Background.

Environmental surveys have characterized trace elements such as lead (Pb), cadmium (Cd) and arsenic (As) as potential risk factors for non-communicable diseases. There have been few studies conducted in the Caribbean region to explore, define or clarify such findings locally. Furthermore, local pollution control efforts are often juxtaposed against more seemingly immediate economic concerns in poor communities.

Objectives.

The present commentary is a call to action for the evaluation of potentially hazardous elements as potential risk indicators and/or factors of common noncommunicable diseases in the Caribbean.

Discussion.

Findings from Jamaican studies have identified exposure to potentially hazardous elements (PHE) via water, food, and other anthropogenic activities to the detriment of the resident population. Several attempts have been made to abate toxic metal exposure in children with relative success. However, high levels of PHE have been noted in vulnerable populations such as patients with hypertension, diabetes mellitus and chronic kidney disease. Currently, there is low priority towards infrastructure building within the Caribbean region that would promote and sustain long term monitoring and better inform environmental polices impacting chronic diseases.

Conclusions.

Further investigations are needed to clarify the role that PHE play in increasing the risk or progression of non-communicable diseases, especially in vulnerable groups.

Competing Interests.

The authors declare no competing financial interests.

Introduction

Trends in non-communicable diseases (NCD) such as chronic kidney disease (CKD), hypertension and diabetes mellitus in the Caribbean mirror the global NCD pandemic which predicts an exponential increase in incidence and prevalence over the next decade.1,2  These NCD, as well as others, are responsible for almost 70% of global deaths.3  At the 13th Annual Conference on Nephrology and Hypertension held in Kingston, Jamaica on January 2021, it was reported that there were currently more than 2700 CKD patients in Jamaica.2,4  Since the first lifestyle survey in 2000/2001 carried out in Jamaica, the prevalence of hypertension and diabetes has risen by 11% and over 8%, respectively.5,6  Factors such as poor dietary practices, sedentary lifestyle, tobacco smoking and excessive alcohol use have been the focus of patient management and education, and the common target for policymakers and clinicians. However, environmental contamination must be seriously investigated for its contribution to NCD.

Discussion

The health hazards of acute exposure to potentially hazardous elements (PHE)—non essential trace elements, such as cadmium (Cd), mercury (Hg), arsenic (As) and lead (Pb) have been well documented.7  Several studies in Jamaica have identified potential sources of Pb, including backyard smelters and the proximity of residential districts to Pb factories and contaminated river sources, playpens and re-purposed cooking materials.811  There has been some success in mitigating such exposures, especially through blood lead level (BLL) screening of the pediatric population, collaboration with caregivers and primary health care workers, government policies, and community clean-up and education efforts.8,12  Overall, Pb levels in children continue to decline.9 

However, the ongoing campaign by residents and environmentalists to prohibit bauxite mining near the Cockpit Country Protected Area highlights the most recent concerns towards pollution of ground water sources which supply 40% of Western Jamaica.13  While contamination in air, water and plastics are well known, the potential effects of PHE at low and chronic levels in patients with NCD are not well studied in the wider Caribbean region. The engagement of other regional stakeholders is limited without the scientific groundwork to investigate and characterize those potential effects.

Studies carried out by the International Centre of Environmental and Nuclear Sciences have indicated higher Cd levels in soil in Jamaica than found globally.14  The maximum naturally occurring Cd concentrations in soil exceeds 900 mg/kg, versus the global range of 0.1–0.5 mg/kg.14  Elevated concentrations of PHE in locally grown food products, and the kidney and liver of grazing cattle and residents in areas of high concentration, however, did not correlate directly to health indicators such as mortality rates or life expectancy.15,16  However, a study by Lalor et al. found that Cd was accumulated in human kidneys.17 

