Nephrotic Syndrome Made Easy

Welcome to our nephrotic syndrome series! In this first post, you’ll find a general overview of the findings of nephrotic syndrome and how to approach diagnosis.

Nephrotic syndrome is the constellation of signs and symptoms that arises when the glomerular filtration membrane is damaged and protein begins passing into the urine in large quantities. It is defined as the combination of heavy proteinuria with associated hypoalbuminemia, edema, and hyperlipidemia.

A decrease in plasma albumin lowers the plasma oncotic pressure and leads to a fluid shift from the intravascular space into the tissue.  When the kidneys recognize that the intravascular volume is low, they will begin retaining fluid, exacerbating the edema. The liver also attempts to correct the decrease in oncotic pressure by producing more lipoproteins which leads to the associated hyperlipidemia. Together, these factors combine to form the “underfill hypothesis” of the pathophysiology behind nephrotic syndrome.

All patients with nephrotic syndrome should be monitored for certain complications. Order a CMP to evaluate for hyperalbuminemia, hyponatremia, and hypocalcemia along with a lipid panel to assess for hypercholesterolemia.


Heavy proteinuria in a patient with edema is diagnostic of nephrotic syndrome. Classically, this is defined as losing more than 3.5 grams of protein in 24 hours of collected urine. Measuring the ratio of protein to creatinine in a single urine sample is commonly used as a screening test since it correlates well to the 24-hour protein measurement and does not require the patient to collect a day’s worth of urine. Heavy proteinuria is considered to be any ratio greater than 3.5.

After determining that the patient has nephrotic syndrome, the next step is understanding why. Nephrotic syndrome is the result of either a primary renal process or secondary to a systemic disease, such as diabetes or hypertension. While some patients will eventually need a biopsy, certain labs should be ordered first to evaluate for primary renal causes. These labs include ANA, anti-dsDNA, HIV, complements, anti-PLA2R, and a hepatitis panel.

There are four primary renal diseases that cause nephrotic syndrome:

·     Minimal change disease

·     Focal segmental glomerulosclerosis

·     Membranous nephropathy

·     Membranoproliferative glomerulonephritis

Each of these have a unique pathophysiology and generally have distinct natural courses of progression. We’ve dedicated an upcoming post to renal biopsies and to each primary cause so that we can dive deep into these diseases—stay tuned!

Brought to you by Jennifer Kaplan and Sayna Norouzi, MD


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