Nephrotic Syndrome

1. Definition
   1. Conditions causing Proteinuria, edema, hypoalbuminemia and Hyperlipidemia
2. Epidemiology
   1. Uncommon
3. Pathophysiology: Edema in Nephrotic Syndrome
   1. Underfill mechanism (children)
      1. Significant Proteinuria results in hypoalbuminemia
      2. Decreased oncotic pressure results in edema
   2. Overfill mechanism (adults)
      1. Proteinuria Causes tubulointerstitial inflammation
      2. Sodium retention leads to edema
4. Causes
   1. Primary glomerulonephropathy progresses to Nephrosis
      1. Occurs in 20% of cases
   2. Children
      1. Minimal Change Disease (NIL Lesion)
   3. Adults
      1. Membranous Nephropathy (33%)
      2. Focal Segmental Glomerulosclerosis (33%)
      3. Minimal Change Disease (25%)
      4. Other
         1. Systemic Lupus Erythematosus
         2. Membranoproliferative Glomerulonephritis (MPGN)
         3. IgA Nephropathy
         4. Diabetic glomerulosclerosis (Diabetes Mellitus)
         5. Multiple Myeloma
         6. Hepatitis B Infection
         7. Hepatitis C Infection
         8. HIV Infection
         9. Amyloidosis
         10. Goodpasture's Syndrome
         11. Hodgkin's Lymphoma
         12. Preeclampsia or Eclampsia
         13. Medications
             1. NSAIDs
             2. Penicillamine
             3. Gold
         14. Infection (includes PSGN)
5. Signs and Symptoms
   1. Edema
      1. Initial: Progressive lower extremity edema
      2. Later: Periorbital edema, scrotal edema, Pleural Effusion, Ascites
      3. May present with acute Congestive Heart Failure
   2. Hypoalbuminemia
   3. Hyperalbuminuria (Proteinuria >3.5 grams per day)
   4. Hypertension
   5. Hyperlipidemia
   6. Renal Insufficiency
6. Labs: Diagnosis
   1. Urinalysis
      1. Urine Dipstick with 3+ protein suggests nephrotic range Proteinuria
      2. Use only for initial screening and then confirm with Urine Protein to Creatinine Ratio
   2. Urine Protein to Creatinine Ratio
      1. Ratio >3 to 3.5 suggests nephrotic range Proteinuria (correlates with 3 to 3.5 grams protein in 24 Hour Urine Protein)
      2. Efficacy is equivalent to a 24 Hour Urine Protein collection
   3. Serum Albumin
      1. Serum Albumin <2.5 g/dl
   4. Lipid profile
      1. Total Cholesterol >300 mg/dl (>50% of patients with Nephrotic Syndrome)
7. Labs: Initial Evaluation of Causes to consider
   1. HIV Test
   2. Hepatitis B Serology (HBsAg)
   3. Hepatitis C Serology (Hepatitis C Antibiody, xHCV)
   4. Serum Protein Electrophoresis or Urine Protein electrophoresis (Multiple Myeloma, Amyloidosis)
   5. Rapid Plasma Reagin (Syphilis)
   6. Antinuclear Antibody (Systemic Lupus Erythematosus)
8. Management
   1. Consult with nephrology
   2. Test for underlying cause (often idiopathic)
   3. Fluids and electrolytes
      1. Limit daily sodium intake to 3 grams/day
      2. Consider limiting oral fluids to <1.5 Liters daily
   4. Diuretics
      1. Do not exceed 1-2 pounds (0.5 to 1 kg) per day (risk of Acute Renal Failure)
      2. Loop Diuretics (e.g. Furosemide)
         1. Often requires high dose (e.g. Furosemide 80 to 120 mg)
         2. May require IV dosing as oral absorption may be reduced due to intestinal edema
      3. Adjunctive Diuretics
         1. Thiazide Diuretics
         2. Spironolactone
         3. Metolazone (Zaroxolyn)
   5. ACE Inhibitor (or Angiotensin Receptor Blocker if ACE Inhibitor intollerant)
      1. Typically recommended to reduce Proteinuria even if normotensive
      2. Enalapril (Vasotec) 2.5 to 20 mg per day (dosing used in studies)
      3. Lisinopril
   6. Corticosteroids
      1. Minimal Change Disease (especially in children)
         1. Corticosteroid responsive
      2. Focal Glomerulosclerosis and Membranous Nephropathy
         1. Variable response to Corticosteroids
         2. Management per local consultant recommendations
   7. Other measures
      1. Avoid nephrotoxins (e.g. NSAIDs)
      2. Maintain Blood Pressure less than 130/80
      3. Control Hyperlipidemia
      4. Avoid unproven strategies
         1. Avoid intravenous albumin
         2. Avoid prophylactic antibiotics
9. Complications
   1. Deep Vein Thrombosis
      1. Relative risk of 1.4 to 1.7
      2. Risk factors
         1. Age 18 to 39 years
         2. Nephrotic Syndrome onset in last 6 months
         3. Membranous Nephropathy as the cause of Nephrotic Syndrome
         4. Serum Albumin <2.0 to 2.5 g/dl
   2. Infection
      1. May be related to serum IgG and complement loss (Proteinuria), as well as Nephrotic Syndrome management (Corticosteroids)
      2. Risk factors
         1. Children
         2. Nephrotic Syndrome relapse
         3. Corticosteroid use
      3. Most common infections
         1. Cellulitis
         2. Peritonitis
         3. Sepsis
   3. Acute Renal Failure
      1. Rare complication
      2. Appears to be multifactorial
         1. Sepsis
         2. Excessive diuresis
         3. Renal vein thrombosis
         4. Renal interstitial edema
10. References
    1. Karnath (2007) Hosp Physician 43(10): 25-30
    2. Kodner (2009) Am Fam Physician 80(10): 1129-36