Urinary Potassium Excretion

Introduction

See related article, pp 769–776

There are multiplicities of factors that have been proffered as physiological/dietary prompts for the new onset of hypertension. Such physiological factors generally center on changes in volume homeostasis, an excess of sympathetic nervous system activity, or either relative or absolute increases in various components of the renin–angiotensin–aldosterone system; however, population-based screening for changes in neurohumoral and volume-related factors associated with the new onset of hypertension is rarely done in clinical practice and for the most part, when attempted, has been sparingly predictive. Alternatively, at the individual patient level, the good clinician by virtue of an oftentimes thoughtfully applied algorithmic approach to treatment and simple neurohumoral testing can in a post hoc manner uncover the pathobiologic prompt to a newly developed hypertensive state.

Dietary factors actively involved in the genesis of hypertension have, however, received much more play because large population-based studies can be more readily initiated and outcomes tracked in a more longitudinally revealing manner. Of the many dietary factors invoked as causal in new-onset hypertension, sodium, potassium, magnesium, and calcium have been most commonly advanced as potentially etiologic and worthy of study. The details of many of these dietary studies have oftentimes been methodologically convoluted in that they have commonly relied on estimates of nutrient excretion or either spot or 12-hour overnight urine collections of these same nutrient cations and thus have been subject to critique based on the implied nature of the developed estimates.¹ In that regard, in a prospective population-based cohort study, Kieneker et al²—Prevention of Renal and Vascular End-Stage Disease (PREVEND)—have chosen a more rigorous form of study in attempting to identify the relationship between urinary potassium excretion and the risk of developing hypertension by the use of 24-hour urine collections, the gold standard for assessing urinary nutrient/cation excretion and doing so in a time-wise fashion over a median follow-up of 7.6 years in a cohort of 5511 normotensive individuals aged 28 to 75 years.

The 24-hour urine excretion of potassium is, moreover, preferable for studies such as these in that it eliminates the interpretive considerations relative to the circadian variation in urinary excretion of potassium.³ Of note, several renal potassium transporters have been identified that have a circadian rhythmicity consistent with the observed daily fluctuations in urinary potassium excretion, making this phenomenon one of the several that need to be summed in the interpretation of urine potassium excretion measured in a longitudinally comparative fashion.⁴ In that regard, there is a well-established decrease in urinary potassium excretion at night, an observation that reverses in patients with chronic kidney disease.⁵

Assessing the time-wise intake of potassium by virtue of sequential 24-hour urine collections is not without other issues beyond the simple accuracy of the collection. To be able to reliably compare potassium content in urine collections obtained sequentially over time requires that potassium absorption be maintained as a constant percentage of intake; determinants of renal potassium handling remain comparable in their level of activity; cellular uptake of ingested potassium remains similar at the times of urine collection; and finally environmental conditions do not lead to varying and potentially excessive losses of potassium in sweat. Population-based studies such as the one performed by Kieneker et al² are not designed to evaluate these influencing variables requiring that all 4 such variables be presumed to have been constant at the time of each urine collection. There is no certainty that this is the case until studied. For example, in other studies for as of yet not clearly established reasons, it has been shown that potassium excretion in black individuals, on both random diets and diets fixed for potassium intake, is commonly less than intake, making urine collections difficult to interpret if used in a singular fashion to approximate potassium intake.⁶

The question remains as to whether increasing the potassium intake of the population shifts the blood pressure distribution curve in favor of less incident hypertension as has been suggested for lowering the sodium intake in the general population. Be that as it may, there remains no single factor that a high potassium intake changes that can be seen as a standard for blood pressure reduction or preventing the transition from a normotensive to a hypertensive state. Factors considered in that regard include a greater natriuretic response to an increased potassium intake as well as decreased vascular responsiveness to vasopressor substances and increased sensitivity of the baroreceptor reflex. In addition, it has been shown that potassium supplementation converts otherwise normotensive salt-sensitive nondippers to dippers in the absence of an effect on daytime blood pressure.⁷ The issue of night-time blood pressure change was not intended for study by Kieneker et al,² but one could speculate that in those with an implied higher potassium intake this might favorably influence overnight blood pressure. In so doing the impetus for daytime blood pressure increases, which might develop as a byproduct of higher nighttime readings or possibly a nocturnal nondipping state could conceivably be lessened.

Implicating intake/urinary excretion of potassium in the new onset of hypertension requires that other dietary nutrients be considered for their contribution to the developed state of hypertension. This same population in the PREVEND study has had the association of urinary magnesium excretion, as an indicator of intestinal magnesium absorption, also explored. In that regard, urinary magnesium excretion was found to be inversely associated with the risk of hypertension across the entire range of habitual dietary intake⁸; this association remained intact after adjustment for a wide range of variables, including urinary excretion of sodium, potassium, and calcium. The fact that this and the potassium excretion studies being reported were observational means that confounding variables of a dietary nature may have had some play in the findings. Moreover, one must wonder as to how the individual patient and his/her blood pressure responded to the dietary cross-talk occurring between potassium and magnesium intake.

In summary, the work of Kieneker et al² provides support for what is a developing consensus that an increased potassium intake favorably influences both hypertension and the natural trajectory of blood pressure increase in the general population as well as the risk of incident stroke.⁹ Moreover, there seems to be no adverse effects from an increased potassium intake as related to lipid concentrations, catecholamine levels, or renal function as long as the patient so treated does not have renal disease in which case the risk of hyperkalemia becomes a relative deterrent to such an approach. Intervention trials including potassium consumption as high as 400 mmol per day from food for several weeks and 115 mmol per day for up to a year reported no adverse effects from increased potassium intake.¹⁰ This study, however, does not and cannot provide insight into what is an optimal potassium intake/urinary potassium excretion, and even the cut points for urinary potassium excretion offered have to be taken with a grain of salt as to their generalizability in that a homogeneous, nonethnically diverse population was being evaluated in the PREVEND study.