Kidney Precision Medicine Project (KPMP) - COVID-19 Protocol

• Conditions: Sars-CoV-2 Infection; Acute Kidney Failure; Acute Renal Failure; Renal Failure, Acute; Acute Kidney Insufficiency; Acute Renal Injury; Kidney Insufficiency, Acute; Renal Insufficiency, Acute; Covid19; Kidney Failure, Acute

• Registration Number: NCT05384899
• Lead Sponsor: University of Washington

Brief Summary

Since its inception, KPMP has developed sophisticated protocols for collection and analysis of human kidney tissue, and for collection of biofluids. Members of the consortium have wide-ranging expertise in conducting clinical studies, processing kidney tissue, advanced structural and molecular analysis and complex bioinformatics analysis, which will be used to leverage effectively as a group to better understand kidney disease.

This joint protocol aims to synergize the COVID-19 study efforts of KPMP academic research centers, to collectively study COVID-19, including its renal presentation using kidney tissue and/or biofluids from patients suffering from COVID-19. This will increase the breadth and depth of data available to the public to expedite discoveries, identify therapeutics, and improve outcomes for patients with COVID-19. It will additionally bring the expertise of KPMP investigators to bear against this pandemic.

Detailed Description

The COVID-19 pandemic has drastically altered life globally and killed thousands since its emergence in December of 2019. Unfortunately, the global toll will only continue to increase. Sars-CoV-2, the virus responsible for COVID-19, may directly infect kidney cells, with currently known clinical manifestations of Acute Kidney Injury or nephrotic range proteinuria. Individuals with chronic kidney disease (CKD), diabetes and hypertension are at increased risk of severe COVID-19 infections.

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.

Since its inception, KPMP has developed sophisticated protocols for collection and analysis of human kidney tissue, and for collection of biofluids. Members of the consortium have wide-ranging expertise in conducting clinical studies, processing kidney tissue, advanced structural and molecular analysis and complex bioinformatics analysis, which will be used to to leverage effectively as a group to better understand kidney disease.

This joint protocol aims to synergize the COVID-19 study efforts of KPMP academic research centers, to collectively study COVID-19, including its renal presentation using kidney tissue and/or biofluids from patients suffering from COVID-19. This will increase the breadth and depth of data available to the public to expedite discoveries, identify therapeutics, and improve outcomes for patients with COVID-19. It will additionally bring the expertise of KPMP investigators to bear against this pandemic.

Study Timeline

• Study Start: 2021-06-15
• Study First Submitted: 2021-06-16
• Status Verified: 2022-05
• Study First Submitted QC: 2022-05-18
• Last Update Submitted: 2022-05-18
• Study First Posted: 2022-05-20
• Last Update Posted: 2022-05-20
• Primary Completion: 2022-06-30
• Study Completion: 2022-10-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Any potential participant meeting any one of the general or safety exclusion criteria will not be eligible for enrollment in the KPMP COVID-19 Substudy. Exclusion criteria include non-transient conditions that would not allow for enrollment in the main KPMP study.

Determined at time of Eligibility Assessment prior to consent:

• Non-English or Spanish language
• Less than 18 years of age
• Severe allergy to iodinated contrast
• Transplant recipient (kidney or non-kidney, including solid organ and bone marrow transplantation)
• Additional vulnerable individuals (incarcerated, institutionalized, or otherwise unable to participate in the study)
• Inability to provide informed consent or obtain surrogate consent from a legally authorized representative (LAR)
• Unwilling to receive blood transfusion (if needed)
• Baseline eGFR less than 15 ml/min/m2

If known at the time of enrollment, or determined by kidney ultrasound before the biopsy procedure (may be the same day as the biopsy procedure)

• Kidney size less than 8 cm (percutaneous biopsies only)
• Solitary or single functioning kidney
• Evidence of urinary tract obstruction or hydronephrosis
• Multiple bilateral kidney cysts

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Observational: Biorepository of Blood and Urine Specimens	Date of hospital admission through day 28 or hospital discharge [whichever is sooner]. Three month follow-up visit.	Establish a biorepository of blood and urine specimens from patients with AKI in the setting of COVID-19 disease. For COVID-19 positive patients, in-hospital blood and in-hospital urine are collected within 24 hours of hospital admission. At a follow up visit 3 months after hospital admission, participants will be asked to participate in further bio-specimen collection and/or consent to participate in the main KPMP protocol.
Observational: Biopsy-Related Outcomes	During hospital visit or through study completion if participant wants to enroll into KPMP (up to 10 years, depending on enrollment date of participant)	For patients who are scheduled for a clinically indicated kidney biopsy in the setting of COVID-19 disease, a segment of remnant tissue may be obtained. We will access the participant's pathology report and store images from their kidney biopsy in the KPMP Digital Pathology Repository. If there is no residual tissue available for analysis, the images will be stored in the KPMP Digital Pathology Repository.
Observational: Longitudinal Follow-Up for KPMP Protocol	Through study completion (up to 10 years, depending on enrollment date of participant)	At a follow-up visit 3 months after hospital admission, participants will be asked to participate in further biospecimen collection and/or consent to participate in the main KPMP protocol.
Observational: Phenotypic Clinical Information	Date of hospital admission through day 28 or hospital discharge [whichever is sooner]	Collection of basic contact information, clinical phenotypic inpatient data relevant to kidney complication of COVID-19 infection, demographics, and linkage to external databases (NDI, USRDS, etc).

Trial Locations

Locations (4)

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

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

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

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