1. When Using DOPPS Slides
Modifying DOPPS data, analyses, tables, and graphics in any form is not permitted without prior approval from the DOPPS coordinating center staff.
Each DOPPS slide used must include the citation of the associated publication and feature the corresponding DOPPS logo.

2. DOPPS Slide Use Guidelines
Modifying DOPPS data, analyses, tables, and graphics in any form is not permitted without prior approval from the DOPPS coordinating center staff.
Each DOPPS slide used must include the citation of the associated publication and feature the corresponding DOPPS logo.

3. Hypercalcaemia is associated with poor mental health in haemodialysis patients: results from Japan DOPPS
The Dialysis Outcomes and Practice
Patterns Study (DOPPS) reported high incidence of
depression in haemodialysis patients. Hypercalcaemia
and high parathyroid hormone (PTH) levels are
aetiological factors of psychological disorders. We
examined the association between mineral metabolism
abnormalities and mental health in Japanese-DOPPS
patients.
Using baseline data of Japan-DOPPS,
Phase 1 (2755 patients, 1999–2001) and Phase 2 (2286
patients, 2002–03), we analyzed mental
health using the mental health domain of SF-36. We
examined the association between serum corrected
calcium, phosphorus, calcium*phosphorus product
and intact PTH concentrations, and mental health
using analysis of covariance and also the associations
between corrected calcium levels and current use of
vitamin D and calcium-containing phosphate binder.

4. Methods We used baseline data of Japan-DOPPS,
Phase 1 (2755 patients, 1999–2001) and Phase 2 (2286
patients, 2002–03). The outcome variable was mental
health using the mental health domain of SF-36. We
examined the association between serum corrected
calcium, phosphorus, calciumphosphorus product
and intact PTH concentrations, and mental health
using analysis of covariance and also the associations
between corrected calcium levels and current use of
vitamin D and calcium-containing phosphate binder.

5. KDQOL SF-36
The Japanese version of patient self-reported, health-related
quality of life (QOL) questionnaire (SF-36 Health Survey,
hereafter SF-36) was distributed to patients for response. The
SF-36 is a QOL scale that permits quantitative evaluation of
subjective health status and its impact on daily function and
social function. The SF-36 consists of 36 questions and when
all questions are answered, a score ranging from 0 to100 is
calculated for each of the eight domains (e.g. physical
function, mental health, social function, role-physical, role-emotional,
bodily pain, general health and vitality). A low
mental health score represents poor mental health.
Patients who were unable to complete the questionnaire,
such as those with ostensible cognitive deficits, were excluded.

6. Analysis Methods
Results are expressed as mean +/- SD unless otherwise stated. We
examined the correlations between mental health scales and
serum corrected calcium, phosphorus and intact PTH concentrations.
In this study, pooled data from Phase 1 and Phase 2
studies from Japan-DOPPS were analysed. Based on the
Kidney Disease Outcomes Quality Initiative (K/DOQI)
guidelines, serum corrected calcium, phosphorus and
intact PTH concentrations were categorized by the following
cut-off concentrations: serum corrected calcium: 8.4, 10.2
and 11.0 mg/dl, phosphorus: 2.5, 3.5 and 5.5 mg/dl, and
intact PTH: 150, 300 and 600 pg/ml. Cut-off points of Ca*P
product were defined based on 25, 50 and 75 percentiles of
Ca*P product levels. First, we examined the correlations
between corrected calcium, phosphorus, intact PTH concentrations
and Ca*P product levels, with mental health scores
from the SF-36 using analysis of variance (crude analysis).
Then, analysis of covariance was used to examine the
associations with adjustment variables. In this analysis,
independent variables in the multivariate model were the
following: corrected calcium, phosphorus, intact PTH concentrations,
sex, age, duration of dialysis, serum albumin,
haemoglobin, use/non-use of vitamin D preparation, use/
non-use of calcium-containing phosphate binder, presence/
absence of comorbidity (13 variables) and history of PTX.
When the association between Ca*P product level and
mental health was examined, the independent variables in the
multivariate model were Ca*P product level, intact PTH
concentrations, sex, age, serum albumin, haemoglobin, use/
non-use of vitamin D preparation, use/non-use of calciumcontaining
phosphate binder, presence/absence of comorbidity
(13 variables) and history of PTX.

