Kidney Precision Medicine Project

Recruiting

• Conditions: Acute Kidney Failure; Acute Renal Injury; Kidney Failure, Acute; Kidney Insufficiency, Acute; Renal Failure, Acute; Acute Renal Insufficiency; Chronic Kidney Insufficiency; Acute Kidney Insufficiency; Kidney Insufficiency, Chronic; Acute Renal Failure
• Interventions: Procedure: Kidney Biopsy

• Registration Number: NCT04334707
• Lead Sponsor: University of Washington

Brief Summary

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.

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 A poor understanding of AKI and CKD heterogeneity 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.

A number of research centers across the United States are collaborating to bring state-of-the-art technologies together to:

* Ethically obtain and evaluate kidney biopsies from participants with AKI or CKD

* Define disease subgroups

* Create a kidney tissue atlas

* Identify critical cells, pathways, and targets for novel therapies

The KPMP is made up of three distinct, but highly interactive, activity groups:

* Recruitment Sites: The recruitment sites (RS) are responsible for recruiting participants with AKI or CKD into the longitudinal study and performing the kidney biopsy.

* Tissue Interrogation Sites: The tissue interrogation sites (TIS) are responsible for developing and using innovative technologies to analyze the biopsy tissue.

* Central Hub: The central hub is responsible for aggregating, analyzing, and visualizing the generated data and providing scientific, infrastructure, and administrative support for the KPMP consortium.

Detailed Description

The Kidney Precision Medicine Project (KPMP) is a prospective cohort study, whose goal is to use deep molecular phenotypes of kidney biopsies, along with longitudinally collected clinical phenotypic data, in order to develop new disease ontologies, classification systems, and treatments for acute kidney injury (AKI) and chronic kidney disease (CKD). Since its inception, the KPMP has sought out and included substantive patient-representative feedback regarding disease experience, lack of innovation in new kidney disease therapies and patient tolerance for risk levels in balance with potential benefits both to the individual and society.

The KPMP Has publicly and operationally committed itself to always put participants and their best interests first and this foundational principle informs and undergirds every facet of the study. Both AKI and CKD are conditions that impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. The network will utilize state-of-the-art methods to perform molecular interrogation of the tissue and to link the molecular data to kidney structure and clinical information in the form of a kidney tissue atlas.

Molecular and imaging data derived from kidney tissue will be integrated with clinico-pathologic and genetic information, as well as other data derived from analyses of fluid biospecimens, including peripheral blood, urine, and stool. Using advanced analytics to integrate the data, KPMP will aim to define kidney disease subgroups in molecular terms by identifying critical cells, pathways and targets for novel therapies.

Patients with AKI or CKD will be recruited from clinical care encounters (e.g., clinic visits for CKD patients, hospitalization or emergency room visits for AKI patients) and from electronic resources (e.g., existing registries, electronic health records). All study procedures are designed to optimize participant safety and will be ethically conducted, ensuring subjects fully understand the scope of the study and any possible risks.

For each participant, kidney tissue will be obtained for molecular phenotyping and clinical diagnosis. The diagnostic interpretation will be returned to the participant's primary caregiver to inform clinical care, but no treatment interventions will be prescribed by the KPMP. In addition to kidney biopsy, the study will involve collection of baseline (time of biopsy) and longitudinal biospecimens (including urine, plasma, serum, DNA and stool) and demographic, clinical, and laboratory data. Participants will be followed through scheduled in-person and remote (telephone) study visits, as well as through periodic review of electronic health records.

Study Timeline

• Study Start: 2019-09-01
• Study First Submitted: 2020-03-23
• Study First Submitted QC: 2020-04-01
• Study First Posted: 2020-04-06
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-18
• Last Update Posted: 2022-05-19
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

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Exclusion Criteria

• Under 18 years of age
• Body Mass Index (BMI) greater than 40 kg/m2
• Allergy to iodinated contrast (any reaction)
• Pregnancy
• Malignancy - Receiving active chemotherapy or radiation to treat malignancy (except for nephrectomy tissue for reference and feasibility studies)
• Transplant recipient (includes solid transplant and bone marrow)
• Additional vulnerable individuals (incarcerated, institutionalized, or otherwise unable to participate in the study)
• Inability to provide informed consent
• Clinical diagnosis of kidney disease from an autoimmune disease, dysproteinemia, viral disease or glomerular disease other than DKD or H-CKD
• Unwilling to receive blood transfusion (if needed)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Acute Kidney Injury Cohort	Kidney Biopsy	The focus will be on acute intrinsic non-glomerular disease, primarily on acute tubular necrosis (ATN). KPMP will also include a special population of patients at risk for AKI or with early AKI captured by an open (surgical) kidney biopsy performed at the time of clinically indicated laparotomy.
Chronic Kidney Diseases Cohort	Kidney Biopsy	High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD). A special population of people with long-standing type 1 diabetes (more than 25 years) who remain free of clinically-evident DKD will also be included.

Primary Outcome Measures

Name	Time	Method
Kidney disease progression outcomes	Through study completion (up to 10 years, depending on enrollment date of participant)	Longitudinal change in urine albumin excretion defined by the following: -Change of Kidney Disease Improving Global Outcomes (KDIGO) albuminuria stage
Biopsy-related outcomes	Immediately after the procedure for up to 6 months	Biopsy-related complications will be collected by KPMP study staff using standardized case report forms. Clinical utility of the biopsy results will be assessed using standardized surveys of clinical providers, and participant-reported outcomes will be assessed using standardized questionnaires. Biopsy-related outcomes data will be collected around the time of the biopsy and within the six months following procurement of the kidney biopsy.

Trial Locations

Locations (8)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas at Southwestern; 🇺🇸 Dallas, Texas, United States

Columbia University; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Joslin Diabetes Center; 🇺🇸 Boston, Massachusetts, United States

Brigham & Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States