Nephrotic Syndrome Pearl of the Day

Nephrotic Syndrome


Think about it like this: Glomerular basement membrane problem, you spill all your protein (albumin) from your plasma into your urine, leading to high urine protein, low serum protein, and edema. It may help to simply think of it as decreased oncotic pressure causing movement of fluid from the intravascular space to the interstitial space; in reality the pathophysiology of edema in nephrotic syndrome is a little more complicated - has to do with a combination of primary (due to renal disease) and secondary (via RAS pathway) sodium retention.


nephrotic syndrome is defined by:

1. Heavy proteinuria

(protein excretion > 3.5 g/24 hours; UPEE>3.5; >2 in children)

2. Hypoalbuminemia

(< 3 g/dL; <2.5 in children)

3. Peripheral edema

(Hyperlipidemia and thrombotic disease are frequently observed with nephrotic syndrome but not required for the diagnosis, may also be immunosuppressed)

(UA should have no significant hematuria, casts, or RBCs which would suggest a nephritic picture)

Measuring Proteinuria 

The most convenient way is to calculate a 

Urinary Protein Excretion Estimation (UPEE)

(insert infantile bathroom humor here)

UPEE (g/day) = (urine protein (mg/dL)) / (urine creatinine (mg/dL))

This works because a random urine protein to urine creatinine ratio very closely approximates the true 24 hour urine protein excretion, as shown below.

Image result for urine protein to creatinine ratio


UPEE <2.0 g/day —> Within normal limits

UPEE 2.0–3.5 g/day —> Above normal limit - investigate further

UPEE >3.5 g/day —>Nephrotic range

Nephrotic vs Nephritic

Remember to always think of nephrotic syndrome in contrast to nephritic syndrome! I love this image:

Image result for nephrotic nephritic



Make the diagnosis: urinalysis, urine protein, urine creatinine, serum albumin, a lipid panel, basic metabolic panel

2. Consider further testing to differentiate primary vs secondary on a case-by-case basis: HIV, ANA, complement (C3/C4 and total hemolytic complement), serum free light chains and urine protein electrophoresis and immunofixation, syphilis serology, hepatitis B and hepatitis C serologies, and the measurement of cryoglobulins; when in doubt, run it by nephrology

3. Consider testing for complications: POCUS for pleural effusion/ascites; CXR for pleural effusion, dopplers or CTA for venous thromboembolism; antithrombin III, plasminogen, protein S (hyper coagulability); immunoglobulins; 

3. Usually renal biopsy is required for definitive diagnosis


In children 10 years or younger, it is minimal change disease (MCD) 90% of the time. Most MCD responds to corticosteroids.

In children >10 years, it is MCD >50% of the time.

In adults focal segmental glomerulosclerosis (FSGS) is the most common etiology (35%). It can be primary/idiopathic, or associated with other disease processes, most commonly HIV or massive obesity.


In most cases, a biopsy will be needed in order to confirm diagnosis.

Admit patients with severe edema, pulmonary effusions or respiratory symptoms, or signs and symptoms suggestive of systemic infection or thrombotic complications to the hospital.

Discharge with nephrology follow up ASAP and low salt diet if only mild-moderate edema.

In kids age 1-10, may consider starting a course of steroids (

Prednisone 2 mg/kg/day x 6 wks then 1.5 mg/kg every other day x 6 wks) only if:

  • Age 1-10

  • No renal insuficiency

  • No macroscopic hematuria

  • No sx systemic disease

  • No HTN

  • Normal C3 levels

Special scenarios

Nephrotic syndrome + chest pain?

DDX: PE and myocardial ischemia because hyperthrombotic, pneumonia (immunosuppressed), pleural effusion

Consider POCUS, CXR, CTA, EKG, cardiac enzymes

Severe edema:

Requires lasix

May need albumin infusion prior to lasix if anasarca or signs of intravascular depletion

Hopefully you’ve already consulted ICU if you’re having to do this

Significant hypertension:



Pleural effusions/ascites are common in severe fluid overload

Both are extra susceptible to infection in this state

Low threshold for diagnostic paracentesis/thoracentesis


Uptodate: Overview of heavy proteinuria and the nephrotic syndrome

Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e: Chapter 134: Renal Emergencies in Children

Michael Mojica, MD. “PEM Guides.” NYU Langone Medical Center, 2015. iBooks.

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