ReviewAchieving the Benefits of a High-Potassium, Paleolithic Diet, Without the Toxicity
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
References (81)
- et al.
Sodium and potassium intakes among US adults: NHANES 2003-2008
Am J Clin Nutr
(2012) - et al.
The evolution-informed optimal dietary potassium intake of human beings greatly exceeds current and recommended intakes
Semin Nephrol
(2006) - et al.
Early and late adjustment to potassium loading in humans
Kidney Int
(1990) - et al.
Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride
Cell Metab
(2015) - et al.
Liddle's syndrome
Am J Med
(1998) Gut sensing of potassium intake and its role in potassium homeostasis
Semin Nephrol
(2013)- et al.
Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice
Kidney Int
(2013) - et al.
Need to quickly excrete K+? Turn off NCC
Kidney Int
(2013) The role of aldosterone in renal sodium transport
Semin Nephrol
(2006)- et al.
Sodium surfeit and potassium deficit: keys to the pathogenesis of hypertension
J Am Soc Hypertens
(2014)
Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence
Mayo Clin Proc
Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women
Am J Clin Nutr
Potassium causes calcium retention in healthy adults
J Nutr
A rat model of chronic kidney disease-mineral bone disorder
Kidney Int
Metabolic acidosis and the progression of chronic kidney disease
BMC Nephrol
Urinary ammonia and long-term outcomes in chronic kidney disease
Kidney Int
Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors
Am J Clin Nutr
Estimation of the diet-dependent net acid load in 229 worldwide historically studied hunter-gatherer societies
Am J Clin Nutr
Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy
Kidney Int
Dietary Guidelines for Americans [published online ahead of print January 07, 2016]
JAMA
Paleolithic nutrition: a consideration of its nature and current implications
N Engl J Med
Potassium's cardiovascular protective mechanisms
Am J Physiol
Adaptation to chronic potassium loading in normal man
Miner Electrolyte Metab
Regulation of potassium homeostasis
Clin J Am Soc Nephrol
Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct
Am J Physiol Renal Physiol
Regulation of cation transport in the distal nephron by mechanical forces
Am J Physiol Renal Physiol
Control of potassium excretion: a Paleolithic perspective
Curr Opin Nephrol Hypertens
Requirements for a high rate of potassium excretion in rats consuming a low electrolyte diet
J Physiol
Dietary K+ regulates apical membrane expression of maxi-K channels in rabbit cortical collecting duct
Am J Physiol Renal Physiol
Consequences of potassium recycling in the renal medulla: effects of ion transport by the medullary thick ascending limb of Henle's loop
J Clin Invest
Effect of acute potassium load on reabsorption in Henle's loop in the rat
Am J Physiol
Potassium-induced inhibition of proximal tubular fluid reabsorption in rats
Am J Physiol
Distal convoluted tubule
Compr Physiol
Why your mother was right: how potassium intake reduces blood pressure
Trans Am Clin Climatol Assoc
Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb
Am J Physiol Renal Physiol
Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models
Hum Mol Genet
Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo
J Am Soc Nephrol
WNK1 kinase isoform switch regulates renal potassium excretion
Proc Natl Acad Sci U S A
Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms
Proc Natl Acad Sci U S A
Cited by (76)
In the “Plant-Based” Era, Patients With Chronic Kidney Disease Should Focus on Eating Healthy
2024, Journal of Renal NutritionNew Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease
2023, Journal of Renal NutritionPotassium homeostasis – Physiology and pharmacology in a clinical context
2023, Pharmacology and TherapeuticsOutcomes Associated With Potassium Abnormalities in CKD: It Is Time to Move to Clinical Trials
2023, American Journal of Kidney Diseases