ORIGINAL ARTICLE

Oral paricalcitol versus oral calcitriol in continuous ambulatoryperitoneal dialysis patients with secondary hyperparathyroidism

Ema J. Jamaluddin • Abdul Halim Abdul Gafor •

Loo Chee Yean • Rizna Cader • Rozita Mohd •

Norella C. T. Kong • Shamsul Azhar Shah

Received: 4 October 2012 / Accepted: 16 July 2013

� Japanese Society of Nephrology 2013

Abstract

Background Secondary hyperparathyroidism (SHPT) is

common in end-stage renal disease. Our primary objective

was to evaluate the efficacy of oral paricalcitol versus oral

calcitriol on serum intact parathyroid hormone (iPTH) and

mineral bone parameters in continuous ambulatory perito-

neal dialysis (CAPD) patients with SHPT. The secondary

objective was to analyze highly sensitive C-reactive protein

(hsCRP) and peritoneal membrane function in both groups.

Methods This was a prospective randomized control trial.

CAPD patients with SHPT were randomized to paricalcitol

or calcitriol for 15 weeks. Serum intact iPTH, calcium,

phosphate and alkaline phosphatase (ALP) were measured

at baseline and every 3 weeks. Serum hsCRP and perito-

neal membrane functions were measured at baseline and at

week 15.

Results A total of 26 patients were enrolled and ran-

domized—12 to paricalcitol and 14 to calcitriol. Serum

iPTH reduced significantly in both groups and there was no

difference in the incidence of C50 % reduction of iPTH

between both groups. There was a significant increase in

serum calcium in both groups but there were no differences

in serum phosphorus across the visits. The incidence of

hypercalcemia was the same in both groups. Serum

calcium–phosphorus (Ca 9 P) product increased in the

paricalcitol group but decreased in the calcitriol group.

Serum ALP decreased significantly in both groups. There

were also no differences in pre- and post-treatment serum

hsCRP and peritoneal function test (PFT) in both groups.

Conclusion Both oral paricalcitol and calcitriol were

equally efficacious in reducing serum iPTH but were

associated with significantly higher serum calcium. Serum

Ca 9 P product increased in the paricalcitol group and

decreased in the calcitriol group. Serum hsCRP level and

PFT were not affected by either treatment. A larger ran-

domized controlled trial is indicated to confirm these initial

findings.

Keywords Calcitriol � Continuous ambulatory

peritoneal dialysis � Intact parathyroid hormone �Paricalcitol � Secondary hyperparathyroidism

Introduction

Chronic kidney disease-mineral and bone disorder (CKD-

MBD) is a new term describing abnormalities of bone and

mineral metabolism in CKD patients. It encompasses renal

osteodystrophy as well as cardiovascular complications

arising from CKD [1]. The spectrum of bone and mineral

metabolism disorders includes secondary hyperparathy-

roidism (SHPT) which is characterized by high bone turn-

over, and adynamic bone disease which is characterized by

low bone turnover and, in some patients, a combination of

the two [2, 3]. Due to end-organ resistance to parathyroid

hormone (PTH) in uremic patients, some degree of SHPT is

needed to maintain normal bone turnover in hemodialysis

(HD) patients. The Kidney Disease Improving Global

Outcome organization suggested that intact PTH (iPTH)

E. J. Jamaluddin � A. H. A. Gafor (&) � L. C. Yean �R. Cader � R. Mohd � N. C. T. Kong

Nephrology Unit, Department of Medicine, University

Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif,

Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

e-mail: halimgafor@gmail.com

S. A. Shah

Department of Epidemiology and Biostatistics, University

Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif,

Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

123

Clin Exp Nephrol

DOI 10.1007/s10157-013-0844-2

levels should be 2–9 times the upper normal limit in the

dialysis population [1]. The development of CKD-MBD is

related to the complex interaction among disordered min-

eral, bone and parathyroid metabolism, calcium-based oral

phosphate binders, dialysate calcium levels and vitamin D

therapy [3]. Vitamin D deficiency commonly occurs in

CKD patients due to inadequate conversion of 25(OH)2D3

to the active form of 1,25(OH)2D3 [4].

