What is nephrotic syndrome?

Nephrotic syndrome is characterized by the combination of the presence of protein in your urine- more than 3 grams of protein in urine in one day- and oedema.  Oedema is the medical term for swelling which particularly occurs around your eyes and in your feet and ankles.

This disease occurs as a result of damage caused to the kidneys which may be due to diabetes mellitus, minimal change disease, systemic lupus erythematosus and membranous nephropathy amongst others.  The damage caused leads to release of excess protein into your urine which manifests as oedema and a foamy urine.  In children, the first sign is swelling of the face followed by swelling of the entire body.

Nephrotic syndrome affects people of all ages and races.  In the United States, diabetic nephropathy- kidney disease due to diabetes mellitus- is the most common form of nephrotic syndrome which affects 50 people per million population.

To treat nephrotic syndrome effectively, the cause must be identified and treated accordingly.  Adjusting your diet while taking the medications your doctor prescribed, will increase your rate of recovery.

What are the causes and risk factors of nephrotic syndrome?

There are tiny blood vessels called glomeruli, found inside your kidneys that provides blood for filtration.  The filtration process is important as it removes unwanted substances from the body though urine and reabsorbs or keeps the necessary substances.  In nephrotic syndrome this process is impaired as the damage caused to the glomeruli allows excess proteins known as albumin to be excreted in urine.  Albumin is responsible for the maintenance of the right amount of fluids in your body and excessive loss of albumin (proteinuria) results in accumulation of water in your tissues.  The possible causes of nephrotic syndrome include:

·         Minimal change disease: It is the most common form of nephrotic syndrome in children.  When a sample of your kidney tissue is examined under the microscope, it will appear normal or nearly normal despite you having an abnormal kidney function.  In addition, the exact cause for the deranged kidney function cannot be found.

·         Diabetic kidney disease:  This is also known as diabetic nephropathy.  This is when you suffer from diabetes mellitus for a long time and diabetic nephropathy occurs as a complication.  The elevated blood sugar level affects the glomeruli which results in excess loss of albumin.

·         Membranous nephropathy: This is when your antibodies made by your immune system get deposited in the membranes within the glomeruli resulting in the thickening of the membranes.  It may be associated with systemic lupus erythematosus (SLE) and hepatitis B infection amongst others.  Around 6000 American citizens are affected by membranous nephropathy each year.

·         Focal segmental glomerulosclerosis: This is when there is presence of scar tissue in some parts of the glomeruli which results in inappropriate filtration.

·         Amyloidosis: Amyloidosis is the accumulation of amyloid proteins within the organs of the body.  When these proteins accumulate in your kidneys, it may damage the kidney’s filtering property.

·         Medications: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has been associated with minimal change nephropathy.  There are certain drugs which were used to treat rheumatic diseases such as gold and penicillamine that may lead to membranous nephropathy.  Intravenous bisphosphonates and lithium were linked to focal segmental glomerulosclerosis.

·         Certain infections: Human immunodeficiency virus (HIV), hepatitis B & C and malaria can increase your risk of developing nephrotic syndrome.

·         Pre-eclampsia: This is when your blood pressure increases during pregnancy and there are often signs of organ damage to the liver and kidneys.  Proteinuria occurring in 3^rd trimester pregnant women is the typical finding in someone suffering from pre-eclampsia.

What are the signs and symptoms of nephrotic syndrome?

The signs and symptoms of nephrotic syndrome include:

·         Oedema: In children, the first sign of nephrotic syndrome is swelling of the face which is followed by the swelling of the entire body.  In adults, oedema is present particularly around your eyes and in your feet and ankles.

·         Foamy urine: The presence of excess proteins in your urine will make it appear foamy.

·         Weight gain:  The accumulation of fluids due to loss of albumin will increase your weight.

·         Loss of appetite

·         Excessive fatigue

·         Pleural effusion:  This is when there is fluid accumulation in between your lungs and chest cavity.