Currently, research projects in Jamaica are attempting to bridge the gap of information investigating the association of PHE levels with CKD and hypertension. One such study investigated the relationship of 15 trace elements including Hg, Pb, Cd, As, selenium (Se), vanadium (V), chromium (Cr), nickel (Ni), iron (Fe) and zinc (Zn) with chronic kidney disease patients.18  This study revealed increased levels of toxic elements such as Cd, Pb and As, while essential elements, such as Fe and Zn were significantly depleted in patients with end stage renal disease (ESRD). Strontium (Sr), a little-known trace element in Caribbean medicine, was also surprisingly elevated in CKD patients and has been postulated as a potential biomarker for the disease.18  The implications for calcium substitution in the bone for Sr have been a source of debate surrounding the protective role Sr may provide against osteoporosis and paradoxically, its own contribution to Sr-induced osteomalacia.19  Where this may lead in improving knowledge of CKD-mineral bone disease and how this may affect the prognosis of those affected are relevant avenues for further research. To further complicate those findings, hemodialysis, the most common therapy for ESRD in Jamaica and the Caribbean, is an imperfect solution to the removal of these PHE.18  During hemodialysis, essential elements significantly decrease, and potentially contribute to overall deficiency in dialysis patients, while strontium levels further increase.18  It must be emphasized that in ESRD patients, renal excretion markedly decreases and thus is vulnerable to PHE retention within the body.1921  This, by extension, increases exposure to nephrotoxic elements.

Abbreviations

    Abbreviations
     
  • CKD

    Chronic kidney disease

  •  
  • NCD

    Non-communicable disease

  •  
  • PHE

    Potentially hazardous elements

Another study followed Cd measurements in the blood from study participants from every parish in Jamaica and their correlation with elevated blood pressure.1  The study investigated the association between blood Cd levels with blood pressure levels and the prevalence of hypertension in a representative sample of Jamaican adults living in parishes across levels of Cd in local soil. Data were collected through structured questionnaires, blood pressure readings and analyzed using spectrometric techniques. Some association between increased blood Cd levels and elevated blood pressure was observed using logistic regression analysis for Kingston/St. Andrew and St. Catherine parishes of Jamaica. This gives further credence to the involvement of environmental factors amongst the complex interactions leading to the prevalence of hypertension.

Internationally, via studies such as the United States National Health and Nutrition Examination Survey (NHANES),22,23  and its Korean counterpart (KNHANES),24  Cd has been identified as a possible risk factor to CKD in diabetic and hypertensive patients even at sub-level exposure. The NHANES also revealed associations of blood Pb-levels with hypertension in non-Hispanic blacks and Mexican-Americans despite declining Pb-levels.25  In another study, Cd and Pb were highlighted for their potential role in increasing the risk of cardiovascular disease.26  Arsenic exposure has been implicated as a risk factor for diabetes mellitus in several populations in Mexico,27  the United States,28,29  Bangladesh30  and Taiwan.31,32 

The use of study findings to influence policy is impacted by study heterogeneity. Clinical outcomes, dietary habits, patient health status and recreational habits are not always consistently reported where these are factors that determine or influence exposure rates.24,33,34  Comparative analyses between studies are also limited due to differences in study design. The few nationally representative surveys which are consistently reported do not usually employ a longitudinal design. Thus, cause and effect relationships via epidemiological survey could only be approximated via conjecture as causation could not be established. Furthermore, environmental studies have been predominantly carried out in non-black populations, despite black populations being the more vulnerable racial/ethnic group prone globally to NCDs.35,36 

A further challenge is presented as the outcome of PHE exposure varies based on the route/duration of exposure, biochemistry or toxicological profile of the specific contaminant, metabolic pathways altered as a consequence of exposure, and dietary habits of the population being investigated.3739  Potentially hazardous elements tend to accumulate for long periods of time in various body systems, including bone, kidneys and liver and have sub-clinical effects in the body.38,4042 

