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American Diabetes Association 2019

Highlighting Links Between Kidney, CV Disease in Diabetes

Mary Caffrey
The connections among diabetes, cardiovascular (CV) disease, and kidney failure have been a theme of the 79th Scientific Sessions of the American Diabetes Association, which featured a joint session with the American Society of Nephrology.
Precision Medicine in Diabetes and Kidney Disease
At the ADA/ASN joint session, Alice Cheng, MD, FRCPC, of the University of Toronto, said that diabetes medicine for many years took a “one-size-fits-all” approach. As recently as 2009, the guidelines had minimal options: metformin, basal insulin, sulfonylureas, and intensive insulin.

Now, there are multiple options and physicians can be more precise, she said. Diabetes is not where oncology is in the use of biomarkers to match treatments with patients based on individual characteristics, but it’s moving in that direction.

More work on the genetics of diabetes is allowing researchers to hone in on variables such as insulin deficiency, insulin resistance, or whether diabetes is obesity related or age related.

“In diabetic kidney disease, this is clearly an area of interest,” Cheng said. Use of biomarkers and data integration will eventually allow better risk stratification—and when drugs are tested, researchers will be able to “identify those who will respond the best.”

She outlined how work by the Berthier research group has led to findings about the role of JAK1/JAK2 inflammation in the progression of kidney disease, and in turn this led to phase 2 findings that JAK1/JAK2 inhibition with baricitinib decreased albuminuria in patients with T2D and diabetic kidney disease.

This kind of work involves the “omics,” as in the proteomics, genomics, and more—and there may be more than one pathway toward a target, depending on the patient. It all starts with tissue, and Cheng said this is a key issue, because while studies show patients are willing to share samples of blood and tissue to create data banks, they have some concerns and many want results back.

In the future, clinical trial designs may look very different based on this type of work, she said. “There will be many therapeutic options in the future,” and when considering the needs of an individual, “We want to capture the diagnostics and patient preferences of course, and ultimately fit the right drug for the right stage.”

“We really require early engagement of stakeholders for this to be successful,” she said.

Inflammation in Kidney Disease
Also at the ADA/ASN session, Aruna Pradham, MD, MPH, MSc, of Harvard and Brigham and Women’s Hospital, discussed the CANTOS trial for canakinumab in atherosclerotic cardiovascular disease and asked, “What does the CANTOS trial tell us about inflammation and diabetes risk—and these 2 connected pathways?”

Pradham talked about the role of C-reactive protein (CRP), which is a blood test marker for inflammation in the body. “Inflammation is a consistent predictor a year before one develops a myocardial infarction,” she said, so the thinking was that treating patients with a history of high CRP would prevent events.

Inflammation as a marker, especially for patients with CKD, turned out to be extremely important. Among patients in CANTOS with CKD (estimated glomerular filtration rate <60 cc/min/1.73 m2), those taking canakinumab saw an 18% reduction in major adverse vascular events, and the benefits were greatest among those whose CRP was greatly reduced.

“Independent of other risk factors, these data suggest the signal is real,” she said.

Those with high CRP and high levels of low-density lipoprotein cholesterol had the worst outcomes, so Pradman suggests a dual therapy to treat both conditions is needed.

Understanding the Role of Uric Acid
Diana Jalal, MD, a nephrologist at the University of Iowa concluded the ADA/ASN session by discussing  conflicting results from trials involving uric acid. High levels of uric acid are seen in kidney disease, and hyperuricemia is linked to both cardiovascular and kidney disease, with strong associations with heart failure and obesity.

“The data do suggest a link between hyperuricemia and outcomes in patients with diabetes and chronic kidney disease,” she said, and thus, lowering uric acid may improve outcomes.

However, Jalal reviewed trials and found that studies that showed lowering uric acid led to better outcomes were not adequately powered and could not be replicated, and “None were designed to evaluate hard outcomes in patients with DKC and type 2 diabetes.”

More work is needed to understand whether the elevation of uric acid “is a manifestation of disease,” she said.

 
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