The damage done by chronic kidney disease is irreversible: once the illness has taken hold, the organ can't be healed. Patients' prospects and quality of life would be much improved if the condition could be spotted sooner. An EU-funded project has developed a biomarker test to pick up very early signs of diabetic kidney disease, and identified possible improvements in the approach to therapy.
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Diabetes significantly raises the risk of developing chronic kidney disease. High glucose levels trigger processes that eventually damage tiny blood vessels such as those on which the kidneys filtering abilities rely.
Diabetic kidney disease is induced by glucose, but the progression of the disease is caused by a wide variety of factors, says Gert Mayer of the Medical University of Innsbruck, Austria, head of the R&D steering committee of the SysKid project. This disease is a mystery. It progresses in many patients, but not in all, and patients dont necessarily respond to the same treatments.
Chronic kidney disease is usually detected when problems have already set in in fact, it is commonly diagnosed by means of a urine test that measures an indicator of damage. SysKid, Mayer explains, developed a way to diagnose specific forms of the disease more precisely and earlier, and refine its treatment.
The new method for early diagnosis involves testing urine samples for signs of molecular changes linked with the onset of the disease. These biomarkers are peptides or small proteins coming from the kidney, which all reflect the status of this organ, says lead scientist Harald Mischak of Mosaiques Diagnostics in Hannover, Germany.
Poring over proteins
No single biomarker can clearly distinguish between a healthy kidney and one where the illness is unfolding, Mischak explains. SysKids test is based on a set of 273 biomarkers associated with the condition, which jointly provide a clearer picture.
The test, which has been patented, is already available to patients under the brand name DiaPat® DN-PROteom Test, Mischak adds, and the partners are interacting with the relevant authorities of a national health care system in Germany regarding the potential reimbursement. With some 10 % of the worlds population affected by chronic renal disease (including diabetes-induced kidney damage), the stakes are high both in medical terms and from a financial point of view. Early detection and more targeted treatment, the SysKid partners argue, will delay the progression of the disease, or potentially even stop it in its tracks.
I think SysKid was one of the first major initiatives launched to advance the understanding of a very complex multifactorial disease using a multidisciplinary approach, says Mayer. The project involved systems biologists, bioinformaticists and clinicians in a bid to unravel the cellular and molecular mechanisms associated with the onset and progression of the condition. It made a significant contribution to the development of methodology to underpin this type of joint exploration, he adds.
Towards timely, targeted treatment
Based on the outcomes of SysKid, which ended in December 2014, an intervention trial named Priority is in progress, Mayer reports. The aim of this EU-funded trial is to establish whether treatment with Spironolactone following early detection by means of the CKD273 test can indeed delay or stall the progression of the disease in diabetic patients.
Another possible use of the SysKid results, says Mayer, is to identify particular forms of developing diabetic kidney disease in order to target the treatment for better results. Patients with diabetic kidney disease are not a homogeneous group, he notes. We have developed methods to subgroup the patients so that you dont necessarily apply the same therapy to everybody. This idea is further pursued by Beat-DKDB, a project funded by the Innovative Medicines Initiative.
The opportunity to nip diabetic nephropathy in the bud could very significantly reduce, or possibly even halve, the number of cases resulting in end-stage disease or death, says Mischak. However, he notes, it will take another 10 years until such a reduction can be proved, to allow for the timeframe typically involved in the progression from disease onset to severe consequences in those cases where it does occur.