Tag: potassium

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Calculating the fractional excretion of potassium and the urine potassium to creatinine ratio (using those crazy American units)

Since the demise of TTKG I have had to retrain my brain to determine if hypokalemia is due to renal wasting or extra-renal potassium losses (as well as intracellular shift). The is not so important in the evaluation of hyperkalemia as persistent hyperkalemia is always due to decreased renal clearance of potassium.

There are two methods of looking at renal potassium wasting, the first is Fractional Excretion of Potassium. Super easy calculation.

The values are from this Skeleton Key group article at the Renal Fellow Network. They pulled it from this study of 84 hypokalemic individuals: Fractional excretion of potassium in normal subjects and in patients with hypokalaemia. From the abstract:

The mean FEK+ in normal subjects was 8% (range 4-16%). FEK+ was positively correlated with serum potassium (r = 0.74, p < 0.0001) and inversely with serum creatinine (r = -0.51, p < 0.001). The mean FEK+ in patients with hypokalaemia of external origin was 2.8% (range 1.5-6.4%). On the contrary, the mean FEK+ in hypokalaemic patients in whom renal potassium loss was the main aetiologic factor for the pathogenesis of hypokalaemia was 15% (range 9.5-24%).

Even though the creatinine is measured in mg/dL and the potassium is measured in mEq/L the units don’t mess you up because the serum and urine creatinine units cancel each other out.

The other way to look at hypokalemia is urine potassium creatinine ratio. Just divide the urine potassium by the urine creatinine and if it is greater than 1.5 you have renal potassium wasting. But alas this only works if the urine creatinine is measured in mmol/L. I get urine creatinines in mg/dl, so to make this conversion you need to multiply urine creatinine by 88 to get micromol/L of creatinine and then divide it by 1000 to convert to mmol/L. In one step it looks like this:

The line in the sand of 2.5 comes from this study, Laboratory Tests to Determine the Cause of Hypokalemia and Paralysis published in JAMA Internal Medicine.

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Medical management of hyperkalemia

My team was consulted for acute kidney injury (AKI) and hyperkalemia. Before we saw the patient they had already been given the standard, calcium, bicarb, and insulin/glucose cocktail. This had no effect. Potassium went from 6.4 to 6.4.

The patient was still making urine. The AKI was due to emergency surgery with an impressive estimated blood loss (translation: blood loss measured in liters). We gave a liter of NS, 80mg of IV furosemide and 0.2 mg of oral fludrocortisone. Potassium went from 6.4 to 3.4 despite a further increase in the serum creatinine.

Remember to use the kidney for treating hyperkalemia. Even in AKI you can get impressive results.

Renal clearance of potassium is entirely dependent on the cortical collecting duct, specifically the principal cells. It is a multi-step process:

  1. reabsorption sodium down its chemical gradient through eNaC
  2. The chemical gradient to allow sodium resorption is generated and maintained by the Na-K-ATPase
  3. Movement of sodium without an anion(or a cation going in the opposite direction creates a negative charge in the tubular fluid which pulls potassium down an electrical and chemical gradient from the cells into the tubule. This occurs through ROMK and BIGK.

That is how potassium is excreted but, how is potassium regulated? There are two primary components to regulation:

  1. Aldosterone stimulates the transcription of all three transporters (ENaC, Na-K-ATPase, and ROMK) as well as transcribing versions of the proteins which are more active.
  2. Tubular flow. Increased distal sodium delivery provides plenty of sodium to be reabsorbed into the principal cell providing the negative charge, as well as washes away any secreted potassium to maintain the chemical gradient favoring potassium excretion.

The medical management we provided takes care of both aspects of potassium regulation, the furosemide and saline makes sure there is a robust supply of sodium delivered distally and the fludrocortisone makes sure there is ample aldosterone activity to assist with potassium clearance.

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The TTKG is dead, now what?

Halperin has declared the TTKG dead.

And therefore never send to know for whom the bell tolls; It tolls for the TTKG

However we still need to assess patients for hypokalemia and differentiate between renal and extra-renal losses.

Measuring a fractional excretion of potassium (FEK) doesn’t physiologically make sense. The idea behind the fractional excretion calculation is calculating what percentage of the filtered potassium (in this case, but can be anything) ends up in the urine. But potassium doesn’t work that way. Essentially all of the filtered potassium is reabsorbed in the proximal tubule and thick ascending limb of the loop of Henle so that the fractional excretion of potassium is zero at that point. Then in the late distal convoluted tubule and the medullary collecting duct all of the potassium that is destined for the toilet is secreted. So all of the potassium that is cleared by the kidney is secreted but the distal nephron/tubules not filtered by the glomerulus. That said the FEK is just a calculation and you can do it. I reviewed the the best data on it here:

FERE: Fractional excretion of random electrolytes

So what calculation do I use? I use the TTKG, but that’s because I’m a dinosaur. What I should be doing is the urine potassium to creatinine ratio.

The answer is 13 mEq/g creatinine.

In this study of hypokalemic periodic paralysis versus patients with increased renal potassium excretion, the K:Cr ratio neatly divided the two groups.

the dividend line here was 2.5 mmol K/mmol Cr or 22 mEq/g Cr

If you know of a better reference for the potassium to creatinine ratio, tweet me up.

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You knew that proteinuria is protective against amphotericin induced hypokalemia. Right?

All of you #NephMadness players crying into your coffee about Proteinuria getting beat out by Patient Reported Outcomes need to understand that proteinuria isn’t always bad*.

*I am being sarcastic here, proteinuria is always bad, and the only reason I am writing this post is because of this interesting quirk where it appears to be protective.

Proteinuria protects against amphotericin b induced hypokalemia. In patients on amphotericin, heavy proteinuria, a protein concentration of 3 g/L (3+ on dipstick), is protective against amphotericin b induced hypokalemia.

The study was done on normal formulations (as opposed to liposomal preparations) of amphotericin B.

Amphotericin B is highly protein bound. With standard doses, the normal amphotericin concentration in the urine will be 1-2 micromol/L. With 3+ urine protein, the albuminuria concentration is over 40 micromol/L, and this is apparently enough to bind and neutralize amphotericin’s collecting duct toxicity. Amphotericin’s anti-fungal property comes from its ability to tear open fungi cell membranes. Unfortunately it does a doozy on the membranes of the collecting tubules as well, allowing potassium to flow down its contraction gradient from the cells to the tubular fluid (and out in the urine). Similarly hydrogen flow from the tubular fluid back into the cells causing metabolic acidosis. It is an unusual cause of renal potassium loss without increased aldosterone levels.

For you #NephMadness geeks, toad bladder was instrumental to working out the mechanism for amphotericin induced hypokalemia.

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FERE: Fractional excretion of random electrolytes

Magnesium:

  • 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

Potassium

  • 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
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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)

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Pseudohyperkalemia

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.

Regrets…