Vol 6 No 2 full text.indd
Althea Medical Journal. 2019;6(2)
55
Serum Calcium Levels in Chronic Kidney Disease Patient Stratified By
Body Mass Index
Anthoni,1 Rudi Supriyadi,2 Siti Nur Fatimah3
1Faculty of Medicine Universitas Padjadjaran, 2Department of Internal Medicine Faculty of
Medicine Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung, 3Department of
Public Health Faculty of Medicine UniversitasPadjadjaran
Correspondence: Anthoni, Faculty of Medicine, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang Km. 21,
Jatinangor, Sumedang. E-mail: anthoni15002@mail.unpad.ac.id
Introduction
Chronic kidney disease (CKD) is a chronic
inflammatory condition of the kidney that
present for more than 3 months and
accompanied by structural and functional
abnormalities, with implications for health.1,2
Estimated prevalence of CKD is 13.4%
worldwide and 0.2% in Indonesia.3,4 Based on
Global Burden of Disease 2015, kidney disease
ranks 12th as the main cause of death,5 whereas
in Indonesia, CKD ranks 2nd as the highest
expense of Indonesia’s Badan Penyelenggara
Jaminan Sosial (BPJS).3 Chronic kidney disease
is classified into five stages based on glomerular
filtration rate (GFR) and/or on presence or
absence of changes of kidney structure, each
stage corresponds to the decreased quality
of life, morbidity rate, and mortality rate.2,6
Kidney has an important role in body fluid,
electrolyte regulation, and acid-base balance,
hence, CKD can cause complications to heart,
lungs, blood vessels, mineral and bone, muscle,
nerves, and other organs.6,7 Patients with CKD
stage or end-stage renal disease (ESRD) need
kidney replacement therapy.3
Patients with CKD experience changes in
body mineral level and bone density resulting
in metabolic and clinical consequences,
including the increase of fibroblast growth
AMJ. 2019;6(2):55–9
Abstract
Background: Most of the chronic kidney disease (CKD) patients have low blood calcium levels, yet
hypercalcemia has a worse outcome in CKD patients. Interestingly, CKD patients with higher body
mass index (BMI) have better outcomes. This study aimed to elucidate the difference in blood calcium
levels stratified by BMI categories in patients with CKD.
Methods: The study was conducted using a comparative analytical cross-sectional study design.
Patients with CKD (n100), aged over 18 years old were included, Patients with the following were
excluded: the history of hemodialysis, history of antioxidants, calcium and vitamin D supplement
consumption, history of infection and malignancy. BMI of patients was categorized into underweight
(<18.5 kg/m2), normal (8.5-22.9 kg/m2), and overweight or obese (≥23 kg/m2). Data were analyzed
to compare blood calcium in different categories of BMI (Kruskal-Wallis test).
Results: The age of patients with CKD included in this study had median age of 61 years old,
predominantly was men (57%). The blood calcium level of CKD patients was on the lower border
of the normal range. Median BMI was 23.48 kg/m2, of which 53% was categorized as overweight
or obese. There was a trend that overweight/obese patients had higher blood calcium levels than
underweight and normal-weight patients, however, no statistically significant difference between the
BMI category (p=0.982).
Conclusions: The blood calcium level in chronic kidney disease varies across the BMI category,
however, no correlation with the BMI.
Keywords: Blood calcium, body mass index, chronic kidney disease
Althea Medical Journal. 2019;6(2)
56 AMJ June 2019
factor-23, parathyroid hormone (PTH),
and blood phosphate; and a decrease of
1.25(OH)2D level and blood calcium level.8
The decrease of blood calcium levels in CKD
patients is caused by lower calcium intake,
failure of absorption, distribution, and
utilization as the consequence of the decrease
of vitamin D activities.6,9
Interestingly, overweight/obesity serves
a one of the risk factors of CKD, and this
overweight is related to hemodynamical,
physiological, anatomical, and/or pathological
changes of the kidney.3,10,11 However, conflicting
result occurs, showing that obesity may have a
higher survival rate of CKD patient, even though
obesity is associated with mortality caused by
the increased risk of metabolic syndrome and
cardiovascular disease in a non-CKD patient,
known as the obesity paradox.10,12-14
Another study result has shown that CKD
patients with overweight/obese have higher
blood calcium levels compared to those with
underweight and normal weight.15 Blood
calcium level higher than normal is correlated
with a worse prognosis.16 In light with those
contradicting results, this study aimed to
explore blood calcium levels in CKD patients
stratified based on body mass index (BMI).
