New diagnostic approaches for early identification of patients at high risk of rapid loss of kidney function

May 31 2006

Doctor Harry Holthvfer, M.D., Ph.D, at the University of Helsinki, Finland, coordinates a new EU-funded project, which aims to develop new diagnostic approaches for early identification of patients at high risk of rapid loss of kidney function.

The project links together researchers from Finland, the Netherlands and Switzerland and four SMEs from Finland, the Netherlands and Italy. The EU has granted 4.4 million euro funding for this project.

Chronic kidney disease (CKD) is an increasing health threat in Europe. Presently already 12 % of population suffers from some degree of CKD. The most immediate challenge is to better understand the connection between CKD, diabetes and cardiovascular risks. The risk of sudden death in cardiovascular causes is 2-4 times higher in diabetics while diabetics with kidney damage increases this risk up to 100 times of that of the general population. Moreover, more than 70 % of CKD patients die before achieving the specific CKD treatments including dialysis and transplantation.

With current trends of CKD and diabetes increase, specific treatments will further escape the escalating needs. Similarly, management of the cardiovascular consequences of CKD will be untolerable for any health care systems because of cost, loss of active working years and, most importantly, due to individual suffering.

Better predictive diagnostics should aim at early detection of those at risk of kidney loss and targeting of already presently available effective therapies properly. However, only strong basic research can lead to better understanding mechanisms and pathways involved and thus improvements in targeted treatments.

"We will utilize the latest knowledge on the pathophysiology of diabetic nephropathy and newly identified urinary markers of diabetic kidney damage to develop a predictive diagnostic test to follow disease progression", Dr. Holthvfer says.

Biomarkers identified, in particular those preceding the development of diabetic kidney damage during the pre-microalbuminuric stage, will be evaluated in patient sample material banks collected as a wide, well organized national effort relying on voluntary contributions of patients and health care professionals alike. This material is used by the researchers to find additional markers from diabetic urines, and identify new metabolic end products useful in diagnostics.

Two separate approaches will be used to develop diagnostic tests, one based on nanobead technology and the other on a multiplexing platform allowing combination of several measurables into a single test. Both technologies will utilize antibody capture methods and newly developed antibody libraries. This will translate into early identification of patients at high risk of rapid loss of kidney function. The validation of the diagnostic tests emerges form the use of the largest European urine, serum and DNA databases of diabetic nephropathy with the meticulously collected follow-up samples.

Subsequent steps of the test development include premarketing evaluation, transfer of the test into patient use, market and competitor analyses and search for best market channels for the test in international markets by SMEs.

This approach directly aiming at developing a clinical urinary test will be supported by extensive basic research on the mechanisms and biomarkers of diabetic nephropathy at the level of the kidney. These include a novel method of in vivo biotinylation and state of the art proteomics on kidney samples during the development of experimental diabetic nephropathy, Dr. Holthvfer tells.