Background

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. Community feedback indicates that—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, and a poor understanding of AKI and CKD heterogeneity [Kidney Research National Dialogue 2014; AKI Outcomes Meeting 2015; Kidney Precision Medicine Meeting 2016].

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.

Approach

Recent advances in the multi-scale interrogation of human tissue and single cells have set the stage for precision medicine to be applied to AKI and CKD. The objectives of the KPMP are to ethically obtain and evaluate human kidney biopsies from participants with AKI or CKD, create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies.

The KPMP will be made up of three distinct, but highly interactive, activities:

  • Recruitment Sites recruit people with AKI or CKD for longitudinal cohort studies that include a kidney biopsy
  • Tissue Interrogation Sites develop and use innovative technologies to analyze human kidney tissue
  • The Central Hub is responsible for aggregating, analyzing, and visualizing all of the samples and data, and provides scientific, infrastructure, and administrative support for the entire project

Patient Involvement

One unique aspect of the KPMP is our commitment to patient involvement. The KPMP consortium involves patients in every facet of the project.

Our patient advocates are active participants in working groups, face-to-face meetings, and ad hoc teams, tackling issues ranging from ethics to data analysis strategies.

Timeline

It is anticipated that the KPMP will be conducted in stages:

STAGE 1

  • Optimize and validate tissue processing and interrogation methods
  • Establish common clinical protocols and cohort studies enrolling a small number of AKI or CKD patients
  • Assess the quality of phenotype data and biopsy protocols at each site
  • Begin work on the kidney tissue atlas
  • Optimize next-generation assays

STAGE 2

  • Small-scale proof of concept studies to determine if clinical and analytic pipelines are robust
  • Enrich the kidney tissue atlas
  • Implement next-generation tissue interrogation assays
  • Expand longitudinal cohort studies in initial AKI or CKD populations

STAGE 3

  • Expand to larger cohort studies (expected to occur in next project period)

Governance

To provide a community resource for advancing research in this area, all KPMP activities must meet rigorous sharing and quality control standards. Given the risk of complications from a biopsy, the KPMP will hold ethical and participant safety considerations paramount. The KPMP will work closely with participants to ensure that their viewpoints, priorities, and preferences inform all aspects of the project.

All of the KPMP activities will be overseen by a Data and Safety Monitoring Board (DSMB) constituted by the NIDDK that will focus on participant safety, study burden and scientific validity of the clinical data; and an External Evaluation Panel (EEP) constituted by the NIDDK that will focus on the overall scientific progress and direction of the KPMP.

Frequently Asked Questions

What is the Kidney Precision Medicine Project (KPMP)?

The Kidney Precision Medicine Project (KPMP) is an ambitious, multi-year project funded by the NIDDK with the purpose of understanding chronic kidney disease (CKD) and acute kidney injury (AKI).

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

  1. Ethically obtain and evaluate human kidney biopsies from participants with AKI or CKD
  2. Create a kidney tissue atlas
  3. Define disease subgroups
  4. Identify critical cells, pathways, and targets for novel therapies.

What is precision medicine?

Precision Medicine” means health care that puts the person at the center. Precision medicine is aimed at developing treatment plans that get the right treatment to the right patient at the right time.

What does the KPMP hope to do?

The KPMP hopes to make precision medicine possible for kidney diseases. KPMP will help scientists understand the kidney at a very detailed level.  KPMP scientists will make a map of the kidney to show important cells, regions, and disease pathways. Ultimately, KPMP research will find new markers and treatment targets that make personalized, effective, and safe treatments possible for kidney diseases.

What is chronic kidney disease (CKD)?

CKD means that the kidneys have become damaged over time, and they can’t filter blood like they should. This damage can cause wastes to build up in the body. CKD may get worse over many years and lead to kidney failure. Kidney failure is sometimes called end-stage kidney disease.

What is acute kidney injury (AKI)?

AKI is a sudden and short-term loss of kidney function. But, AKI can harm the kidneys and lead to CKD over time.

What is a kidney biopsy?

A kidney biopsy is when a doctor takes out a small piece of the kidney to look at under a microscope. The doctors who perform kidney biopsies are nephrologists (kidney specialists), interventional radiologists (specialists who perform procedures using imaging equipment), or surgeons (specialists who perform operations). A pathologist (a doctor who specializes in diagnosing diseases) examines the kidney tissue in a laboratory. The tissue is studied to understand how the kidney has been damaged, and what disease process could have caused that damage, so that appropriate treatment can be chosen.

In the KPMP, scientists will use the kidney biopsies to find new information about the mechanisms leading to acute and chronic kidney diseases. These studies will help doctors know the best way to treat a person’s kidney disease. The knowledge from this research will help answer important questions for people with kidney disease, such as:

  • What type of kidney disease do I have?
  • What will happen to me?
  • What can I do about it?

What are the benefits and risks of a kidney biopsy?

Benefits:

The kidney biopsy shows kidney injury. From a biopsy, the type of injury can be determined, as well as how extensive the injury is and whether the injury is likely to get better or continue to progress. The kidney biopsy will also help KPMP scientists create new tests to understand kidney disease. The tests will dive deeply into kidney cells, and spaces in-between cells, to create a “map” of the kidney. This map will help scientists find new genes, gene products, proteins, metabolic products, and other clues that will indicate how the kidney got injured and what may be done to repair the injury.

Risks:

Because a kidney biopsy involves putting a needle into the organ which cleans the blood, the most common complication is bleeding. Based on data published in the scientific literature, the overall rate of any bleeding complication is 12.5% or about 1 out of every 8 kidney biopsies. Most often, this is having blood visible in the urine (occurs in 1 out of every 25 kidney biopsies) or developing a swelling of blood (a bruise) next to the kidney (occurs in 1 out of every 10 kidney biopsies). Sometimes, people need a blood transfusion after kidney biopsy because of the bleeding (occurs in less than 1 out of every 50 kidney biopsies). Rarely, people need a procedure to stop bleeding (occurs in about 1 out of every 140 kidney biopsies). After a biopsy, people are asked to rest for a few hours and are monitored closely for any bleeding complications.

Infection is very rare after a kidney biopsy. Less than one out of every 200 people get an infection from a kidney biopsy. To treat infections, doctors typically prescribe medicines called antibiotics to fight the bacteria that are causing the infection.

Death related to kidney biopsy is exceedingly rare, but has been estimated to occur in 1 out of every 2,500 kidney biopsies.

How is the KPMP working to minimize kidney biopsy risks in study participants?

All kidney biopsies will be done by experienced doctors, nephrologists (kidney specialists), interventional radiologists (specialists who perform procedures using imaging equipment), or surgeons (specialists who perform operations) at the KPMP recruitment sites. The biopsies will be performed either with ultrasound to image the kidney throughout the procedure or direct view of the kidney for patients undergoing surgery. Patients who have had prior bleeding problems or other conditions that put them at higher risk of bleeding will not be eligible to participate.

What happens to the kidney sample?

In the KPMP, a pathologist will look at the kidney sample to look for signs of kidney disease. Then, the kidney sample will go to the KPMP research sites where scientists will study the tissue samples to better understand the structural and molecular make-up of CKD and AKI. This understanding will be used to create a “map” of the kidney that will help scientists find unusual genes, gene products, proteins, and other abnormal findings that could indicate the presence CKD or AKI. In addition, any clinically relevant biopsy results will be returned to the patient.