FENa and FEUrea revisited

At Renal Week I went to Mark Perazella's talk on "Urine Microscopy for Diagnosis and Prognosis in Hospital-acquired AKI." Perazella published the interesting paper in CJASN in 2008 on using urinalysis microscopy for prognosis. His talk focused on the same subject. The gist is that a trained observer of urine microscopy is not only more accurate at diagnosing the etiology than FENa and FEurea abut can additionally provide prognostic information. Additionally urine microscopy performs as well as the novel biomarkers: KIM-1, NGAL and IL-18.

As part of his talk Perazella threw-up some slides with some surprising statistics on the diagnostic utility of FEUrea and FENa:

From Pepin AJKD 2007: 50:566-573
A sensitivity of 48% without diuretics? A specificity of 33% with diuretics? Terrible. A second study showed similar terrible numbers:

From Darmon et al. Critical Care 2011: 15 R178.
Only a bit better than a coin toss.

I felt shamed. I had been teaching and using urinary acute renal failure indices for 20 years and to see that they sucked sucked, kinda hurt. But then as I thought about it, I remembered seeing hard data that quite a bit more compelling. So I went back and took a look at some of the data.

The fractional excretion of sodium was invented in 1976 by Carlos Hugo Espinel. His initial series was published in JAMA. In that initial study he found 100% sensitivity and specificity in 17 oliguric patients.

Holy shit! Shrier is a member of the
Indiana Basketball Hall of Fame!
The study that is usually referenced as the mother of the fractional excretion of sodium comes from Mr. Sodium himself, Robert Schrier (fun fact: the founding member of my practice, Joseph Beals, was college roomates with Robert Schrier). This group found excellent performance of FENa in 85 patients:

Dr. Kohn is in the middle
FEUrea was invented by Kaplan and Kohn in 1992 (Fun fact: Dr. Kohn was one of my professors at University of Chicago) but the technique was not validated until 2002 when Cavounis et al prospectively looked at 102 patients with AKI. I remember reviewing the Cavounis article in journal club with Dr. Kohn in the room.

Results for using FENa to diagnose pre-renal disease (<1 br="br">
  • 92% sensitivity without diuretics
  • 48% sensitivity with diuretics
  • 76% sensitivity for the entire cohort
Results for FEUrea to diagnose pre-renal disease (<35 div="div">
  • 90% sensitivity without diuretics
  • 88% sensitivity with diuretics
  • 89% sensitivity for the entire cohort
Kim et al looked at 107 patients with acute kidney injury. Instead of pre-renal versus ATN they used transient versus persistent. They also looked at the performance of the AKI indices in the context of diuretics. (disclosure, I just read the abstract)

Results for using FENa to diagnose pre-renal disease (<1 p="p">
  • 96% sensitivity 100% specificity without diuretics
  • 63% sensitivity 98% specificity with diuretics
Results for FEUrea to diagnose pre-renal disease (<30 div="div">
  • 92% sensitivity 87% specificity without diuretics
  • 96% sensitivity 83% specificity with diuretics
Diskin et al looked at 100 oliguric patients and evaluated FENa and FEUrea. They used 40% for the line with FEUrea and 1% for FENa.
  • FENa 54% sensitivity
  • FEUrea 95% sensitivity
This was all the data I could find on trials that look at FENa and FEUrea. Overall the it performed quite well in most studies. In fact the two trials that Perazella quoted were the only two with the indices embarrassing themselves.

Jonathon Gotfried's article in the Cleveland Clinic Journal was a great resource for this article.