FERE: Fractional excretion of random electrolytes


  • 142 controls: 1.8% (range 0.5-4%)
  • 74 hypomagnesemic
    • Extra-Renal origin 1.4% (range 0.5-2.7%)
    • Renal origin 15% (range 4-48%)
  • Authors conclusion: >4% per cent is indicative of inappropriate renal magnesium loss


  • 312 normal subjects: 8% (range 4-16%)
  • 84 hypokalaemic patients
    • Extra-renal origin: 2.8% (range 1.5-6.4%)
    • Renal origin: 15% (range 9.5-24%)
  • Authors conclusion: >6.5% per cent is indicative of inappropriate renal potassium loss

hypokalemia and metabolic alkalosis

A few years ago I was talking one of my mentors at Kidney Week, John Asplin. He mentioned

that he taught an integrated lecture on metabolic alkalosis and hypokalemia. I thought this was an inspired idea.

Teaching separate classes on both subjects results in a lot of overlap because the renal mechanisms for both disease are the same, this means that many of the diseases that cause one, also cause the other.

Additionally hypokalemia can cause metabolic alkalosis and metabolic alkalosis can cause hypokalemia, so it makes sense to teach both of these conditions in an integrated lecture.

Lastly, teaching each electrolyte individually in isolation from each other is a missed opportunity. One can only appreciate the beauty of electrolyte physiology when one understands how each electrolyte fits together and how abnormalities in one is associated and affects all of the other electrolytes.

Unfortunately, I botched the lecture. I gave this lecture for the first time for the Oakland University Beaumont Medical School this past August. I knew it didn’t go too well, but this week I received the class feedback. Overall my statistical evaluations were excellent but when I read the comments the students were jackals. They savaged this lecture.

Timing was on my side, I was scheduled to give this lecture the day after I received feedback. I’m not done tweaking it but what I did for my Tuesday lecture was add more connective tissue between the concepts, and fill in with some additional summary slides.

Right now, I’m using it as a lecture to follow-up my potassium lecture, but at OU the students didn’t have any baseline potassium knowledge. In order for this lecture to work the students must already understand the basics of potassium, especially the central role that renal potassium handling has in potassium homeostasis. Hopefully I will be able to negotiate another hour into the GU schedule for this lecture.

My next plans for this lecture is to cut out a lot of the opening slides. The purpose of those slides is to quickly move from introducing potassium and hypokalemia to getting to the truth that hypokalemia is almost solely a disease of increased renal losses.

I want to add a slide about disease opposites:

  • Pseodohypoaldosteronism type 1 and Liddle syndrome
  • Godon’s syndrome and gittleman’s syndrome
  • Adrenal insufficiency and AME

I want to add some slides on how hypokalemia causes (specifically, maintanes) metabolic alkalosis and then how metabolic alkalosis causes hypokalemia.

Here is the lecture (Keynote version | PDF)


The highest potassium I have ever seen? That would be 15.5 mEq/L.

It’s not real. It was pseudohyperkalemia from leukocytosis. The patient had chronic lymphocytic leukemia with a white count of 300,000. If you are not familiar with this condition, check out these posts on Renal Fellow Network: Westervelt and Nate. Nice full text references here and here (pdf).

The pseudohyperkalemia merit badge

The first time I saw this was when I was senior resident. I was sleeping in the call room my pager buzzed. It was the oncology floor with a potassium of 9. The patient had CML and was in a blast crisis. His leukocyte count around 100,000. I immediately suspected pseudohyperkalemia and ordered a whole blood potassium from the ABG lab. It was normal so I went back to sleep. The next morning I received an angry call from the Hemo-Onc fellow. The patient was coding and he was furious that I only ordered an ABG instead of treating the hyperkalemia.

I don’t know if the patient coded from hyperkalemia, but I wish that I had gotten out of bed and evaluated the patient. I solved the problem the nurses alerted me to, but if I assessed him, maybe I could of averted an arrest.


