Keywords
calbindin-D28K - renal dialysis - oral health - chronic kidney disease (CKD)
Background
Chronic kidney disease, or CKD, is a serious worldwide health issue. Approximately
8 to 10% of people worldwide suffer from mild to moderate renal impairments, and the
number of instances of CKD is rapidly increasing.[1] Like other systemic diseases, CKD is linked to oral health issues that are brought
on by the condition or its management. Their prognosis and general oral health may
worsen if these lesions are not treated.[2] Calcium ions (Ca2+) are firmly bound by soluble intracellular proteins called calbindins, which are
vitamin D-dependent. One of the main calbindins found in many mammalian organs, including
the kidney, is calbindin-D28k protein (calbindin-D28k-1 alpha,25-dihydroxyvitamin
D3-dependent calcium-binding protein). It plays a crucial role in calcium transport
and intracellular calcium level regulation, both of which are essential for renal
calcium absorption and healthy kidney function, and most importantly it absorbs calcium
in micromolar range. Vitamin D3 binds to its receptor in the regulatory region of
calbin-D28k and stimulates synthesis of calbindin, that is, transcription of calbindin-D28k.
Therefore, biologically active vitamin D (1,25-dihydroxy vitamin D) is important for
the availability of levels of calbindin-D28k. In patients with renal dialysis, oral
health poses a potential predictor of health outcomes due to the effect of variation
in vitamin D3 levels and, therefore, calbindin-D28k.[3]
[4] Compared to the general population, adults with renal disease have been found to
have a wide range of oral complications, such as caries, periodontitis, altered salivary
composition and pH, reduced salivary flow, enhanced dental calculus configuration,
elevated salivary buffering capacity, and decreased levels of calcium. Additionally,
poor oral hygiene has been linked to higher mortality rates.[5] CKD impairs vitamin D, mineral metabolism with reduced calcium reabsorption, and
decreased antimicrobial property of antimicrobial peptides. Calbindin-D28k is believed
to perform a functional role in controlling the reabsorption of calcium in the distal
nephron and vitamin D3 plays a potential role in distal convoluted tubule (DCT).[6]
[7] Tooth needs calcium for its maturation, these calcium ions are transported by cytosolic
calbindin-D28k, a protein that is found in the kidney's DCT, which plays an important
role in active calcium transport and antimicrobial property. Renal dialysis may alter
CBD-28k levels, impacting oral health and periodontal health. Although marked variations
in the level of calbindin-D28k expression have been observed in other diseases, recent
study suggests a possible association between calbindin-D28k (CBD-28k), a calcium-binding
protein implicated in calcium homeostasis, and dental health in individuals receiving
renal dialysis. Nonetheless, concrete data demonstrating a causal connection between
calbindin-D28k levels and oral health outcomes in this cohort is absent. Although
research has noted modifications in salivary content and a heightened incidence of
oral problems, including caries and periodontal disease, in dialysis patients, the
precise function of calbindin-D28k in these alterations has yet to be elucidated.
In light of these information gaps, this work seeks to examine the correlation between
calbindin-D28k expression and oral health measures in persons undergoing renal dialysis,
to further understanding of the underlying processes and potential therapeutic ramifications.[8]
[9]
Their role in CKD individuals with poor oral health is less studied. Hence, the present
study aims to investigate the potential of salivary calbindin-D28k as a predictor
of oral health in subjects with CKD, offering valuable insights into the interplay
between renal function and oral health.
Material and Methods
Study Design
This case–control study was carried out at Justice K.S. Hegde Charitable Hospital,
Nitte Deemed to be University, AB Shetty Memorial Institute of Dental Sciences (ABSMIDS)
and Central Research Laboratory (K.S. Hegde Medical Academy) Deralakatte, Mangalore,
Karnataka, India. The study was approved by the Nitte (Deemed to be University) Ethics
Committee (Approval number: NU/CEC/2023/0215), dated: August 20, 2023.
Subjects
A total of 100 subjects diagnosed with CKD and 100 age-matched individuals between
24 and 77 years were included after obtaining informed consent.
The sample size was calculated using:
where expected odds ratio (OR) = 2.0, P
0 = 0.30, α = 0.05 (95% confidence level), power = 0.90, and case–control ratio = 1:1.
