Researchers identify cause and potential therapeutic approach for diabetic kidney disease
· News-MedicalDiabetic kidney disease – a complication of diabetes – is considered the leading cause of chronic kidney disease and kidney failure worldwide. It is associated with changes in the structure and function of the kidneys and ultimately leads to kidney damage.
Signaling mechanism triggers oxidative stress
A research team at the University of Leipzig Medical Center has now identified a signalling mechanism that causes damage to kidney cells. Coagulation factor FXII (F12), also known as Hageman factor, is involved in this process.
"Its production is increased in the body when blood sugar levels are high," says Ahmed Elwakiel, lead author of the study and scientist at the University of Leipzig Medical Center. Independent of its normal function in blood coagulation, FXII has a different effect on the tubular epithelial cells of the kidney: through a receptor mechanism, it forms a complex with two other proteins that have different functions in the body. This complex acts like a molecular on-off switch. It sends a signal to produce more oxygen free radicals. This leads to oxidative stress and DNA damage in the cell.
Ahmed Elwakiel, lead author of the study and scientist, University of Leipzig Medical CenterIn contrast to normal cell communication, however, the switch remains on under diabetic conditions; there is no pause button."
In the long term, the constantly increasing oxidative damage can neither be absorbed nor repaired. The kidneys then no longer function properly and the problem worsens over time.
Coagulation factor useful as a diagnostic marker
"In our study, we show that FXII can also be detected in the urine of diabetes patients with kidney disease," explains Professor Berend Isermann, senior author of the current publication. "The concentration of FXII correlates with the severity of the disease: the higher the value, the more damaged the kidney is. This makes the value a useful diagnostic marker," says the head of the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics. FXII can be detected in the early stages of the disease and is therefore an important indicator of whether treatment is likely to be successful.
To determine the presence of FXII in the human organism and how it affects diabetes, the researchers analysed clinical values, kidney biopsies and urine samples from several human cohorts, including the LIFE Adult Study from the Faculty of Medicine at Leipzig University and the HEIST-DiC cohort from Heidelberg University.
FXII inhibition as a possible therapeutic approach
No negative effect on coagulation
According to the authors of the study, no negative side effects on blood coagulation are to be expected from FXII inhibition. "The organism has various blood coagulation factors; it doesn't necessarily need FXII to initiate coagulation. We know from other studies that its inhibition does not result in increased bleeding risk," says Elwakiel.
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