The kidney, for example, as the primary filter of the body, comes into direct contact with PHE.7  Mercury, Pb, uranium and Cd are reported to be nephrotoxic.43  As the body burden of the elements increase, inflammatory mediators are recruited to sites of exposure in the form of oxidising metabolites. These metabolites then induce free radical damage on surrounding kidney cells.44  Chronic interstitial nephritis may be induced by Pb, and apoptosis activated by Cd. Epithelial disruption in the renal tubule by As and Cd and other pernicious effects have been attributed to oxidative damage subsequent to exposure.38,45  Potentially hazardous elements are also actively reabsorbed after glomerular filtration via metal transporters.44,46  Since many heavy metals such as silica (Si), aluminium (Al) and Sr are renally excreted, diminished kidney function increases retention of those PHE, and will exacerbate further kidney damage.43  With progressive kidney damage, there is activation of renin-angiotensin aldosterone system (RAAS) leading to blood pressure dysregulation and cardiac dysfunction.47 

There may be involvement of several PHE in pathways responsible for the regulation of blood pressure and vascular permeability and ultimately endothelial damage, which will affect peripheral resistance and blood pressure auto dysregulation.7  Animal studies suggest increased mediators of the RAAS in response to Pb, Cd, As and Al exposure.40,4851  Chen et al. further reported a possible link by investigating urinary As levels, high risk RAAS genetic polymorphisms and CKD.48  Epigenetic mechanisms exploited by PHE should be explored, especially in racially diverse populations.

Oxidative damage is facilitated by both the enhanced production of reaction oxidative species and free radicals which cause DNA and protein damage, oxidation of lipid moieties and sulfhydryl groups while depleting anti-oxidative defences.52  Protective biomolecules such as Vitamin C, Vitamin E, beta carotene, Se, and anti-oxidative enzymes like catalase, glutathione peroxidase, and superoxide dismutase are in high demand in chronic disease.53  In pre-existing health conditions, the redox balance shifts to make tissue and cellular structures vulnerable to further insults.37  Metals such as Cd, copper (Cu) and Ni in their composite forms have been associated with fatty acid oxidative processes and carcinogenicity.54  In fact, lipid peroxidation has been used as a marker for metal-induced oxidative stress.53  Mitochondrial structures are particularly sensitive to lipid peroxidation and is a primary target in cardiac tissue.55,56  Podocyte damage in the kidney leading to proteinuria has also been the result of mitochondrial dysfunction.55,56  The link between oxidative stress and inflammation will invariably result in exponential cellular and tissue damage, and other underlying pathophysiological mechanisms which promote development and progression of NCD.52 

Another cause for concern in NCD is the possible relationship between malnutrition and PHE. Nutrient deficiencies contribute to the accumulation of toxic elements, since competition between heavy metals and essential trace elements can exacerbate existing trace element deficiencies.46  For a population susceptible to deficiencies of calcium/Vitamin D, Fe, Zn and Se, uptake by non-selective divalent metal transporters in the gut will increase the absorption of PHE such as Cd, Pb, and Hg.38,44,46,57  Consequently, the severity of health effects is linked to accumulation patterns in the body, which are often attenuated by the nutritional and dietary status of individuals.5860  Thus, poor nutrition is one of the underlying contributors to NCD development. Furthermore, dietary restriction—a necessary intervention in CKD patients, and poor appetite—a common sequelae of disease progression—increases the risk of malnutrition, a consequence common in this patient population.61,62  Dewar et al. (2012), for example, found that hemodialysis patients in Jamaica were susceptible to moderate malnutrition.63  The understanding of these interactions is crucial to the management of NCD. Potentially hazardous element absorption and retention is another critical measure in need of further investigation.

Government agencies, private enterprises, and regulatory bodies such as the International Atomic Energy Agency should continue to pursue comprehensive policies that facilitate economic growth as well as monitor and protect long term public health concerns. Some vulnerable communities are solely dependent on backyard smelting for economic means, and chronic exposure to PHE may seem an acceptable risk. Thus, the information and infrastructure to pursue the long-term benefits of seemingly costly but practical interventions must continue to inform clinical management, public health policies and regulations to effectively minimize hazardous exposures.

