A panel of four experts discussed new methods and novel technologies being used to advance therapeutics for people living with diabetic kidney disease (DKD) at the Scientific Sessions.
New Tools to Examine Diabetes-Related Kidney Disease, presented Sunday, June 27, can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.
Jonathan Himmelfarb, MD, discussed a National Institutes of Health initiative to create an “atlas” of dynamic 3D representations of the kidney. The Kidney Precision Medicine Project (KPMP) aims to further the understanding of the mechanisms of DKD, hypertensive kidney disease, and acute kidney injury (AKI) while creating a pathway to new treatment options.
“The KPMP is all about using the kidney biopsy, which is an old tool, to understand kidney disease in a new way by almost turbocharging the information that we get,” said Dr. Himmelfarb, Director, Kidney Research Institute; Co-Director, Center for Dialysis Innovation; and Professor of Medicine, Adjunct Professor of Bioengineering, and the Joseph W. Eschbach MD Endowed Chair in Kidney Research, University of Washington.
Through the KPMP, biopsy information is combined with clinical presentation, digital pathology, tissue interrogation, and omics technologies to define the drivers of clinical outcomes and explain mechanism-based disease types.
“In the future, what we would hope is that you might have three different patients with longstanding diabetes, the same level of albuminuria, the same estimated glomerular filtration rate. But from this study we’d be able to say, ‘These are all individuals and what’s going on in the kidneys of these individuals is very different,’” Dr. Himmelfarb said.
True precision medicine is administering the right treatment to the right patient at the right time, he noted.
“The way to get there is by identifying the critical cells, pathways, and targets that will lead us toward these novel therapies,” he said.
Since the KPMP began four years ago, 42 major academic medical centers and 100-plus active patient participants have joined the effort. More than 90 biopsies have been performed and more than 1,500 de-identified data sets have been shared in the public domain. Additional file sets will be added to the online repository in the coming months and a patient portal is in development. Dr. Himmelfarb anticipates nephropathologists and clinicians will use the KPMP atlas to better diagnose and treat patients.
Early analysis of the data collected indicates a “pathology convergence” in biopsies with AKI (from sepsis or hypotension, for example) and biopsies with chronic injury (from metabolic changes due to diabetes or hypertension, for example), he said.
“In many of the chronic kidney disease biopsies, we’re seeing acute tubular changes that you might have called AKI. And conversely, we’re seeing what you would call chronic changes in the biopsies of individuals with AKI,” Dr. Himmelfarb said. “We’re seeing that same kind of convergence with the omics data, the tissue interrogation, at the level of molecular pathways.”
Another speaker, Laura Barisoni, MD, Professor of Pathology and Medicine, Director, Renal Pathology Service, and Co-Director, Division of Artificial Intelligence & Computational Pathology, Duke University, explained what she called the “digital nephropathology ecosystem” while making the case that research kidney biopsies are more important than ever.
“Encoded in the kidney tissue are extractable information that can enhance our ability to characterize and classify kidney disease into functional categories,” Dr. Barisoni said. “Computational pathology approaches operating in the new digital pathology ecosystem play a central role in this process.”
The three-step process begins with an analog-to-digital conversion of a glass slide to a whole-slide image. In the knowledge extraction phase, human or artificial intelligence transforms the whole-slide image into meaningful data through data transcription and translation, and visual assessment.
“The digital pathology-derived knowledge is the input for the following phase, which is the knowledge integration phase where it is useful with other domains (input) and becomes actionable intelligence for patients’ care,” Dr. Barisoni continued.
Yuliya Lytvyn, PhD, MD(C), Division of Nephrology, University Health Network, University of Toronto, Canada, provided an overview of how hemodynamics, inflammation, and fibrosis are affected by hyperglycemia in patients with type 1 and type 2 diabetes.
“Diabetes duration changes renal hemodynamics from afferent dilation early in the disease to efferent constriction with chronic hyperglycemia,” she explained. “This allows a great opportunity for us to intervene pharmacologically with SGLT2 (sodium glucose co-transporter 2) inhibitors at the afferent end and with RAAS (renin-angiotensin-aldosterone system) inhibitors at the efferent end.”
These therapies have been shown to improve mitochondrial function and reduce hypoxia, inflammation, and fibrosis, she continued.
Petter Bjornstad, MD, Assistant Professor of Pediatrics and Medicine, and Boettcher Investigator, University of Colorado, discussed the evolving role of imaging in clinical diabetic kidney disease research.
Magnetic resonance imaging, nuclear magnetic resonance imaging, and positron emission tomography scans provide comprehensive and granular interrogation of kidney bioenergetics, hemodynamic function, and tissue characteristics without kidney biopsies, he said.
Clinical trials are increasingly incorporating functional kidney imaging as part of their outcomes, but this approach should not replace kidney biopsies, Dr. Bjornstad continued. Imaging and biopsies provide distinct yet complementary data.
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