NEPHROTIC SYNDROME

:''Not to be confused with nephritic syndrome''
'Nephrotic syndrome' is a disorder where the kidneys have been damaged, causing them to leak protein from the blood into the urine. It is characterised by proteinuria (>3.5g/ day) hypoalbuminemia, hyperlipidemia and edema.

★ 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.

★ Hypertension (rarely)

★ Some patients may notice foamy urine, due to a lowering of the specific gravity by the severe proteinuria. Actual urinary complaints such as hematuria or oliguria are uncommon, and are seen commonly in nephritic syndrome.

★ May have features of underlying cause, such rash associated with SLE, or neuropathy with diabetes.

★ Examination should also exclude other causes of gross edema- especially the cardiovascular and hepatic system.

Contents

Investigations

Pathogenesis

Causes of nephrotic syndrome

Differential diagnosis of gross edema

Treatment

Complications

Prognosis

References

External links

Investigations

The following are baseline, essential investigations

★ Urine sample shows proteinuria. It is also examined for active casts; which is more a feature of active nephritis.

★ Hypoalbuminemia: albumin levels in blood < 30g/L

★ High levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL

★ Electrolytes, urea and creatinine (EUCs): to evaluate renal function
Furher investigations are indicated if the cause is not clear

★ Biopsy of kidney (not usually done in children)

★ Auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis)

Pathogenesis

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 inflammation and hyalinisation so that small proteins, such as albumins immunoglobulins and anti-thrombin can pass through the kidneys into urine.
Albumin is the major protein in the blood which maintains colloid osmotic pressure- this prevents leakage of blood from vessels into tissue. However, experiments show that the edema formation in nephrotic syndrome is more so due to microvascular damage and intense salt and water retention by the damaged kidneys (due to increased angiotensin secretion). The mechanism is very complex and still not fully understood.
In response to leakage of albumin, the liver begins to make more of all its proteins, and levels of large proteins (such as alpha 2-macroglobulin and lipoproteins) increase. The excess lipoproteins end up in the urine filtrate, which is then rebsorbed by the tubular cells, which end up shedding and forming oval fat bodies or fatty casts.

Causes of nephrotic syndrome

A) Primary renal diseases
Any of the glomerulonephritides can cause nephrotic syndrome; but in adults the most common ones are membranous, FSGS, and minimal change disease. In children 95% of cases are due to minimal change disease.
B) Secondary renal diseases
Many and varied. Causes include

★ Diabetes

★ SLE

★ Amyloidosis
However, ''Idiopathic Nephritic syndrome'', has no known causes.

Differential diagnosis of gross edema

When someone presents with generalised edema, the following causes should be excluded
1) Heart failure:
The patient is older, with a history of heart disease.
Jugular venous pressure is elevated on examination, might hear heart murmurs
An echocardiogram is the gold standard investigation
2) Liver failure:
History suggestive of hepatitis/ cirrhosis: alcoholic, IV drug user, some hereditary causes
Stigmata of liver disease are seen: dilated veins over umbilicus (caput medusae), scratch marks, enlarged spleen, spider angiomata, encephalopathy, bruising, nodular liver
3) Acute fluid overload in someone with kidney failure
These people are known to have kidney failure, and have either drunk too much or missed their dialysis.
4) Metastatic cancer:
When cancer seeds the lungs or abdomen it causes effusions and fluid accumulation due to obstruction of lymphatics and veins as well as serous exudation.

Treatment

Treatment includes:
A) General measures (supportive)
Monitoring and maintaining euvolemia (the correct amount of fluid in the body)
- monitoring urine output, BP regularly
- fluid restrict to 1L
- diuretics (IV furosemide)
Monitoring kidney function
-do EUCs daily and calculating GFR
Prevent and treat any complications [see below]
Albumin infusions are generally not used because their effect last only transiently.
B) Specific treatment of underlying cause
Immunosupression for the glomerulonephritides (steroids, cyclosporin)
Achieving stricter blood glucose control if diabetic
BP control. ACE inhibitors are the drug of choice. Independent of their blood pressure lowering effect, they have been shown to decrease protein loss.

Complications

Venous thrombosis: due to leak of anti-thrombin 3, which helps prevent thrombosis. This often occurs in the renal veins. Treatment is with heparin.
Infection: due to leakage of immunoglobulins, encapsulated bacteria such as ''Haemophilus influenzae'' and ''Streptococcus pneumonia'' can cause infection.
Acute renal failure is due to hypovolemia. Despite the excess of fluid in the tissues, there is ''less'' fluid in the vasculature. Decreased blood flow to the kidneys causes them to shutdown. Thus it is a tricky task to get rid of excess fluid in the body while maintaining ciculalatory euvolemia.
Pulmonary edema: again due to fluid leak, sometimes it leaks into lungs causing hypoxia and dyspnoea.
Do not give diuretics.

Prognosis

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).

References

★ Brenner & Rector's The Kidney, seventh edition, Brenner, Barry M. (editor), , , W.B. Saunders Company, 2004, ISBN 0-7216-0164-2

★ www.emedicine.com

External links

★ NephCure Foundation Only organization solely committed to support research seeking the cause of Nephrotic Syndrome and FSGS, improve treatment and find the cure.

★ 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

★ KidComm - An online resource for parents dealing with childhood kidney diseases (FSGS, Nephrotic Syndrome and others). Features an email support group for parents plus an email support group for adults with kidney disease (YakTalk).