Nephropathy Development Factors

Whether nephropathy ever develops and how rapidly it progresses vary immensely from patient to patient. For some, the risk of kidney damage increases with the duration of diabetes, but the risk does fall when the diabetes is continuously well controlled. For others, however, hereditary factors are also important.

Even among those who have high blood sugar levels for years, there are some people who never develop nephropathy. On the other hand, there are people with fairly good diabetes control who nevertheless develop kidney damage. We know that children from families with diabetes in which one member already has a renal problem have a much higher risk, from the onset, of developing nephropathy.

Unfortunately, there is as yet no definite known marker in the blood or the urine that can predict the risk of developing nephropathy for an individual patient. This would naturally be a great help, as patients at higher risk could then be managed much more intensively.

Since this is not yet possible, patients and doctors must all try to reduce, or at least to retard, kidney damage via the factors that we can influence. The most important is good blood sugar control and good management of high blood pressure. Sometimes, it is helpful to eat less protein.

If that is not enough, protein excretion in the urine and its detrimental effects can be treated with special medicines. Levels of blood fats should not be too high and intensive management of the diabetes should be started as soon as possible. Another factor that increases the risk of kidney damage is smoking, so giving up is a helpful step to take.

Nephropathy Signs and Symptoms

Like other complications of diabetes, diabetic kidney damage does not usually cause overt signs for a long time. This ‘secret’ progression means that an advanced stage of kidney impairment has often been reached by the time the first symptoms appear. These symptoms are frequently caused by increased water retention:

  • Feet and ankles swell, shoes pinch, socks cause blisters; you can sometimes make an indent in the lower thigh by pressing with the thumb. These symptoms are known as ‘oedema’ and are often present only in the evening. In the morning, after a night’s rest, they disappear again.

Other signs or symptoms, which may appear in parallel or individually, are:

  • Breathlessness, which arises at first only during exercise but later also when at rest.
  • High blood pressure, with values greater than 140/90 mmHg.
  • General symptoms that are not specific to kidney failure, such as headache, tiredness, bodily weakness, loss of concentration.

If these symptoms prompt you to go to the doctor, he or she will usually establish that there is already a marked increase in protein excretion (macroalbuminuria), that the markers of kidney function are bad and that blood pressure is high. Kidney damage may already have reached stage 4 or stage 5.

At this point, an eye examination will often reveal diabetes-induced damage to the retina, which is complicated by high blood pressure. The heart may also, at this advanced stage of kidney failure, show the first signs of damage.

Diabetic nephropathy doesn’t affect everyone. 50–70% of people with diabetes never develop kidney damage. Of those who do, for some it is due to their genetic inheritance, for others it is due to factors such as how well their blood sugar levels and blood pressure are controlled.

So far, there is no way of telling who is at risk of developing diabetic nephropathy on the basis of their genetic make-up. If this were possible, it would be the ideal situation as then doctors and patients would be able to initiate intensive management of the diabetes of those at greatest risk.

At present, we can only keep a look out for early signs of nascent kidney damage in order to be able to treat it promptly. Nephropathy is not detected through symptoms such as problems with urinating, tiredness or headache.

Even blood parameters that give information about kidney function, such as creatine concentration, may stay normal for years, including after the diabetes has begun to damage the kidneys. The earliest sign of diabetes associated kidney damage is the appearance of microalbuminuria.

Even before the filtration capacity of the kidney corpuscles has been compromised, proteins such as albumin, which otherwise never appear in the urine or only at very low concentrations, may be excreted.

This is a warning signal. An albumin concentration in the urine of 20–200 mg/l is a sign of ‘microalbuminuria’ (literally, ‘little albumin in the urine’). If the rate of albumin excretion rises, this is known as ‘macroalbuminuria’ (literally, ‘much albumin in the urine’).

Detection of Microalbuminuria

There are many different, fast tests available for establishing the presence of microalbuminuria. These can determine within a few minutes whether there are tiny amounts of albumin in the urine. Such tests may be performed in any doctor’s surgery.

If protein is detected, the result of the quick test should be confirmed by a more exact measurement of the urine albumin concentration in a laboratory analysis. Measurement of the albumin concentration is often imprecise because it depends on the amount of urine as well as the amount of excreted albumin.

For example, in people who have drunk a lot of liquid before giving a urine sample, there will be a dilution effect, such that the measured albumin concentration will be too low. To compensate for this, the albumin concentration can be compared with the amount of creatine excreted in the urine.

The best method, however, is to calculate the rate of albumin excretion. For this, the urine has to be collected over a given time (24 hours or overnight) and the amount of albumin excreted is divided by the set time. The range of microalbuminuria measured using different urine collection methods and time periods.

It is not only diabetes-associated damage that causes the kidneys to excrete albumin. Protein may also be found in the urine during physical stress, urinary tract infection, hypertension or fever. Once these conditions are resolved, the albumin usually disappears from the urine.

Therefore, to be sure that microalbuminuria truly indicates the onset of diabetic nephropathy, the test should be repeated after a gap of two to four weeks. If the test is still ‘positive’, it is probably a sign of the start of kidney damage. What’s more, microalbuminuria is not just a sign of nephropathy.

Studies have shown that people with microalbuminuria have a much higher risk of circulatory problems or a heart attack than does the general population. In fact, urine collected at any time of day may be tested.

However, early morning urine is usually taken, since constant conditions have generally applied during the night before collection. For people with Type 1 diabetes, the experts recommend that an annual microalbuminuria test is performed starting five years after diagnosis of the diabetes.

In children, the annual test is usually initiated at the onset of puberty. For people with Type 2 diabetes, the tests are best begun at the time of diagnosis of the diabetes, because many of these patients have already had high blood sugar levels for years, without knowing about it.