The case's inclusion criteria comprised adult CKD subjects in the predialysis state
with a Decayed, Missing, and Filled Teeth (DMFT) (dental caries prevalence) of > 3.
While for the control, age-matched healthy individuals without CKD with a DMFT < 0
visiting the outpatient clinic for routine examinations were included. The study excluded
subjects with other systemic diseases, pregnancy, and any other malignant diseases.
Baseline Questionnaire
Basic detailed information regarding the patient's details was recorded in a predesigned
pro forma and medical records were used to record biochemical parameters.
Clinical Examination
The number of caries-related decaying (D), filled (F), and missing (M) teeth was calculated
based on the clinical examination results and the DMFT score of the samples. Data
was gathered by questions by means of direct examination and observation of the subjects'
teeth using a Medisporex catheter and mirror number 4. Dental mouth mirror and probes
were used to examine dental caries, and following each patient's examination, the
periodontal score was calculated and the results were documented in the pro forma.
Sample Collection
Individuals were restrained from eating 2 hours prior sample collection, mouth was
rinsed with normal water, and samples were collected in between 9 and 10 a.m. to maintain
the time duration and uniformity among the individuals. A sample of unstimulated saliva
was collected on the mouth's floor. A Tarson saliva collection tube was used to collect
5 mL. The patient's saliva was collected, centrifuged, and the supernatant was kept
for further examination at –20°C.
Biochemical Estimation
Saliva calbindin-D28k was estimated by enzyme-linked immunosorbent assay (ELISA; using
a commercially available kit [Cat. No. LAB3789], Labrecon, India) and measured using
an ELISA reader (Spark Tecan).
Statistical Analysis
The statistical software SPSS (IBM, version 22.0, SPSS Inc, Chicago, Illinois, United
States) was used to analyze the data. Qualitative data were represented as numbers
and percentages. Quantitative data of both cases and controls were reported as mean ± standard
deviation for normally distributed data by applying an unpaired independent t-test and for skewed data, Mann–Whitney U test was applied for the median-interquartile range. Pearson's and Spearman's correlation
coefficients were used for correlation studies. The association between salivary calbindin-D28k
levels and oral health was determined using the chi-square test and by calculating
the OR at a 95% confidence interval. A p-value of less than 0.05 was considered statistically significant in relation to the
groups.
Results
To Study the Baseline Characteristics With and Without Kidney Dialysis
This case–control study had 200 subjects, out of which 100 subjects were diagnosed
with CKD in the predialysis stage with a poor oral health, DMFT of > 3. Whereas subjects
without CKD and good oral health with a DMFT of 0 were considered controls. [Table 1] provides baseline characteristics of the study population, showing a considerable
difference in age between the two groups. While comparing the gender between the groups,
the percentage of male population was higher in case when compared to control and
it was statistically significant. The percentage of periodontal score[3]
[4] was significantly high in case subjects compared to control.
Table 1
Baseline characteristics of the study population
|
Parameters
|
Case
(n = 100)
|
Control
(n = 100)
|
p-Value
|
|
Age
|
52.21 ± 11.68
|
30.26 ± 5.59
|
0.000[a]
|
|
DMFT score
|
2.01 ± 0.62
|
0.36 ± 0.48
|
0.272
|
|
Gender (%)
Male
Female
|
58.33
41.66
|
26.66
73.33
|
0.000[a]
|
|
Periodontal scoring (%)
0–2
3–4
|
40
60
|
96.66
3.33
|
0.000[a]
|
Abbreviations: DMFT, Decayed, Missing and Filled Teeth; SD, standard deviation.
Note: Age and DMFT scoring is represented as mean ± SD. Gender and periodontal scoring
is expressed in percentage (%). p-Value was calculated using the Student's t-test for parametric variables.
a
p < 0.0001. The statistical significance of case–control differences was tested for
categorical variables using a chi-square test.
Hematological and Biochemical Characteristics in Subjects with Chronic Kidney Disease
and Control
While comparing the hematological and biochemical characteristics between the group,
the level of hemoglobin, bicarbonate (mmol/L), sodium (mmol/L), and calcium (mg/dL)
was significantly less in subjects with CKD and poor oral health. Whereas phosphate-buffered
saline, random blood sugar (RBS), phosphorous (mg/dL), and potassium (mmol/L) levels
were significantly high in case subjects when compared to control. Hematological and
biochemical characteristics of the study population are given in [Table 2].
