Symposium 0.6 – Future scenarios for renal disease

SUMMARY REPORT

Written by Jasna Trbojevic-Stankovic
All the speakers reviewed and approved the contents

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Climate changes in nephrology

Richard J. Johnson, United States of America

Mean temperatures have increased by 0.8°C since 1880, with two-thirds of this change occurring since 1975. According to scientists they are likely to increase by 3°C to 4°C by the end of the 21st century. Global warming is also responsible for 75% of moderate heat extremes throughout the globe.

Figure 1. World Temperatures are Increasing

One of the major health consequences of extreme heat is heatstroke. Heatstroke can occur during heat waves and also in association with exercise or labor in the heat. Electrolyte abnormalities, acute kidney injury (AKI), and chronic kidney disease (CKD) are common kidney manifestations of this condition. Heatstroke manifests with low serum potassium, sodium, phosphate, and magnesium, which are all associated with increased excretion of these electrolytes through sweat or urine. AKI can appear as classical rhabdomyolysis, often associated with hyperuricemia and signs of dehydration, or as acute interstitial nephritis, with leukocyturia and hematuria. Moreover, patients who suffered heatstroke have a 4-fold increased risk of CKD and a 9-fold increased risk of ESRD in later life.

There are several arguments for the concept that climate change-associated heat stress causes CKD. Firstly, the CKD epidemic occurs most commonly in regions with frequent heat waves (e.g. Central America, India, etc.). Secondly, this epidemic correlates with rising temperatures. It mainly affects heavy physical workers in hot temperatures (e.g. sugar cane workers). The disease is less frequent in a cooler climate, such as in regions at high altitudes. Individuals who develop CKD often have acute presentations that resemble acute heat stroke (e.g. fever, vomiting, back pain, leukocytosis, AKI, etc.). CKD can be induced in mice by recurrent heat and dehydration. Lastly, hydration and shade have been shown to protect against heat stress caused by kidney injury.

Experimental studies show that the primary substance associated with heat stress might be uric acid, due to its increased generation following exercise-induced muscle damage and the urinary acidification that occurs during the concentrating process. Indeed, a study revealed that sugarcane workers exhibit a rise in serum uric acid and creatinine and a decrease in urine pH, thus leading to an increased risk for uric acid crystal formation.

As global warming continues, major efforts are required to assure adequate hydration and prevent overheating in vulnerable populations who are at risk for heatstroke. Heat warning systems, changes in occupational practices, and public health initiatives also are needed. Most importantly, scientific investigations should be directed at identifying how to slow, stop, and reverse global warming.

Demographic changes in different parts of the world

Hans Groth, Switzerland

The Earth today is inhabited by 7.8 billion people of which 6.5 billion people live in less developed countries, whereas 1.3 billion people live in developed countries. Each year the world grows by 80 million people. About 3.4% of the global population live outside their countries of birth. The overall fertility rate has decreased all across the globe. It ranges from <1 child per woman in South Korea to 7 in Niger. The global infant mortality rate has declined since 1970 from 94 infant deaths per 1000 births to 29 deaths in 2020. Life expectancy at birth is higher than ever before with 71 years in less developed countries and 80 years in developed countries.

Higher longevity, decreasing global fertility, and migration present challenges to the world and society that have to be acted upon to capture their potential for growth and sustainable development on the one hand, but also to prevent the emergence of major imbalances within and across nations. It is still unclear if a longer average life will equate to a healthy life for all equally. Thus, there is a rising concern that a higher long-run inequality of health is taking root in society.

Figure 2. Our next world: Different qualities, different quantities

In Africa, the working-age population (15-64 years) will increase from 600 million to 2 billion by 2060, and 65+ cohorts will increase by at least 200 million. For instance, in Nigeria, the country’s population is projected to increase to 263 million in 2030 and 401 million in 2050 when it will become the third most populous country in the world. In Asia, from 2040 on, its working-age populations will start to decrease. By 2060, 1.2 billion from the 65+ cohorts will live on this continent. In China, this dynamic has already started and is gaining momentum. India is set to surpass China as the world’s most populous country by 2030.

In Europe, working-age populations have already shrunk. By 2060, the working-age population will decrease by 120 million, while 65+ cohorts will increase by 60 million. In North America, both the working-age population and 65+ cohorts continue to increase, but the elderly increase more rapidly. In Latin America, from 2050 the working-age population will decrease by >100 million, while 65+ cohorts will increase by 180 million in this century. In Oceania, both the working-age population and elderlies will grow at a similar pace.

