In the United States, diabetic kidney disease, or DKD, is responsible for more than half of all new cases of end-stage renal (kidney) disease. What’s more, over the last few decades we saw improvements in all major diabetic complications, but end-stage kidney disease rates declined the least, and it is still a cause of premature death from diabetes.
Predicting who will develop end-stage kidney disease is a challenge. There has been limited progress in identifying predictive biomarkers, making it hard to identify those most likely to encounter this complication. But two recent publications shed light on which people with diabetes will develop kidney disease. One is for protective factors, and the other predicts rapid decline in kidney function.
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The team, under the direction of JDRF grantee Andrzej S. Krolewski, M.D., Ph.D., asked the question: “What if individuals with impaired kidney function, but slow or minimal kidney decline, have protective factors, which makes them not develop end-stage kidney disease?”
And, you know what? They were right!
They studied the proteins that were elevated in those with slow or minimal kidney decline and considered them as candidate protective factors. They identified eight proteins. When these eight proteins were considered together, only three—ANGPT1, TNFSF12, and FGF20—showed a strong, independent protective effect against progressive kidney decline.
These three protective proteins may serve as biomarkers to stratify individuals according to risk of progression to end-stage kidney disease, giving those at risk the information they need to employ preventative strategies. They might also be investigated as potential therapies to delay or prevent the onset of kidney decline.
Another publication focused on different players: lipids—a group of compounds, including fats, oils, cholesterol, and hormones, which do not dissolve in water. The team, led by JDRF-funded Kumar Sharma, M.D., and Subramaniam Pennathur, M.D., found that a biological signature, or unique presence, of free fatty acids and phospholipids were able to predict early rapid kidney decline in T1D. This finding may be used to identify high-risk people at an early stage of T1D, when preventive strategies could provide opportunities to preserve kidney function.
This was funded by the JDRF Center of Excellence at the Elizabeth Weiser Caswell Institute at the University of Michigan to identify biomarkers of diabetic kidney disease, to enable the development of early intervention therapies and better designed clinical trials.