Table 2
Hematological and biochemical characteristics of the study population
|
Biochemical parameters
|
Case
(n = 100)
|
Control
(n = 100)
|
p-Value
|
|
Hemoglobin (g/dL)
|
10.05
(8.70–10.65)
|
11.90
(11.70–12.57)
|
0.002[b]
|
|
PBS (mg/dL)
|
152.48
(142–160)
|
100
(97–102)
|
0.032[a]
|
|
RBS (mg/dL)
|
129
(114–146)
|
100
(97.0–102)
|
0.000[b]
|
|
Albumin (g/dL)
|
3.90
(3.60–4.20)
|
4.20
(4.00–4.45)
|
0.086
|
|
Bicarbonate (mmol/L)
|
9.0
(6.1–12.0)
|
22.0
(21.00–23.00)
|
0.000[b]
|
|
Phosphorous (mg/dL)
|
6.95
(4.00–6.37)
|
3.00
(2.80–3.1)
|
0.002[b]
|
|
Sodium (mmol/L)
|
128.00
(125.00–143.00)
|
138.5
(137.00–139.00)
|
0.000[b]
|
|
Potassium (mmol/L)
|
5.20
(4.50–5.47)
|
4.00
(3.90–4.00)
|
0.000[b]
|
|
Calcium (mg/dL)
|
6.05
(5.50–8.50)
|
9.00
(9.00–9.30)
|
0.012[b]
|
Abbreviations: PBS, phosphate-buffered saline; RBS, random blood sugar.
Note: Biochemical parameters are represented as median values (interquartile range).
p-Value was calculated using the Kruskal–Wallis test.
a
p < 0.001 was considered statistical significant.
b
p < 0.0001 was considered statistical significant.
Estimate of Salivary Calbindin-D28k Levels in Subjects With and Without Kidney Dialysis
Further, in our major topic of interest, we estimated salivary calbindin-D28k levels
in subjects with and without CKD and we observed a significant reduction in the level
of salivary calbindin-D28k levels in subjects with CKD and poor oral health. The result
obtained is shown in [Fig. 1].
Fig. 1 Salivary levels of calbindin-D28k (pg/mL) between the chronic kidney disease case
and control subjects; Data are shown as median (interquartile range); p-value was calculated using the Mann–Whitney U test. ***p < 0.0001, indicated as significant.
Evaluation of the Association between the Intracellular Protein Calbindin-D28k in
Patients with Renal Dialysis and Their Oral Health
Further, to find the association of calbindin-D28k in subjects with CKD and their
oral health we obtained the best cutoff value for salivary calbindin-D28k using the
receiver operating characteristic (ROC) curve, that is, 29.04 pg/mL, with the area
under the curve of 0.828, and the results obtained were significant. The results are
depicted in [Fig. 2] and [Table 3].
Table 3
To evaluate the association of intracellular protein calbindin-D28k in patients with
renal dialysis and their oral health
|
Area under
the curve
|
Sensitivity
|
1-specificity
|
p-Value
|
|
0.828
|
0.767
|
0.250
|
0.000[a]
|
Note: p-Value was calculated at 95% confidence.
a
p < 0.0001 was considered as statistically significant. The area under the receiver
operating characteristic (ROC) curve for the levels of calbindin-D28k was 0.828, the
best cutoff value was 29.04 pg/mL.
Fig. 2 The area under the receiver operating characteristic (ROC) curve for the levels calbindin-D28k
was 0.828, the best cutoff value was 29.04 pg/mL.
Risk Estimates of Oral Health Based on the Levels of Calbindin-D28k in Patients with
Chronic Kidney Disease
After obtaining the best cutoff value for calbindin-D28k, we estimated the risk of
oral health based on the levels of calbindin-D28k in subjects with CKD. Here, we understood
that the lower level of salivary calbindin-D28k in subjects with CKD were associated
with the higher risk of developing poor oral health. This was confirmed with the higher
periodontal score obtained in case subjects with CKD ([Table 4]).
