Kidney Precision Medicine Project

ConditionsAcute Kidney Failure Acute Kidney Insufficiency Acute Renal Failure Acute Renal Injury Acute Renal Insufficiency Kidney Failure, Acute Kidney Insufficiency, Acute Renal Failure, Acute Renal Insufficiency, Acute Chronic Kidney Diseases Chronic Kidney Insufficiency Chronic Renal Diseases Chronic Renal Insufficiency Kidney Insufficiency, Chronic Type 1 Diabetes (T1D)

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorIcahn School of Medicine at Mount Sinai

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Use of glucose-lowering therapy (insulin or oral or other subcutaneous agents)

International Classification of Diseases (ICD) 9/10 diagnostic code for diabetes

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

Disqualifiers

Under 18 years of age

Severe allergy to iodinated contrast

Pregnancy

Transplant recipient (includes solid transplant and bone marrow)

Trial population

The KPMP will focus on participant populations that account for large proportions of the public health burden of acute and chronic kidney diseases as evidenced by research and federal data. For CKD, 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. For AKI, 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. The rationale for including this special AKI population is that AKI often occurs early in the clinical course of conditions like sepsis, major surgery and trauma.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Kidney Biopsy
Procedure/Surgery
A kidney biopsy is a procedure that involves taking a small piece of kidney tissue for examination with a microscope. A licensed health care provider will perform a kidney biopsy.
MRI
Other intervention
Images will be acquired using 3.0T whole body scanner. The participant will undergo a series of sequences (e.g., BOLD, diffusion-weighted, ASL MRI, native T1, and fat fraction sequences). The participant will receive 20 mg of IV furosemide as a bolus. BOLD MRI sequences will be repeated 15 minutes after furosemide administration. ASL sequences are acquired using investigational protocols that are not FDA-approved. Siemens machines will use Body ASL PCASL Perfusion WIP 1023, Phillips will use Body ASL 2D PCASL Perfusion software, and GE machines will use Body ASL PCASL Perfusion software.
Retina Scan
Other intervention
Fundus photography, fluorescein angiography, optical coherence tomography, optical coherence tomography angiography, and ophthalmologic exam and history will take place during one retina study visit. The retina visit will take place up to 6 weeks prior to the KPMP kidney biopsy OR up to 8 weeks post-biopsy.

Treatment groups

1,000 Participants

are divided into 4 treatment groups

Group A: Acute Kidney Injury Cohort1 intervention

Group B: Chronic Kidney Diseases Cohort3 interventions

Group C: Type 1 Diabetes (T1D)3 interventions

Group D: Diabetes Mellitus-Resistant (DM-R)2 interventions

Trial outcomes

Primary outcomes

Biopsy-related outcomes

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.

Time frame

Immediately after the procedure for up to 6 months

Kidney disease progression outcomes

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)

Time frame