Nephrotic syndromes: Pathology review

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Nephrotic syndromes: Pathology review



Nephrotic syndromes: Pathology review

USMLE® Step 1 questions

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USMLE® Step 1 style questions USMLE

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A 62-year-old woman comes to the clinic due to progressive fatigue, weight loss, and ankle swelling for the past two months. Physical examination shows 2+ pitting edema around the ankles. Cardiovascular and respiratory examinations are non-contributory. Laboratory results show a serum creatinine level of 3.1 mg/dL, albumin of 2.2 g/dL, and total cholesterol concentration of 290 mg/dL. Urinalysis results show 3+ proteinuria without hematuria or red cell casts. Renal biopsy is performed, and the results are shown below:  

Reproduced from: Wikipedia    

Which of the following is the most likely explanation for this patient’s condition?  


On the Nephrology ward, two people came in with the same symptoms: peripheral and periorbital edema.

One of them is a 10 year old caucasian boy named Brian who had recently been stung by a bee, and the other one is a 55 year old Hispanic individual named Gregory.

Lab tests show that both of them have hypoalbuminemia, hyperlipidemia and urinalysis showed frothy urine with fatty casts.

A 24-hour protein collection was done which showed massive proteinuria with more than 3.5 grams of protein lost through urine per day.

Both Brian and Gregory have nephrotic syndrome, but Brian has minimal change disease, while Gregory has focal segmental glo-merulo-sclerosis.

Nephrotic syndrome happens when the glomeruli are damaged and they become more permeable, so they start letting plasma proteins pass from the blood to the nephron and then into the urine.

This leads to proteinuria, which is when more than 3.5 grams of protein is excreted through the urine per day.

One of the proteins lost through urine is albumin and this leads to hypoalbuminemia.

This causes peripheral and periorbital edema since there’s less oncotic pressure in the blood vessels and the fluid leaks out.

On your tests, a nephrotic patient could also present with a hypercoagulable state and you will need to understand the pathology.

The reason for this is that the person is also losing antithrombin III proteins which is the body’s anticoagulant.

This means that individuals with nephrotic syndrome are prone to thrombotic and thromboembolic complications.

Immunoglobulins are another type of proteins lost through urine, which means that there’s a higher risk for infection.

Now, apart from proteins, lipids are also lost through urine, which gives the urine a frothy or foamy appearance.


Nephrotic syndrome is a kidney disorder characterized by abnormal filtration in the glomeruli, because glomeruli are damaged and are unable to properly retain proteins in the blood. This can lead to protein in the urine, low protein levels in the blood, and swelling.

Nephrotic syndrome is characterized by proteinuria that exceeds 3.5 grams per 24 hours. Loss of such a large amount of proteins leads to swelling (edema) in the legs, ankles, and other parts of the body, as well as an increased risk of infections and blood clots. Nephrotic syndrome can be caused by various conditions, including kidney diseases, diabetes, and lupus. It is usually treated with medications to control the underlying cause.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Comprehensive Clinical Nephrology E-Book" Elsevier Health Sciences (2018)
  4. "Minimal Change Disease" Clinical Journal of the American Society of Nephrology (2016)
  5. "Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants" Kidney International (2006)
  6. "Prophylactic Anticoagulation in Nephrotic Syndrome: A Clinical Conundrum" Journal of the American Society of Nephrology (2007)
  7. "Pathogenesis of membranous nephropathy: recent advances and future challenges" Nature Reviews Nephrology (2012)
  8. "Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014" JAMA (2016)

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