Table 4
Risk estimates of oral health based on the levels of calbindin-D28k in patients with
renal dialysis
|
Parameter
|
Control
(n = 100)
|
Case
(n = 100)
|
Odds ratio (95% CI)
|
p-Value
|
|
Salivary
calbindin-D28k
|
Low
|
20
|
75
|
0.26 (0.15–0.45)
|
0.000[a]
|
|
High
|
80
|
15
|
3.20 (2.02–5.05)
|
|
Periodontal score
|
Low
|
83.33
|
41.66
|
0.50 (0.363–0.689)
|
0.000[
a
]
|
|
High
|
16.66
|
58.33
|
3.50 (1.91–6.40)
|
Abbreviations: CI, confidence interval; ROC, receiver operating characteristic.
Note: The area under the ROC curve for the levels of calbindin-D28k was 0.828, the
best cutoff value was 29.04 pg/mL.
a
p < 0.0001were considered to indicate statistical significance.
The obtained cutoff value of periodontal scoring is 3 (greater than 3 is considered
as worst and lesser than 3 is considered as good). Which was further divided into
lower and higher value groups, p-value derived from the chi-square test for each parameter.
Analyzing Biochemical Parameters in Patients with Chronic Kidney Disease
Further, we analyzed the biochemical parameters in patients with CKD ([Table 5]). Here, we observed significant increase in the level of alkaline phosphatase (ALP)
(U/L), serum glutamic oxaloacetic transaminase (SGOT) (U/L), and serum glutamic pyruvic
transaminase (SGPT) (U/L) in liver function test (LFT) of case subjects when compared
to control. Whereas in renal function test (RFT), we observed that the urea (mg/dL),
creatinine (mg/dL), and uric acid (mg/dL) were significantly higher in case subjects.
Table 5
Biochemical parameters in patients with chronic kidney disease
|
LFT
|
Case (n = 100)
|
Control (n = 100)
|
p-Value
|
|
Alkaline phosphatase (U/L)
|
148.00
(107–267.25)
|
51.00
(50.00–53.00)
|
0.000
[a]
|
|
SGOT (U/L)
|
21.00
(15.45–26.90)
|
17.00
(15.00–19.00)
|
0.000
[a]
|
|
SGPT (U/L)
|
16.50
(9.00–20.00)
|
14.00
(14.00–17.00)
|
0.000
[a]
|
|
RFT
|
|
|
|
|
Urea (mg/dL)
|
103.00
(75.00–110.75)
|
19.00
(18.00–21.00)
|
0.000
[a]
|
|
Creatinine (mg/dL)
|
10.10
(8.40–11.70)
|
0.70
(0.70–0.70)
|
0.000
[a]
|
|
Uric acid (mg/dL)
|
5.70
(3.70–7.1)
|
3.50
(3.20–3.80)
|
0.000
[a]
|
Abbreviations: LFT, liver function test; RFT, renal function test; SGOT, serum glutamic
oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase.
Note: Biochemical parameters are represented as median values (interquartile range).
p-Value was calculated using the Kruskal–Wallis test.
a
p < 0.0001 was considered statistically significant.
Association of Intracellular Protein Calbindin-D28k in Patients with Renal Dialysis
and Their Oral Health
Further, while associating calbindin-D28k in patients with renal dialysis with their
oral health, periodontal scoring showed significant association with salivary calbindin-D28k
([Table 6A]). The association of salivary calbindin-D28k was continued with RFT and LFT, and
a significant result was observed between RFT and salivary calbindin-D28k levels ([Table 6C]); this table indicates that individuals with lower level of calbindin-D28k were
significantly associated with RFT. However, the association between LFT and salivary
calbindin-D28k did not show significant result. The area under the ROC curve for the
levels calbindin-D28k was 0.828, the best cutoff value was 29.04 pg/mL. The obtained
cutoff value of periodontal scoring is 3 (greater than 3 is considered as worst and
lesser than 3 is considered as good). Which was further divided into lower and higher
value groups, p-value derived from the chi-square test for each parameter ([Table 6B]).