Conclusions

Variability in habitat and culture predetermine exposure rates of a population to PHE, thereby precluding the superimposition of international study findings on local and regional populations in the Caribbean. Consequently, dialogue is needed in the public health sector in Caribbean countries to investigate potential environmental hazards and related social determinants of health increasing the risk of NCDs.

Acknowledgments

Special thanks to the administration and staff of the Department of Physics for their support towards this research project. Also special thanks to Professor André Desrochers, Mrs. Smitarani Mohanty and Professor Keiko Hattori for facilitating collaborative research with the University of Ottawa, Canada.

Research grants were received from Office of the Registrar, Graduate Studies & Research, University of the West Indies, Mona, Jamaica. Additionally, Canadian-CARICOM scholarship was awarded by Global Affairs Canada to facilitate collaborative research with the University of Ottawa.

References

1.
Barbosa
ECD,
Ramirez
A,
Beaney
T,
et al.
May measurement month 2017: Latin America
.
Hypertension
.
2020
;
38
(
6
):
1183
1188
. https://doi.org/10.1097/HJH.0000000000002370
2.
Soyibo
A.
Prevalence of Chronic Kidney Disease in the Caribbean - Update
.
Paper presented at: Targeting Chronic Non-Communicable Diseases in the Caribbean 2019
;
Knutsford Court Hotel.
3.
World Health Organization.
Non-communicable disease and their risk factors
.
Accessed [2019 January 29]. Available from: https://www.who.int/ncds/introduction/en/
4.
Kramer
H,
Soyibo
AK,
Foster
T,
Boyne
M,
Markossian
T,
Durazo-Arvizu
R
et al.
The burden of chronic kidney disease and its major risk factors in Jamaica
.
Kidney Int
.
2018
;
94
(
5
):
840
842
. https://doi.org/10.1016/j.kint.2018.07.025
5.
Cunningham-Myrie
Colette,
Younger-Coleman
Novie,
Tulloch-Reid
Marshall,
et al.
Diabetes mellitus in Jamaica: sex differences in burden, risk factors, awareness, treatment and control in a developing country Trop
.
Med. Int. Health
.
2013
;
18
(
11
):
1365
-
1378
. https://doi.org/10.1111/tmi.12190
6.
Jamaica Health and Lifestyle Survey III (2016 - 2017).
Ministry of Health and Wellness, Jamaica
.
Updated (2018 September 10]. Accessed [2021 January 19] Available from: https://www.moh.gov.jm/jamaica-health-and-lifestyle-survey-iii-2016-2017/
7.
Duruibes
J.,
Ogwuegbu
M.,
Egwurugwu
J.
Heavy metal pollution and human biotoxic effects
.
Int J Phys Sci
.
2007
;
2
(
5
):
112
-
118
.
8.
International Centre of Environmental and Nuclear Sciences.
Mitigating Lead Poisoning in Rural Communities
.
9.
Henriques
S.
Toxic Playpens. International Atomic Energy Agency
.
Accessed [2021 March 10] Available from: https://www.iaea.org/sites/default/files/51105816164.pdf
10.
Ramikie
T,
Rattray
V,
Voutchkov
M.
Bioavailability of lead-contaminated soils in a tropical environment: Jamaica
.
Int J Environ Sci Technol
.
2020
;
17
(
4
):
2017
2026
