How is Glomerular Disease Diagnosed?
Glomerular disease results in one or both of two major presentations:
- Hematuria (blood in the urine)
- Proteinuria/albuminuria (excretion of protein in the urine)
Hematuria is easily identified by dipstick or quantitated by microscopic examination of a urine sample. The finding of red blood cell casts (compressed red blood cell masses that pass out of the tubule intact) indicates glomerulonephritis, an intrinsic glomerular disease. Except for that, the urinalysis is not helpful in identifying specifically the cause of blood in the urine. Hematuria can result from anything, from a stone to cancer.
Protein spillage is identified on a simple dipstick, but that is just the beginning of the diagnostic journey. Protein excreted into the urine can occur from other causes other than glomerular disease, and diagnostic tests are important to differentiate it from the other causes.
- Transient proteinuria: After exercise or exertion. It is temporary, normal, and benign.
- Orthostatic proteinuria: Common in adolescents, this is an unknown mechanism of altered glomerular function affected by standing (upright morning urine collection demonstrating proteinuria) vs. not standing (supine position, as with nighttime urine collection, demonstrating no proteinuria). It is easily identified or ruled out by repeated qualitative testing in both positions.
- Tubular proteinuria: Smaller proteins that are filtered by the glomerulus are normally reabsorbed through the tubules back into the blood. When this process is abnormal, reabsorption does not occur and the protein can end up in the urine.
- Overflow proteinuria: Overproduction of proteins, as in multiple myeloma (white blood cell “plasma cell” cancer) and other leukemias.
- Post-renal proteinuria: Due to inflammation in the urinary tract.
Testing in Glomerular Disease
Qualitative testing: this is useful if a positive dipstick for protein repeats as negative, which would indicate a benign transient proteinuria.
Quantitation: the amount of protein excreted in the urine is helpful in identifying the cause, because when < 1-2 g/day, is usually an isolated and benign phenomenon.
- The standard for quantitation is the 24-hour urine collection: Normal results are <150 mg/day. Because of its accuracy, it is done first, followed by urine protein-to-creatine ratio spot checks for follow-up.
- Urine protein-to-creatine ratio: Done by deriving a ratio from the dipstick values on a first or second morning-urine sample. A spot sample of protein concentration (mg/dL) is divided by the urine creatinine concentration (mg/dL). It allows an estimate of what the 24-hour urine total protein should be (in grams): normal is < 200; >3500 would be consistent with nephrotic syndrome.
Kidney biopsy is indicated on anyone with more than 3.5 g/day of proteinuria or when there is less proteinuria which is associated with hematuria or cellular casts in a microscopic urinalysis.
Testing Used in Hematuria Unrelated to Glomerular Disease
Since hematuria is simply the presence of red blood cells in the urine, testing should investigate other possible causes:
- X-ray to identify or rule out a stone
- CT or MRI to identify or rule out malignancy
- Urine culture and sensitivity to identify or rule out a urinary tract infection
- Renal ultrasound to identify renal structural (anatomical) problems
- Genetic testing to screen for polycystic kidney disease