This session from #KidneyWk 2015 nicely captured some basic science aspects – starting off at the cellular level, and then transitioned quite smoothly to clinical trials and ending up with population level public health data on this topic.
To start things off, Dr Wang from New York and Dr Hoorn from Erasmus showed some of the effects of potassium on channels in the tubule. Some of the fascinating insights they provided were related to the role of Kir4.1, an inward reflecting channel, expressed on the cortical limb of the thick ascending limb. Dr Hoorn’s talk focused on the effects of a potassium load, which curiously causes natriuresis, mediated by early dephosphorylation of the NCC channel in the DCT, and later followed by ENaC activation. This effect is reported after oral or intravenous potassium, and is maintained even in a state of low sodium diet. Indeed, even serum potassium correlates (negatively) with NCC activation. The prior data is mostly from animals, but there is a fascinating mechanistic feeding human study published recently, of 36 individuals placed on a baseline low sodium diet. Compared to the same diet (placebo intervention), there was a nice decrease in blood pressure with potassium supplementation in the cross-over phase.
Dr Rajiv Agarwal from Indiana, not only a guru in hypertension, but the guru in hypertension in CKD, was up next. He started off with the factoid that way back in the 1920s, potassium chloride was known to be a diuretic – see this paper in the CMAJ from 1928! He then discussed the WHO-conducted systematic review published in the BMJ in 2013 by Aburto et al. This meta-analysis put back the idea of potassium and hypertension back on the map and lead to a WHO guideline recommending a dietary intake of 90 mmol/day of potassium. The meta-analysis reported a significant lowering of systolic and diastolic blood pressure irrespective of the source and the actual intake (or baseline intake). In addition, with respect to hard outcomes, it also reported a reduction in stroke, arguably the clinical outcome most strongly linked to blood pressure. Also, data from the PREVEND study, which was a prospective cohort of 5,500 normotensive individuals, suggested that a urinary potassium excretion of < 70 mmol/day (corresponding to ~ 90 mmol/day dietary intake) was strongly (and non-linearly) linked to subsequent hypertension development. Indeed, after adjustment for other factors, the proportion of hypertension attributable to low potassium intake was estimated to be 6.2%. Moving on to the intriguing hypothesis of the role of potassium in the high CKD risk in African-Americans, there is urinary excretion data which not only demonstrates lower baseline potassium excretion in blacks (compared to whites), but that this difference persists even after they are provided a diet richer in potassium. Adjustment for possibly higher fecal and sweat potassium does not explain this difference, and there seem to be more questions than answers in this field. Unfortunately, a small trial of varying potassium intake (40 vs 100 mmol/day) in patients with CKD, called the CKD-K trial, has not been published yet, 3 years after completion.
Andrew Mente, an epidemiologist from McMasters finished this session with some population level public health data. Firstly, though everyone has noted that sodium intake is higher in most adults, the same NHANES data (based on dietary recall) also shows that <2% US adults consume more than the recommended potassium (4700 mg/day, corresponding to 120 mmol/day). At a population level, the role of potassium and hypertension has been previously also noted in the Scottish Heart Study, and more recently in the PURE studies (for more on the latter see #nephjc discussion here). Lest one criticize the inaccuracy of dietary recall from the NHANES data, he showed the PURE-24 data which reported a mean 24 hour urinary potassium excretion of about 2500 – 3000 mg/day (about 65 to 77 mmol/day) in urban Canadians. He speculated that another factor to consider while interpreting some of these studies is that higher potassium intake may represent a healthier diet (eg, Mediterranean or DASH).
Post by Dr. Swapnil Hiremath, AJKD Blog Contributor.
Check out all of AJKD Blog’s coverage of Kidney Week 2015!