Selenium and Kidney Function

Here are the main points from a recent review article on the topic of aging and exposure to heavy metals and kidney function:

• 

  The efficiency with which the kidneys remove waste and excess fluid from the blood declines with age in individuals who are older than 50–60 years.

• Exposure to metal pollutants may be detrimental to the kidneys of normal healthy adults and exacerbates the functional decline of the kidneys in seniors. Given the prevalence of these heavy metal toxicants in the environment, it is nearly impossible for people to avoid exposure.

• Studies have shown that exposure to mercury, cadmium, and/or lead is associated with an increase in the incidence and the severity of kidney disease in elderly individuals. There is some reason to think that adequate selenium status helps to protect against the damage of heavy metal toxicants.

• Unfortunately, the early signs of kidney dysfunction often go unnoticed.

Mercury, Cadmium, Lead – Difficult to Avoid

Prof. Aaseth et al. write that toxic metals are so abundant in the environment that it is almost impossible for humans to avoid contact with them.

The kidneys are the body’s major route of excretion, so the kidneys are especially vulnerable to the toxic damage caused by mercury, cadmium, and lead.

Cumulative exposure of elderly individuals to these pollutants may result in progressive kidney deterioration.

Mercury

Mercury is dangerous, even in minor exposures, to the kidneys in three forms: elemental mercury, methylmercury, and inorganic mercury. Observational studies have shown that both acute and chronic exposure to the various forms of mercury can damage the kidneys.

Cadmium

Several observational studies have reported adverse health effects associated with environmental exposure to cadmium, sometimes even at low levels of exposures, in groups in China, Japan, Europe, and the USA.

In the liver and other tissues, cadmium ions form a complex with the protein metallothionein. Metallothionein can be transported to and filtered in the kidneys and then reabsorbed into the proximal renal tubuli. Inside the renal tubular cells, the MT-complex releases excess free cadmium ions, causing kidney damage.

Lead

Lead compounds are absorbed readily by the intestines and the lungs upon exposure.

A cohort study has shown that the observed decline in kidney function in middle-aged and elderly individuals depends both on lead stored in the body and circulating lead; the decline in kidney function was most pronounced among the individuals with diabetes or hypertension.

A second cohort study of individuals almost 60 years old at the start of the study and with a follow-up period of 16 years has shown that even low-level lead exposure was associated with decreased kidney function.

Selenium’s Role in Aging and in Kidney Disease

Prof. Aaseth has explained the process of aging as follows:

• Aging is linked to a redox imbalance in the cells.
• The redox imbalance is characterized by increased production of harmful free radicals and/or decreased efficiency in the neutralizing of the harmful free radicals.
• The result is impaired cellular function.
• Supplementation with selenium has been reported to enhance protective
  antioxidant capacity in the cells.
• Selenium supplementation is associated with increased antioxidant enzyme activity by the selenoproteins in the glutathione peroxidase (GPX) family, and by GPX3 in particular.  GPX3 is synthesized in the kidneys and is found accumulated in the membrane surrounding the proximal tubules in the kidneys.

Prof. Aaseth has noted the following relationships between selenium status and kidney disease.

• Low serum selenium status is commonly reported in patients with advanced kidney disease.
• Low serum selenium levels are frequently seen in patients on hemodialysis or peritoneal dialysis and may be related to the body’s diminished selenium retention because of the associated chronic oxidative stress.
• End-stage kidney disease patients with low serum selenium status (<63 mcg/L) showed an increased mortality risk compared to patients with normal or high selenium (>118 mcg/L) in a cohort study.

Combined Selenium and Coenzyme Q10 Supplementation in the KiSel-10 Study

In the randomized controlled trial, the KiSel-10 Trial, researchers administered a combination of 200 mcg of selenium in a selenium-enriched yeast tablet and 2 x 100 mg of Coenzyme Q10 in capsules daily for four years to senior citizens (average age: 78 years).

• Analysis of the data from the study showed an association between low selenium status and reduced kidney function.
• The combined selenium and CoQ10 supplementation regime significantly improved kidney function.
• The researchers attributed the improvement to optimized function of antioxidative selenoenzymes such as the GPXs and the thioredoxin reductases [Alehagen 2020].