. https://doi.org/10.1007/s13762-019-02596-w
11.
Lalor
G,
Vutchkov
M,
Bryan
S.
Blood lead levels of Jamaican children island-wide
.
Sci Total Environ
.
2007
;
374
(
2–3
):
235
241
. https://doi.org/10.1016/j.scitotenv.2006.12.045
12.
Lowe
H,
Smith
R,
Campbell
N,
Morrison
EY.
Lead pollution and amelioration measures in the community of Frazers Content, St Catherine, Jamaica
.
West Indian Med J
.
2002
;
51
(
3
):
160
163
.
13.
Threats to Biodiversity in Cockpit Country.
Accessed [2021 March 10] Available from: https://www.cockpitcountry.com/threats.html.
14.
Lalor
G.
A Geochemical Atlas of Jamaica
.
The University of the West Indies, Jamaica;
1995
.
15.
Howe
A,
HooFung
L,
Lalor
G,
Rattray
R,
Vutchkov
M.
Elemental composition of Jamaican foods 1: a survey of five food crop categories
.
Environ Geochem Health
.
2005
;
27
(
1
):
19
-
30
. https://doi.org/10.1007/s10653-004-5671-7
16.
Nriagu
J,
Boughanen
M,
Linder
A,
et al.
Levels of As, Cd, Pb, Cu, Se and Zn in bovine kidneys and livers in Jamaica
.
Ecotoxicol Environ Saf
.
2009
;
72
(
2
):
564
571
. https://doi.org/10.1016/j.ecoenv.2008.05.001
17.
Lalor
G,
Rattray
R,
Williams
N,
Wright
P.
Cadmium levels in kidney and liver of Jamaicans at autopsy
.
The West Indian Med J
.
2004
;
53
(
2
):
76
80
.
18.
Fevrier-Paul
A,
Soyibo
AK,
DeSilva
N,
McGrowder
D,
Mitchell
S,
Voutchkov
M.
Trace Elements and Chronic Kidney Disease: A cross-sectional study in Jamaica
.
Eur Med J
.
Accepted May 4 2021.
19.
Fevrier-Paul
A,
Soyibo
AK,
Mitchell
S,
Voutchkov
M.
Role of Toxic Elements in Chronic Kidney Disease
.
Journal of Health and Pollution
.
2018
;
8
(
20
). https://doi.org/10.5696/2156-9614-8.20.181202
20.
Shanmugam
L,
Green
SR,
Radhakrishnan
H,
et al.
Trace Elements in Chronic Haemodialysis Patients and Healthy Individuals-A Comparative Study
.
J Clin Diagn Res
.
2016
;
10
(
10
):
OC14
OC17
. https://doi.org/10.7860/JCDR/2016/22031.8618
21.
Palaneeswari
S,
Rajan
P,
Silambanan
S,
Jothimalar
.
Blood Arsenic and Cadmium Concentrations in End-Stage Renal Disease Patients who were on Maintenance Haemodialysis
.
J Clin Diag Res
.
2013
;
7
(
5
):
809
813
. https://doi.org/10.7860/jcdr/2013/5351.2945
22.
Ferraro
PM,
Costanzi
S,
Naticchia
A,
Sturniolo
A,
Gambaro
G.
Low level exposure to cadmium increases the risk of chronic kidney disease: Analysis of the NHANES 1999–2006
.
BMC Public Health
.
2010
;
10
(
1
). https://doi.org/10.1186/1471-2458-10-304
23.
Buser
M,
Ingber
SZ,
Raines
N,
Fowler
DA,
Scinicariello
F.
Urinary and blood cadmium and lead and kidney function: NHANES 2007–2012 Int J Hyg Environ Health
.
2016
;
219
(
3
):
26
-
67
. https://doi.org/10.1016/j.ijheh.2016.01.005
24.
Kim
H-J,
Lim
H-S,
Lee
K-R,
et al.
Determination of Trace Metal Levels in the General Population of Korea
.
Int J Environ Res Public Health
.
2017
;
14
(
702
). https://doi.org/10.3390/ijerph14070702
25.
Soisungwan
S,
Vesey
DA,
Gobe
GC.
Kidney Cadmium Toxicity, Diabetes and High Blood Pressure: The Perfect Storm
