Evolutionary Health and Kidney Disease

Modern day humans exist in a world that is vastly different from that in which our closest ancestors did. Homo sapiens first appeared some 300,000 years ago and evolved living on a diet consisting of animals and plants. Modern human genetics have remained largely unchanged in the past 40,000 years and since the agricultural revolution some 10,000 years ago when human diets shifted more towards a reliance on grain crops. It is estimated that early humans prior to the agricultural revolution consumed approximately 35% of their diet by weight in animal products and 65% by weight from plants (Eaton and Konner, 1985). This diet is dramatically different from modern day with not only the amounts of food being changed, but also their composition. In even more recent times a new change to the human diet has introduced food processing. Modern ultra-processed foods contain not only unnatural compounds (eg. trans-fatty acids, plastics, antibiotics), they also contain unnatural compositions of foods in proportions not normally found in nature. The invention of processed foods allows for the pairing of high-fat, high carbohydrate foods together to create a new class of hyper-palatable foods, ones that override satiety signals from the brain while being devoid of essential micronutrients. This shift in food intake and composition has created a healthcare crisis, contributing to the increase in preventable diseases such as type 2 diabetes (T2D), heart disease, cancer, chronic kidney disease (CKD) and their related disorders. Kidney diseases are the 9th leading cause of death in the US and contributes to the development of hypertension and precipitating cardiovascular disease, the leading cause of death in the US, and cardiovascular related events (eg. stroke, heart failure). CKD currently affects  around 15% of the US population and 10-13% of the population worldwide (US Department of Health and Human Services, Centers for Disease Control and Prevention, 2019). In 2017 alone, the US medicare costs for CKD was $84 billion with another $36 billion coming from end stage renal disease. T2D is one of the leading causes of kidney disease and contributes to the growing number of patients seeking dialysis for end-stage renal disease. T2D currently affects ~30 million Americans and is projected to reach 44 million by 2034 (American Diabetes Association, 2018). Currently, T2D alone costs the US $327 billion a year or 1 out of every 7 dollars spent on healthcare (Association, 2018). Cardiovascular disease costs totaled $555 billion in 2015 and are anticipated to cost $1 trillion by the year 2035, effectively bankrupting the US if left unchecked (American Heart Association, 2017). With healthcare costs growing at ~5% a year, they are projected to reach 20% of US GDP by 2025 (Keehan et al., 2016). This costly future is certainly avoidable if actions are taken before it is too late to act. 
    It is certainly reasonable to assume that the mismatch in human physiology and environment may underlie the health predicament that we find ourselves in, but it also offers us the solution to our growing healthcare costs and diminishing societal health. Ancestral diets consisted of large quantities of plants and animals, unprocessed, and rich in micronutrients. While the agricultural revolution introduced more grains in place of animal products, food remained generally unprocessed until the 20th century with the invention of refrigeration and the supermarket. This change in the way that food was stored and consumed altered the composition of food and increased the need for added preservatives to keep food stable longer. This alteration in the modern versus ancestral diet resulted in a dramatic reduction in potassium intake for increased amounts of sodium, majorly in the form of sodium chloride or coupled with preservatives (eg. benzoate, sorbate). Ancestral diets were estimated to contain a 1:10 ratio of sodium/potassium whereas modern diets are estimated to contain a 3:1 ratio of sodium/potassium (Frassetto et al., 2001). This alteration in the sodium/potassium ratios also comes at the expense of decreased alkali consumption. Alkali is generally associated with the intake of plant material and decreased alkali in turn contributes to chronic metabolic acidosis, bone mineral loss, calcium excretion, osteoporosis, kidney stones, decreased kidney function, kidney disease and the extrarenal diseases associated with kidney function decline such as hypertension, heart disease and stroke. 
    The intake of highly processed foods is therefore a multifaceted problem. Humans now have access to more calories, yet are lacking essential micronutrients such as potassium. Consumption of highly processed  foods come accompanied with inflammatory compounds (eg. refined sugar, nitrites, oxidized lipids and carbohydrates), high levels of sodium and chloride, an increase in total body acid load and  a decrease in total alkali consumption. This combination wreaks havoc on the kidney and is a major contributor to decreased kidney functioning and in turn extrarenal manifestations. Maintaining and caring for kidney function can therefore be an effective strategy at improving our overall health and the health of our society at large. 
    Pulling a page from our ancestors, increasing our intake of plant material, rich in potassium and alkali could do wonders at increasing our overall kidney function. But could such a simple intervention be so effective? A recent meta-analysis of chronic kidney disease (CKD) prognosis found that both high and low serum potassium were predictors of adverse outcomes (Kovesdy et al., 2018). Potassium depletion is associated with increased blood pressure and sodium retention and potassium supplementation with potassium chloride or potassium citrate were both found to lower blood pressure in healthy individuals (Braschi and Naismith, 2008). Urinary potassium excretion, used as an estimate for dietary intake, found that increased potassium excretion was associated with a lower risk for CKD in healthy individuals. Similarly, higher urinary potassium in diabetic patients was associated with lower odds for renal replacement. However, higher urinary potassium in individuals with decreased kidney function (eGFR between 20-70 mL/min) was associated with increased risk of incident end-stage renal disease (Gritter Martin et al., 2019). While the risk of excessive potassium in late stage CKD has been well documented, these studies highlight how important a role potassium can play prior to the development of late stage kidney disease for preserving and maintaining healthy kidney function. 
    Taking proactive steps to support our health is in our hands and in our food choices. Our modern society has crafted a food system of convenience, abundant in calories yet lacking in substance. By drawing on our evolutionary past, we can make informed decisions and choose to nourish and feed our bodies the nutrients it needs to keep it healthy and functioning optimally. 

References:

Association, A.D. (2018). Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care.
Braschi, A., and Naismith, D.J. (2008). The effect of a dietary supplement of potassium chloride or potassium citrate on blood pressure in predominantly normotensive volunteers. British Journal of Nutrition 99, 1284–1292.
Eaton, S.B., and Konner, M. (1985). Paleolithic Nutrition — A Consideration of Its Nature and Current Implications. N Engl J Med 31, 283–289.
Frassetto, L., Morris, Jr., R.C., Sellmeyer, D.E., Todd, K., and Sebastian, A. (2001). Diet, evolution and aging. Eur J Nutr 40, 200–213.
Gritter Martin, Rotmans Joris I., and Hoorn Ewout J. (2019). Role of Dietary K+ in Natriuresis, Blood Pressure Reduction, Cardiovascular Protection, and Renoprotection. Hypertension 73, 15–23.
Keehan, S.P., Poisal, J.A., Cuckler, G.A., Sisko, A.M., Smith, S.D., Madison, A.J., Stone, D.A., Wolfe, C.J., and Lizonitz, J.M. (2016). National Health Expenditure Projections, 2015–25: Economy, Prices, And Aging Expected To Shape Spending And Enrollment. Health Affairs 35, 1522–1531.
Kovesdy, C.P., Matsushita, K., Sang, Y., Brunskill, N.J., Carrero, J.J., Chodick, G., Hasegawa, T., Heerspink, H.L., Hirayama, A., Landman, G.W.D., et al. (2018). Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis. Eur Heart J 39, 1535–1542.
US Department of Health and Human Services, Centers for Disease Control and Prevention (2019). Chronic Kidney Disease in the United States, 2019.
Cardiovascular Disease Costs Will Exceed $1 Trillion by 2035, Warns the American Heart Association.
https://newsroom.heart.org/news/cardiovascular-disease-costs-will-exceed-1-trillion-by-2035-warns-the-american-heart-association

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