Kidney Precision Medicine Project - Technology Development and Validation (R41/R42)

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. Community feedback indicates that—despite significant effort from industry and academia—development of pharmacologic therapies for AKI and CKD has been hampered by non-predictive animal models, the inability to identify and prioritize human targets, the limited availability of human kidney biopsy tissue, and a poor understanding of AKI and CKD heterogeneity [Kidney Research National Dialogue 2014; AKI Outcomes Meeting 2015; Kidney Precision Medicine Meeting 2016]. 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.

Recent advances in multi-scale interrogation of human tissue and single cells have set the stage for precision medicine to be applied to AKI and CKD. The objectives of the KPMP are to ethically obtain and evaluate human kidney biopsies from participants with AKI or CKD, create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways and targets for novel therapies. The KPMP will be made up of three distinct, but highly interactive activities:

1.  Recruitment Sites: recruit people with AKI or CKD for longitudinal cohort studies that include a research kidney biopsy (RFA-DK-16-026).

2.  Tissue Interrogation Sites: use and develop innovative technologies to analyze human kidney tissue (RFA-DK-16-027).

3.  Central Hub: aggregate, analyze and visualize all data and samples, and provide scientific, infrastructure and administrative support for the entire KPMP (RFA-DK-16-028).

The KPMP website will facilitate the sharing of all de-identified data and samples with the broader research community.

As technology has enabled the KPMP, so will technology needs emerge over its course. These needs, defined both by the KPMP investigators and the broader research community, may be met by research and development conducted by small businesses. Proposed technologies may be de novo or repurposed, so long as there is a substantial research and development component in kidney tissue. These include, but are not limited to:

• Biopsy technologies, including better imaging methods, that improve the safety profile and accuracy of the kidney biopsy.
• In vivo imaging of kidney structure, function, health/disease, fibrosis, or nephron endowment, etc., which may be useful for targeting kidney biopsy sites.
• Imaging or biopsy technologies that improve the utility of a kidney biopsy specimen for downstream interrogation.
• Technologies that provide immediate feedback on the size, composition, or quality of kidney biopsy specimens.
• Methods and reagents to preserve key analytes during collection and storage of kidney biopsy specimens and methods or reagents to extract these analytes from preserved specimens (i.e., frozen or formalin-fixed, paraffin-embedded archived tissue).
• Instrumentation or reagents that preserve key analytes or anatomical structures in a kidney biopsy specimen for downstream interrogation.
• Instrumentation or reagents for isolation of single-cells from a kidney biopsy specimen for downstream interrogation.
• Imaging or microscopy technologies for molecular or functional interrogation of a kidney biopsy specimen.
• Next generation tissue interrogation technologies that probe the structural, functional and molecular complexities of kidney tissue.
• Technologies that analyze single cells dissociated from kidney tissue, including high-throughput technologies.
• Technologies, including software, that classify and locate ('paint') different cell types, cell states (healthy, injured, dying, recovering, undergoing adaptive/maladaptive repair, etc.) and interstitial components (collagens, proteoglycans, signaling molecules, etc.).
• Technologies that identify cell, structural, and regional heterogeneity throughout the kidney biopsy, and allow for interrogation of compartments that are currently difficult to visualize (e.g., interstitium, glomerulus).
• Technologies that improve the diagnosis, staging, grading, prognosis, subgroup stratification, and drug effect prediction in AKI and CKD.

See Section VIII. Other Information for award authorities and regulations.