The essence of medical management of SHPT is to

correct the two most important pathogenetic factors which

are hyperphosphatemia and calcitriol deficiency. The goal

of vitamin D therapy is to prevent skeletal complications

by suppressing serum iPTH levels. Calcitriol therapy in

dialysis patients has proven effective in halting the pro-

gression of SHPT [5]. However, calcitriol therapy may

elevate both calcium and phosphorus levels or over-sup-

press iPTH levels. Furthermore, emerging data suggest that

the adverse effects of treatment for CKD-MBD play an

important role in vascular calcification and the excess risk

of death from cardiovascular causes among patients

undergoing dialysis [6–11].

This conundrum has led to the development of newer

analogs, in particular paricalcitol, which was developed and

approved for use in 1998 [12]. Paricalcitol has been shown to

be efficacious yet safe in patients receiving chronic hemod-

ialysis [12, 13]. Paricalcitol suppresses PTH faster and is also

associated with smaller changes in serum calcium and

phosphorus [12]. This may be due to the fact that paricalcitol

does not upregulate vitamin D receptor in the gut [14] and

does not stimulate intestinal calcium and phosphorus

absorption [15]. In our earlier study, we found that intrave-

nous paricalcitol may be superior to calcitriol in HD patients

with severe SHPT [16]. However, only a few studies have

been reported in the literature with regards to the effects of

paricalcitol in peritoneal dialysis (PD) patients.

Most CKD patients will die of cardiovascular events and

not renal failure [17]. Vitamin D insufficiency is associated

with inflammation as evidenced by increased circulating

matrix metalloproteinase-9 and C-reactive protein (CRP)

[18]. This provides a possible mechanism for tissue dam-

age in chronic inflammatory conditions, including coronary

artery disease [18]. Lower 1,25(OH)2D3 levels may be

associated with higher vascular calcification which aggra-

vates arteriosclerosis and endothelial dysfunction in dial-

ysis patients [19, 20]. Thus, correcting vitamin D

insufficiency may reduce inflammation and correct endo-

thelial dysfunction in dialysis patients.

Patients and methods

This is a single-center prospective open-labeled random-

ized control study on patients undergoing continuous

ambulatory peritoneal dialysis (CAPD) in the Nephrology

Unit, Universiti Kebangsaan Malaysia Medical Centre. The

study proposal was reviewed, approved and granted by

the Ethics and Research Committee of the Universiti

Kebangsaan Malaysia Medical Centre (Study Code

FF-262-2010).

The primary objective of this study was to evaluate the

efficacy and safety of oral paricalcitol versus oral calcitriol

on parameters of mineral bone metabolism in CAPD

patients with SHPT. Our primary efficacy goal was the

achievement of C50 % reduction in serum iPTH at the end

of the study compared to baseline. Our primary safety end-

point was the occurrence of hypercalcemia [serum calcium

[2.8 mmol/L (11.2 mg/dL)] at any time during the study

period.

Our secondary objective was to evaluate the improve-

ment of highly sensitive CRP (hsCRP) (a marker of

inflammation) and peritoneal membrane function in

patients receiving oral paricalcitol and calcitriol.

End-stage renal disease patients receiving CAPD for

C3 months with a serum iPTH of C50 pmol/L were eligible

for this study. Patients who were allergic to calcitriol or other

vitamin D compounds, had baseline serum calcium levels

C2.6 mmol (10.4 mg/dL), were post-parathyroidectomy, or

had experienced events of peritonitis were excluded from the

study. Prior to randomization, patients who were receiving

calcitriol (intravenous or oral), 1-a calcidol, bisphosphonate

and calcitonin underwent a 4-week washout period. Patients

were randomized into paricalcitol and calcitriol groups. The

treatment period lasted for 15 weeks. At baseline, blood for

serum iPTH, calcium, phosphate, alkaline phosphatase

(ALP) and hsCRP level were measured. The baseline

demographics, routine dialysis blood tests, measurements of

dialysis adequacy and medications were recorded. Mea-

surements of dialysis adequacy in terms of peritoneal

membrane function test were calculated using the peritoneal

function test (PFT) and Kt/V at baseline and at week 15.

