How does diabetes affect the kidneys

Generally, the changes produced in the kidneys by diabetes occur very slowly, taking place over years (Table 2.2, Figure 2.4). 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 hyperfunction 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 haemoglobin A1c (HbAlc) 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 HbAlc 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

Table 2.2 Stages of the development of nephropathy and typical findings

Stage

Time

Characteristic symptoms

1. Increase in size and activity of the kidney

2. First changes to the kidney tissue

3. Onset of nephropathy

4. Clinical manifestation of nephropathy

5. Renal insufficiency

At diabetes Enlarged kidney, higher blood flow diagnosis and rate of filtration

2-5 years Thickening of the basal membrane

5-15 years Microalbuminuria, rise in blood pressure

10-25 years Macroalbuminuria, falling blood flow and filtration rate, high blood pressure in 60-80% of patients 15-30 years Rise in serum creatine concentration, near-permanent hypertension 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

Kidney function decreases as protein excretion increases

Kidney function decreases as protein excretion increases

Duration of diabetes (years)

Figure 2.4 If the amount of albumin excreted into the urine increases with the duration of diabetes, this has bad consequences for kidney function.

Duration of diabetes (years)

Figure 2.4 If the amount of albumin excreted into the urine increases with the duration of diabetes, this has bad consequences for kidney function.

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 (Figure 2.5).

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

What you should know:

Even at this stage, kidney damage can be stopped! Blood sugar levels and blood pressure must be lowered. The protein damage should be reduced, for example by drug treatment.

Figure 2.5 Kidney corpuscles magnified 20-fold. Compared with a healthy kidney (top panel), the corpuscles in someone who has had diabetes for many years are totally blocked with protein deposits and are no longer functional (bottom panel).

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

Figure 2.6 Children from families with diabetes in which a member already has kidney disease have a much higher inherent risk of developing

Figure 2.6 Children from families with diabetes in which a member already has kidney disease have a much higher inherent risk of developing nephropathy.

tear, which means that they are destroyed more rapidly (Figure 2.7). 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.

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