Outline
- Why is Proteinuria a Problem?
- Measuring and Determining the Severity of Proteinruia
- Nephrotic Syndrome
- Glomerular Diseases that Cause Proteinuria
- Treatment of Proteinuria
- Treatment of Edema
- 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:
- Single urine protein concentration
- Common but can be problematic
- If urine is dilute, protein concentration will low be independent of amount and vice versa
- Common but can be problematic
- 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”
- Single urine protein/creatinine ratio
- Predicts 24 hour urine protein
- 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
- ACE inhibitor or ARB
- 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!
[…] There are different ways of quantifying proteinuria – spot collections (e.g., Albumin/Creatinine Ratios and Protein/Creatinine Ratios), or 24-hr collections. Each of these has practical and clinical advantages and disadvantages. These are nicely summarized in a previous CMR Blog post here. […]