Table 6
Association of intracellular protein calbindin-D28k in patients with periodontal scoring
in individuals with chronic kidney disease
|
(A)
|
|
Parameter
|
Periodontal score
|
p-Value
|
|
High
(58.33)
|
Low
(41.66)
|
|
Salivary
calbindin-D28k
|
21.11 (15.40–29.41)
|
0.009[b]
|
|
(B)
|
|
LFT
|
Salivary calbindin-D28k
|
p
-Value
|
|
High
(15)
|
Low
(45)
|
|
|
Alkaline phosphatase (U/L)
|
148.00
(107–267.25)
|
0.097
|
|
SGOT (U/L)
|
21.00
(15.45–26.90)
|
0.152
|
|
SGPT (U/L)
|
16.50
(9.00–20.00)
|
0.201
|
|
(C)
|
|
RFT
|
Salivary
calbindin-D28k
|
p
-Value
|
|
High
(15)
|
Low
(45)
|
|
|
Urea (mg/dL)
|
103.00
(75.00–110.75)
|
0.096
|
|
Creatinine (mg/dL)
|
10.10
(8.40–11.70)
|
0.05[a]
|
|
Uric acid (mg/dL)
|
5.70
(3.70–7.1)
|
0.05[a]
|
Abbreviations: LFT, liver function test; RFT, renal function test; SGOT, serum glutamic
oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase.
Note: The parameters are represented as median values (interquartile range).
a
p ≤ 0.05 considered to indicate statistical significance.
b
p ≤ 0.001 was considered to indicate statistical significance.
Correlation between Intracellular Protein Calbindin-D28k in Patients with Renal Dialysis
and Their Oral Health
Further, we performed a correlation analysis between the intracellular protein calbindin-D28k
in patients with renal dialysis and their oral health. Here, we observed significant
positive correlation between intracellular protein calbindin-D28k and biochemical
parameters such as sodium and RBS, whereas significant negative correlation was observed
between calcium and salivary calbindin-D28k levels ([Table 7A]). Further, we continued correlating calbindin-D28k with periodontal scoring and
liver health and renal health and we obtained significant negative correlation between
salivary calbindin-D28k levels and periodontal scoring in cases with CKD and poor
oral health ([Table 7B]).
Table 7
Correlation between intracellular protein calbindin-D28k in patients with chronic
kidney disease and their oral health
|
(A)
|
|
Variables
|
|
HB
|
Sodium
|
Potassium
|
Albumin
|
Phosphorous
|
Calcium
|
Bicarbonate
|
PBS
|
RBS
|
|
Salivary
calbindin-D28k
|
R
|
0.023
|
0.296
|
0.014
|
0.134
|
–0.036
|
–0.326
|
–0.066
|
–0.053
|
0.287
|
|
Sig
|
0.864
|
0.022[a]
|
0.915
|
0.308
|
0.787
|
0.011[a]
|
0.614
|
0.686
|
0.026[a]
|
|
(B)
|
|
Variables
|
|
Oral health
|
Liver health (LFT)
|
Renal health (RFT)
|
|
|
Periodontal
scoring
|
ALP
|
SGOT
|
SGPT
|
Urea
|
Creatinine
|
Uric acid
|
|
Salivary
calbindin-D28k
|
r
|
–0.265
|
0.089
|
–0.139
|
0.093
|
–0.063
|
0.077
|
0.113
|
|
Sig
|
0.04[a]
|
0.501
|
0.291
|
0.478
|
0.630
|
0.557
|
0.390
|
Abbreviations: ALP, alkaline phosphatase; HB, ; hemoglobin; LFT, liver function test;
PBS, phosphate-buffered saline; RBS, random blood sugar RFT, renal function test;
SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase.
Note: Spearman's correlation was done for all nonparametric variables.
a
p ≤ 0.05 is considered as statistically significant (two-tailed).
Discussion
Individuals with CKD frequently have variations in their oral cavities, such as periodontitis,
and different signs of oral health problems can lead to morbidity and death.[10]
[11]
[12]
[13] In the current study, the age of subjects on kidney dialysis was between 24 and
77 years, and the mean age was 52.21 years, while the male population was higher,
and both age and gender significantly differed between the two groups. Clinical assessment
revealed that the population under study had a very high DMFT index score on average,
which was not significant, while the periodontal score was significantly higher in
case subjects. The data indicates that CKD is most prevalent among patients in their
50s, Additionally, the study suggests a slight male predilection for CKD, aligning
with previous research.[14]
[15]
[16] High DMFT score in CKD subjects corroborated with previous research.[17]
[18] CKD has been empirically linked to dental deterioration, culminating in tooth loss.