Table 1 Clinical Characteristics of the Chronic Kidney Disease from Bandung
Characteristic n (%) Median (min-max)
Sex
Male 57 (57%) 61 (24-78)
Female 43 (43%) 23.48 (10.54–37.99)
Age (years) 17.24 (10.5 –18.21)
BMI (kg/m2) 21.45 (18.72-22.94)
Underweight 7 (7%) 26.26 (23.01-37.99)
Normal 40 (40%)
Overweight/obese 53 (53%)
Note: BMI: body mass index; categorized into underweight (<18.5 kg/m2), normal (8.5-22.9 kg/m2), and overweight or
obese (≥23 kg/m2).
Methods
This study was conducted using a comparative
analytical cross-sectional study design.
Secondary data from previous study
“Correlation of Total Antioxidant Capacity,
Vitamin D, Calcium, and Sclerostin to Body
Composition of Patients with CKD Stage
3-5” had been retrieved upon approval of
the Research Ethics Committee Universitas
Padjadjaran, Bandung, Indonesia (794/
U6.KEP/EC/2018). Data on age, gender, blood
calcium level, GFR, and BMI were collected.
Blood calcium levels were categorized as low
(<8.5 mg/dL) and normal (8.5-10.5 mg/dL),
and BMI of patients were categorized into
underweight (<18.5 kg/m2), normal (8.5-22.9
kg/m2), and overweight or obese (≥23 kg/m2).
Patients with chronic kidney disease (CKD)
stage 3, 4, or 5, aged more than 18 years
old were included from three hospitals in
Bandung; Dr. Hasan Sadikin General Hospital
Bandung, Ny. R. A. Habibie Kidney Hospital,
and Dustira Hospital. Patients with a history
of hemodialysis, use of vitamin D, calcium,
and antioxidants (vitamin C and vitamin E)
supplements, other chronic diseases, infection,
and malignancy were excluded.
Table 2 Blood Calcium Level among Chronic Kidney Disease
Calcium level n (%) Median (min-max)
Calcium level (mg/dL) 8.6 (4.2-10.2)
Low 39 (39%) 7.9 (4.2-8.4)
Normal 61 (61%) 8.9 (8.5-10.2)
Note: Calcium level was categorized as low (<8.5 mg/dL) and normal (8.5-10.5 mg/dL)
Althea Medical Journal. 2019;6(2)
57Anthoni et al.: Serum Calcium Levels in Chronic Kidney Disease Patient Stratified By Body Mass Index
Comparative analysis between blood
calcium level among different BMI was
conducted using Kruskal-Wallis test and post-
hoc Mann-Whitney test. A post-hoc test was
conducted to elaborate the difference between
BMI groups. A significant result was reached
when p<0.05 (IBM® SPSS® Statistics 22
program).
Results
In a total sample of a previous study (n=100),
there were 57% male CDK patients as shown
in Table 1. The median age was 61 years old
(range 24–78 years old). Overweight/obese
was observed in 53% of the cases, and 7% was
underweight.
The characteristic of blood calcium levels in
subjects is shown in Table 2. Median of blood
calcium level was 8.6 mg/dL, 61% subject had
normal calcium level.
The CKD patients were categorized into body
mass index (BMI) as followed underweight
(BMI<18.5 kg/m2), normal (BMI=18.5-22.9 kg/
m2), and overweight/obese (BMI≥23 kg/m2)
(Table 3). There was no difference in age and
gender group. Interestingly, the GFR tended
to increase in overweight/obese although the
increase was not statistically significant (p
0.509) (Table 3).
Blood calcium levels based on BMI category
was shown in Table 4. Overall, blood calcium
levels in CKD patients were at the lower limit
of the normal value of blood calcium. Statistical
test results revealed no difference in blood
calcium levels in each BMI category.
Discussion
Chronic kidney disease (CKD) affects males
predominantly as shown in our study,
consisting of a male (57%) and female (43%).
