Kidney Precision Medicine Project
Overview
- Phase
- Not Applicable
- Intervention
- Kidney Biopsy
- Conditions
- Acute Kidney Failure
- Sponsor
- Icahn School of Medicine at Mount Sinai
- Enrollment
- 1000
- Locations
- 15
- Primary Endpoint
- Biopsy-related outcomes
- Status
- Recruiting
- Last Updated
- 18 days ago
Overview
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.
Investigators
Jonathan Himmelfarb
Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •Chronic Kidney Disease Subjects Inclusion Criteria Diabetic kidney disease (DKD)
- •Diagnosis of diabetes mellitus (type 1 or 2) established by at least one of the following criteria:
- •o Hemoglobin A1C greater than or equal to 6.5%, confirmed with a repeat test within the past year
- •o Fasting blood sugar greater than or equal to 126 mg/dL, confirmed with a repeat test within the past year
- •Use of glucose-lowering therapy (insulin or oral or other subcutaneous agents)
- •International Classification of Diseases (ICD) 9/10 diagnostic code for diabetes
- •Evidence of persistent kidney damage, manifest as any of the following present on at least two clinic assessments prior to enrollment and at least 3 months apart and excluding people with acute medical illnesses and changing kidney function:
- •Estimated glomerular filtration rate 30-59 mL/min/1.73m2 or
- •Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73m2 with urine albumin excretion greater than or equal to 30 mg/g creatinine (or mg/day) or
- •Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73m2 with urine protein excretion greater than or equal to 150 mg/g creatinine (or mg/day)
Exclusion Criteria
- •Under 18 years of age
- •Severe allergy to iodinated contrast
- •Pregnancy
- •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)
- •Safety Exclusion Criteria:
- •Potential participants will be excluded if the risk of kidney biopsy is considered too high by either the clinicians caring for the potential participant or the investigators at the RS.
Arms & Interventions
Acute Kidney Injury Cohort
The focus will be on acute intrinsic non-glomerular disease, primarily on acute tubular necrosis (ATN).
Intervention: Kidney Biopsy
Chronic Kidney Diseases Cohort
High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD).
Intervention: Kidney Biopsy
Chronic Kidney Diseases Cohort
High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD).
Intervention: MRI
Chronic Kidney Diseases Cohort
High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD).
Intervention: Retina Scan
Type 1 Diabetes (T1D)
Clinical diagnosis of Type 1 diabetes without evidence of other diabetes types (monogenic, secondary to pancreas disease, etc.) and has or is at risk of CKD.
Intervention: Kidney Biopsy
Type 1 Diabetes (T1D)
Clinical diagnosis of Type 1 diabetes without evidence of other diabetes types (monogenic, secondary to pancreas disease, etc.) and has or is at risk of CKD.
Intervention: MRI
Type 1 Diabetes (T1D)
Clinical diagnosis of Type 1 diabetes without evidence of other diabetes types (monogenic, secondary to pancreas disease, etc.) and has or is at risk of CKD.
Intervention: Retina Scan
Diabetes Mellitus-Resistant (DM-R)
Diabetes Mellitus-Resistant: 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.
Intervention: Kidney Biopsy
Diabetes Mellitus-Resistant (DM-R)
Diabetes Mellitus-Resistant: 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.
Intervention: Retina Scan
Outcomes
Primary Outcomes
Biopsy-related outcomes
Time Frame: 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.
Kidney disease progression outcomes
Time Frame: Through study completion (up to 10 years, depending on enrollment date of participant)
Longitudinal change in estimated glomerular filtration rate (eGFR): * Primary composite longitudinal outcome, defined by any of the following: * ESRD, defined as initiation of maintenance dialysis or kidney transplantation * Sustained decline in eGFR by 40% or more from baseline * Individual components of the primary composite outcome * Slope of eGFR change (from baseline to the latest value)