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Kidney Precision Medicine Project focused on expanded use of biopsies
In 2016, the National Institutes of Diabetes and Digestive and Kidney Diseases at the NIH launched the Kidney Precision Medicine Project. Nephrology News & Issues interviewed Paul L. Kimmel, MD, FASN, MACP, FRCP, a senior advisor in the division of kidney, urologic and hematologic diseases at the National Institutes of Diabetes and Digestive and Kidney Diseases and a clinical professor of medicine at George Washington University, on the progress of the project.
NN&I: Can you summarize the long-term goals of the Kidney Precision Medicine Project (KPMP)?
Paul L. Kimmel, MD, FASN, MACP, FRCP: Recent advances in multi-scale interrogation of human tissue and single cells have set the stage for precision medicine to be applied to kidney disease. The objectives of the KPMP are to ethically obtain and evaluate human kidney biopsies from participants with [acute kidney injury] AKI or [chronic kidney disease] CKD, create a kidney tissue atlas, define disease subgroups and identify critical cells, pathways and targets for novel therapies.
Specifically, the KPMP aims to develop or facilitate:
- a public resource – Establish a publicly available data hub with clinical, imaging, cellular and molecular data. Anonymized data will be available to the research community upon validation;
- kidney tissue atlas – Create a set of maps used to classify and locate different cell types and interstitial components. The atlas will help define disease subgroups and identify cells, pathways and targets for novel therapies;
- state/transition markers – Identify a set of cellular and molecular markers that classify cells as healthy, injured, activated or undergoing recovery via adaptive or maladaptive repair;
- disease subgroups – Use all available data, including the kidney tissue atlas, to define participant subgroups and allow for clinical stratification into distinct endophenotypes;
- molecular pathways – Use data to identify and understand healthy and disease pathways that are activated in a particular cell type in a particular subgroup of participants; and
- biomarkers – Discover a set of subgroup and pathway biomarkers; ideally, plasma or urine protein/antibody pairs, but could be urinary exosomes, miRNA, epigenetic marks, etc.
NN&I: How much money will the NIDDK dedicate to this project?
Kimmel: It will be at least $7.5 million per year for 5 years.
NN&I: What kind of small business programs will the project be supported by?
Kimmel: The NIDDK has invited small businesses to apply for grants under the Small Business Innovation Research and Small Business Technology Transfer programs. Program announcements were issued with the objective of encouraging small businesses to address the technological needs of the KPMP. Proposed technologies are expected to improve the safety of the human kidney biopsy or enhance interrogation of human kidney tissue, thus ensuring that the kidney biopsy yields useful research or clinical information.
NN&I: What are the timelines associated with the project?
Kimmel: The study began in September 2017. KPMP has a first 2-year phase in which progress and satisfaction of milestones will be assessed by the NIDDK and external experts. A second phase will last 3 years. NIDDK envisions the project will continue over time, providing new insights into clinical subtypes and knowledge regarding pathways of injury and repair, as well as identification of targets for medical therapies. The availability of future resources will play a key role in NIDDK’s planning regarding subsequent research opportunities.
NN&I: Have sites been identified to date?
Kimmel: We have nine central hub sites, six recruitment sites and five tissue interrogation sites. The complete list is at kpmp.org/for-researchers/for-researchers- kpmp-study-sites.
NN&I: Have any ethical issues been raised over obtaining human kidney biopsies?
Kimmel: This is an important issue linked to the success of the KPMP. This program is groundbreaking in that the consortium will be studying patients and clinical syndromes that have not been assessed by renal biopsies in the past, including patients with diagnoses such as acute tubular necrosis, hypertensive kidney disease and diabetic kidney disease. Consortium researchers think much information will be learned about clinical subtypes, with different disease courses and perhaps responses to therapy. Patient participation in follow-up over time will be important. Perhaps most importantly, patients will be undergoing kidney biopsies – procedures which entail more than minimal risk for altruistic purposes. The consortium cannot promise participants that the biopsies will improve or even affect their medical care at this point, although benefits may be outlined as the study proceeds.
Because of these considerations, the NIDDK has worked with the kidney research and clinical communities to develop a framework in which these biopsies can be obtained safely and ethically. The workshop that preceded the initiation of the KPMP focused on maximizing patient safety and ensuring high ethical standards. The attendees concluded that biopsies could be performed under the circumstances of the proposed research, as long as informed consent procedures ensured clarity and transparency regarding the balance of risks and benefits.
The scientific and ethical work of the consortium has been enhanced by the participation of an external expert panel (EEP), composed of researchers with basic science, clinical and ethical expertise. Members of the EEP have participated in meetings of the consortium and have provided insight regarding study progress.
As the KPMP started its work, a community engagement working group (CEWG) – composed largely of people with kidney disease, with a variety of experiences, including undergoing kidney biopsies and receiving kidney transplants – advised the consortium regarding the feasibility, safety and ethical implications of proposed study procedures. The CEWG produced the first draft of the informed consent documents and has worked with the consortium to obtain no fault insurance for participants in the study. CEWG members participate in all face-to-face meetings of the steering committee and have contributed to vigorous dialogue with the researchers. In addition, to ensure safety and ethical conduct of the study, besides institutional review board oversight, a data and safety monitoring board has been constituted by the NIDDK, with expertise in ethics, nephrology and biostatistics.
References:
https://grants.nih.gov/grants/guide/pa-files/PA-16-451.html
https://grants.nih.gov/grants/guide/pa-files/PA-16-452.html
www.niddk.nih.gov/research-funding/research-programs/kidney-precision-medicine-project-kpmp