Selenium’s Role in Protecting Against Mercury

Mercury binds to selenium compounds and is thus “detoxified”; however, both Ralston & Raymond and Spiller et al. have made the argument that the most important consequence of exposure to mercury poisoning is the resultant selenium-deficient state, especially in the brain.

In other words, selenium is the target of the toxic mercury. Yes, selenium can bind to the mercury, but that means that there is then less selenium available for the bio-synthesis of the selenoenzymes that are needed to prevent and reverse oxidative damage in the brain [Ralston & Raymond 2018]. The signs and symptoms of the excessive oxidative damage in the brain are the characteristic effects of mercury toxicity.

In cases of exposure to mercury, selenium supplementation is needed to help restore selenoprotein concentrations and to allow for the reactivation
of some of the existing selenoproteins. Supplementation with selenium can increase the distribution of mercury away from target organs to less sensitive organs, can increase mercury elimination, and can help sequester mercury and render it harmless [Spiller et al. 2021].

Spiller et al. acknowledge that the proper dosing and duration of selenium supplementation in cases of mercury exposure are not known; they recommend an initial selenium supplementation of 100 mcg/day in asymptomatic patients and 500 mcg/day in symptomatic patients for 90 days. Continuing the selenium treatment beyond 90 days should depend on the physicians’ evaluation of patient factors including the patient’s response to treatment, adherence, and the presence and severity of any adverse effects that may warrant discontinuance [Spiller et al. 2021].

Selenium’s Role in Protecting Against Cadmium and Lead

Cadmium

Zwolak in a 2020 review article explains that selenium has been seen to reduce cadmium-associated toxicity in the liver, kidney, spleen, brain, or heart in animal models and in cell culture studies. Selenium counters the toxicity of cadmium primarily by sequestering cadmium into biologically inert complexes and possibly also through the action of selenium containing antioxidant selenoenzymes.

Lead

The possible beneficial role of selenium supplementation alone on lead-induced oxidative stress is still unclear in humans; however, supplementation with selenium remains a potential option because of selenium’s antioxidant properties.
Pawlas et al. [2016] enrolled 324 males whose work exposed them to unusually high levels of lead in the air: 0.083 ± 0.12 mg/cubic meter to investigate the relationships between/among serum selenium concentrations, chronic lead exposure, oxidative stress bio-markers, and parameters characterizing the functioning of the antioxidant defense system.

The researchers divided the men into a low selenium group and a high selenium group. The two groups did not differ significantly with respect to age, height, weight, number of years worked, smoking habits, or whether the men had been diagnosed with coronary artery disease, hypertension, or diabetes.

The big difference between the two groups was in the men’s serum selenium concentrations: 57.9 +/- 8.62 mcg/L in the low selenium group and 90.1 +/- 15.6 mcg/L in the high selenium group.

The study showed that the lead concentrations were significantly lower in the higher selenium group than in the low selenium group. The glutathione level and the activity of the antioxidant enzymes glutathione peroxidase and catalase were significantly higher in the high selenium group.

The study results are thought provoking but are not sufficient for the researchers to recommend selenium supplementation for chronic lead exposure except in cases of selenium deficiency.

Sources

Aaseth J, Alexander J, Alehagen U, Tinkov A, Skalny A,,Larsson A., Crisponi G, Nurchi VM. The Aging kidney—as influenced by heavy metal exposure and selenium supplementation. Biomolecules 2021, 11, 1078.

Alehagen U, Aaseth J, Alexander J, Brismar K, Larsson A. Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial. Nutrients. 2020 Dec 9;12(12):3780.

Pawlas N, Dobrakowski M, Kasperczyk A, Kozłowska A, Mikołajczyk A, Kasperczyk S. The Level of Selenium and Oxidative Stress in Workers Chronically Exposed to Lead. Biol Trace Elem Res. 2016;170(1):1-8.

Ralston NVC, Raymond LJ. Mercury’s neurotoxicity is characterized by its disruption of selenium biochemistry. Biochim Biophys Acta Gen Subj. 2018 Nov;1862(11):2405-2416.

Spiller HA. Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity. Clin Toxicol (Phila). 2018 May;56(5):313-326.

Zwolak I. The Role of Selenium in Arsenic and Cadmium Toxicity: an Updated Review of Scientific Literature. Biol Trace Elem Res. 2020 Jan;193(1):44-63.

The information presented in this review article is not intended as medical advice and should not be used as such.

30 September 2021