Serum iPTH, calcium, phosphorus and ALP were measured

every 3 weeks and hsCRP measured at baseline and at week

15. At each 3-weekly visit, doses of oral vitamin D were

tailored according to serum iPTH (Table 1). The targeted

serum iPTH was \50 % from the baseline level. Patients

were strongly advised to adhere to the study drugs given and

to report any adverse reaction either by telephone or during

clinic visits. They were also advised to adhere to their

phosphate binders, continue similar dietary habits (protein

and phosphorus intake) and maintain their PD calcium

concentration at 1.25 mmol/L.

Measurements

Blood investigations were sent to a single laboratory for

measurement. Serum iPTH levels were measured using the

Clin Exp Nephrol

123

chemiluminescence assay and other parameters were

measured using standard laboratory techniques. Serum

calcium concentrations were corrected to serum albumin.

PFT and Kt/V were measured using Fresenius Medical

Care software (PatientOnLine).

Dosing regimen

Initial oral paricalcitol dose was calculated based on

baseline iPTH level [calculation: serum iPTH (pmol/L)

divided by 7 or serum iPTH (pg/ml) divided by 60] every

other day up to a maximum initial dose of 32 lg [21]. The

initial dose of calcitriol was 0.5 lg daily. Subsequent

titrations of dosages were individualized based on the most

recent iPTH and calcium levels (Table 1).

Randomization

Prior to randomization, patients who were receiving cal-

citriol (intravenous or oral), 1-a calcidol, bisphosphonate

and calcitonin underwent a 4-week washout period. On

entering the study, patients were advised to adhere to their

normal medication and not to change their eating habits,

oral calcium-based phosphate binders and peritoneal fluid

calcium concentration.

Randomization was conducted by 3 CAPD personnel.

Once inclusion criteria were met, CAPD patients who were

eligible were randomized into either group A or group B

for paricalcitol or calcitriol, respectively. Within each

group, random allocation was made in blocks of 4. A short

sequence of 4 probable alphabetical order A/B combina-

tions were put into an envelope and pulled-out according to

a patient’s CAPD clinic visit. Patients were blinded to the

drugs they were receiving.

Statistical analysis

An earlier study had shown that iPTH levels were signifi-

cantly suppressed in the paricalcitol group but not in the

calcitriol group [22]. We calculated the sample size using

PS2 Calculator Version 3.0.10 by using t-test and using the

mean difference in iPTH between the 2 groups during the

previous study. The sample size calculated was 17 patients

in each arm. To provide a slight margin of error given the

possibility of subject attrition, 20 patients were to be

recruited in each arm.

Analysis of data was performed using the SPSS version

19.0 statistical package using intention-to-treat analysis.

Continuous data were expressed as mean ± standard

deviation for parametric data or median (interquartile

range) for non-parametric data. Mann–Whitney U test was

used to compare between 2 variables at each time point.

Freidman’s test (using mean ranks) was used as a non-

parametric alternative to repeated measure ANOVA for[2

levels of related samples. Wilcoxon signed rank’s test was

used to identify the level of significance. Categorical data

were compared using Fisher’s exact test and chi-squared

test. A p value \0.05 was considered significant.

Results

Of the initial 40 patients who were screened, 1 patient did

not consent, 1 patient developed peritonitis on study

entry, 1 patient had recently started on CAPD, 5 patients

had serum iPTH levels \50 pmol/L, 2 patients had

undergone parathyroidectomy, 3 patients had serum cal-

cium levels [2.6 mmol/L (10.4 mg/dL) and 1 patient had

to be converted to temporary hemodialysis due to peri-

tonitis. The remaining 26 eligible patients who provided

consent were randomized to the study drugs. There were

12 patients in the paricalcitol group and 14 in the calci-

triol group. All baseline characteristics and demographic

data were comparable at baseline (Table 2). All patients

received calcium carbonate as their phosphate binder. The

calcium carbonate doses were comparable between both

groups and all patients were advised to keep to same dose

throughout the study period (Table 2). Baseline mineral

bone parameters were the same between both groups

(Table 3).

