Kidney Disease

A new study from Joslin Diabetes Center has proven that certain biological protective factors play a large role in preventing diabetic kidney disease in certain people. The study was publish online in Diabetes Care. This study built on the findings from a 2017 Joslin Medalist Study of protective factors and diabetic kidney disease (or DKD).

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

The protective factors

The research team was led by Hetal Shah, MD,MPH, Research Associate at Joslin Diabetes Center and HMS Instructor in Medicine, Daniel Gordin, MD, Ph.D., Adjunct faculty at Joslin and Associate Professor at University of Helsinki, Finland, and George King, MD, Joslin Senior Vice President and Chief Scientific Officer and HMS Professor in Medicine,

In their new study, Drs. Shah, Gordin and 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 use as both biomarkers and, potentially, targets for DKD intervention.

The researchers set out to investigate three questions relate 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?

The postmortem kidneys

To answer the first question, they study the postmortem kidneys donate by people; hence in all of the cohorts they want to investigate. For the second question, they use cutting edge proteomic and metabolomic techniques; so to study the circulating plasma of Medalists. For the third question, they look at the plasma; also identify a number of metabolites and proteins that were also elevated. They map the associate genetic pathways to understand the cause and effect of the elevations.

They were able to replicate the findings of the elevate PKM2 in those with good kidney function; hence in both type 1 and type 2 diabetes,” says Dr. Shah. “Also, through the plasma proteomic and metabolomic studies in the Medalists; they find that there’s this amyloid precursor protein, or APP, that shows up as a potential protective factor against diabetic kidney disease.”

The identification of APP as a possible protective factor was surprising; so considering its main know association is an increase risk for Alzheimer’s disease. [But it also seems to be] potentially protective in multiple vulnerable tissues in people with diabetes. With that said, we would need further studies to confirm this,” says Dr. Shah.

Once the protective mechanisms are explicitly mapped, they could even be use as therapeutic targets. Diabetic kidney disease is a devastating disease,” says Dr. Gordin. “It is a powerful driver of cardiovascular disease, and also, eventually, mortality. We have urgent need to find something to help these people. All [these studies] take time, but this is very promising.