.
Tohoku J Exp Med
2017
;
241
:
65
87
. https://doi.org/10.1620/tjem.241.65
26.
Bukhari
IH,
Hassan
MN,
Haleem
A,
Bhatti
M.
Role of metals (Cadmium and lead) in patients of hypertension and their relationship with Ischemic Heart Disease
.
Res J Agric Biol Sci
.
2005
;
1
(
2
):
190
194
.
27.
Coronado-González
JA,
Razo
LM,
García-Vargas
G,
Sanmiguel-Salazar
F,
Peña
JE.
Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico
.
Environ
.
2007
;
104
(
3
):
383
-
389
. https://doi.org/10.1016/j.envres.2007.03.004
28.
Navas-Acien
A,
Silbergeld
EK,
Pastor-Barriuso
R,
Guallar
E.
Arsenic Exposure and Prevalence of Type 2 Diabetes in US Adults
.
J Amer Med Assoc
.
2008
;
300
(
7
):
814
822
. https://doi.org/10.1001/jama.300.7.814
29.
Navas-Acien
A,
Umans
JG,
Howard
BV,
et al.
Urine Arsenic Concentrations and Species Excretion Patterns in American Indian Communities Over a 10-year Period: The Strong Heart Study
.
Environ Health Perspect
.
2009
;
117
(
9
):
1428
1433
. https://doi.org/10.1289/ehp.0800509
30.
Rahman
M,
Tondel
M,
Ahmad
S,
Axelson
O.
Diabetes Mellitus Associated with Arsenic Exposure in Bangladesh
.
Am Journal Epidemiol
.
1998
;
148
(
2
):
198
-
203
. https://doi.org/10.1093/oxfordjournals.aje.a009624
31.
Wang
SL,
Chiou
JM,
Chen
CJ,
et al.
Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan
.
Environ Health Perspect
.
2003
;
111
(
2
):
155
-
159
. https://doi.org/10.1289/ehp.5457
32.
Tseng
CH,
Tai
TY,
Chong
CK,
et al.
Long-Term Arsenic Exposure and Incidence of Non–Insulin-Dependent Diabetes Mellitus: A Cohort Study in Arseniasis-Hyperendemic Villages in Taiwan
.
Environ Health Perspect
.
2000
;
108
(
9
):
847
-
851
. https://doi.org/10.1289/ehp.00108847
33.
Kunhikrishnan
A,
Go Woo
R,
Park
J-H,
et al.
Heavy Metal/(loid) Levels in Paddy Soils and Brown Rice in Korea
.
Korean Journal of Soil Sci Fert
.
2015
;
48
(
5
):
515
-
521
. https://doi.org/10.7745/KJSSF.2015.48.5.515
34.
Henriquez-Hernandez
LA,
Luzardo
OP,
Boada
LD,
et al.
Study of the influencing factors of the blood levels of toxic elements in Africans from 16 countries
.
Environ Pollut. (Barking, Essex : 1987)
.
2017
;
230
:
817
828
. https://doi.org/10.1016/j.envpol.2017.07.036
35.
Davis
HT,
Aelion
CM,
Liu
J,
et al.
Potential sources and racial disparities in the residential distribution of soil arsenic and lead among pregnant women
.
Sci Total Environ
.
2016
;
551–552
:
622
630
. https://doi.org/10.1016/j.scitotenv.2016.02.018
36.
Norton
JM,
Moxey-Mims
MM,
Eggers
PW,
et al.
Social Determinants of Racial Disparities in CKD
.
J Am Soc Nephrol
.
2016
;
27
(
9
):
2576
2595
. https://doi.org/10.1681/ASN.2016010027
37.
Jan
AT,
Azam
M,
Siddiqui
K,
Ali
A,
Choi
I,
Haq
QM.
Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants
.
Int J Mol Sci
.
2015
;
16
(
12
):
29592
29630
. https://doi.org/10.3390/ijms161226183
38.
Ernesto
S,
Robles-Osorio
ML.
Renal health and the environment: heavy metal nephrotoxicity
.
Nefrologia
.
2012
;
32
(
3