Six patients (50 %) in the paricalcitol group and 9

patients (64 %) in the calcitriol group achieved C50 %

reduction of iPTH levels compared to baseline (p = 0.692)

(Table 4). Serum iPTH levels were measured at baseline

Table 1 Dose adjustment for

oral paricalcitol and calcitriolDose maintained Dose increased (by 50 %) Dose reduced (by 50 %)

iPTH C10 pmol/L iPTH level did not decrease C50 %

from baseline

iPTH \10 pmol/L

AND AND OR

iPTH level reduced C50 %

from baseline

Serum calcium \2.8 mmol/L

(11.2 mg/dL)

Serum calcium[2.8 mmol/L

(11.2 mg/dL)

AND

Serum calcium \2.8 mmol/L

(11.2 mg/dL)

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123

and at 3-week intervals. Both groups showed a significant

reduction in serum iPTH across the visits (Fig. 1). Inter-

group analyses were performed between both study groups

at weeks 3, 6, 9, 12 and 15, respectively. There were no

differences in the median serum iPTH reduction between

both groups at each time point. However, patients in the

paricalcitol group showed a trend towards earlier reduction

of serum iPTH at week 3.

Table 2 Baseline

characteristics and demographic

data in both study groups

All continuous variables are

expressed as median (IQR);

inter-group analysis: Mann–

Whitney U test

IQR interquartile range

Paricalcitol (n = 12) Calcitriol (n = 14) p value

Age (years) 48.33 (12.05) 39.07 (12.67) 0.084

Gender (male:female) 7:5 6:8 0.348

Race (Malay:Chinese:Indian:Others) 8:4:0:0 11:3:0:0 0.422

Weight (kg) 66.92 (16.88) 61.62 (11.48) 0.719

Height (cm) 160.17 (8.91) 159.43 (7.01) 0.877

Body mass index (kg/m2) 24.33 (8.49) 24.02 (5.23) 0.607

Baseline co-morbidities (%)

Diabetes mellitus 4 (33.3 %) 4 (28.6 %) 0.563

Hypertension 12 (100 %) 10 (71.4 %) 0.067

Hyperlipidemia 4 (33.3 %) 4 (28.6 %) 0.563

Smoking 1 (8.3 %) 0 % 0.462

Ischemic heart disease 2 (16.7 %) 2 (14.3 %) 0.641

Etiology of end-stage renal disease

Unknown cause 4 (33.3 %) 6 (42.9 %) 0.952

Diabetes 2 (16.7 %) 4 (28.6 %)

Hypertension 3 (25 %) 2 (14.3 %)

Immunoglobulin A nephropathy 1 (8.3 %) 1 (7.1 %)

Obstructive uropathy 1 (8.3 %) 1 (7.1 %)

NSAID 1 (8.3 %) 0 %

CAPD duration (years) 4.00 (3.00) 3.00 (3.00) 0.266

Phosphate binder

Calcium carbonate dose (g/day) 3.0 (3.0) 3.0 (3.0) 0.79

Table 3 Baseline minerals and

bone parameters in both groups

All data expressed as median

(IQR); inter-group analysis:

Mann–Whitney U test

IQR interquartile range

Parameters Paricalcitol (n = 12) Calcitriol (n = 14) p value

Serum iPTH

(pmol/L) (NR 1.5–7.6) 85.65 (46.6) 98.9 (70.5) 0.700

Serum ALP

(IU/L) (NR 32–104) 119.00 (53.0) 82.00 (53.0) 0.150

Serum corrected calcium

mmol/L (NR 2.14–2.58) 2.24 (0.49) 2.25 (0.34) 0.758

mg/dL (NR 8.56–10.32) 8.96 (1.96) 9.00 (1.36)

Serum phosphorus

mmol/L (NR 0.71–1.36) 1.65 (0.65) 2.02 (0.71) 0.095

mg/dL (NR 2.20–4.21) 5.11 (2.01) 6.25 (2.20)

Ca 9 P product

mmol2/L2 3.83 (1.82) 4.67 (1.49) 0.900

mg2/dL2 47.88 (22.75) 58.38 (18.63)

Clin Exp Nephrol

123

Four patients in each group developed at least one epi-

sode of hypercalcemia [serum calcium [2.8 mmol/L

(11.2 mg/dL)] during the study period (p = 1.00) (Table 4).

