Review
Achieving the Benefits of a High-Potassium, Paleolithic Diet, Without the Toxicity

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Abstract

The average US dietary intake of K+ is well below the current recommended nutritional requirements. This deficiency is even more striking when comparing our current intake with that of our ancestors, who consumed large amounts of dietary K+. K+ deficiency has been implicated in many diseases including cardiovascular disease, kidney stones, and osteoporosis. Importantly, dietary supplementation of K+ has favorable effects on reducing blood pressure, decreasing the risk of stroke, improving bone health, and reducing the risk of nephrolithiasis. For this comprehensive review, we scanned the literature using PubMed and MEDLINE using the following search terms: potassium intake, renal potassium excretion, and prevention of hyperkalemia. Articles were selected for inclusion if they represented primary data or review articles published between 1980 and 2015 in high-impact journals. The normal kidney has the capacity to tightly regulate K+ homoeostasis. We discuss new findings with respect to sensing mechanisms by which the kidney maintains K+ homeostasis in the gastrointestinal tract and distal tubule. There are widely prescribed hypertensive medications that cause hyperkalemia and thus require dietary K+ restriction. We conclude by discussing newly approved drugs capable of binding K+ in the gastrointestinal tract and speculate that this new pharmacology might allow diet liberalization in patients at risk for hyperkalemia, affording them the numerous benefits of a K+-rich diet.

Section snippets

Overview of Renal K+ Handling

K+ is freely filtered by the glomerulus, and then mostly reabsorbed in the proximal tubule and thick ascending limb such that only a small amount reaches the distal nephron. Reabsorption in the proximal tubule is primarily through the paracellular pathway and is in rough proportion to Na+ and water. The apical membrane Na+-K+-2Cl cotransporter mediates transcellular K+ transport in the thick ascending limb of Henle. In the early distal convoluted tubule (DCT), K+ secretion begins and

Distal Tubule as a K+ Sensor

The DCT is composed of a proximal portion (DCT1) in which salt transport is driven exclusively by the thiazide-sensitive NaCl cotransporter (NCC) (Figure 1). In the distal portion of the DCT (DCT2), electroneutral NaCl transport coexists with electrogenic Na+ and K+ transport pathways.18, 19 Aldosterone sensitivity begins in the DCT2 and extends to the collecting duct. Changes in transport in the early DCT control the delivery of NaCl to the downstream connecting tubule and collecting duct in

Enteric Sensing of K+ Intake

A number of enteric solute sensors capable of responding to dietary Na+, K+, and phosphate have been identified that signal the kidney to rapidly alter ion excretion or reabsorption.34, 35, 36 In this regard, the ability to sense K+ within the gastrointestinal tract may have evolved as a way to rapidly initiate the kaliuretic response, thereby facilitating maintenance of K+ homeostasis in the setting of high K+ intake. For example, the kaliuretic response to a K+ load is greater when given as a

Hypertension

Epidemiological studies41 have established that K+ intake is inversely related to the prevalence of hypertension. In addition, K+ supplements and avoidance of hypokalemia, lower blood pressure in people with hypertension, whereas blood pressure increases in people with hypertension placed on a low-K+ diet. This increase in blood pressure is associated with increased renal Na+ reabsorption.42

A total of 17,000 adults participated in the NHANES III, and data obtained from this study43 suggested

Use of K+-Enriched Diet in Chronic Kidney Disease

Although ingestion of a K+-enriched diet can safely provide the aforementioned benefits to patients with normal renal function, development of life-threatening hyperkalemia may limit the ability to use such a diet in patients with chronic kidney disease (CKD). This toxicity creates a therapeutic dilemma because a diet rich in fruits and vegetables may offer benefits that are unique to patients with CKD. These benefits are discussed below.

Implementation of K+-Enriched Diets in Patients at Risk for Hyperkalemia

In a recent observational study81 of patients with type 2 diabetes, higher urinary K+ excretion was associated with lower cardiovascular complications and a slower decline of renal function, further supporting the association between increased K+ intake and cardiovascular benefits. Importantly, participants in this trial had normal baseline renal function. There are no long-term studies examining the benefits of a K+-enriched diet in patients with CKD because of the concern for development of

Conclusion

There are abundant data suggesting that ingestion of K+-rich foods is beneficial and may reduce the incidence of stroke, hypertension, nephrolithiasis, and osteoporosis. The data on dietary consumption indicate that Western diets are high in processed foods, high in Na+ content, and low in K+. The kidney is designed to handle significantly higher K+ loads than are currently consumed in our diet. Furthermore, patients who could most benefit from increasing their intake of K+-rich foods are the

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