Climate change and kidney

Climate Change and Kidneys

Kamilė Počepavičiūtė
Vilnius University Faculty of Medicine

Prepared according to Richard J. Johnson, Laura G. Sánchez-Lozada, Lee S. Newman, Miguel A. Lanaspa, Henry F. Diaz, Jay Lemery, Bernardo Rodriguez-Iturbe, Dean R. Tolan, Jaime Butler-Dawson, Yuka Sato, Gabriela Garcia, Ana Andres Hernando, Carlos A. Roncal-Jimenez.

Introduction

The world is experiencing an increase in temperature. Over the past 50 years, the average temperature has risen by about 0.8 °C. While this temperature rise may not seem significant, it is already having a huge impact on human health [1].

The Impact of Heatwaves

One of the most obvious consequences is the significant increase in extreme heat events, known as heatwaves [2–4]. Heatwaves are the most common cause of death related to weather events in the United States (including tornadoes, hurricanes, and lightning) [5]. Globally, heatwaves ranked among the top ten causes of death from natural disasters between 1980 and 2017.

Definitions and Frequency of Heatwaves

Different definitions are used to classify heatwaves, but one of the most commonly used is when the temperature rises by 5 °C from the average daily temperature and remains at least 5 days [6]. Most studies have shown an increasing frequency of heatwaves worldwide [7]. For example, based on some calculations, in 2015 alone, 175 million more people were affected by heatwaves due to climate change [7].

Consequences of Heatwaves

Heatwaves are dangerous not only because of the risk of overheating but also due to the increasing mortality from cardiovascular and respiratory diseases [6]. One of the deadliest heatwaves, which claimed 73,000 lives, hit Europe in August 2003 [8]. However, heatwaves have caused many deaths worldwide - in Chicago (1995) [9], Andhra Pradesh (2014 and 2015) [10, 11], and Karachi, Pakistan (2015) [12]. Heatwaves and extreme heat affect work productivity and efficiency [13] and can also impact crop yields [14]. Certain heatwaves have been associated with such high temperatures that are dangerous for all living beings. This suggests that in the future, these regions may become uninhabitable [15–17].

Importance of Body Temperature Regulation and Hydration

The regulation of body temperature is essential for survival. Ensuring adequate body hydration is crucial for thermoregulation, but it also raises additional concerns as the availability of clean water is decreasing worldwide. Evidence has shown that 10% of the world's population faces a dangerous lack of water accessibility [18, 19]. Moreover, studies reveal that many people, including children and adults with access to water, still do not consume it as much as needed [20].

Impact of Climate Change on Kidney Diseases

This article discusses the impact of climate change on kidney diseases. The kidneys play a crucial role. They regulate blood volume to maintain blood pressure and extracellular and intracellular osmolality necessary for normal metabolism. One of the key functions is urine concentration - reducing fluid loss and eliminating nitrogen waste from the body.

Susceptibility of Kidneys to Damage

Unfortunately, the active metabolism due to climate change, as well as the excretion of concentrated metabolic products, make the kidneys very susceptible to damage. Studies have shown that as temperatures rise, there is an increase in the number of people seeking emergency care for a wide range of kidney disorders, such as acute kidney injury, chronic kidney disease, kidney stones, and urinary tract infections [21, 22].

Occupational Exposure and Kidney Diseases

Occupational exposure to heat is also associated with an increased prevalence of kidney diseases [23] and decreased work productivity due to impaired kidney function [13]. This article discusses some of these relationships and possible connections to the increased prevalence of chronic kidney disease of unknown etiology in hot regions of the world.

Heat Stroke and Acute Kidney Injury

One of the most severe health consequences of extreme heat is heat stroke. It occurs when the body cannot adequately control its temperature, leading to hyperthermia (a temperature rise >40.6 °C, >105 °F). Symptoms of heat stroke include delirium, coma, seizures, and multi-organ failure [5]. Heat stroke can occur during heatwaves (epidemic or classic heat stroke) or during exercise or work in hot conditions (exertional heat stroke) [24].

Exertional and Epidemic Heat Stroke

Exertional heat stroke is very common among military personnel, marathon runners [25–28], and people working in mines and agricultural industries (especially sugarcane fields) [29]. This type of heat stroke is widespread among new, unacclimatized workers and overweight individuals [29]. Epidemic heat stroke, usually associated with heatwaves, affects individuals who are ill, elderly, obese, or have diabetes. It is particularly dangerous for individuals with poor nutrition, those living in poorly ventilated spaces, and those suffering from heart and lung diseases.

Acute Kidney Damage from Heat Shock

Both classic and physical heat shock can be severe, characterized by confusion and delirium, often accompanied by acute liver and kidney failure. Acute kidney damage frequently develops after an epidemic heat shock. For instance, during a heatwave in Chicago in 1995, over 50% of individuals who experienced heat shock developed acute kidney damage [9]. Acute kidney damage can accompany severe forms of heat shock, such as coma or liver failure, while milder forms may manifest only as fever and isolated acute kidney damage.

The hypothesis suggests two types of acute kidney damage [24]. The first type, characterized by classic rhabdomyolysis (creatine kinase >1,000 U/l), often associates with hyperuricemia and signs of dehydration, typically from physical exertion-induced heat shock. The second type presents with normal or slightly elevated creatinine phosphokinase concentrations and is more common after an epidemic heat shock [24]. Unlike rhabdomyolysis, which often causes acute tubular damage, the second type frequently presents as acute interstitial nephritis with urinary leukocytosis and hematuria, identified as acute tubulointerstitial nephritis on kidney biopsy. This condition is believed to result from ischemia, temperature-induced oxidative stress, and declining intracellular energy reserves [30, 31].

