How does the disease develop

The development of diabetic nephropathy is still controversial, with the so-called “metabolic theory” being considered the most likely. This theory assumes that the permanently elevated blood sugar level initially leads to damage of these structures and associated functional changes due to the attachment of sugar molecules to body proteins, such as those found in the kidneys (basement membrane of the renal glomeruli, walls of the blood vessels). In the blood vessels, this leads to so-called “diabetic microangiopathy” (= damage to the smallest vessels).

In addition, there is increased blood flow to the kidney, which together with this damage leads to a loss of selectivity of the kidney filter, which normally strictly controls the blood components that are filtered into the urine, so that larger components such as proteins are increasingly excreted in the urine. This results in a deficiency of these blood components, which can lead to various symptoms. The presence of diabetic nephropathy usually goes unnoticed for years, as the initially occurring increased blood flow in the kidney does not cause any symptoms.

Over the years, the structural changes described above develop in the vessels of the kidney and in the tissue itself, which after a long time lead to increased excretion of the main blood protein (albumin) as the first symptom; a microalbuminuria with a loss of up to 300 mg albumin per day is present. At this stage, the disease is not yet associated with symptoms for the patient, there may be a beginning permanent increase in blood pressure.If therapy is started immediately at this stage, the progression of the disease can be delayed or prevented. If this is not done, there is a steady increase in albumin excretion, which is characterized by a transition to macroalbuminuria (excretion of more than 300 mg per day).

If the progress continues, the kidney becomes increasingly insufficient and more and more blood components (including larger proteins) are lost to the body unintentionally via urine, which also leads to an accumulation of toxins (especially creatinine and urea) in the blood, which would have to be excreted via the kidney. In advanced stages, there is also a permanent increase in blood pressure which has a negative effect on other organs besides the kidneys, such as the heart. Since 1983, the disease has been divided into five stages, with increasing primary urine excretion being characteristic of the first stage.

In stage II, renal function appears to be normal; although there is no protein loss yet, microscopic examination of a kidney sample (biopsy) already reveals typical changes. From stage III on, microalbuminuria occurs, which, due to the transition to macroalbuminuria, exceeds the threshold to stage four. In stage V, the kidney is damaged to such an extent that chronic renal replacement therapy, for example by dialysis, becomes unavoidable.

“Visible” symptoms usually only occur as soon as more than 3.5 grams of protein are excreted via the kidney in 24 hours, resulting in a significant protein deficiency in the blood, which causes water from the vessels to pass into the surrounding tissue (edema formation). In addition to the “water in the legs“, patients often report the associated increase in weight and foaming urine. As a complication, the risk of forming blood clots (thromboses) increases; furthermore, the abnormal excretion of sugar via the urine leads to an increased rate of urinary tract infections.