Diagnosis and delay: an approach to addressing diabetic kidney disease

Health Europa takes a look at the causes, diagnosis and treatment of diabetic kidney disease and investigates what is being done at a European level to combat its threat to patients.

Common in those living with diabetes is kidney disease, also known as diabetic nephropathy, which can lead to kidney failure. As a result, treatment aims to either prevent, or postpone, the progression of diabetic kidney disease, as well as reducing the risk of developing cardiovascular diseases, whether that be the risk of heart attack or stroke. The condition is characterised by a process whereby the glomeruli, the kidney’s filter, becomes damaged. Subsequently, the kidneys begin to leak albumin – a protein – of a volume outside the realm of normality into the urine.

Here, Health Europa takes a look at the causes, diagnosis and treatment of diabetic kidney disease and investigates what is being done at a European level to combat its threat to patients.

Setting the standard of normality

With a minimal amount of albumin release in the urine being considered normal, raised levels are attributed to the symptoms of damage to the kidneys as a result of diabetes. Divided into two main categories, diabetic kidney disease is categorised by the level of albumin lost through the kidneys. The two categories are:

Microalbuminuria: this stage of the disease sees the release of 30-300mg of albumin each day, also known as incipient nephropathy; and

Proteinuria: in some cases, patients release in excess of 300mg per day, also known as macroalbuminuria and overt nephropathy.

Resulting from the raised glucose levels of diabetes patients, a simultaneous rise in the chemicals within the kidney can also be identified. Therefore, the increase of such chemicals has the ability to cause more leakages from the glomeruli and, consequently, enables albumin to leak into the urine. Furthermore, raised blood glucose levels also have the potential to allow proteins in the glomeruli to combine, whereby the combined proteins can then lead to localised scarring, called glomerulosclerosis.

The effect over time

Over time, and as the condition continues to worsen, glomerulosclerosis starts to replace healthy kidney tissue with damaged tissue, consequently lessening the ability of the kidneys to filter blood. The reduction of the kidney’s ability leads to a gradual failure, before reaching end-stage kidney failure. One indicator of this is the microalbuminuria stage; however, the effects of microalbuminuria can lesson, remain stable, or progress to proteinuria – an irreversible stage; proteinuria signifies the start of a process which progresses towards end-stage kidney failure.

Diagnosing diabetic kidney disease

In Type 1 diabetes, neither microalbuminuria nor proteinuria are commonly present upon diagnosis. However, within five years, around one in seven will have developed the lesser stage, microalbuminuria. Over a longer period of time – 30 years – approximately four in ten will have developed microalbuminuria, whilst others may have progressed to the irreparable stage of kidney disease. Meanwhile, in Type 2 diabetes, around one in eight diabetes patients have microalbuminuria, whilst one in 50 have proteinuria. Moreover, diabetic kidney disease is more prevalent in Asian and Afro-Caribbean people.

When the level of albumin in the urine exceeds normal ranges, and with no other obvious explanation, diabetic kidney disease can be diagnosed. Using urine tests as per routine for diabetes patients, the level of albumin protein can be measured in order to detect the disease. Comparing the amount of albumin with the level of creatine in a urine sample, the routine urine test measures albumin-creatine ratio.

Moreover, a blood test can identify kidney function through measuring the level of creatine, of which is normally cleared from the blood via the kidneys. Therefore, in an instance where the level of creatine in the blood is increased, it can be assumed that the kidneys are not working. Through drawing comparisons between sex, age and creatine levels in the blood, an estimate of kidney function can be drawn, also known as glomerular filtration rate.

A European approach to addressing diabetic kidney disease

One European project, ‘Systems biology towards novel chronic kidney disease diagnosis and treatment’ (SysKid), explored how an integrated strategy, based upon the principles of systems biology, could simultaneously:

- Identify patients at risk of developing chronic kidney disease;
- Understand the molecular processes which trigger the onset of chronic kidney disease, as well as identifying the associated biomarkers;
- Develop novel approaches to diagnosis and treatment, subsequently controlling progression of the disease; and
- Perform preclinical verification of innovative therapeutic approaches, as well as performing clinical testing of diagnostic approaches.

As reported by the European Commission, Gert Mayer, Medical University of Innsbruck, Austria, and head of the R&D steering committee for the SysKid project, said: “Diabetic kidney disease is induced by glucose, but the progression of the disease is caused by a wide variety of factors. This disease is a mystery. It progresses in many patients, but not in all, and patients don’t necessarily respond to the same treatments.”

Expanding upon traditional approaches through testing urine, the SysKid project tests urine samples for signs of molecular changes which are linked with the onset of diabetic kidney disease. Lead scientist Harald Mischak, Mosaiques Diagnostics, Hannover, Germany, added: “These biomarkers are peptides or small proteins coming from the kidney, which all reflect the status of this organ.” Although no single biomarker can definitively differentiate between a healthy kidney and one which is experiencing the onset of kidney disease, the test – CKD273 – established by SysKid is based upon a set of 273 biomarkers which are associated with the condition.

Following the conclusion of the SysKid project in 2014, a spin-off trial which focuses on intervention has been established – Priority. The EU-funded trial works to establish whether prescription of Spironolacture, following early detection using the CKD273 test, could delay or inhibit the progression of kidney disease in diabetic patients.