Electrolyte Imbalance and Long-term Effects

Heat shock frequently associates with electrolyte imbalance [24, 32]. A study of 66 individuals who experienced heat shock due to physical exertion found that 91% had acute kidney damage, 53% had hyponatremia, 71% had hypokalemia, and 35% had hypermagnesemia [32]. Low serum potassium, phosphate, and magnesium concentrations were linked to increased urinary excretion of these electrolytes, indicating kidney tubular damage. Sodium and potassium loss through sweat may also contribute. Some subjects exhibited respiratory alkalosis, reducing serum phosphate concentration, although metabolic alkalosis is more common.

For 10–30% of patients experiencing heat shock-related acute kidney damage, dialysis may be necessary [32]. If the patient survives acute damage, kidney function usually recovers [32]. However, heat shock can progress to chronic kidney disease over a few months, with chronic tubulointerstitial nephritis identified on biopsy [33, 34].

Heat Stress Nephropathy and Chronic Kidney Disease Epidemic

In recent years, an epidemic of chronic kidney disease has been observed in various hot regions of the world, primarily affecting people performing manual labor in very high temperatures [35]. One of the largest areas where this disease is prevalent is along the coast of the Pacific Ocean in Central America, particularly among sugarcane workers and other agricultural communities [36]. Evidence suggests that the epidemic has been progressing since 1970 [37]. The disease is common in hot regions of Central Africa, where workers experience heat stress [38, 39]. The hypothesis has been raised that climate change is driving this disease [40]. A recent study showed that working in sugarcane fields is associated with higher humidity and that heatwaves are influenced not only by increased average temperatures but also by El Niño events [41].

Mechanisms and Evidence of Kidney Damage from Heat Stress

There is increasing evidence that chronic kidney disease can develop after repeated subclinical or clinical acute kidney injuries triggered by heat shock [42]. Recent reports show recurrent acute kidney injuries among sugarcane plantation workers during their shifts [43–46]. While most cases remain asymptomatic, some patients experience fever, leukocytosis, leukocyturia, and acute kidney damage, which may require hospitalization [47–49]. It often takes time for chronic kidney disease to develop [48], similar to cases of heat shock induced by physical exertion [34].

Experiments confirm this relationship as repeated heat stress and dehydration can cause chronic inflammation and kidney tubular damage in mice and rats [50–52]. Mechanisms of kidney damage likely relate to increased internal body temperature, the hyperosmolality effect activating the polyol fructokinase pathway, and chronic vasopressin action causing tubular and glomerular damage [50–52]. Clinical studies show that heat exposure and dehydration lead to increased urine concentration and acidity, causing urate crystal formation in the kidneys and damaging the tubules [53]. Experimental data suggest reducing urine acidity can protect the kidneys [54, 55].

Cases of acute kidney injury have been reported from agricultural communities in hot regions around the world, including India (Andhra Pradesh), Sri Lanka (Northern Central Province), Mexico (Veracruz), Central Florida, and the Central California Valley. Most of these areas have also reported outbreaks of chronic kidney disease, raising concerns that rising temperatures and heatwaves, which are precursors to these outbreaks, may be the cause.

Another heat stress impact on the kidneys: kidney stones and infection

Kidney stone disease (nephrolithiasis) is a condition whose prevalence is only increasing. It is speculated to be related to the rise in air temperature due to climate change. Heat stress and dehydration are associated with increased urine concentration and decreased urine volume, which increases the risk of stone formation. For example, it is predicted that the so-called "stone belt" in the United States, describing the hottest regions in the southern United States, will move northward due to ongoing climate warming. Experimental studies have revealed that the primary substrate for kidney stones related to heat stress, due to increased formation after physical exertion-induced muscle damage and increased urine acidity during concentration, is uric acid. Urinary tract infection can also be related to inadequate body hydration, likely prompted by climate change. Recent studies have shown that increased water consumption can increase urine volume and simultaneously reduce the risk of urinary tract infection.

The impact of soft drinks on heat stress-related kidney damage

Soft drinks contain fructose, sugar, which when metabolized in the kidneys, causes local damage to the kidney tubules, inflammation, and oxidative stress. According to recent studies, soft drinks can increase the risk of acute and chronic kidney damage. Experiments have shown that rehydration with soft drinks can increase kidney damage in dehydrated rats. Despite the fact that fructose metabolism can cause kidney damage, it also possibly stimulates vasopressin, which in turn increases kidney damage. According to the latest clinical research data, rehydrating the body with soft drinks in individuals exercising in high temperatures can increase markers of kidney damage, although this association has not been proven in epidemiological studies conducted in a hot environment.

Additional impact of toxins and toxicants

One theory suggests that due to heat and dehydration, natural toxins and human-made toxic substances - toxicants, in recurring acute kidney injury, may accumulate in the kidneys. Investigated substances include potentially nephrotoxic agricultural chemicals, heavy metals, nonsteroidal anti-inflammatory drugs, tobacco, and silicon dioxide. Research is ongoing, examining environmental influences, including meteorological conditions.

Conclusion

In conclusion, although kidneys play a crucial role in protecting the host from the effects of heat stress, they are the target of heat stress-related damage. The impact of heat can lead to both acute and chronic kidney damage, electrolyte imbalances, kidney stone disease, and urinary tract infections. With global warming continuing, it is essential to ensure adequate hydration and protect the most vulnerable population groups at risk of heatstroke. Warning systems about heat, changes in occupational activities, and public health initiatives are also crucial. Most importantly, scientific research should be directed towards slowing down and stopping global warming.

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Journal "Kidney and Cardiovascular Diseases" 2019