Hyperkalemia or not

A patient came to the hospital with a swollen arm. The ED suspected a DVT and ordered a doppler ultrasound which confirmed their suspicion. The admission labs included a chem-7 which revealed a potassium of 7. Her creatinine was 1 and she wasn’t taking an ACEi, ARB, aldactone, ketoconazole, or potassium supplements. The ER was surprised and repeated the study and checked an EKG:

Narrow QRS and unimpressive T-waves

The EKG gave no hint of hyperkalemia, though EKG changes are not a sensitive marker for hyperkalemia. The ED gave insulin, glucose and Kayexalate for the lab finding of hyperkalemia. We were consulted to determine the cause of the hyperkalemia. The patient’s past medical history was significant for primary thrombocytosis and during the hospital stay her platelet count rose to over a million.

dats a lot o’platelets

We presumed that his hyperkalemia was actually pseudohyperkalemia due to the high platelet count. Platelets release potassium when they clot and the risk of pseudohyperkalemia rises as the platelet count approaches a million.

You remember this classic NEJM article from 1962. 

We then sent the patients blood to the ABG lab in a heparinized syringe rather than a red top and the potassium normalized. Platelets release potassium when they are activated. By measuring the potassium in whole blood rather than serum, the contribution of platelet activation is prevented. The ABG results are the electrolytes to the far left in the screen-grab below (click to enlarge).

– Posted using BlogPress from my iPad

Highest TTKG with hypokalemia

Patient with a lifelong history of hypokalemia. He came to me for a second opinion, his previous nephrologist had been nudging up his potassium dose on every visit and the patient was now on 70 mEq of KCl daily and was getting uncomfortable with endlessly increasing doses of potassium.

At the time I saw him these were his labs (he had decreased his potassium supplementation to 20 mEq/day):

  • Blood
    • sodium: 128
    • glucose: 90
    • potassium: 2.8
    • Creatinine: 0.9
    • BUN: 11
    • Magnesium: 1.8
    • Calculated osmolality: 265
  • Urine 
    • sodium: 135
    • potassium: >100
    • Osmolality: 637
Trans-tubular potassium gradient: 14.9. That’s crazy high for a patient with hypokalemia, one should expect it to be less than 2 for hypokalemia of extra-renal origin, and only 7 or 8 for hypokalemia from hyperaldosteronism. Halperin et al. were not able to get the TTKG that high even when they took normokalemic patients and doped them with fludrocortisone and 50 mEq of oral potassium. 
And that 14.9 is assuming the urine potassium is 100, our lab doesn’t do serial dilutions so who knows what the actual potassium is? 120? 140?
I’m still waiting for the renin and aldo but I smell some Bartter’s

Pregnant Gitelman Patient follow-up

Last week I posted on my pregnant patient who has Gitelman’s Syndrome. I am managing her with amiloride and a mixture of oral potassium and a mixture of oral and IV magnesium.

I received the following letter from a reader who went through a similar experience:

I am not a doctor, but I have Gitelman’s, and 16 years ago, was pregnant and ended up having to go on amiloride at the start of my second trimester, because my potassium and magnesium levels just tanked.   Being part of proving the track record on the viability of amiloride in pregnancy was a scary time, I tell you what.  Your patient’s experiences are similar to mine, though I did not require the magnesium IVs she apparently does during gestation. 

The great news is my son turned out healthy, and without any sign of potassium disorders of any sort, so far as we can tell at nearly 16.  He’s healthy, bright, nearly 6 ft – no indication at this time  that he was harmed in any way by the fetal exposure to amiloride. 

And another point to pass along – after he was born, I had my breast milk checked for traces of amiloride, and it passed whatever screens were applied. Therefore I nursed him for about 9 months, though I supplemented with formula.  It was an acceptable risk for me – since I know the literature does not record any data on nursing while on amiloride, I thought I’d pass along one uncontrolled anecdote for you to ponder. [Note: on further communication the patient clarified that she did not take amiloride during breast feeding

Anyway, please pass this information along to your patient – I am sure it will help her peace of mind to know another successful long term outcome.  It was a scary time for me, and without the widespread use of Internet back in 1995, the only piece of mind I got was by tracking down Dr. Almeida, who wrote the 1989 paper about Gitelman’s in pregnancy.  I spoke to one of his nurses to see if they could give me some info on long term followup on the baby, but the mother had disappeared after giving birth, and they had nothing to report.    