There was a significant increase in serum calcium for both

groups at the last study visit (Fig. 2). Serum calcium

reached its highest peak of 3.15 mmol/L (12.6 mg/dL) and

3.12 mmol/L (12.48 mg/dL) in the calcitriol and paricalc-

itol groups, respectively, occurring at week 12. Hypercal-

cemic episodes tended to occur only if serum iPTH

precipitously plummeted to very low levels (serum iPTH

\10 pmol/L). Serum calcium returned to normal levels

once the dose of active vitamin D analog was reduced.

These episodes were asymptomatic and did not require

hospital admission.

Overall, there were no differences in serum phosphorus

across the visits for both groups. Serum Ca 9 P product

was significantly higher in the paricalcitol group

(p = 0.025) and significantly lower in the calcitriol group

(p = 0.010) at the end of the study compared to the

baseline (Fig. 3). However, there were no intergroup dif-

ferences at intervening visits. Both treatment groups

showed a significant reduction in serum ALP across visits.

Overall, changes in the serum ALP between both treatment

groups for other visits were not different at each time point.

There were no significant differences in hsCRP, Kt/V

urea and D/P creatinine between the paricalcitol and

calcitriol groups at baseline and at the end of the study.

There was also no statistical significance in pre- and post-

treatment hsCRP, Kt/V urea and D/P creatinine in both

treatment groups (Figs. 4, 5, 6).

Using the recommended formula, the median dose for

the paricalcitol group was calculated to be highest at 13.00

(7.75) lg every other day at the start of treatment and the

dosage required decreased over time across visits to its

lowest value of 3.00 (5.25) lg given on alternate days at

week 15. In the calcitriol group, however, the treatment

dose was highest at 0.75 lg daily at week 6 and decreased

to 0.5 (0.69) lg daily by week 12.

Both study groups had no reports of adverse affects and

had good adherence to the study medications.

Discussion

Previous studies of the effects of paricalcitol on CKD-

MBD have been performed but mostly in chronic HD

patients. A small number of studies have included some PD

patients as a sub-population but these were not separately

analyzed [21]. Hence clinical data on the effects of pari-

calcitol in PD patients remain scarce.

Table 4 Incidence of C50 % reduction of iPTH from baseline and

incidence of hypercalcemia (serum calcium [2.8 mmol/L)

Paricalcitol

(n = 12)

patient (%)

Calcitriol

(n = 14)

patient (%)

p value

C50 % reduction of iPTH

from baseline

6 (50) 9 (64) 0.692

Hypercalcemia [serum

calcium [2.8 mmol/L

(11.2 mg/dL)]

4 (33) 4 (29) 1.00

Analysis using Fisher’s exact test

Fig. 1 iPTH levels in both groups across the study period. Analysis

using Freidman’s Test

Fig. 2 Corrected calcium levels in both groups across the study

period. Analysis using Freidman’s Test

Fig. 3 Ca 9 P levels in both groups across the study period.

Analysis using Freidman’s Test

Clin Exp Nephrol

123

Transperitoneal calcium flux during PD is an important

factor that can influence iPTH secretion and the develop-

ment of CKD-MBD. A positive calcium balance may

suppress hyperparathyroidism. Unfortunately conflicting

results have been published on the measurement of

peritoneal calcium transfer [23]. This may be due to the

fact that transperitoneal calcium flux not only depends on

calcium concentration in PD fluids but also on dialysate

glucose concentration and ultrafiltration rate [24]. In our

study, all patients were asked not to change their PD pre-

scriptions and calcium concentration in PD fluids.

