In nutrition, feeding studies are one of the best ways for researchers to investigate cause and effect relationships. I think of it as akin to a drug trial. In a drug trial, we give a patient X medication and check to see what happens for Y outcome. For example, we give a patient ozempic and see what happens to their blood glucose.
Today’s post is a continuation of my nutrition research methods series. With a specific look into studies investigating potassium balance in CKD. This is today’s article.
What did they do?
The supervising author on this paper (who is always the last author listed) is Lawrence Appel. Dr. Appel is the famous creator and researcher of the DASH diet.
So in this study, Dr. Appel studied two diets – one high in potassium and one low in potassium. The high potassium diet was modelled after the DASH. The study was done in 29 adults living with Stage 3 CKD. The main outcome in this paper was to understand the impact these diets would have on blood pressure. We can also look at their results to help us understand potassium balance.
All meals were provided to participants. Each menu was analyzed in the lab, so the researchers knew exactly how much potassium people were being given. The participants ate each diet for 4 weeks, with a 3-4 week period in between where they could eat their regular diets.
An important note about this studies exclusion criteria: Anyone with a history of hyperkalemia was excluded. So this study can’t tell us anything about the safety of high potassium diets for adults with CKD who already have hyperkalemia.
What did they find?
Blood Pressure
The high potassium, DASH style diet was associated with a 2mmHg systolic and 4mmHg diastolic lower blood pressure than the low potassium diet. This wasn’t statistically significant. And as a clinician, I think it is safe to say that we wouldn’t find this clinically significant either.
Potassium Balancing and Handling
To measure adherence to the diet, 24 hour urine potassium samples were taken during both the high and low potassium feeding sessions. For the low potassium feeding, 39.9mmol (out of 40mmol) were recovered in the 24 hour urine. That’s a really close match! For the high potassium feeding 81.4mmoL out of 100mmol were recovered in the urine.
For the purposes of this study, the authors stated that this showed good adherence to the diet. They achieved a statistically significant change in potassium. What that means is, for the question they were trying to answer (Do higher potassium diets lower blood pressure in CKD?), is they can answer their question.
However, from a potassium balance perspective, this result leaves me with some questions. 100 – 81.4 = 18.6mmol. At about 40mmol per gram of potassium, that means that 744mg of potassium are unaccounted for in the urine sample. That’s a clinically significant amount! Where did it go? There are several possibilities that this study design doesn’t allow us to answer, but that as readers we could ask:
- Did the potassium get pooped out? If the DASH diet is higher in fruits and vegetables, then maybe the potassium in this diet had lower bioavailability and therefore didn’t leave the GI tract and enter the blood stream. If this is the case, then stool samples might have given us a clue.
- Did the potassium stay in the body? For example, is the intra-cellular space. The DASH diet is more alkaline, which has the potential to force a net shift of potassium into the cells. In this case, there would have been less for the kidney’s to filter and excrete into the urine.
- Were the participants actually compliant with the diet? It is possible, that they didn’t recover all of the potassium because the participants didn’t actually eat all of the potassium provided to them. Though, since they also looked at sodium in the urine and didn’t find differences there, this option is less likely.
- Is the potassium accumulating in the blood? Our current care paradigm, is that high potassium diets will overload the ability of this kidney to excrete excess potassium and result in more potassium staying in the blood and cause hyperkalemia. Let’s dig into this possibility a bit more.
Are the kidneys able to keep up with high amounts of potassium intake in CKD?
The fact that 744mg of dietary potassium is unaccounted for in the urine, could suggest that this high amount of potassium intake, is overwhelming the kidney’s ability to excrete potassium.
If this were true, one might expect to see high levels of potassium in the blood. When the authors looked at the serum levels, there was a statistically significant increase in serum potassium during the high potassium diet. This increase was only 0.21mmol/L, which isn’t particularly clinically significant. However, they also looked at hyperkalemic events. They reported a 2.5 times higher likelihood of hyperkalemia, defined as a K>5.5mmol/L, during the high potassium feeding period.
Additionally, two participants weren’t able to complete the high potassium feeding due to hyperkalemia, with one person, who was on tacrolimus, reaching a potassium of 7.1mmol/L. The other person had diabetes and was on RAASi. So both of these people had risk factors for hyperkalemia. But ultimately, this could aligns with the hypothesis that the reason we saw less potassium in the urine, is because the kidneys weren’t excreting it and it was accumulating in the blood.
Author Conclusions
The authors of this article concluded that the higher potassium diet did not appear to lower blood pressure, and potentially has safety concerns.
Take Aways
This study gives me lots of food for thought. That 744mg of potassium went unaccounted for in the urine and that this was combined with increases in serum potassium levels, suggest to me that there is likely a component of inadequate secretion, at least for some people who have kidney disease. This study also makes me question the validity of using 24 hour urine samples in this population as a surrogate marker of potassium intake.