Best of luck to your patient – I know what she’s going through. 

Final note for your patient going forward: Getting my levels back up after the birth was a bit of a challenge, I recall.  But many of the details have been lost to time and the fog of war, I’m afraid – I will just say that the first month post-partum was pretty rough on me.

Gitelman syndrome and Pregnancy

One of my Gitelman patients (whom I kidding, “one of my Gitelman patients”, how about “my only Gitelman patient”) finally got pregnant. We had been managing her with amiloride and a truck load of oral potassium and magnesium supplements. I was shocked to find that amiloride is acceptable in pregnancy with a track record of successful births. Prior to starting amiloride the patient was taking twenty-eight 20 mEq pills of KCl a day. She abandoned her prior nephrologists when she was told to further increase her potassium pills.

from UpToDate

We are now using magnesium sulfate infusions 4 grams twice a week to keep her magnesium north of zero. She was able to keep her magnesium around 1.4 with oral supplements and amiloride prior to being pregnant but now, despite 8 grams of weekly IV magnesium her magnesium is sitting around 1.1. This probably represents one of downsides of the up-regulated GFR of pregnancy.

Interestingly, she saw her labs and saw that her sodium was 132. Modest hyponatremia is a normal finding in pregnancy, so she decided to increase her dietary sodium intake. Bad move, increased renal sodium loads increases renal magnesium losses. Her serum mag fell 30% to 0.8.

Hyperkalemia as an indication for dialysis

A few weeks ago we admitted a patient who has been approaching ESRD for a number of years. Most of her medical care had been provided in the hospital as she bounced from admission to admission. Though we tried to get her into our CKD clinic she always failed to show up. You can track the progression of her CKD from hospitalization to hospitalization with a gradually increasing baseline creatinine.

On this most recent admission, she came in with the triple 8s:

  • Hemoglobin 8.8
  • Creatinine 8.1
  • Potassium 8.6

Here is her initial EKG with that potassium:

The most remarkable part of the EKG was the profound bradycardia, heart rate of 30. Also she has beautifully peaked T waves. I’m surprised by the lack of a prolonged QRS. She had a great response to medical management with her K falling to the 5s. The repeat EKG was rather unremarkable.
The patient received dialysis on the day of admission and the following day I set her up for chronic dialysis. Whenever a patient progresses to chronic dialysis from CKD I always try to remind myself of how rare this event is. As nephrologists it is too common and seeing that unfortunate outcome alters our perception so that we may overestimate its frequency. End-stage renal disease is an exceptional, not a routine outcome of CKD. The vast majority of patients with CKD ultimatly expire of something other than renal failure. Let’s review three important studies to emphasize this:
Keith et al looked at the five-year outcome of 28,000 patients with chronic kidney disease. He divided them by CKD stage and found that of the 11,278 patients with CKD stage 3, only 1.1% of then received dialysis and 0.2% received a transplant. A quarter of them died (24.3%). The authors summarized the results:

The likelihood of renal replacement therapy, either transplant or dialysis, was near zero (≤1.3%) for patients in all stages except stage 4, where 2.3% ± 1.1% of patients received a transplant and 17.6% ± 2.7% had dialysis initiated.

Eriksen et al found similar results in a 10-year study, with a 4% risk of renal failure for patients with CKD stage three compared to a 51% risk of death.
And lastly, O’Hare, et al’s VA study that looked explicitly at renal failure and the competing outcome of death. They asked, “At what age and GFR is renal failure more likely than death?”. Obviously, at a younger age, when death is a more remote possibility, a higher GFR will have the time to deteriorate to the point of requiring renal replacement therapy. The results showed surprisingly low GFRs:
To read the graph, find your patients age and then line it up with their GFR. If the intersection is in the black, they are more likely to die, if it is in the grey then hello Mr. Fresenius, nice to meet you Ms. Tacrolimus. Note, that in a 75 year old with a GFRas low as 16 mL/min, death is still more likely than ESRD.
So, the next time you see a patient initiating dialysis after a long run of chronic kidney disease don’t be frustrated by the fact that they didn’t do enough to prevent this, be amazed that they survived to this outcome.