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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.
From sessions on treatment choices for cardiorenal protection, to multiple clinical trials on cardiovascular and renal outcomes, to the choice of a leading researcher in diabetes and renal care to deliver the annual Bierman Lecture—it’s been hard to miss a theme of cardiorenal care at the 79th Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, California.

Researchers have known for years that people with diabetes face higher cardiovascular risk—they are up to 4 times more likely to die from heart disease. It is also well-known that diabetes is linked to kidney failure; about 30% of those with type 1 diabetes (T1D) and 10% to 40% of those with type 2 diabetes (T2D) will progress to this stage.

But, as Peter Rossing, MD, DMSc, of the Steno Diabetes Center in Copenhagen, Denmark, said Monday after accepting the Edwin Bierman Award, more work is being done to understand the functional links between chronic kidney disease (CKD) and cardiovascular disease, and how to treat them.

“Diabetes, cardiovascular disease, and renal disease—that’s an unfortunate triad,” he said. CKD, in particular, “is a disease multiplier,” because of its effect on life expectancy. A 30-year-old with diabetes and CKD can expect to lose 15 to 16 years of life due to the complications, Rossing said.

This work is informing guidelines for clinical care, he said, and in 2019 the ADA has issued 2 guidelines updates based on the DECLARE and CREDENCE trials, with the most recent one coming June 3, 2019.

The wave of cardiovascular outcomes trials (CVOTs) for sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists produced secondary outcomes that show these classes have cardiorenal benefits; drugs in the SGLT2 class, in particular, are now being studied in dedicated renal outcomes trials.

Mechanisms for these findings were not understood at first, Rossing said. “How can it be that that these glucose-lowering agents protect the kidney and the heart? It must not be about glucose—it must be about something else.”

And it is likely that lowering uric acid and volume contribute to these results, he added.

Whatever the reason, having new options is important, Rossing said, because data show relying on lifestyle changes alone for people with diabetes to reach targets in glycated hemoglobin, blood pressure, and cholesterol won’t work.

Both in the Bierman Lecture and at length the day prior, during a session between ADA and the American Society of Nephrology (ASN), Rossing discussed work on blocking the hormone aldosterone, given the increased understanding of its role as an independent facilitator of kidney damage. He called attention to 2 ongoing trials, FIDELIO and FIGARO, that are investigating, respectively, whether the compound finerenone can (1) reduce the progression of kidney disease and (2) cardiovascular mortality and morbidity in patients with T2D and diabetic kidney disease.

Rossing also discussed the importance of biomarkers. “Many of the markers in kidney disease are also good markers in cardiovascular disease,” he said.

He discussed the role of inflammation, oxidative stress, uric acid, as well as new work that could signal gut microbiota as a potential treatment target. Studies of adipose tissue are revealing inflammatory markers, but said, “I think we need a lot more data in this area to know how to use adipose tissue as a marker or target.”

On the horizon, Rossing is working on the PROMINENT trial, which is looking at pemafibrate to treat triglycerides and reduce cardiovascular events.



 
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