Chronic kidney disease (CKD) is rapidly becoming a global health problem. The prevalence of CKD remains high and the incidence of end stage kidney disease or kidney failure continues to rise. According to the Centers for Disease Control and Prevention (CDC), more than 1 in 7 US adults are estimated to have kidney disease. Many factors contribute to the increase in CKD prevalence, including psychological stress (we will refer to this as “stress”). In this blog, we will discuss the link between stress and kidney health.
Types of Stress
Generally speaking, there are three types of stress:
- Major catastrophic life events that require considerable behavioral modification such as the death of a loved one, divorce or loss of a job.
- Chronic strains that are persistent stressors which require some adjustment over a long period of time such as poverty or disability.
- Daily hassles that occur over the course of the day such as traffic issues or unpleasant personal interactions.
The way people perceive and handle stress varies from person to person, with some people better equipped to handle stress than others. Certain factors, which we detail below, impact a person’s ability to cope with stress. These include genetics, environment, and in utero exposure. Furthermore, previous traumatic life experiences may affect future handling of stress in an individual.
Most of the early literature on stress focused on the first two types listed above, but research is now looking at the third type and its effect on health.
According to Selye, there are three phases of behavioral adjustments to stressors. The first phase is the alarm stage in which a person will have a “fight or flight” response. If the stressor persists, the person enters into the resistance or adaptation stage. Finally, long term exposure to the stressor will eventually lead to the exhaustion stage.
Factors that influence stress
Although we all experience stress, some individuals are better suited to handle stress than others. There may be some individual variability due to various genetic and environmental factors, as well as the impact of trauma and adverse childhood experiences.
Genetics
Small differences in our genes, called single nucleotide polymorphisms (SNPs), can affect our hormonal responses and enzymes that are associated with psychological responses. One example is a SNP in catechol-O-methyltransferase (COMT) gene which produces an enzyme that breaks down dopamine, epinephrine, and norepinephrine (neurotransmitters associated with the fight-or-flight response). Mutations in the way this gene is expressed, can lead to an increased stress response.
Another example is a protein called brain-derived neurotrophic factor (BDNF) which protects and improves signaling between brain cells. Any SNPs in BDNF or its receptors can decrease resilience to stress. In fact, the impact of stress on BDNF has been strongly associated with affective disorders.
Environment
The area and physical environment where a person lives and works can be a stressor. Environmental stressors such as living in disadvantaged neighborhoods, limited access to supermarkets, residential density, availability of recreational resources, and distance to wealthy areas, are associated with the development of insulin resistance, type 2 diabetes, obesity, and cardiovascular disease, all of which are risk factors for CKD. It is important to know this is subjective and environmental stressors for one individual may not be stressful to another.
In Utero Exposure
The stress a woman experiences during pregnancy can greatly impact the development of the baby while in utero, leading to lifelong complications. Prenatal stress has been shown to affect hypothalamic-pituitary-adrenal (HPA) axis programming of the fetus, making it more difficult for the offspring to handle stress in the future. Furthermore, this altered HPA activity has been linked to low birth weight which may result in a decrease in nephron endowment (the number of filtering units the baby is born with), as well as metabolic syndrome and cardiovascular disease, known risk factors for CKD.
Nutrition as a Stress Mediator
Research suggests that some nutrients can heighten the response to stressors while other nutrients relieve it. For example, magnesium and zinc can help a person feel more calm. In addition, omega-3 fatty acids and foods high in probiotics can reduce stress and anxiety. On the other hand, caffeine can make a person feel anxious. It is important to note that genetics play a role in caffeine metabolism and its effects.
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Stress and Kidney Health
Indirect Effect of Stress on the Kidney
Stressors can lead to changes in the hypothalamic-pituitary-adrenal axis (HPA axis) and neuroendocrine hormones. These changes are associated with increased cortisol levels, increased epinephrine, and inflammatory cytokines which are linked to the development of insulin resistance, metabolic syndrome, high blood pressure and type 2 diabetes.
Direct Effect of Stress on the Kidney
Studies have shown that the sympathetic system innervates all segments of the kidneys including the blood vessels and tubules. Stimulating the sympathetic system can affect blood flow to the kidneys and lead to sodium retention at the level of the tubules, resulting in the progression of kidney disease.
The Vicious Cycle
As we have seen above, epinephrine and norepinephrine can play a role in the psychological stress response on the kidneys. These neurotransmitters are usually broken down in our bodies by two major enzymes: monoamine oxidase (MAO) and COMT. Recently, a new enzyme, renalase, was found to be produced by the kidneys and involved in the breakdown of these neurotransmitters.
Renalase is a flavoprotein that metabolizes catecholamines (epinephrine, norepinephrine, and others) to aminochromes. It utilizes NADH as a cofactor. Therefore, deficiencies in vitamin B2 and B3 can affect its function. Studies have shown that renalase levels in the blood correlate with normal kidney function and kidney mass. Decreased level of renalase leads to elevated blood pressure and heart rate, physiological responses to stress. Furthermore, it’s been shown that decreased levels of renalase increase the sensitivity of the heart and the kidneys to ischemia (decreased blood flow).
This creates a vicious cycle in which stress causes kidney disease, and the latter, in turn, amplifies the effect of stress on the body.
In essence, the interplay between stress and kidney disease can be summarized in this diagram.
The Bottom Line on stress and kidney health
Our increasingly stressful lives can lead to increased cortisol levels, insulin resistance, and inflammation. Stress has been linked to increased levels of epinephrine and norepinephrine. These changes lead to the development and progression of kidney disease. Genetics, environment, and nutrition all play important roles in augmenting these changes. It’s essential that a stress management practice is part of a comprehensive Integrative and Functional Medicine approach to kidney health.
