Nephrotic syndrome is a disorder where the kidneys have been damaged, causing them to leak protein from the blood into the urine. It is a fairly benign disease when it occurs in childhood, but may lead on to chronic renal failure, especially in adults, or be a sign of an underlying serious disease such as systemic lupus erythematosus or a malignancy.

Signs and symptoms

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• The most common sign is excess fluid in the body. This may take several forms:
  • Puffiness around the eyes, characteristically in the morning.
  • Edema over the legs which is pitting (i.e. leaves a little pit when the fluid is pressed out, which resolves over a few seconds).
  • Fluid in the pleural cavity causing pleural effusion.
  • Fluid in the peritoneal cavity causing ascites.
• Renal failure
• Hypertension (rarely)
• Some patients may notice foamy urine, due to a lowering of the specific gravity by the high amount of proteinuria. Actual urinary complaints such as hematuria or oliguria are uncommon, and are seen commonly in nephritic syndrome.

Laboratory Findings

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• Proteinuria (Nephrotic syndrome is arbitrarily defined as urinary protein loss of greater than 3.5 g/day)
• Hypoalbuminemia
• High levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL
• Lipiduria
• Coagulation abnormalities: renal vein thrombosis more common than thrombosis in nonrenal circulation.

Diagnosis

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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 or a random albumin to creatinine ratio (ACR). A diagnosis of nephrotic syndrome requires more than 3.5 grams of proteinuria per 1.73 square meter surface area in adults. It is important to note, however, that nephrotic syndrome can be associated with lesser degrees of proteinuria, and many of the complications of nephrotic syndrome are due to hypoalbuminemia and the resultant decreased plasma oncotic pressure. Therefore, the same consequences can result independently of the level of proteinuria, as long as the same degree of hypoalbuminemia is achieved.

Once the diagnosis of nephrotic syndrome is reached, further investigations must focus on the underlying disease process.

Pathogenesis

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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 glomeruli become damaged due to diabetes, glomerulonephritis, or even prolonged hypertension (high blood pressure) so 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.

Edema usually occurs due to salt and water retention by the diseased kidneys as well as sometimes due to the reduced colloid oncotic pressure (because of reduced albumin in the plasma). Cholesterol levels are also increased, and though the mechanism isn't fully understood, it is thought to be due to the increased synthesis of lipoproteins in the liver. There is an increased tendency for thrombosis (up to 25%), perhaps due to urinary loss of inhibitors of clotting such as antithrombin III.

Similar loss of immunoglobulins increases the risks of infections and relevant immunisation is recommended against pneumococcus, Haemophilus influenzae, and meningococcus.

Differential diagnosis

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Primary renal diseases

• Minimal change disease: The most common cause (80%) of nephrotic syndrome in children. It is so called because on renal biopsy there is no change on light microscopy, only electron microscopy reveals fusion of foot processes.
• Membranous glomerulonephritis: The most common primary renal cause of nephrotic syndrome in adults in developing countries.
• Focal segmental glomerulosclerosis
• Membranoproliferative glomerulonephritis
• Mesangial proliferative glomerulonephritis

Secondary renal diseases

• Genetic disorders: Alport syndrome, congenital nephrotic syndrome, sickle cell disease
• Metabolic diseases: Diabetes mellitus is the most common cause of secondary nephrotic syndrome in adults in developing countriesamyloidosis; amyloidosis
• Autoimmune diseases: Systemic lupus erythematosus, Henoch-Schonlein purpura, vasculitides
• Malignant diseases: Multiple myeloma; cancer: lung, colon, breast, and stomach; leukemia, lymphoma
• Infectious diseases
  • Bacterial: Infectious endocarditis
  • Viral: Human immunodeficiency virus, hepatitis B, hepatitis C
  • Protozoal: Malaria
  • Helminthic: Schistosomiasis

Others

• Drugs: Nonsteroidal antiinflammatory agents, gold, heroin, interferon alfa, lithium, penicillamine, mercury, probenecid, captopril
• Pregnancy: Preeclampsia
• Transplant rejection

Treatment

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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 disease) and/or other immunosuppressive therapy. 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.

Prognosis

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The prognosis depends on the cause of nephrotic syndrome. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. However other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).

Reference

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External links

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• Childhood Nephrotic Syndrome - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
• Adult Nephrotic Syndrome - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
• Nephcure - a foundation that supports people coping with FSGS and nephrotic syndrome.
• KidComm - a site devoted to kidney disorders in children.

Nephrology | Pediatrics | Syndromes

Syndrome néphrotique | Nefrotiskt syndrom | ネフローゼ症候群 | Nefrotisch syndroom | Síndrome nefrótica