7. Table 1. Percentage of patients using vitamin D or calcium-containing phosphate binder categorized by corrected calcium levels
Table 1 shows the distribution of patients
categorized by corrected calcium levels according
to the use/non-use of intravenous vitamin D or its
analogue for control of PTH and calcium-containing
phosphate binder within one week of the investigation
date. The percentage of patients receiving intravenous
active vitamin D preparations or calcium-containing
phosphate binder was significantly higher in dialysis
patients with hypercalcaemia than those without
(P<0.0001).

8. Table 2. Baseline Characteristics (1)
The mean age of 4115 patients of
Phase 1 and 2 studies was / and /- 12.9
years, respectively, and males formed 63 and 61%,
respectively, of the population.

9. Table 2. Baseline Characteristics (2)
The duration of dialysis
was less than 6 months in 757 patients. Furthermore,
58% of the patients used vitamin D preparations and
79% used calcium-containing phosphate binders.

10. Table 2. Baseline Characteristics (3)
Hypertension and diabetes were the most commonly observed
comorbid conditions among this population of HD patients.

11. Table 2. Baseline Characteristics (4)
Serum concentrations of albumin, calcium,
phosphorus and PTH remained relatively constant
between the first and second phases of DOPPS.

12. Association between mental health (MH) score of the SF-36 Health Survey and (A) serum corrected calcium and (B) phosphorus
As shown in Figure 1A, 64.0% of
patients had the target serum calcium levels, 15.4%
had less, and 20.6% had more than that. The mean
mental health scores of the group with corrected
calcium levels <8.4 mg/dl, 8.4 to <10.2 mg/dl,
10.2 to <11.0 mg/dl and 11.0 mg/dl were 64.1
[95% confidence interval (CI): 62.2–66.1], 64.3
(95%CI: 63.4–65.2), 65.6 (95%CI: 63.6–67.6) and
58.9 (55.9–61.9), respectively. The group with corrected
calcium levels 11 mg/dl had a significantly
lower mental health score than that with <8.4 mg/dl.
The difference was 5.2 points (P¼0.04) and its effects
size (ES) was Similarly, the group with corrected
calcium levels 11 mg/dl had a significantly lower
mental health score than that with levels 8.4 to
<10.2 mg/dl, and the group with 10.2 to <11.0 mg/dl.
The differences were 5.4 points (P¼0.009) and 6.7
points (P¼0.003), respectively, and their ESs were
0.25 and 0.31, respectively.
Furthermore, 40.8% of patients had the target serum phosphorus
levels, 6.0% had less and 53.2% had more than the
target (Figure 1B). There were no associations between
serum phosphorus and mental health by crude analysis.

13. Association between mental health (MH) score of the SF-36 Health Survey and (C) parathyroid hormone (PTH) concentrations and (D) Ca x P product
As shown in Figure 1C, 26.1% of
patients had target serum intact PTH levels, 51.4% had
less and 19.5% had more than the target.
There were no associations between serum intact
PTH and CaP product and mental health by crude
analysis (Figure 1C–D).

14. Table 3. Differences in mental health score between serum corrected calcium levels by multiple comparison
After adjustment for age, sex, serum albumin concentration, haemoglobin,
serum phosphorus concentration, use/non-use of vitamin
D preparation, use/non-use of calcium-containing
phosphate binder, presence/absence of comorbidity (13
variables) and history of PTX, the differences between
the group with corrected calcium levels 11.0 mg/dl
and groups with 8.4 to <10.2 mg/dl and 10.2 to
<11.0 mg/dl were significant.
That is, the mental health score of patients with corrected calcium
levels of 11.0 mg/dl was 5.0 (95% CI: 0.5–9.6) points
lower than that of the group with 8.4 to <10.2 mg/dl
and 6.7 (95% CI: 1.6–11.8) points lower than the group
with 10.2 to <11.0 mg/dl.

15. Conclusion In this study, we found a possible association between
hypercalcaemia and poor mental health in dialysis
patients. Our study also shows that treatment with
intravenous active vitamin D preparations and/or oral
calcium salts is responsible for the development of
hypercalcaemia in dialysis patients. While a cause–
effect relationship between hypercalcaemia and deterioration
of mental health needs further confirmation
through longitudinal studies as well as prospective
randomized studies, our observational findings suggest
the importance of control of serum calcium concentration
in dialysis patients treated with active vitamin D
preparations or calcium salts.