·         Hypertension

Making a diagnosis

To make a diagnosis, your doctor will take a detailed history from you to know more about your symptoms.  After the history taking, he/she will perform a thorough physical examination to look for signs of nephrotic syndrome.  Your doctor will order some tests in order to confirm the diagnosis and these include:

·         Urine studies: Urinalysis is the first test used to diagnose nephrotic syndrome.  On a urine dipstick a range of proteinuria of +3 or +4 can be obtained.  Urine sediment examination is used to identify red blood cells in the urine sample.  24 hour urine protein measurement is done to measure the total amount of protein being excreted by the kidney in one day- in nephrotic syndrome is it usually more than 10 milligram.  Urine protein electrophoresis is used to determine the exact type of the protein- this is because if the proteinuria does not include albumin the diagnosis may be wrong such as in the case of multiple myeloma where the protein involved is Bence-Jones proteins.

·         Kidney biopsy: In children, kidney biopsy is usually required if there is suspicion of congenital nephrotic syndrome and if the child is above the age of 8 years at onset amongst others.  In adult, if the cause of the nephrotic syndrome cannot be determined, a kidney biopsy is requested.  To perform a kidney biopsy, your doctor will insert a needle into your skin to reach your kidneys where a small sample of your kidney tissue will be removed.  The sample is then sent to the laboratory to be examined under the microscope.

·         Blood tests:  Serum creatinine is ordered to assess your kidney function- an increase in creatinine level indicates an impairment in kidney function.  Serum albumin level is typically low in nephrotic syndrome and is usually below 3.5-4.5 g/dL.  Test for HIV, hepatitis B & C and SLE are also done.

What are the treatments for nephrotic syndrome?

The treatment of nephrotic syndrome depends on the cause.  The treatments of nephrotic syndrome include:

·         Diuretics: These are also known as water pills.  These medications help to remove the excess fluids from your body and hence relieve your symptoms.  Examples include furosemide, spironolactone and thiazides.

·         Anticoagulants: These drugs are also known as blood thinners and are used to reduce your blood’s ability to clot.  Examples include warfarin, heparin, apixaban and dabigatran.

·         Statins: Statins are cholesterol-reducing drugs.  Examples include atorvastatin, lovastatin, rosuvastatin and simvastatin.

·         Immunosuppressant drugs: These drugs are used to decrease the strength of your immune system.  This is done because while your body is trying to repair the damaged caused, it is causing inflammation which is worsening your condition.  Examples include corticosteroids, cyclophosphamide, mycophenolate and calcineurin inhibitors.  In children, corticosteroids are the mainstay of the management of nephrotic syndrome.

·         Antihypertensive medications: These drugs are used to reduce your blood pressure in order to limit further damage caused to the glomeruli.  Examples include angiotensin converting enzyme inhibitors (ACE inhibitors and examples include enalapril, captopril and lisinopril.  Another class of medication can be used and is known as angiotensin receptor blockers.  Examples include losartan and candesartan.

·         Diet modifications: Eating a low salt diet and drinking less fluids may help to increase your rate of recovery.

What are the complications of nephrotic syndrome?

If nephrotic syndrome is left untreated, several complications may ensue and these include:

·         Thrombosis: Formation of blood clots in your veins due to loss of blood proteins which are responsible to prevent clotting, known as coagulation factors.

·         Elevated cholesterol and triglyceride levels: These levels increases in an attempt to make more albumin by your liver.

·         Weight loss: This is due to the loss of too much protein leading to malnutrition.

·         Anaemia: This is due to the loss of red blood cells along with albumin in urine.

·         High blood pressure: This occurs due to the damage of your glomeruli which leads to even more fluids being accumulated.

·         Acute kidney injury: As your kidney’s ability to clean your blood diminishes, the waste products accumulates which may require emergency dialysis.

·         Chronic kidney disease: With time, your kidney loses its function and dialysis or a kidney transplant will be required.

·         Infections: People affected by nephrotic syndrome are more prone to infections.

Prognosis

The prognosis for people with minimal change nephropathy is excellent.  However, for those affected by focal segmental glomerulosclerosis, only 20% of people will be continue to have proteinuria.  Seeking medical help early is essential to prevent complications and help improve the prognosis.

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Sinnakirouchenan, R., 2020. Nephrotic Syndrome Workup.