Table 3 Glomerular Filtration Rate among Chronic Kidney Disease Based on Body Mass
Index
Characteristics
BMI
p-valueUnderweight
(n=7)
Normal
(n=40)
Overweight/obese
(n=53)
Gender
Male(n=57) 2 (28.57%) 22 (55%) 33 (62.26%) 0.226*
Female(n=43) 5 (71.43%) 18 (45%) 20 (37.74%)
Age (years)
≤50 years(n=27) 3 (42.86%) 9 (22.50%) 15 (28.30%) 0.509*
>50 years(n=73) 4 (57.14%) 31 (77.50%) 38 (71.70%)
GFR (mL/min/1,73m2) 10.54 (6.64-42.85) 14.36 (2.38-58.64) 18.81 (1.85-58.01) 0.458**
CKD Stage 3(30-59) 1 (14.29%) 9 (22.5%) 11 (20.75%) 0.083*
CKD Stage 4 (15-29) 0 (0%) 11 (27.5%) 23 (43.40%)
CKD Stage 5 (<15) 6 (85.71%) 20 (50%) 19 (35.85%)
Note: BMI: body mass index; categorized into underweight (<18.5 kg/m2), normal (8.5-22.9 kg/m2), and overweight or
obese (≥23 kg/m2).*Chi-square test; **Kruskal-Wallis test; GFR: glomerular filtration rate; CKD: chronic kidney disease
Table 4 Blood Calcium Level Based on Body Mass Index
BMI Category n %
Blood calcium level
p-value
Median (min-max)
Underweight 7 7% 8.6 (7.1-9.5) 0.982*
Normal 40 40% 8.6 (5.6-10.2)
Overweight/obese 53 53% 8.8 (4.2-10.0)
Note: *Kruskal-Wallis test; BMI: body mass index
Althea Medical Journal. 2019;6(2)
58 AMJ June 2019
These findings are consistent with other
studies in Canada and Japan.15,16 These studies
have also resulted that most of the patients
are over 50 years old, confirming that CKD is
more frequent to be found in older age, as the
glomerular filtration rate (GFR) decreases.2
Patients with CKD have decreased kidney
function, marked by the declining of GFR.1
Decreasing GFR causes phosphate retention
which will increase the synthesis of FGF-
23.17 Increased levels of FGF-23 to reduce
the function of the enzyme 1-α hydroxylase,
therefore, the synthesis of 1.25(OH)2D will
decrease.9,17 Decreased levels of 1.25(OH)2D
results in reduced calcium absorption in the
intestine, increased calcium excretion, and
decreased calcium resorption from bone, and
thus, blood calcium levels will decrease.9,17 This
explains the condition of our CKD patients that
calcium level, in general, is at the lower limit of
the normal value of blood calcium levels.
The distribution of blood calcium levels
in each BMI group showed that there is a
tendency for higher blood calcium levels in
the overweight/obese group (Table 4). This
finding confirms that blood calcium levels
are significantly higher in obese groups.18
The abnormal calcium metabolism occurs in
the overweight/obese group due to reduced
25 (OH) D levels.18,19 This situation results in
reduced calcium absorption in the intestine,
reduced bone mineralization process, and
increased calcium excretion which causes
increased parathyroid hormone (PTH),
therefore, the blood calcium levels will
increase. Furthermore, overweight/obese
groups tend to have a higher fat mass, and
this will indirectly increase the activity of pro-
inflammatory cytokines so that osteoclast
activity and bone resorption increase.9,18 This
increase causes blood calcium levels in the
overweight/obese group to be higher than
those with underweight and normal BMI.
The overweight/obese group has higher
GFR than those with underweight and normal
BMI (Table 2). The Glomerular filtration rate is
higher, blood phosphorus and FGF-23 levels are
decreased, so that 1.25(OH)2D level increase.16
Increased levels of 1.25(OH)2D will cause
blood calcium levels to increase,16 resulting in
higher calcium levels in the overweight/obese
group of CKD patients.
The limitation of this study was that this
study is not considering other factors that
affect blood calcium levels, including the
amount of calcium intake, vitamin D levels,
PTH levels, FGF-23 levels, and phosphate
levels.17
To conclude, our study failed to show the
difference in blood calcium levels in chronic
kidney disease in various body mass indexes.
Further research that considers the factors
that influence blood calcium levels needs to
be explored to determine the relationship
between calcium levels in patients with
chronic kidney disease with various body
mass index groups.
