Diabetic nephropathy: Everything you need to know!

What is diabetic nephropathy? 

Diabetic nephropathy is a kidney disease that develops after several years of insulin-dependent or non-insulin-dependent diabetes, and results in impaired filtering functions of the kidneys.

Elevated blood sugar level (hyperglycaemia) alters the function of the small blood vessels, as well as that of the kidneys.

Kidneys form urine by filtering the blood. In diabetic patients, the kidney filter becomes clogged and the filter membranes thicken. This means that the kidneys can no longer eliminate certain waste products and allow certain molecules that should not be present there, to pass into the urine.

The damaged kidney lets through more and more albumin (the main protein circulating in the blood) which is toxic for it, thus leading to the aggravation of the already existent nephropathy. Initially, albuminuria is moderate (also called microalbuminuria), with 30-300 mg of albumin excreted into the urine per day, but gradually it progresses to frank proteinuria (protein excretion is greater than 500 mg/d). 

Diabetic nephropathy sets in quietly, without any clinical signs, until late in the course of the disease, at which point patients may develop high blood pressure.

In type 1 diabetes, there are 5 stages of diabetic nephropathy:

• Stage 1: appearing at the onset of diabetes, it is characterised by an increase in glomerular filtration rate (the volume of blood filtered by the glomeruli of the kidneys) and kidney hypertrophy,
  
• Stage 2: occurs 2-5 years later and is characterised by damage to the kidney tissue. At this stage, there are still no symptoms, that is why the condition is called "silent nephropathy". Some diabetics do not progress beyond this stage,
  
• Stage 3: diabetic nephropathy sets in and manifests itself by the appearance of microalbuminuria and high blood pressure. This affects a bit less than one in two diabetics. Stage 3 usually occurs 6 to 15 years after diagnosis. Glomerular filtration rate (GFR) appears to have gone back to normal but cellular damage is still present,   
• Stage 4: diabetic nephropathy is confirmed by proteinuria that exceeds 500 mg/d,
  
• Stage 5: End-stage kidney disease, or end-stage kidney failure, occurs. Proteinuria is significant and hypertension is severe.
  

In type 2 diabetes, the evolution of diabetic nephropathy is more complicated and, in almost a third of patients, the deterioration of renal function can occur without the appearance of microalbuminuria. In one in three cases, the glomerular damage may even be different from typical diabetic glomerulopathy. 

It is therefore essential to identify the early signs of diabetic nephropathy in order to avoid the most severe forms of this complication. 

How can diabetic nephropathy be detected? 

The presence of even a small amount of albumin in the urine (also known as microalbuminuria) is the first sign that the kidneys are no longer filtering the body's waste products properly.

Systematic screening for diabetic nephropathy (looking for the presence of albumin in the urine) is therefore essential and should be carried out at least once a year.

If the presence of albumin in the urine is confirmed, the doctor usually prescribes a microalbuminuria test once or several times a year, to be able to monitor the progression of the condition. He or she can then quickly start treatments in order to prevent or delay the onset of diabetic nephropathy.

The progression of the disease differs from one patient to another. Regular monitoring is therefore crucial, and helps adapt the treatment. If kidneys are not protected, the kidney filter will continue to deteriorate. The term chronic kidney disease (or chronic kidney failure) is used when the kidneys' filtering functions are insufficient.

In addition to urine tests, regular blood tests are carried out to identify the first signs of kidney damage and to assess kidney function.

The kidneys' filtering capacity is measured by means of a creatinine blood test.

In patients with diabetes, kidney tests are recommended at least once a year, in addition to a glycated haemoglobin (HbA1c) test every 3 months.

It is important to remember that other factors can aggravate kidney damage: high blood pressure, certain diseases such as heart failure and cardiovascular risk factors such as high cholesterol, obesity, sedentary lifestyle or unbalanced diet.

How is diabetic nephropathy treated?

Managing the patient's diabetes, as well as monitoring their hypertension and hypercholesterolemy, if present, is essential for protecting their kidneys from potential kidney damage.

Proper glycaemic control must be ensured through anti-diabetic treatment, as high blood sugar levels favour the onset and progression of diabetic nephropathy.

Blood pressure must also be kept under control, that is, below 130/80 mmHg, with the help of effective anti-hypertensive medications.

The standard of care is usually an ACE inhibitor or an angiotensin II receptor blocker (ARB II) as they have nephroprotective effects, but combinations of several antihypertensive drugs are often necessary to achieve the blood pressure target. In this case, a thiazide diuretic is usually added.

To minimise proteinuria (the presence of protein in the urine), an ACE inhibitor can be combined with an ARB II (provided the diuretic treatment intake is increased) or the doses of ARB II can be increased.

Direct renin inhibitors, a new class of antihypertensive drugs, were also shown to have nephroprotective effects. 

In cases of dyslipidaemia (a very high concentration of lipids in the blood), the primary objective is to reduce the LDL cholesterol level to below 1g/l by means of lifestyle and dietary changes and drug treatments, if necessary.

Vaccination against hepatitis B is mandatory.

In addition, patients must stop smoking because it is toxic for the kidneys, and avoid cardiovascular risk factors, such as obesity or sedentary lifestyle.

Finally, in the case of end-stage kidney disease, the treatment is based on peritoneal dialysis, haemodialysis and transplantation (kidney alone, kidney-pancreas or islets of Langerhans).