Kidney Precision Medicine Project (KPMP)

General Description

KPMP is a prospective cohort study with a focus on the use of deep molecular phenotypes of kidney biopsies to develop new disease ontologies and treatments for acute kidney injury (AKI) and chronic kidney disease (CKD). Participants with AKI or CKD are recruited from recruitment sites during clinical care encounters and from electronic resources. Baseline and longitudinal biospecimens, demographic, clinical, and laboratory data are collected. Kidney tissue is obtained from each participant for the purposes of conducting molecular phenotyping and clinical diagnoses. While diagnoses and interpretations will be provided to the participant’s caregiver, no treatment interventions are provided by KPMP.

For information on available data: https://www.kpmp.org/available-data

For information on KPMP’s Kidney Tissue Atlas: https://atlas.kpmp.org/

For information on collaborating with KPMP: https://www.kpmp.org/collaboration

Objectives

The primary objective of the KPMP study is to better understand the mechanisms of AKI and CKD to facilitate identification of drug targets and pathways to individualized care for people with AKI and CKD.

Outcome Measure

Biopsy-related outcomes:

• Biopsy-related complications will be collected 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:

• Longitudinal change in estimated glomerular filtration rate
• Longitudinal change in urine albumin excretion

Other outcome measures:

• All-cause mortality
• Cardiovascular events
• New AKI events after KPMP enrollment
• Hospital admissions and discharge diagnoses after KPMP enrollment
• Duration of AKI
• Recovery from AKI
• ICU admission
• Need for dialysis
• Length of hospital stay

Criteria

Inclusion criteria for CKD participants:

• Diabetic Kidney Disease (DKD)
• Diagnosis of diabetes mellitus (type 1 or 2)
• Evidence of persistent kidney damage
• Hypertension-associated CKD (H-CKD)
• Diagnosis of hypertension (HTN)
• Evidence of persistent kidney damage

Inclusion criteria for AKI participants:

• Baseline estimated glomerular filtration rate greater than 45mL/min/1.73m2
• Elevated/Index serum creatinine (greater than or equal to 1.5 times Baseline serum creatinine
• AND at least one of the following:
• A repeat serum creatinine within 48 hours of Elevated/Index serum creatinine, showing a further increase of 0.3 mg/dL
• Positive kidney injury urine biomarker
• Urine microscopy suggestive of acute tubular necrosis defined as a urine microscopy score of greater than or equal to 2

Exclusion Criteria:

• Non-English language
• Less than 18 years of age
• Severe allergy to iodinated contrast
• Pregnancy
• Transplant recipient
• Additional vulnerable individuals
• 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-DKD
• Kidney infection, perirenal infection, or cutaneous infection that compromised the kidney
• Chronic anticoagulation
• Inability to withdraw aspirin, clopidogrel, cilostazol, or similar anti‐platelet agents for at least 7 days prior to biopsy
• Blood pressure of more than 160 mmHg systolic or 100 mmHg diastolic
• Ventilator-dependent patient
• Hypotension or any pressor support requirement at screening or biopsy visit
• Any other condition where the biopsy cannot be performed safely
• Unwilling to receive blood transfusion if needed
• Kidney depth more than 13 cm
• Kidney size less than 8 cm
• Solitary or single functioning kidney
• Evidence of urinary tract obstruction or hydronephrosis
• Multiple bilateral kidney cysts
• Any other imaging abnormality
• International Normalized Ratios (INR) greater than 1.4
• Platelet count less than 100,000/uL
• Hemoglobin less than 9g/dL

Outcome

The Kidney Precision Medicine Project (KPMP) is an ambitious, multi-year project funded by the NIDDK with the purpose of understanding and finding new ways to treat chronic kidney disease (CKD) and acute kidney injury (AKI). Together with our patient representatives, researchers, and clinicians, the KPMP is committed to meet the goals of the study and the needs of the kidney disease community.

The first two years of KPMP were dedicated to creating resources and processes that would support the project and kidney disease community long-term. All KPMP developed protocols, informed consent forms, manuals of operations (MOPs), policies, fact sheets, clinical data dictionary and codebook, and other documents are publicly available on the KPMP website www.kpmp.org/for-researchers. State of the art tissue analysis technology protocols are posted to the KPMP workspace in protocols.io www.protocols.io/workspaces/kpmp. Our software tool coding, and kidney specific ontologies are publicly available in the KPMP GitHub space github.com/KPMP.

Study participant enrollment began in 2019. KPMP collects many different types of data from participants www.kpmp.org/available-data. De-identified clinical, pathology, blood urine and stool biomarker, and tissue analysis data are made available publicly online after the data have been quality checked, cleaned, and have gone through a process to ensure participant confidentiality is maintained. This data can be downloaded for use from the KPMP Atlas Repository atlas.kpmp.org/repository. The KPMP Atlas atlas.kpmp.org/ has several tools to allow users to visualize and work with KPMP data. Many other data files are available for use after signing a Data Use Agreement. KPMP participants can securely access and view their own biopsy images through a KPMP built Participant Portal.

The kidney tissue, blood, urine and stool participant samples are stored in a central repository. Kidney tissue samples are shared with researchers within KPMP after their analysis technology has been internally approved. Blood, urine and stool samples are accessible to the researcher community through a KPMP Ancillary Study www.kpmp.org/ancillary-studies. KPMP values collaboration has set up streamlined processes for different stakeholders to work with KPMP www.kpmp.org/collaboration.