Generally, the changes produced in the kidneys by diabetes occur very slowly, taking place over years. If they are recognized early, they can – with the right treatments – be reversed. The changes start, at the onset of diabetes, with an increase in the size of the kidneys and in the amount of blood passing through them.

This first, early stage is known as ‘the hypertrophy and hyper function stage’ (stage 1) because of the enlarged kidneys, enriched in blood. Even at this stage, a rise in the amount of protein in the urine is often observed. If the diabetes is properly controlled, these changes can usually be reversed within weeks or months.

The protein also disappears from the urine. The progression of these changes in the kidneys depends strongly on the state of the body’s metabolism. If the blood composition is good – that is, if the hemoglobin A1c (HbA1c) concentration is near-normal, namely between 6% and 7%, the diabetes will barely affect the kidneys in the ensuing years.

But if the blood sugar level (as assessed by the HbA1c concentration) remains too high over years, this leads to damage to the basal membrane, which filters the blood. Such damage is initially detectable only through laboratory investigations of the blood and urine.

However, if you could remove a small piece of the kidney and examine it under a microscope, you would be able to see a marked thickening of the basal membrane – stage 2 of kidney damage. If the blood sugar level is still not brought under control, the filtration ability of the basal membrane gradually falls.

It becomes permeable to proteins, which are normally retained within the circulation. The blood protein albumin is found at slightly higher concentrations in the urine. Because only a small amount of albumin is excreted, this stage is known as ‘microalbuminuria’.

The presence of albumin in the urine makes it plain to both the doctor and the patient that the diabetes has led to kidney damage and therefore that nephropathy has begun (stage 3). If even greater damage to the basal membrane is not prevented by taking the appropriate measures, the filtration capacity is further compromised.

Large amounts of albumin and other proteins pass through the membrane and are excreted in the urine. When the albumin concentration in the urine exceeds 200 mg/l, this is called ‘macroalbuminuria’, which means ‘high albumin excretion’. This is stage 4; it represents clinical nephropathy.

The onset of macroalbuminuria makes it clear that the filtration apparatus of the kidneys is already seriously damaged. But the increased amounts of protein in the urine don’t just act as markers of renal impairment – albumin and other proteins also contribute to further damage.

They get stuck between the small blood vessels (capillaries) and block the kidney corpuscles. Without blood flow through the corpuscles, these can no longer operate. This process can be accelerated by another detrimental factor – high blood pressure (hypertension).

Because the kidneys are involved in the regulation of blood pressure, many patients develop hypertension during the stages of micro- and macroalbuminuria. When not properly treated, this can damage the kidney corpuscles directly and indirectly.

Since the incoming vessels can no longer be narrowed protectively, the high blood pressure impacts unhindered on the corpuscles and contributes to their destruction. The filtration pressure also rises and more proteins are excreted, which leads to further blockage of the corpuscles.

If nothing is done at this stage either, more and more corpuscles cease to function and finally creatine and urea concentrations in the blood rise as a sign of the ongoing kidney failure. This is stage 5. At this point, a vicious circle often develops. The surviving kidney corpuscles must take over the function of those that have been destroyed.

They have to work harder, which means more wear and tear, which means that they are destroyed more rapidly. So the rate of kidney failure accelerates continuously. Only two or three decades ago, when the therapeutic options for hypertension and diabetes were still limited.

It was often only a few months before the kidneys failed completely and dialysis became necessary. Today, the vicious circle can be slowed or even broken for a time by good management of blood pressure and diabetes. The need for dialysis can be postponed for years or even decades.