Skip to main content

Saturn Medic

Clinical Subject Page

Nephrotic Syndrome

Nephrotic Syndrome is a clinical syndrome caused by increased glomerular permeability to proteins, resulting in heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia

Also called

protein-losing nephropathy

ICD-10

N04

Specialty

Nephrology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

–Nephrotic Syndrome is characterized by:

  • Heavy proteinuria
  • Hypoalbuminemia
  • Generalized edema
  • Hyperlipidemia

 

-It may be caused by a primary glomerular disease or secondary systemic disease.

-Common primary causes include:

      • Minimal Change Disease
      • Focal Segmental Glomerulosclerosis
      • Membranous Nephropathy

Etiology & Risk Factors

-Etiology

–Primary Renal Causes

  • Minimal Change Disease
  • Focal Segmental Glomerulosclerosis
  • Membranous Nephropathy

 

-Secondary Causes

  • Diabetes Mellitus
  • Systemic Lupus Erythematosus
  • Amyloidosis
  • Hepatitis B/C
  • HIV
  • Malignancy
  • Drugs such as NSAIDs

 

-Risk Factors:

  • Diabetes Mellitus
  • Systemic Lupus Erythematosus
  • Obesity
  • Chronic infections
  • Malignancy
  • Nephrotoxic medications

Pathophysiology

-Glomerular injury → ↑ glomerular permeability → heavy urinary protein loss → ↓ serum albumin → ↓ plasma oncotic pressure → fluid shifts into tissues → edema

-Protein loss + hepatic compensation → ↑ hepatic lipoprotein production → hyperlipidemia

-Urinary loss of anticoagulant proteins → hypercoagulability → thrombosis

-Urinary loss of immunoglobulins → impaired immunity → increased infection risk

Clinical Presentation

-Symptoms:

  • Periorbital edema
  • Leg swelling
  • Generalized edema
  • Frothy urine
  • Weight gain from fluid retention
  • Fatigue
  • Reduced urine output in severe cases

 

-Signs:

  • Massive edema
  • Ascites
  • Pleural effusion
  • Acute kidney injury
  • Thromboembolism
  • Severe infection
Nephrotic Syndrome Overview
Nephrotic Syndrome Overview

History Taking

-Ask about:

  • Onset and progression of edema
  • Frothy urine
  • Reduced urine output
  • Weight changes
  • Diabetes
  • Hypertension
  • Autoimmune disease
  • Recent infections
  • Hepatitis or HIV risk
  • Malignancy symptoms
  • Medication use, especially NSAIDs
  • Thrombotic symptoms

 

Physical Examination

-General Examination

  • Blood pressure
  • Weight
  • Degree of edema
  • Hydration status

 

-Look for:

  • Periorbital edema
  • Peripheral edema
  • Ascites
  • Pleural effusion

 

-System-Specific Examination:

  • Signs of systemic autoimmune disease
  • Diabetic complications
  • Infection
  • Deep vein thrombosis
  • Pulmonary embolism

Investigations

-Urine Testing

  • Urinalysis

  • Urine protein measurement

  • Urine protein-to-creatinine ratio (UPCR) or albumin-to-creatinine ratio

 

-Blood Tests

  • Serum albumin

  • Serum creatinine

  • Urea

  • Electrolytes

  • Lipid profile

 

-Evaluation for Secondary Causes

Depending on clinical suspicion:

  • HbA1c/glucose

  • ANA and complement

  • Hepatitis B and C testing

  • HIV testing

  • Serum protein electrophoresis/immunofixation

  • Serum free light chains

  • Other autoimmune or infectious tests when indicated

 

-Imaging

Renal Ultrasound

May be performed to:

  • Assess kidney size and structure

  • Exclude obstruction

  • Support evaluation of underlying renal disease

-Special / Confirmatory Tests

Kidney Biopsy

Used when the underlying cause cannot be established clinically or when histological diagnosis will change management.

Diagnosis

-Diagnosis of Nephrotic Syndrome is established by:

Heavy proteinuria + hypoalbuminemia + edema ± hyperlipidemia → nephrotic syndrome

-Then determine the underlying cause using:

Clinical assessment → targeted blood/urine tests → kidney biopsy when indicated

Home / Home / Clinical Cases / Nephrology System Clinical Cases / Nephrotic Syndrome
Related Topics

Management

1. First-Line / Emergency Management

Urgent treatment is required for complications such as:

  • Severe edema with respiratory compromise

  • Acute Kidney Injury

  • Severe infection

  • Thrombosis

Treat the specific complication while addressing the underlying renal disease.

 

2. Definitive Treatment

Treat the underlying cause.

Examples:

  • Immunosuppressive therapy for selected primary glomerular diseases

  • Glycemic control in diabetic kidney disease

  • Treatment of autoimmune disease

  • Treatment of underlying infection or malignancy

  • Withdrawal of causative drugs

 

3. Medical Treatment

-ACE Inhibitors / ARBs

Used to:

  • Reduce proteinuria

  • Control blood pressure

 

-Diuretics

Loop diuretics are commonly used to control clinically significant edema.

 

-Statins

Used when indicated for persistent dyslipidemia and cardiovascular risk rather than routinely for every patient solely because nephrotic syndrome is present.

 

-Anticoagulation

Considered in selected patients at high risk of thrombosis, particularly with severe hypoalbuminemia and high-risk underlying diseases.

 

-Immunosuppressive Therapy

Used according to the underlying glomerular disease, such as:

  • Corticosteroids

  • Calcineurin inhibitors

Complications

  • Acute kidney injury
  • Chronic kidney disease
  • Venous thromboembolism
  • Renal vein thrombosis
  • Pulmonary embolism
  • Severe edema
  • Pleural effusion
  • Ascites
  • Infections
  • Malnutrition/protein wasting

Prognosis

-Prognosis depends mainly on the underlying cause, degree of proteinuria, renal function, and response to treatment.

-Some causes, such as Minimal Change Disease, have an excellent response to treatment, while others may progress to chronic kidney disease or kidney failure.

Key Points / Clinical Pearls

  • Nephrotic Syndrome is characterized by heavy proteinuria, hypoalbuminemia, and edema.
  • Hyperlipidemia is a common associated finding.
  • Major primary causes include Minimal Change Disease, FSGS, and Membranous Nephropathy.
  • Common secondary causes include Diabetes Mellitus, SLE, and amyloidosis.
  • Glomerular injury causes increased protein permeability.
  • Heavy urinary protein loss causes hypoalbuminemia and reduced plasma oncotic pressure.
  • Reduced oncotic pressure leads to fluid movement into tissues → edema.
  • Urinary loss of anticoagulant proteins increases the risk of thrombosis.
  • Urinary loss of immunoglobulins increases susceptibility to infection.
  • Urine protein quantification and serum albumin are key initial investigations.
  • Renal function should be assessed with serum creatinine and eGFR.
  • Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276. KDIGO .
  • Kodner C. Nephrotic Syndrome in Adults: Diagnosis and Management. Am Fam Physician. 2016;93(6):479-485. American Family Physician .
  • Hull RP, Goldsmith DJA. Nephrotic Syndrome in Adults. BMJ. 2008;336(7654):1185-1189. BMJ .
  • Ronco P, Debiec H. Molecular Pathogenesis of Membranous Nephropathy: Recent Advances. Sci Rep. 2020;10:1441.
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Nephrotic Syndrome in Adults . National Institutes of Health.
  • National Library of Medicine (NIH). Nephrotic Syndrome . StatPearls.