Additionally, CKD adversely affects the oral functioning. Numerous studies have documented
a heightened prevalence of oral pathologies among patients on dialysis with few to
multiple oral complications[19] leading to have implications for dental treatment.[20] The DMFT index has been the most significant indicator for evaluating the state
of oral and dental health for more than 70 years, both internationally and locally,
while periodontal scoring system used to evaluate interproximal gingival health. Patients
with CKD may have higher rates of periodontitis and dental caries, which increases
the risk of tooth loss and difficulty chewing due to insufficient occlusive surfaces
or prosthetic constraints.[21] The pathogenesis of deteriorating oral health can be attributed to the increased
intracellular calcium ions. Calbindin-D28K is located in DCT and coexists with active
vitamin D. The impaired function of calbindin-D28k prevents absorption and regulation
of calcium levels. Free calcium ions perform various biological roles or functions
in cancer cell growth inhibitors, tumor invasiveness, and drug resistance. Intracellular
calcium overload prevents membrane localization and may result in apoptosis of cells.
Therefore, may directly affect the periodontal tissues and provide ideal environment
for growth of bacteria to cause tooth surface demineralization.[22] Prior research has found that the CKD patients in the study had noticeably higher
plaque scores when compared to healthy controls.[23]
[24]
[25] The use of antidiuretic medications, which may reduce salivary flow and lubricate
the oral cavity less effectively, may be connected to the association between poor
oral hygiene and CKD. This could lead to an increased risk of plaque accumulation.
Additionally, these patients' oral hygiene may have gotten worse due to inadequate
oral health care practices.[14]
When the hematological and biochemical characteristics of case subjects were compared
with control, we observed a decline in hemoglobin, bicarbonate, sodium, and calcium
levels in CKD subjects with poor oral health. More precisely, anomalies in the metabolism
of phosphate and calcium can affect tooth mineralization and periodontal health, suggesting
a potential link with calcium-regulating proteins such calbindin-D28k. Pallor of the
mucosa, primarily from anemia (lower erythropoietin synthesis), is the most frequent
oral finding in dialyzed patients with reference to the mucosal and glandular involvement.[26]
[27] Renal anemia and changes in platelet aggregation maintain these patients' propensity
to bleed.[26]
[28] Furthermore, hemodialysis increases the risk of oral mucosal bleeding, petechiae,
and ecchymoses.[29]
[30] It is imperative to evaluate the accessibility of dental health services for individuals
suffering from CKD. This emphasizes the need for a customized oral health program
that is both preventive and therapeutic, as well as ongoing follow-up to help these
subjects understand the importance of oral health given their systemic illness.[31]
Further, to understand the role of salivary calbindin-D28k in oral health, a significant
decrease in salivary calbindin-D28k levels in subjects with CKD and poor oral health
was observed. Calbindin expression in ameloblasts has also been reported by numerous
researchers, and CB28k has been detected in a variety of mammalian tissues. Moreover,
CB28k has been detected in cells of the epithelial rests of Malassez, odontoblasts,
and fibroblasts found in periodontal ligaments, as well as in places devoid of enamel.[6] Calbindin-D28k is known for its role in facilitating calcium absorption and maintaining
calcium balance within cells. The significant reduction in salivary calbindin-D28k
levels in CKD patients with poor oral health could have several implications. First,
it may indicate a systemic disruption of calcium metabolism, which is commonly seen
in CKD due to impaired renal function. The kidneys play a crucial role in regulating
calcium and phosphate levels, and dysfunction in these organs can lead to imbalances
that affect various tissues, including the oral cavity. In the context of oral health,
decreased salivary calbindin-D28k levels could contribute to weakened dental structures
and increased susceptibility to caries and other oral diseases. Calcium is vital for
maintaining the integrity of enamel and dentin, and reduced levels of calbindin-D28k
might result in insufficient calcium availability in saliva, thereby compromising
the remineralization process of teeth. This could partly explain the high prevalence
of advanced carious lesions, as indicated by the elevated PUFA (Pulpal Involvement,
Ulceration, Fistula, Abscess) index in CKD patients. Moreover, the reduction in salivary
calbindin-D28k levels might also be associated with a diminished ability to buffer
acids in the oral environment, leading to an increased risk of dental erosion and
caries formation.
