New treatment for diabetic kidney disease

Researchers at UC Davis, USA, have shown that: Preventing TLR2 receptors, which can slow or even prevent diabetic nephropathy, is a complex complication that has very little Good treatment, often fatal for diabetics. The results of this study were published online in Biological Arteriosclerosis, Congestion, and Blood Vessels, the first study to clarify the role of receptors, such as the role of receptor 2, or TLR2 receptor in diabetic nephropathy is involved.

" Diabetic kidney disease is one of the most serious complications of diabetes and the most common consequence is kidney failure ," says Ishwarlal Jialal, professor of endocrinology, diabetes and metabolism. work at Davis UC University, USA and the main author of this study. " This is an improvement and eventually, instead of having regular dialysis or kidney transplantation for patients, we now have an accurate target at the molecular level to completely treat diabetic kidney disease. this ".

Kidney complications affect about 30% of diabetics, this complication becomes apparent from the first year to 25 years after you receive a diabetes diagnosis. Renal complications occur when blood glucose levels are high, often you have high blood pressure because the complex dialysis system of the kidneys overworked, eventually causing the system to break down. Renal complications are often diagnosed in the middle of the disease process, when the kidneys enlarge and protein appears in the urine.

Dr. Ishwarlal Jialal and Dr. Sridevi Devaraj

" At present, we cannot fully predict why some people with diabetes (including well-controlled cases) have complications in the kidneys while others are uncomplicated ," according to Jialal. The work at the Laboratory specializes in studying the role of inflammation in heart disease and diabetic complications. " Our goal is to find ways to identify and prevent kidney complications as early as possible, before dialysis is needed. "

TLRs are immune system receptors that provide protection for the body from bacteria and other pathogens. Previous research by Jialal and the team showed that diabetics have increased the activity of TLR receptors and marked inflammation in their immune systems, the more severe the illness in patients. Microvascular complications, especially kidneys. Research by other research groups has shown that a special receptor, TLR2, is expressed in higher numbers in the kidney biopsy sample of diabetic kidney disease patients .

" We want to find out whether this receptor can have a causal relationship with kidney disease ," said Sridevi Devaraj, professor of pathology, UC Davis University, USA and the lead author of the study. assist. " We also want to take the next step and whether we can identify the unique biomarker, which can be used to detect diabetic kidney disease soon ."

The team used mice with genetic genes that lack TLR2 to see if it had an effect on developing kidney complications. They divided 80 experimental mice into two groups: 40 with genetic genes that lack TLR2 and 40 that were wild mice without genetic changes. Type 1 diabetes was caused in both groups, and then all were tested for the features of diabetic kidney disease complications, including: marked inflammation, significantly increased kidney weight and especially increasing albumin 10 times, this is a blood protein, present in urine.

In the 14th week, the wild mouse group did not have genetic changes, complications in the kidneys, while the group of 40 mice had genetic genes that lacked TLR2, and there were no complications in the kidneys. In addition, renal tissue biopsy of wild rats showed an abundance of TLR2 and macrophage inflammation created an increase in important biological response modulators such as interleukin - 6 (IL - 6 ) and a monoclonal monoclonal protein (MCP - 1). This result was not found in the group of mice with genetic genes that lack TLR2.

" The discovery of abundance of TLR2 receptors and inflammation in kidney tissues suggests that it is possible that TLR2 receptors are associated with diabetic nephropathy ," according to Jialal. " And the absence of TLR2 receptors, also means that the kidneys will be strongly protected showing the development of a drug that helps block TLR2 receptors, acting as a great commitment to prevent kidney disease. due to diabetes . "

Further tests showed that cells called podocytes and proteins called podocin , both help maintain kidney filtering barriers and prevent albumin loss, in a group of mice with TLR2-deficient genes. . Because tissue biopsy to determine changes in podocyte cells is not easy to obtain, Jialal is working to find out whether a biomarker in the blood is used to track podocin protein or indicators. Other functions of podocyte cells.

" If so, this biomarker could act as a characteristic sign of the onset of complications in the kidneys, giving doctors the opportunity to intervene before more kidney damage usually occurs. , "according to Jialal.

In the future, Jialal will test if the genetic gene lacks another important receptor called TLR4, which may also prevent the progression of diabetic kidney disease . Jialal hopes to find an inhibitor of both TLR2 receptors and TLR4 receptors to conduct clinical trials in animal models and, if safe, will apply to diabetics.

" Currently we have identified the absence of TLR2 as important, in preventing diabetic nephropathy along with a potential index of the onset of kidney disease, we are excited, continue to confirm determine the potential of the findings on clinical treatment for diabetics , "Jialal said.

The new findings will be published in the Journal of Biological Arteriosclerosis, Thrombosis and Blood Vessels, in August 2011.

This study was funded by the Juvenile Diabetes Research Foundation and the US National Institute of Medicine. Rajendra Ramsamooj and Alaa Afify researchers from UC Davis University, USA. Peter Tobias of Scripps Research Institute, and Balakuntalam Kasinath, of the Medical Research Center, University of Texas, USA.