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Signs and symptoms
The most common sign of nephrotic syndrome is oedema of the periphery which is pitting (i.e. leaves a little pit when the fluid is pressed out, which resolves over a few seconds). Fluid is also accumulated elsewhere, e.g. in the pleural cavity and the peritoneal cavity. Occasionally, thrombosis is the first symptom of nephrotic syndrome, or high levels of cholesterol or hypertension.
High urine levels of protein can readily be detected with a dipstick. The best way to make a diagnosis is to quantify the amount of protein in a 24-hour urine sample. When this is more than a few grams in the presence of the above symptoms, there is a diagnosis of nephrotic syndrome. Other investigations might include blood tests (creatinine, urea, electrolytes, glucose), renal ultrasound, and occasionally renal biopsy.
The glomeruli of the kidneys are the parts that normally filter the blood. They consist of capillaries that are fenestrated (leaky, due to little holes called fenestrae or windows) and that allow fluid, salts and other small solutes to flow through, but normally not proteins.
In nephrotic syndrome, the glomerulus has been damaged by diabetes, glomerulonephritis or even prolonged hypertension (high blood pressure). This means that small proteins, such as albumin can pass through the kidneys into urine.
Nephrotic syndrome is characterised by proteinuria (detectable protein in the urine), and low albumin levels in blood plasma. As a compensation, the liver begins to make more of all its proteins, and levels of large proteins (such as alpha 2-macroglobulin) increase.
Lack of albumin will cause oedema (swelling), as water moves from the blood into the tissues. Cholesterol levels are also increased, and though the mechanism isn't fully understood, it is thought to be a result of cholesterol processing enzymes being lost into urine. There is an increased tendency for thrombosis (up to 25%) due to renal loss of antithrombin III and Factor X.
In children, 80% of nephrotic syndrome is caused by minimal change nephropathy, so called because on renal biopsy there is very small change of the normal kidney tissue. The remainder have focal segmental glomerulosclerosis or IgA nephritis (which usually does not present with nephrotic syndrome).
In adults, the main causes are membranous nephropathy and focal segmental glomerulosclerosis (the names are descriptions of the changes in renal tissue on light microscopy), as well as diabetes, hypertension, and lupus erythematosus.
When treating nephrotic syndrome, if the underlying problem is apparent, (e.g. hypertension, diabetes) then this should be addressed. Some types of nephrotic syndrome respond to therapy with steroids (especially minimal change nephropathy). Others are followed up in clinic with management of blood pressure, cholesterol levels, coagulation problems and renal failure. In most types of nephrotic syndrome, the protein excretion improves with the use of ACE inhibitor medication. This is generally used for the treatment of hypertension, but can also improve protein loss, even if the blood pressure is normal.
Nephrotic syndrome can lead to chronic renal failure.
- KidComm - childhood nephrotic syndrome
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