Tuesday, December 22, 2009

Differential Diagnosis of Red Urine

Red urine: it's not always hematuria. The first step in evaluating the patient who complains of grossly red urine is to perform a standard urinalysis, focusing on (a) whether or not the dipstick turns heme-positive, and (b) whether or not there are red blood cells visualized on microscopic examination.

We are all fairly familiar with the basic differential diagnosis for heme-positive urine with RBCs visualized on microsopic exam: the presence of dysmorphic RBCs and casts is consistent with glomerular hematuria (e.g., glomerulonephritis) while non-dysmorphic RBCs warrants a work-up for lower-tract hematuria (e.g., nephrolithiasis, bladder cancer, etc.).

However, a heme-positive urine specimen in which RBCs are NOT seen on microscopic exam suggests the possibility of either myoglobinuria (e.g., rhabdomyolysis) or hemoglobinuria (e.g., hemolytic anemia, paroxysmal nocturnal hemoglobinuria, etc). A simple way to differentiate between these two possibilities is to centrifuge the patient's blood: the serum fraction will be pink in hemoglobinuria, and clear in myoglobinuria. Myoglobin is a 17kD protein which is rapidly filtered and excreted by the kidney; thus, it should generally not be present in high abundance in the serum. In contrast, hemoglobin exists as a tetramer of 69kD which is bound to haptoglobin, thereby restricting its filtration at the glomerulus and causing the serum fraction to be pink-tinged. Other lab values (elevated CK in the tens of thousands in rhabdo; positive Coomb's test and low haptoglobin in hemolytic anemias) can also be instrumental.

The differential for heme-negative red urine includes some more esoteric diagnoses: acute porphyria, ingestion of beets or certain food colorants, drugs (e.g., rifampin, pyridium, doxorubicin).

2 comments:

The Chiefs said...

Great post. There's a nice summary figure in the recent NEJM Rhabdomyolysis review of the ddx of red/brown urine that would compliment your text nicely.

nathanhellman said...

Thanks, here's the NEJM article link:

http://content.nejm.org/cgi/content/extract/361/1/62