Outline

1. Why is Proteinuria a Problem?
2. Measuring and Determining the Severity of Proteinruia
3. Nephrotic Syndrome
4. Glomerular Diseases that Cause Proteinuria
5. Treatment of Proteinuria
6. Treatment of Edema
7. Treatment of Thrombophilia

Why is Proteinuria a Problem?

• Important marker of underlying disease and its severity
• Harmful per se because tubules are exposed to filtered proteins
• Harmful because of urinary loss of key proteins, can lead to:
  • Hypogammaglobulinemia
  • Thrombophilia
    • Membranous nephropathy most likely
    • DVT in 7 – 8% of patients over 2 – 3 years
    • Most likely when Albumin < 28 g/L
    • Leg vein, renal vein
  • Sodium retention

Measuring and Determining the Severity of Proteinuria

Proteinuria can be measured in 4 ways:

1. Single urine protein concentration
   • Common but can be problematic
     • If urine is dilute, protein concentration will low be independent of amount and vice versa
2. 24 hour urine collection
   • Best estimate of disease severity
   • Need to collect for 24 hours, thus inconvenient, prone to errors
   • Must measure urine creatinine excretion to ensure complete collection
   • A “large” amount of proteinuria is more than 3.5 grams/day in an adult = “nephrotic”
3. Single urine protein/creatinine ratio
   • Predicts 24 hour urine protein
4. Single urine albumin/creatinine ratio
   • Most commonly used test to assess quantity of proteinuria, esp. in patients with DM
   • Dividing the urine [protein] or [albumin] by the urine [Cr] “corrects” for the degree of urinary concentration
     • Dilute urine has low [Cr]
     • Concentrated urine has high [Cr]

Nephrotic Syndrome

• Nephrotic syndrome consists of:
  • Heavy proteinuria (> 3.5 g/day/1.73 m²)
  • Hypoalbuminemia
  • Edema
  • Elevated LDL cholesterol
• There are many primary and secondary causes of nephrotic syndrome, with some listed below.
• For more details on the differential diagnosis, investigations and management of nephrotic syndrome see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394708/

Glomerular Diseases that Cause Significant Proteinuria

Treatment of Proteinuria

• Treat underlying disease
• Reduce glomerular capillary pressure
  • ACE inhibitor or ARB
    • Reduce angiotensin II effect on efferent arteriole
    • Reduces glomerular capillary pressure
    • Reduces proteinuria
  • Dietary protein restriction
• Treat associated complications
  • Edema & Thrombophilia

Treatment of Edema from Proteinuria

• It is challenging!
• Filtered protein may bind to intra-luminal diuretic
• Severe hypoalbuminemia reduces delivery of protein-bound diuretic to renal tubule
• Some patients with severe hypoalbuminemia may have low intravascular volume (esp. minimal change disease), and diuresis will worsen this, so proceed with caution
• Patients often need to limit their dietary sodium intake (<100 mmol/day; 3 g/day), restrict their fluid intake (1.5 litres/day), and take diuretics (but avoid aggressive diuresis, target weight loss of 0.5-1 kg a day)

Treatment of Thrombophilia from Proteinuria

• No RCTs of primary prevention
• Controversial!
• More likely to offer anticoagulation if:
  • Membranous nephropathy
  • Severe hypoalbuminemia (< 28 g/L)
  • Online calculator for risk vs benefit (http://www.med.unc.edu/gntools/ )
• Most experience has been with warfarin and LMWH
• No role for screening for DVTs
• Decision should be made in consultation with nephrology team (especially if there is a plan for renal biopsy)

Thank you Dr. Schreiber for leading us through this important topic!