Nephrotic syndrome

The nephrotic syndrome is a medical term for several symptoms that occur in various diseases of the glomerulus ( in glomeruli ).

It is characterized by four main symptoms:

• Large proteinuria
• Hypoproteinemia
• Hyperlipoproteinemia
• Edema

Of the so-called large proteinuria one speaks at a protein excretion in the urine of more than 3 to 3.5 g per 24 hours in children greater than 1 g per square meter of body surface area per 24 hours. The albumin in the serum is reduced to less than 2.5 g / dl.

Pathogenesis

The nephrotic syndrome is caused by an increased permeability of the glomerular proteins (proteins ), it will be filtered protein molecules > 60 kDa. The largest proportion of the protein loss has albumin, which has a mass of about 65 kD and accounts for about 60 % of the dissolved in the blood plasma protein. There will be a hypoproteinemia with hypoalbuminemia as well as by the increased urinary protein excretion of proteinuria. A daily protein excretion of more than 4 g indicates a significant deterioration of the filtering function of the kidneys. Regular less than 0.05 g of protein per day is excreted through the kidneys.

With decreasing albumin level in the blood, it also comes to the so-called hypalbuminämischen edema. These occur due to a loss of protein due to the decreased colloid osmotic pressure in the blood vessels. This leads to loss of fluid from the blood plasma into the tissue surrounding the vessels. The edema is more pronounced the lower the protein or albumin content in the blood.

The loss of protein, the body is now trying to counter by replacing this loss as soon as possible. Leads to an increased production of lipoproteins by the liver, resulting in conjunction with the occurring in the loss of the enzyme lipoprotein lipase proteinuria to the so-called hyperlipidemia. In addition, because of its size and nature of the particles of the loss of cholesterol - and triglyceride -transporting lipoproteins is relatively low, so that the ratio of blood lipids among themselves unfavorably changes ( dyslipidemia ).

The increased loss of fluid from the vessels into the tissue it comes to hypovolemia. This lack of fluid stimulates the now so-called RAAS ( renin -angiotensin -aldosterone system ) of the body. This system is intended to compensate for the fluid loss by ensuring a narrowing of the vessels and thus a rise in blood pressure. Also is retained by the kidneys increased water and sodium in the body. But that this mechanism leads to elevated blood pressure to an increase in glomerular filtration rate (GFR ), and thus to further protein loss ( vicious circle ).

Causes

The nephrotic syndrome is in itself not a disease but a similar symptom complex, behind which hide various diseases. The most common causes of nephrotic syndrome:

• Membranous glomerulonephritis ( with about 30% of most common cause in adults )
• Minimal change disease ( most common in children with > 90% in adults, 20 %)
• Focal segmental glomerulosclerosis (about 15 % in the colored population about 50%)

Rarer causes:

• Membranoproliferative glomerulonephritis ( often approximately 5 %)
• Diabetic glomerulosclerosis
• C1q nephropathy
• Renal involvement in collagen ( esp. systemic LE) and other autoimmune diseases
• Renal involvement in amyloidosis
• Renal injury by a plasmacytoma
• Nierenvenenstauung
• Acute interstitial nephritis, toxic - pharmacological, such as gold, penicillamine, NSAIDs etc.
• Complication of quartan malaria ( Malarianephrose )

Symptoms

Besides the already mentioned cardinal symptoms of nephrotic syndrome exist in the patients nor the symptoms of the underlying disease -causing. In the course of the disease, there is an increased tendency to infections, as passing through the loss of protein to antibodies, especially IgG, is lost. Furthermore, there is a loss of antithrombin III. AT III is a component of blood plasma and has a strong inhibitory effect on blood coagulation. Lost AT III, is leading to increased clotting of blood in the vessels and thus to thrombosis, in particular the renal veins. By continuing damage to the kidneys show signs of renal failure in advanced stages, such as flank pain, bloody urine, decreased urine output.

Therapy

• In the foreground a therapy starts with the treatment of the underlying disease and the elimination of toxic causes as triggers of nephrotic syndrome.
• Salt poor diet
• Adequate protein intake ( 1-2g/kg body weight / day) of natural fat sources with the aim of a positive nitrogen balance. Some sources recommend using more of a protein restriction.
• Restriction of fluid intake and diuretics (especially potassium-sparing diuretics and thiazide diuretics, loop diuretics also possibly later )
• Treatment of bacterial infections and prophylaxis (recommended pneumococcal vaccination), the administration of immunoglobulins makes little sense: they quickly suffer the same fate as the albumins.
• Lower cholesterol by CSE inhibitors
• Treatment of high blood pressure, depending on the degree of renal function. Medium of choice is an ACE inhibitor.
• Standardized prednisolone as causal treatment, because thereby the protein permeability of the basement membrane is affected.
• Upon a decrease of the AT-III to 70% with a Marcumarisierung is indicated.

Classification

• Type I: Complete healing after a thrust
• Type II: tendency to relapse in complete remission
• Type III: Residual renal impairment despite partial remission
• Type IV: Rapid progression with poor prognosis

History

In ancient Greece, the accumulation of body water as a single disease ( dropsy, hydropisis ) was considered. 1827 saw Richard Bright, that some of the patients suffered with dropsy also at an increased urinary protein excretion and renal pathological changes. 1914 Franz Volhard and Theodor Fahr distinction between degenerative ( nephrosis ), inflammatory ( nephritis) and arteriosclerotic ( sclerosis) kidney diseases. 1963 examined George Schreiner urinary protein excretion of 186 patients with clinical signs of nephrotic syndrome. The lowest amount of protein, which he observed it, was 3.5 g per day. 1983 Ginsberg suggested before, instead of collecting urine over 24 hours, the ratio between protein and creatinine in a urine sample spontaneously left to be determined. Since the excretion of creatinine in the urine is coincidentally about 1 g per day, he proposed as limits for nephrotic syndrome before a protein / creatinine ratio in urine of 3.5 g protein / g creatinine. In recent increase the excretion of albumin in the urine is determined, which is to provide more accurate values ​​than the determination of the total protein. As a lower limit of nephrotic syndrome an albumin / creatinine ratio in urine of 2.2 g of albumin per gram of creatinine was proposed by Stoycheff.