molecular terms and identify novel targeted therapies.
Creating the Atlas begins with recruiting participants with either chronic kidney disease or acute kidney injury, or from a reference population, to take part in the study. Consented participants undergo a kidney biopsy procedure, donate blood, urine and stool biospecimens, and answer a variety of questionnaires.
All biospecimens are sent to the KPMP Central Biorepository. The Biorepository sends the specimens to various tissue interrogation sites, where it undergoes further analysis.
The data which is generated from these analyses is returned to the KPMP Central Hub, where it is stored, standardized across sites, further analyzed, and then used to create new visualizations of the kidney. The data and visualizations are combined to create the Kidney Tissue Atlas.
Within the research activity groups from tissue interrogation to data integration, the KPMP consortium manages the resources within the KPMP and externally in the broader scientific community to achieve the following research objectives:
Identify a set of cellular and molecular markers that classify cells as healthy, injured, activated, or undergoing recovery via adaptive or maladaptive repair.
Discover a set of subgroup and pathway biomarkers (ideally plasma or urine protein/antibody pairs, but could be urinary exosomes, miRNA, epigenetic marks, etc.).
Use all available data, including the kidney tissue atlas, to define patient subgroups and allow for clinical stratification into distinct endophenotypes.
Establish a publicly available data hub with clinical, imaging, cellular, and molecular data. Anonymized data will be available to the research community upon validation.
Use data to identify and understand healthy and disease pathways that are activated in a particular cell type in a particular subgroup of patients.
Create a set of maps used to classify and locate different cell types and interstitial components. The atlas will help define disease subgroups and identify cells, pathways, and targets for novel therapies.
It is expected that these resources will seed future partnerships, ancillary studies, investigator-initiated endeavors, and industry collaborations.
One of the unique aspects of the KPMP is our commitment to involving patients in every facet of the project. Our patient advocates are active participants in working groups, face-to-face meetings, and ad hoc teams, tackling issues such as community engagement, biopsy safety, ethics, and data sharing strategies. They bring their unique perspectives to every discussion and provide vital project input during patient panels at each face-to-face meeting.
To provide a community resource for advancing research in this area, all KPMP activities must meet rigorous sharing and quality control standards. Given the risk of complications from a biopsy, the KPMP will hold ethical and participant safety considerations paramount. The KPMP will work closely with participants to ensure that their viewpoints, priorities, and preferences inform all aspects of the project.
All of the KPMP activities will be overseen by a Data and Safety Monitoring Board (DSMB) constituted by the NIDDK that will focus on participant safety, study burden, and scientific validity of the clinical data; and an External Expert Panel (EEP) constituted by the NIDDK that will focus on the overall scientific progress and direction of the KPMP.
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