Excess sodium in heart cells may help explain heart damage linked to kidney disease

18 August 2026

People living with chronic kidney disease (CKD) have a significantly increased risk of developing heart problems, and cardiovascular disease remains the leading cause of death among people with CKD. Exactly how a diseased kidney goes on to damage the heart, however, has remained poorly understood.

Now, researchers from the William Harvey Research Institute at Queen Mary University of London, led by Professor Dunja Aksentijevic and working with international collaborators, have identified a possible culprit: a build-up of sodium inside heart cells.

The team directly measured sodium levels inside intact, beating hearts affected by chronic kidney disease, allowing them to observe changes at a much earlier stage than is usually possible.

They found that sodium begins to accumulate inside heart cells surprisingly early, before the heart develops classic signs of disease such as enlargement or reduced pumping ability. This increase was accompanied by significant changes in how the heart produces and uses energy, as well as its ability to relax properly between beats.

Dunja Aksentijevic, Professor of Cardiovascular Physiology and Metabolism at Queen Mary University of London and corresponding author of the study, said:

"One of the most unexpected findings was that sodium overload appeared before the classical structural features of heart disease. This suggests that metabolic dysfunction begins much earlier than previously recognised and may drive disease progression, rather than simply accompany it."

The researchers then investigated whether the sodium build-up could be reversed using dual SGLT 1 and 1 inhibitor sotagliflozin, a medicine that blocks proteins involved in transporting sodium and glucose.

They found that sotagliflozin rapidly reduced excess sodium inside heart cells and helped restore healthier energy metabolism. The effect was observed within just 20 minutes of exposing isolated hearts to the medicine and occurred only in hearts affected by the disease, with no similar effect seen in healthy hearts.

Professor Aksentijevic added:

"We were also surprised by how rapidly sotagliflozin lowered myocardial sodium. This indicates a direct, disease-selective action on the heart that cannot be explained by improvements in kidney function, blood glucose or circulating hormones."

The findings, published in Cardiovascular Research, suggest that excess sodium inside heart cells may not simply be a consequence of established heart disease. Instead, it could be an early driver of changes in the heart's metabolism and function.

Identifying these early changes could help researchers understand how cardiovascular complications develop in people with CKD and, in the future, identify opportunities to intervene before more permanent damage occurs.

The research builds on earlier work by Prof Aksentijevic at King's College London, which identified sodium inside heart cells as an important regulator of cardiac metabolism. This new study extends that understanding to chronic kidney disease, highlighting sodium handling within heart cells as a potential area for further research.

The findings also complement a related study published at the same time by the Aksentijevic research group, which examined heart disease associated with type 2 diabetes. In that study, sotagliflozin similarly helped restore heart energy metabolism and improve the heart's ability to relax. Together, the studies suggest that the cardiovascular effects of this class of SGLT inhibitor medicines may extend beyond its effects on blood glucose and involve direct changes to metabolism within the heart.

Although this study focused on chronic kidney disease, sodium overload inside heart cells has also been observed in other cardiometabolic conditions, including diabetes and heart failure with preserved ejection fraction (HFpEF). Understanding how sodium influences heart metabolism could therefore have wider implications for cardiovascular research.

Further research will be needed to establish how these findings translate to people living with chronic kidney disease and whether targeting sodium handling within heart cells could ultimately lead to treatments that help protect the heart from cardiovascular damage.