):
279
286
. https://doi.org/10.3265/nefrologia.pre2012.jan.10928
39.
Jenkitkasemwong
S,
Wang
C-Y,
Mackenzie
B,
Knutson
MD.
Physiologic implications of metalion transport by ZIP14 and ZIP8
.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
.
2012
;
25
(
4
):
643
655
. https://doi.org/10.1007/s10534-012-9526-x
40.
Ezomo
Ojeiru F.,
Matsushima
F,
Meshitsuka
S
.
Up-regulation in the expression of renin gene by the influence of aluminium
.
J Inorg Biochem
.
2009
;
103
(
11
):
1563
-
1570
. https://doi.org/10.1016/j.jinorgbio.2009.07.018
41.
Meliker
Jaymie R,
Wahl
Robert L,
Cameron
Lorraine L,
Nriagu
JO.
Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: A standardized mortality ratio analysis
.
J Environ Health
.
2007
;
6
(
4
):
277
286
. https://doi.org/10.1186/1476-069X-6-4
42.
Soderland
P.,
Lovekar
S.,
Weiner
D. E.,
Brooks
D. R.,
Kaufman
J. S
.
Chronic Kidney Disease Associated With Environmental Toxins and Exposures
.
Adv Chronic Kidney Dis
.
2009
;
17
(
5
):
254
264
. https://doi.org/10.1053/j.ackd.2010.03.011
43.
De Broe
Marc E.,
Roch-Ramel
F.
Renal handling of drugs and xenobiotics
.
In:
De Broe GAP
M.E.,
Bennett
W.M.,
Deray
G.
,
ed.
Clinical Nephrotoxins
.
Boston, MA
:
Springer
;
2008
:
43
64
. https://doi.org/10.1007/978-94-015-9088-4_2
44.
Peraza
MA,
Ayala-Fierro
F,
Barber
DS,
Casarez
E,
Rael
LT.
Effects of micronutrients on metal toxicity
.
Environ Health Perspect
.
1998
;
106
(
1
):
203
216
. https://doi.org/10.2307/3433921
45.
Åkerström
M.
Biomonitoring of Cadmium – Relationship between Cadmium in Kidney, Blood and Urine, Interpretation of Urinary Cadmium, and Implications for Study Design
.
In:
University of Gothenburg
;
2014
.
46.
Barbier
O,
Jacquillet
G,
Tauc
M,
Cougnon
M,
Poujeol
P.
Effect of Heavy Metals on, and Handling by, the Kidney
.
Nephron Physiol
.
2005
;
99
(
4
):
105
-
110
. https://doi.org/10.1159/000083981
47.
Aihua
D,
Arndt
MA,
Satriano
J,
et al.
Renal Protection in chronic kidney disease: hypoxiainducible factor activation vs. angiotensin II blockade
.
American Physiological Society
.
2010
;
299
:
1365
1373
. https://doi.org/10.1152/ajprenal.00153.2010
48.
Chen
W,
Huang
Y,
Shiue
H,
et al.
Reninangiotensin--aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease
.
Toxicology Appl Pharmacology
.
2014
;
279
(
2
):
95
-
102
. https://doi.org/10.1016/j.taap.2014.05.011
49.
Goodfriend
Theodore L.,
Ball
Dennis L.,
Elliott
Mary E.,
Shackleton
C.
Lead increases Aldosterone Production by Rat Adrenal Cells
.
Hypertension
.
1995
;
25
(
4
):
785
-
789
. https://doi.org/10.1161/01. HYP.25.4.785
50.
Palacios
J,
Nwokocha
CR,
Cifuentes
F.
Arsenic exposure decreases rhythmic contractions of vascular tone through sodium transporters and K+ channels
.
World J Pharmacol
.
2014
;
3
(
2
):
18
-
23
. https://doi.org/10.5497/wjp.v3.i2.18
51.
Nwokocha
CR,
Baker
A,
Douglas
D,
McCalla
G,
Nwokocha
M,
Brown
P.
Apocynin ameliorates cadmium-induced hypertension through elevation of endothelium nitric oxide synthase