In this study, there was a significant association between the intracellular protein
calbindin-D28k and periodontal scoring in chronic renal dialysis patients with oral
health problems with ROC of 0.828. The lower level of salivary calbindin-D28k in subjects
with CKD was associated with the higher risk of developing poor oral health, confirmed
with periodontal scoring. Ameloblasts, odontoblasts, and cementoblasts are highly
differentiated cells that generate highly mineralized tissues that make up mammalian
teeth. One important function of Ca2+ deposition in these cells is to facilitate their
formation. Ameloblasts have been demonstrated to contain calbindin-D28k in a number
of studies.[6]
[32]
[33] Patients on dialysis may have variations in calbindin-D28k expression, which could
affect the teeth's mineralization process and increase their susceptibility to dental
caries and other mineralization issues. Calbindin-D28k may have an effect on periodontal
health via controlling calcium levels.
The association between salivary calbindin-D28k and RFT was significant, but it did
not show significance with LFT. Because calbindin-D28k is expressed and regulated
differently in different tissues, there is no discernible correlation between calbindin-D28k
(Calb1) and LFTs. In order to support intracellular calcium transport and buffering,
this calcium-binding protein is primarily expressed in calcium-transporting organs
such the kidney, gut, and certain brain areas. On the other hand, it has little to
no expression in the liver, suggesting that it plays a little part in the handling
or metabolism of calcium in the liver. Additionally, the active form of vitamin D
(1,25-dihydroxyvitamin D3) regulates calbindin-D28k expression in a tissue-specific
way. Although vitamin D dramatically increases calbindin-D28k in the kidney and gut,
the liver does not exhibit this regulating effect, indicating that calbindin-D28k
has a restricted function in the liver. The analysis of the association between salivary
calbindin-D28k levels and RFTs versus LFTs in patients with CKD provides important
insights into the specific roles that different organ systems play in regulating this
calcium binding.[34] The significant association observed between salivary calbindin-D28k levels and
RFTs underscores the vital role of kidney function in the regulation and expression
of calbindin-D28k. Calbindin-D28k is a calcium-binding protein that plays a key responsibility
in calcium homeostasis, and the kidneys are central to maintaining calcium and phosphate
balance in the body. In CKD, where renal function is impaired, the dysregulation of
calcium metabolism can lead to alterations in the levels of calcium-binding proteins
like calbindin-D28k. The significant correlation suggests that as kidney function
declines, there may be compensatory or pathological changes in the production or secretion
of calbindin-D28k, which is reflected in its salivary levels. This association is
particularly relevant given the role of calbindin-D28k in various physiological processes,
including its potential impact on bone health and dental structures. In CKD patients,
impaired kidney function often leads to disturbances in calcium and phosphate metabolism,
which can manifest in various systemic and oral health issues, including periodontal
disease and other oral pathologies. The significant relationship between calbindin-D28k
and RFT highlights the potential of this protein as a biomarker for assessing the
extent of renal dysfunction and its systemic repercussions, including its effects
on oral health. On the other hand, the lack of a significant association between salivary
calbindin-D28k levels and LFTs suggests that liver function does not play a major
role in regulating this protein, at least not in the context of CKD. While the liver
is involved in various metabolic processes and the synthesis of many proteins, the
regulation of calbindin-D28k appears to be more closely tied to renal function. This
finding aligns with the understanding that calbindin-D28k is primarily involved in
calcium homeostasis, a process in which the kidneys play a more direct and pivotal
role compared to the liver. The absence of a significant association with LFT indicates
that hepatic function, despite its broad role in metabolism, may not directly influence
the levels of calbindin-D28k in saliva.[35]
The biochemical tests such as LFT (ALP, SGOT, and SGPT) and RFT (urea, creatinine,
and uric acid) levels were significantly higher in CKD subjects than control. Calcium
reabsorption is decreased in CKD, which also affects vitamin D and mineral metabolism.
CKD or its therapy can cause a number of variations in the oral cavity, even though
there are no specific symptoms of the disease.[36] The analysis of biochemical parameters in subjects with CKD provides valuable insights
into the systemic alterations associated with CKD and their potential impact on oral
health, particularly periodontal status. The association between high serum urea and
creatinine levels and poor periodontal status in CKD patients highlights the interconnection
between systemic and oral health. The findings that patients with higher levels of
these renal markers exhibited moderate to severe periodontitis suggest that the systemic
burden of CKD may exacerbate periodontal disease. The exploration of the association
between salivary calbindin-D28k levels and oral health in patients undergoing renal
dialysis, along with its relationship to renal and LFTs, reveals important insights
into the role of this calcium-binding protein in the context of CKD.