From a nephrology perspective, it has been known for decades that eGFR declines in parallel with age. As life expectancy increases, the prevalence of CKD and other age-related kidney disorders will increase as well thus presenting a challenge to the healthcare systems and nephrology community.

Planetary health and burden of lifestyle diseases – what saves the planet saves our health

Peter Stenvinkel, Sweden

Planet Earth has witnessed at least five major mass extinctions over the past 450 million years. Depressing evidence suggests that humans are responsible for the ongoing sixth major mass extinction (Anthropocene), which has led to a multitude of urgent external environmental problems, such as global warming, deforestation, habitat loss, pollution, and a shortage of clean water. In the ‘Living Planet Report 2020’, the World Wildlife Fund reported an alarming 68% decline in the animal population between 1970 and 2016. Progressive loss of biodiversity has catastrophic effects including an increase in the spreading of emerging and existing infective diseases, reduced opportunities for new drug development that comes from the natural world, decrease in animal pollinators, and reduction of gut microbial diversity.

Global health is rapidly being challenged by an aging population and epidemics of the burden of lifestyle diseases that accumulate with age, such as type-2 diabetes, obesity, arteriosclerosis, depression, CKD, cancer, etc. This rapidly growing group of chronic diseases is characterized by low-grade chronic inflammation, termed inflammageing, mitochondrial dysfunction, and oxidative stress that accompanies the aging process. These features are, in part, reflected by the repressed activity of a master regulator of hundreds of cytoprotective genes – the transcription factor Nrf2 that protects against inflammation and oxidative stress.

There are many examples in nature from which we can learn about mechanisms to escape one or several lifestyle diseases that bedevil humans. For example, hibernating bears, despite months of anuria and decreased renal function during winter sleep, do not develop osteoporosis, inflammation, muscle wasting, or atherosclerosis.

Hibernating bears also provide a natural model of reversible, healthy obesity with favorable seasonal changes in insulin resistance. Another example is the giraffe, which is protected from kidney disease and stroke despite alarmingly high blood pressure. Elephants and naked mole rats are protected from cancer, whereas Malaysian pen-tailed tree shrews are protected against the toxic effects of chronic alcohol consumption from floral nectar.

Figure 3. ‘Food as medicine’ concept benefits

In addition, unhealthy diets (e.g. high in sugar, salt, saturated fat, and ultra-processed foods) are a major risk factor for poor health outcomes causing gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature aging, and epigenetic changes – all of which are also common features of CKD. Hence, tailored, healthy diets that include bioactive nutrients could potentially be used to prevent and treat CKD and its complications.

Further reading

Tseng MF, Chou CL, Chung CH, et al. Risk of chronic kidney disease in patients with heat injury: A nationwide longitudinal cohort study in Taiwan [published correction appears in PLoS One. 2020 Sep 2;15(9):e0238826]. PLoS One. 2020;15(7):e0235607. doi:10.1371/journal.pone.0235607

Fischer RSB, Vangala C, Truong L, et al. Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy. Kidney Int. 2018;93(3):681-690. doi:10.1016/j.kint.2017.09.012

Peraza S, Wesseling C, Aragon A, et al. Decreased kidney function among agricultural workers in El Salvador. Am J Kidney Dis. 2012;59(4):531-540. doi:10.1053/j.ajkd.2011.11.039

Roncal Jimenez CA, Ishimoto T, Lanaspa MA, et al. Fructokinase activity mediates dehydration-induced renal injury. Kidney Int. 2014;86(2):294-302. doi:10.1038/ki.2013.492

Vaupel JW, Villavicencio F, Bergeron-Boucher MP. Demographic perspectives on the rise of longevity. Proc Natl Acad Sci U S A. 2021;118(9):e2019536118. doi:10.1073/pnas.2019536118

UN Population Division, World Population Prospects, 2019 Revision.

Mafra D, Borges NA, Lindholm B, Shiels PG, Evenepoel P, Stenvinkel P. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev Nephrol. 2021;17(3):153-171. doi:10.1038/s41581-020-00345-8

Stenvinkel P, Shiels PG, Painer J, Miranda JJ, Natterson-Horowitz B, Johnson RJ. A planetary health perspective for kidney disease. Kidney Int. 2020;98(2):261-265. doi:10.1016/j.kint.2020.03.024

Davis M, Faurby S, Svenning JC. Mammal diversity will take millions of years to recover from the current biodiversity crisis. Proc Natl Acad Sci U S A. 2018;115(44):11262-11267. doi:10.1073/pnas.180490611