.
Cardiovasc
.
2013
;
13
(
4
):
357
-
363
. https://doi.org/10.1007/s12012-013-9216-0
52.
Reyes
JL,
Molina-Jijón
E,
Rodríguez-Muñoz
R,
Bautista-García
P,
Debray-García
Y,
Namorado
MdC
.
Tight Junction Proteins and Oxidative Stress in Heavy Metals-Induced Nephrotoxicity
.
Biomed Res Int
.
2012
;
2013
. https://doi.org/10.1155/2013/730789
53.
Poljšak
B,
Fink
R.
The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution
.
Oxid Med and Cell Longev
.
2014
;
2014
:
671539
. https://doi.org/10.1155/2014/671539
54.
Valko
M,
Morris
H,
Cronin MTD Metals, Toxicity and Oxidative Stress.
Curr Med Chem
.
2005
;
12
(
10
):
1161
208
. https://doi.org/10.2174/0929867053764635
55.
Lentini
P,
Zanoli
L,
Granata
A,
Signorelli
SS,
Castellino
P,
Dell'Aquila
R.
Kidney and heavy metals - The role of environmental exposure
.
Mol Med Rep
.
2017
;
15
(
5
):
3413
-
3419
. https://doi.org/10.3892/mmr.2017.6389
56.
Orr
SE,
Bridges
CC.
Chronic Kidney Disease and Exposure to Nephrotoxic Metals
.
Int J Mol Sci
.
2017
;
18
(
5
). https://doi.org/10.3390/ijms18051039
57.
Keil
Deborah E.,
Berger-Ritchie
Jennifer,
McMillin
GA
.
Testing for Toxic Elements: A Focus on Arsenic, Cadmium, Lead, and Mercury
.
Lab Med
.
2011
;
42
(
12
):
735
742
. https://doi.org/10.1309/LMYKGU05BEPE7IAW
58.
Nwokocha
CR,
Younger-Coleman
N,
Owu
DU,
Asemota
H.,
Iwuala
M,
Lay-Ekuakille
A.
Analysis of Time of Measurement and Modes of Administration of Some Medicinal Plants Additives on Mercury Accumulation in the Livers
.
International Journal of Measurement Technologies and Instrumentation Engineering
2013
;
3
(
3
):
60
-
70
. https://doi.org/10.4018/ijmtie.2013070105
59.
Nwokocha
CR,
Nwokocha
MI,
Aneto
I,
et al.
Comparative analysis on the hepatoprotective effect of Lycopersicon esculentum (Tomato) on metal accumulation in Wistar rats
.
Food Chem Toxicol
.
2012
;
50
(
2070
-
2073
). https://doi.org/10.4103/0974-8490.102263
60.
Nwokocha
CR,
Owu
DU,
Nwokocha
MI,
Ufearo
CS,
Iwuala
M.
Comparative Study on the Hepatoprotection to Heavy Metals of Zingiber Officinale
.
Phcog Res
.
2012
;
4
(
208
-
213
). https://doi.org/10.4103/0974-8490.102263
61.
Gracia-Iguacel
C,
Gonzalez-Parra
E,
Barril-Cuadrado
G,
et al.
Defining protein-energy wasting syndrome in chronic kidney disease: prevalence and clinical implications
.
Nefrologia
.
2014
;
34
(
4
):
507
519
. https://doi.org/10.3265/Nefrologia.pre2014.Apr.12522
62.
Yang
CY,
Wu
ML,
Chou
YY,
et al.
Essential trace element status and clinical outcomes in long-term dialysis patients: a two-year prospective observational cohort study
.
Clin Nutr (Edinburgh, Scotland)
.
2012
;
31
(
5
):
630
636
. https://doi.org/10.1016/j.clnu.2012.02.008
63.
Dewar
D,
Soyibo
AK,
Barton
E.
Nutritional Markers in Patients Undergoing Chronic Haemodialysis in Jamaica
.
West Indian Medical J
.
2012
;
61
(
3
):
284
-
289
.
This is an Open Access article distributed in accordance with Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/).