The significant association between salivary calbindin-D28k levels and periodontal
scoring in renal dialysis patients suggests a close link between calcium metabolism
and periodontal health. Periodontal disease is a common complication in CKD patients,
particularly those undergoing dialysis, due to a combination of factors such as immunosuppression,
altered calcium-phosphate metabolism, and poor oral hygiene. The significant association
observed in [Table 7A] underscores the potential role of calbindin-D28k in maintaining periodontal health,
possibly through its involvement in calcium homeostasis and the maintenance of periodontal
tissue integrity. The continuation of the association between salivary calbindin-D28k
levels and RFTs further supports the idea that disrupted calcium metabolism in CKD
patients has systemic implications, including effects on oral health. The significant
result observed between RFT and salivary calbindin-D28k levels ([Table 7B]) indicates that as renal function declines, there may be corresponding changes in
the levels of calbindin-D28k in saliva. This could be due to impaired renal synthesis
or altered regulation of calcium-binding proteins in response to declining kidney
function. The kidneys play a pivotal role in calcium and phosphate balance, and their
dysfunction could lead to alterations in the production or secretion of calbindin-D28K,
affecting its availability in saliva and thus influencing oral health outcomes. However,
the lack of a significant association between LFTs and salivary calbindin-D28k levels
([Table 7B]) suggests that liver function may not directly influence the levels of this protein
in saliva in the same way that renal function does. While the liver is involved in
various metabolic processes, including the synthesis of certain proteins, the specific
regulation of calbindin-D28k appears to be more closely tied to renal function rather
than hepatic function in the context of CKD.[37] This finding highlights the importance of focusing on renal-related factors when
assessing the role of calbindin-D28k in CKD patients. The differential association
of salivary calbindin-D28k with RFT, but not LFT, also points to the possibility that
salivary calbindin-D28k could serve as a biomarker for monitoring renal function and
its impact on oral health in dialysis patients.
Studying calbindin-D28k in both serum and saliva and correlating various biochemical
levels with dental caries prevalence from the time of diagnosis of CKD till the completion
of treatment in hospital setup, followed by oral hygiene instructions in these patients,
will give us better prospective which is a possible limitation here. The correlation
analysis between intracellular calbindin-D28k levels in patients undergoing renal
dialysis and their oral health, alongside key biochemical parameters, offers further
insights into the complex interactions between systemic health, calcium metabolism,
and oral health result in CKD patients. The significant positive correlations observed
between intracellular calbindin-D28k levels and biochemical parameters such as sodium
and RBS highlight the potential systemic implications of altered calcium-binding protein
levels in CKD patients. Sodium levels are critical in maintaining fluid balance and
blood pressure, which are often dysregulated in CKD. The positive correlation with
calbindin-D28k suggests that this protein may play a role in modulating sodium levels,
possibly through its involvement in calcium-dependent cellular processes. Similarly,
the correlation with RBS could indicate a relationship between calcium homeostasis
and glucose metabolism, both of which are often disrupted in CKD patients, particularly
those with concomitant diabetes. Conversely, the significant negative correlation
between calcium levels and salivary calbindin-D28k indicates a possible compensatory
mechanism where reduced calcium availability in the blood might lead to increased
reliance on calcium-binding proteins such as calbindin-D28k. This inverse relationship
suggests that as calcium levels decrease, the body might upregulate calbindin-D28k
to maintain cellular calcium homeostasis, which could have implications for both systemic
and oral health. The continued correlation analysis revealed a significant negative
correlation between salivary calbindin-D28k levels and periodontal scoring in CKD
patients with poor oral health. This finding indicates that higher levels of salivary
calbindin-D28k are associated with better periodontal health, as reflected by lower
periodontal scores.
Conclusion
The study confirms that low levels of calbindin-D28k in CKD patients with poor health
can be used as a prognostic marker for CKD. Estimating calbindin-D28k levels can help
predict future CKD and prevent it in subjects with poor oral health. Impaired function
of calbindin-D28k proportionally increased intracellular calcium ions that have detrimental
effects. In CKD patients the DCT is effected, therefore renal function of 1,25-dihydroxy
vitamin D is also impaired, which is crucial for calbindin-D28k production ([Fig. 3]).
Fig. 3 Depicts the effect of chronic kidney disease on distal convoluted tubule and its
consequences through calbindin-D28k.