References
1. Kidney Disease: Improving Global
Outcomes (KDIGO) CKD-MBD Update
Work Group. KDIGO 2017 clinical Practice
guideline update for the diagnosis,
evaluation, prevention, and treatment of
chronic kidney disease-mineral and bone
disorder (CKD-MBD). Kidney Int Suppl.
2017;7(1):1–59.
2. Glassock RJ, Rule AD. Aging and the kidneys:
anatomy, physiology, and consequences for
defining chronic kidney disease. Nephron.
2016;134(1):25–9.
3. Pusat Data dan Informasi Kementerian
Kesehatan RI. Situasi penyakit ginjal kronis.
Jakarta: Data dan Informasi Kementerian
Kesehatan RI; 2017.
4. Kementerian Kesehatan RI. Riset kesehatan
dasar. Jakarta: Badan Penelitian dan
Pengembangan Kesehatan Departemen
Kesehatan Republik Indonesia; 2013.
5. Neuen BL, Chadban SJ, Demaio AR,Johnson
DW, Perkovic V. Chronic kidney disease and
the global NCDs agenda. BMJ Glob Health.
2017;2(2):e000380.
6. Dhondup T, Qian Q. Electrolyte and acid-
base disorders in chronic kidney disease
and end-stage kidney failure. Blood Purif.
2017;43(1–3):179–88.
7. Zoccali C, Vanholder R, Massy ZA, Ortiz
A, Sarafidis P, Dekker FW, et al. The
systemic nature of CKD. Nat Rev Nephrol.
2017;13(6):344–58.
8. Hill Gallant KM, Spiegel DM. Calcium
balance in chronic kidney disease. Curr
Osteoporos Rep. 2017;15(3):214–21.
9. Shanahan CM, Crouthamel MH, Kapustin
A, Giachelli CM. Arterial calcification
in chronic kidney disease: key roles
for calcium and phosphate. Circ Res.
2011;109(6):697–711.
10. Kalantar-Zadeh K, Streja E, Kovesdy CP,
Oreopoulos A, Noori N, Jing J, et al. The
obesity paradox and mortality associated
with surrogates of body size and muscle
mass in patients receiving hemodialysis.
Mayo Clin Proc. 2010;85(11):991–1001.
Althea Medical Journal. 2019;6(2)
59
11. Kopple JD, Feroze U. The effect of obesity
on chronic kidney disease. J Ren Nutr.
2011;21(1):66–71.
12. Mafra D, Guebre-Egziabher F, Fouque
D. Body mass index, muscle and fat
in chronic kidney disease: questions
about survival. Nephrol Dial Transplant.
2008;23(8):2461–6.
13. Bonanni A, Mannucci I, Verzola D, Sofia A,
Saffioti S, Gianetta E, et al. Protein-energy
wasting and mortality in chronic kidney
disease. Int J Environ Res Public Health.
2011;8(5):1631–54.
14. Rahimlu M, Shab-Bidar S, Djafarian K.
Body mass index and all-cause mortality
in chronic kidney disease: a dose-response
meta-analysis of observational studies. J
Ren Nutr. 2017;27(4):225–32.
15. Garland JS, Holden RM, Hopman WM, Gill
SS, Nolan RL, Morton AR. Body mass index,
coronary artery calcification, and kidney
function decline in stage 3 to 5 chronic
kidney disease patients. J Ren Nutr.
2013;23(1):4–11.
16. Inaguma D, Koide S, Takahashi K, Hayashi
H, Hasegawa M, Yuzawa Y. Relationship
between serum calcium level at dialysis
initiation and subsequent prognosis. Ren
Replace Ther. 2017;3:2.
17. Blaine J, Chonchol M, Levi M. Renal control
of calcium, phosphate, and magnesium
homeostasis. Clin J Am Soc Nephrol.
2015;10(7):1257–72.
18. Dalfardi O, Jahandideh D, Omrani GH. The
correlation of serum calcium level and
obesity; is there any explanation?. GMJ.
2013;2(1):26–31.
19. Rontoyanni VG, Avila JC, Kaul S, Wong R,
Veeranki SP. Association between obesity
and serum 25 (OH) D concentrations
in older Mexican adults. Nutrients.
2017;9(2):E97.
Anthoni et al.: Serum Calcium Levels in Chronic Kidney Disease Patient Stratified By Body Mass Index