Cause of Kidney Failure in Diabetics Unscrambled

Mini protein Carnosine protects the kidney Gene tests to gage individual risk in preparation.

In collaboration with diabetes experts from Mannheim, the Netherlands and the Czech Republic, Heidelberg geneticists have found that certain variants of a gene predispose diabetics to the development of kidney failure. These results can probably be used as the basis for the development of gene tests to gage the individual risk. Some 40 percent of all diabetics develop chronic kidney failure, mainly due to their genetic disposition.
In the August issue of "Diabetes", the leading internationally renowned journal for diabetes research, the Heidelberg geneticist Dr. Bart Janssen and his colleagues describe the so- called CNDP1-gene on chromosome 18 which is responsible for the production of the enzyme carnosinase. This enzyme splits the mini protein carnosine which the researchers found can prevent kidney cell damage when present at high blood concentrations in the blood.
"High quantities of carnosine are always found when low quantities of carnosinase are present", says Bart Janssen who is a team leader in the Heidelberg University Hospital's Institute of Human Genetics under the directorship of Professor Claus R. Bartram. How much carnosinase is produced depends in turn on the number and combination of DNA bases within the gene CNDP1. The longer the gene, the less carnosinase is produced.
An estimated 60 Million people suffer from diabetes in Europe. Almost 40 percent develop chronic kidney failure in later stages of their disease, the so-called diabetic nephropathy which often has to be treated with dialysis or kidney transplantation. But why are most diabetics spared from the fate? Dr. Janssen and his co-workers, the nephrologists Dr. Irfan Vardarli and Professor Fokko van der Woude, first showed three years ago that resistance against kidney damage had a genetic cause and that the gene was located on chromosome 18.
In their latest publication the Heidelberg geneticists describe three different variants of the gene, the longest containing 2191 DNA bases and presumably the most active one with the highest production of carnosinase enzyme. The other two variants contain 2188 to 2185 bases. The shortest variant is called the "Mannheim variant" because it was found in a patient living in the city of Mannheim. This short version has a very low enzyme production. As expected carriers have a low level of carnosinase.
Likewise, the scientists found in their clinical studies that diabetics without kidney involvement mainly have this shortened Mannheim variant of the gene. Longer genes are mainly found in patients suffering from diabetic nephropathy.
The risk of developing kidney failure can presumably be predicted by a simple gene test. Research on the development of this test is underway under the leadership of the Heidelberg group, and is supported by a grant from the European Union of 1.8 Million Euro.
More Information:,PD Dr. Bart Janssen,,Institute of Humane Genetics,Im Neuenheimer Feld 366,69120 Heidelberg,Tel: [phone],email: [e-mail]
Literature:,1.) B. Janssen, D. Hohenadel, P. Brinkkoetter, V. Peters, N. Rind, C. Fischer, I. Rychlik, M. Cerna, M. Romzova, E. de Heer, H. Baelde, S.J.L. Bakker, M. Zirie, E. Rondeau, P. Mathieson, M.A. Saleem, J. Meyer, H. Koppel, S. Sauerhoefer, C.R. Bartram, P. Nawroth, H.-P. Hammes, B.A. Yard, J. Zschocke, and F.J. van der Woude: Carnosine as a Protective Factor in Diabetic Nephropathy: Association With a Leucine Repeat of the Carnosinase Gene CNDP1. Diabetes, Aug 1, 2005; 54 (8)
2.) Vardarli I, Baier LJ, Hanson RL, Akkoyun I, Fischer C, Rohmeiss P, Basci A, Bartram CR, Van Der Woude FJ, Janssen B. Gene for susceptibility to diabetic nephropathy in type 2 diabetes maps to 18q22.3-23. Kidney Int. 2002 Dec;62(6):2176-83
(The original article can be requested from the press office of the university hospital of Heidelberg under [e-mail])
Please address any inquiries to,Dr. Annette Tuffs,Presse- und Öffentlichkeitsarbeit des Universitätsklinikums Heidelberg und der Medizinischen Fakultät der Universität Heidelberg,Im Neuenheimer Feld 672,69120 Heidelberg,Tel.: 06221 / 56 45 36,Fax: 06221 / 56 45 44,Handy: 0170 / 57 24 725,E-Mail: [e-mail],http://www.klinikum.uni-heidelberg.de
Dr. Michael Schwarz,Press Officer of the University of Heidelberg,phone: [phone], fax: 54317,[e-mail],http://www.uni-heidelberg.de/presse/index.html

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