Kidney cell suicide in diabetes patients

Diabetes is the leading cause of renal failure that requires dialysis. The disease generates such a hostile environment that it forces the kidney cells to kill themselves, progressively reducing the renal functions of the kidneys.

A research group from the department of medicine at the Universidad Autónoma de Madrid (UAM) has studied the causes and consequences of the cell suicide of renal cells.

Diabetes slowly destroys the kidney up to the point where the renal function has to be taken on by dialysis (artificial kidney) or a transplanted kidney. It is the leading cause of end stage renal failure that requires dialysis. The destruction of the kidney comes from the loss of its cells, which recent studies have demonstrated to be caused by apoptosis, a process that, for cells, involves death by suicide. Cells suicide when their environment does not “please” them, when their surroundings feel hostile or stressful. The Spanish team managed by Alberto Ortiz, professor of the department of medicine of the UAM based at the Jiménez Díaz-Capio foundation, has spent years studying the causes and the consequences of kidney cell suicide, specializing in “psycho-cellulology”.

The team analyzed the genes related with apoptosis as a part of a European collaborative effort (European Renal Biopsy Bank) that studies the expression pattern of genes found in patients suffering from diabetic nephropathy. The affected kidneys exhibited an abnormal expression of 112 genes that regulate the cell suicide. Among these genes, the Spanish team identified a protein of the Tumour Necrosis Factor (TNF) family, called TRAIL, as the key to the cell suicide in diabetes affected kidneys.

In these kidneys, large quantities of TRAIL can be found that surprisingly do not come from the increased glucose levels that define the disease, but from the inflammation that accompanies the renal damage. Inflammation and higher glucose levels favour renal damage; the inflammation raises the TRAIL levels while the hyperglycaemia generates a stressful environment that, in the presence of TRAIL, leads to cell suicide.

The role played by inflammation in the cell suicide that leads to renal damage suggests that the treatment of diabetic nephropathies requires a multiple attack to control the glucose levels while also acting on the renal inflammation and lethal proteins like TRAIL.

This study is part of the efforts carried out by the Red de Investigación Renal (RedInRen), financed by the Carlos III institute, to expose the mechanisms of renal lesions and develop new treatments for renal diseases. The results from this study have been published on-line in the Journal of the American Society of Nephrology (J Am Soc Nephrol. 2008, [Epub ahead of print]), the most representative journal for Nephrology and Urology.

http://dx.doi.org/10.1681/ASN.2007050581 and http://www.uam.es/