Scientists identify enzymes that play protective role against diabetic kidney disease

Researchers have identified a group of enzymes that help protect certain people against diabetic kidney disease.

The study published in 'Diabetes Care' is built on the findings from a 2017 Joslin Medalist Study of protective factors and diabetic kidney disease (or DKD).

The 2017 study focused on Joslin Medalists--people who have had diabetes for more than 50 years with little to no complications. The Medalists who never developed kidney disease had higher levels of a group of enzymes involved in glucose metabolism than people who did develop kidney disease.

In their new study, doctors Hetal Shah, Daniel Gordin, and George King were able to show that protective factors are also present in kidney-disease-free people with shorter-duration type 1 diabetes and type 2 diabetes.

This finding indicates that these enzymes, and one in particular known as PKM2, play a strong protective role against kidney disease. The enzymes could be used as both biomarkers and, potentially, targets for DKD intervention.

"The previous study built up the rationale that there must be something protecting these people from diabetic kidney disease. This would explain how these individuals have been able to live with insulin-dependent diabetes for so many years," said Dr Gordin.

The researchers set out to investigate three questions related to the 2017 discovery. First--was PKM2 protective in non-Medalists? Second--was PKM2 circulating in the Medalists' plasma, or was it only found in the kidney? And third--do the Medalists have any other protective factors to be explored?

To answer the first question, they studied the postmortem kidneys donated by people in all of the cohorts they wanted to investigate. For the second question, they used cutting edge proteomic and metabolomic techniques to study the circulating plasma of Medalists. For the third question, they looked at the plasma and identified a number of metabolites and proteins that were also elevated.

"We were able to replicate the findings of the elevated PKM2 in those with good kidney function in both type 1 and type 2 diabetes," said Dr Shah.

"Also, through the plasma proteomic and metabolomic studies in the Medalists, we found that there's this amyloid precursor protein or APP, that shows up as a potentially protective factor against diabetic kidney disease," Dr Shah added.

Understanding the DKD protective factors could have clinical implications. If a biomarker circulates in the bloodstream, it could allow doctors to perform a simple blood test to determine a patient's risk for developing DKD. They could then create personalized intervention courses.

Once the protective mechanisms are explicitly mapped, they could even be used as therapeutic targets.