Chief Corner: Proteinuria

There is Protein in my URINE!!!!

Last week at Senior Report, we discussed proteinuria and it’s management.

Measurement of proteinuria is an important diagnostic tool that helps with a wide range of clinical issues from detecting diabetic kidney disease to the diagnosis of nephrotic syndrome and its secondary causes. But why is it there and what does it all mean?


The Path of the Protein:

- The glomerulus is the first barrier reached it normally has no permeability to large proteins such as albumin and hemoglobin. Smaller molecular weight proteins such as light chains and myoglobin.

- The next stop is the renal tubule where these proteins are typically reabsorbed. This results in only a small amount of protein being excreted in the urine


Causes of Proteinuria: Glomerular vs Tubular vs Overflow!

- Glomerular Disease: Due to the breakdown of the glomerular filtration system at the level of the podocyte, fenestrated endothelial cells and basement membrane. Causes include: Minimal change disease, FSGS, Membranous Nephropathy, Diabetes Mellitus. Each have Primary and Secondary causes which is important but for another day

- Tubular Disease: Increased spilling of low molecular weight proteins can be due to damage to the renal tubular cells resulting in decreased reabsorption. These proteins may not be detected on a urine dipstick or be quantifiable using some lab techniques but signs of tubular damage may be seen during your work up

- Overflow: Due to over production of low molecular weight proteins. Etiologies include: light chains from multiple myeloma and myoglobin in rhabdomyolysis


Measurement of Urine Protein:

Not all are created equal… Some are great screening tools while not accurate for diagnostic or quantification purposes. It’s important that these studies are repeated to rule out transient proteinuria.

-Conventional Spot Urine Dipstick: Sensitive to large amounts of urine protein - specifically albumin will be positive for microalbuminuria (Positive >300 mg/24 h)

- Albumin Specific Urine Dipstick: More sensitive ; can detect microalbuminuria (>30mg /24hrs)

- Spot Albumin or Protein to Creatinine Ratio: Created because of the difficulty collecting 24 hour urine protein. Difficulty lies in variations during time of day. Patients should give several samples taken on different days at the same time. It is also important that creatinine excretion is approximately 1 gram in order for the ratio to correlate with 24hr urine. If done appropriately ratio of >3-3.5 grams represents nephrotic range proteinuria.

- 24 hour urine protein: Should be collected starting after a complete void of urine in the morning and end the following morning including the AM void. “The Gold Standard” in evaluating proteinuria.

Now what?

Evaluation of Urine:

Once proteinuria is determined, the cause can be further elucidated by examining urine for casts or performing urine protein electrophoresis looking for the light molecular weight proteins. Other lab work including albumin and lipid panel can complete your diagnosis of nephrotic syndrome. While investigations into secondary causes with HgbA1c, Auto antibodies and viral serology’s can help guide cause and future treatment.

So much more to talk about when it comes to urine and protein but knowing how to evaluate the labs and classify the type and cause can get you a long way towards helping your patient. More to come stay tuned!