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Nephrotic Syndrome – Causes, Symptoms and Treatment

Nephrotic syndrome is a kidney disorder characterized by excessive protein loss in the urine, fluid retention (edema), and elevated blood lipid levels.

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Things worth knowing about "Nephrotic Syndrome"

Nephrotic syndrome is a kidney disorder characterized by excessive protein loss in the urine, fluid retention (edema), and elevated blood lipid levels.

What is Nephrotic Syndrome?

Nephrotic syndrome is not a single disease but rather a collection of symptoms caused by severe damage to the kidney filters, known as glomeruli. Under normal conditions, the glomeruli prevent proteins from passing into the urine. When they are damaged, large amounts of protein – primarily albumin – are lost through the urine, leading to a characteristic set of clinical findings including edema, low blood protein levels, and lipid abnormalities.

Causes

Nephrotic syndrome can result from primary kidney diseases or secondary conditions caused by systemic disorders.

Primary Causes

Minimal Change Disease: The most common cause in children; the glomeruli appear normal under light microscopy but show changes under electron microscopy.
Focal Segmental Glomerulosclerosis (FSGS): Scarring of parts of the glomeruli; more common in adults.
Membranous Nephropathy: Deposits along the glomerular filtration membrane; frequently seen in older adults.
Membranoproliferative Glomerulonephritis: Inflammatory changes affecting the glomeruli.

Secondary Causes

Diabetes mellitus (diabetic nephropathy)
Systemic lupus erythematosus (lupus nephritis)
Amyloidosis (abnormal protein deposits in organs)
Infections such as hepatitis B, hepatitis C, and HIV
Certain medications and toxins

Symptoms

The classic symptoms of nephrotic syndrome result from protein loss and the metabolic consequences that follow:

Proteinuria: Excessive protein in the urine (more than 3.5 g per day in adults); urine may appear foamy.
Edema: Fluid retention, particularly around the eyelids (especially in the morning), legs, ankles, and abdomen (ascites).
Hypoalbuminemia: Low levels of albumin in the blood due to urinary protein loss.
Hyperlipidemia: Elevated blood fat levels (cholesterol, triglycerides) as the liver compensates for low protein levels.
Lipiduria: Fat particles in the urine.
Fatigue, general malaise, and reduced appetite.
Increased susceptibility to infections due to loss of immune proteins.
Elevated risk of blood clots (thrombosis) due to loss of anticoagulant proteins.

Diagnosis

The diagnosis of nephrotic syndrome is based on clinical evaluation and laboratory findings:

Urine tests: Detection of protein in the urine (proteinuria), foamy urine, and lipiduria.
Blood tests: Low albumin and total protein, elevated lipid levels, and assessment of kidney function (creatinine, urea, GFR).
Kidney biopsy: A small tissue sample taken from the kidney to identify the exact underlying cause; especially important in adults.
Imaging: Ultrasound of the kidneys to assess size and structure.
Additional tests to identify underlying conditions (e.g., autoantibodies for lupus, blood glucose for diabetes).

Treatment

Treatment is directed at the underlying cause of nephrotic syndrome while managing symptoms and preventing complications.

Treating the Underlying Condition

Corticosteroids (e.g., prednisolone) are the first-line treatment for minimal change disease and often produce a good response.
Immunosuppressive agents (e.g., cyclophosphamide, cyclosporine, mycophenolate mofetil, rituximab) are used for steroid-resistant or relapsing forms.
For secondary causes, treating the underlying disease is the priority (e.g., optimizing blood sugar control in diabetes).

Symptomatic and Supportive Therapy

Diuretics to reduce edema (e.g., furosemide).
ACE inhibitors or angiotensin receptor blockers (ARBs) to reduce proteinuria and protect kidney function.
Statins to manage hyperlipidemia.
Anticoagulants in patients with a high risk of thrombosis.
A diet low in salt and adequate in protein, as guided by a physician.

Complications

If left untreated, nephrotic syndrome can lead to serious complications including thrombosis (e.g., renal vein thrombosis), serious infections (due to loss of immune proteins), atherosclerosis (from persistent hyperlipidemia), and in severe cases, chronic kidney failure.

References

Kasper DL et al. - Harrison's Principles of Internal Medicine, 21st Edition. McGraw-Hill Education, 2022.
Kidney Disease: Improving Global Outcomes (KDIGO) - KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney International Supplements, 2012. Available at: https://kdigo.org
Orth SR, Ritz E. - The Nephrotic Syndrome. New England Journal of Medicine, 1998; 338(17):1202-1211.

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