At baseline, both treatment groups had comparable

demographic and laboratory parameters. Our study dem-

onstrated that paricalcitol was as efficacious as calcitriol in

serum iPTH reduction across study visits in the CAPD

population. There were no differences in serum iPTH

reduction at all time points in this population. Paricalcitol

displayed an early precipitous drop in serum iPTH at week

3; however, serum iPTH tended to plateau from week 6

onwards. These findings were consistent with previous

studies by Ross et al. and Sprague et al. [12, 21, 22]. Both

groups reported that oral paricalcitol exhibited significant

serum iPTH reduction starting as early as 2 weeks post

treatment achieving a reduction of 30 % less than baseline

at week 3 and 88 % reduction by week 6 [13, 20, 21]. For

calcitriol patients, we used a standard initial dose of 0.5 lg

calcitriol daily and titrated subsequent doses as per

protocol.

The incidence of hypercalcemia was the same in both

groups. There was a significant increase in serum calcium

for both groups at the last study visit. Llach and Yudd [25]

demonstrated similar effects of rapid and sustained iPTH

reduction with subsequent hypercalcemia after 2 months

of therapy, mainly when levels decrease rapidly to \15

pmol/L. The potent effect of paricalcitol in serum iPTH

suppression causes a sudden drop in bone calcium uptake

resulting in hypercalcemia [21, 25]. The effects of iPTH

suppression and hypercalcemic events in both groups were

reversible. Serum calcium normalized once dose reduction

or temporary withdrawal of the vitamin D was made.

Normalization of serum calcium was seen within 3–5 days

and recovery of serum iPTH levels by 3 weeks.

Hypercalcemia is detrimental to dialysis patients. An

earlier study by Block et al. [26] revealed that 1-year

mortality increased by 16 % with 1 mg/dL (0.25 mmol/L)

increment of serum calcium. The target serum iPTH levels

(2–9 upper limits) were achieved in both groups as early as

week 3. Our experience parallels that of Ross et al. [21]

who recommended that the rapid lowering of iPTH by

paricalcitol, using a dosage regimen of iPTH/7 pmol/L,

may be useful in the early phase of treatment. Nevertheless,

we recommend that a modest dose calculation for pari-

calcitol should be used to achieve a more gradual decline in

iPTH levels to avoid hypercalcemic events. This relates to

a better and more logical approach in real-life clinical

practice as patient compliance is less predictable and fre-

quent blood monitoring is less feasible. Thus, we proposed

a lower initial oral paricalcitol dose of serum iPTH/

Fig. 4 Comparison of hsCRP pre- and post-treatment measurements

in both groups. Analysis with Wilcoxon Signed Ranks Test for paired

samples

Fig. 5 Comparison of weekly Kt/V urea pre- and post-treatment

measurements in both groups. Analysis with Wilcoxon Signed Ranks

Test for paired samples

Fig. 6 Comparison of D/P creatinine pre- and post-treatment mea-

surements in both groups. Analysis with Wilcoxon Signed Ranks Test

for paired samples

Clin Exp Nephrol

123

10 pmol/L and adjusted at follow-up. As the calcitriol

group also showed a drastic reduction in serum iPTH and

hypercalcemia, we suggest that an initial oral calcitriol

dose should be given every other day rather than daily.

Overall, there were no differences in serum phosphorus

at the end of the study in both groups. Although the changes

in serum phosphorus did not reach significance, we

observed a drop in serum phosphorus from 2.02 mmol/L

(6.25 mg/dL) to 1.74 mmol/L (5.39 mg/dL) in the calcitriol

group across the study visits. We do believe that this small

degree of serum phosphorus reduction may be significant in

real-life clinical practice. Serum phosphorus levels changed

by a higher factor than serum calcium; a small drop in

serum phosphorus translates to a larger reduction in calcium

phosphorus product and is the main culprit in causing an

elevated Ca 9 P product in CKD patients [27].

Hence, we noticed a significant reduction of serum Ca 9 P

product in the calcitriol group but a significant increase in the

paricalcitol group; however, there were no differences

between both groups at each visit. Our finding was similar to a

previous study by Ross et al. [21] who also reported higher

Ca 9 P product in patients receiving oral paricalcitol com-

pared to those on placebo. The Ca 9 P product has been

regarded as a ‘non-traditional’ cardiovascular risk factor in

the dialysis population. Block et al. [11] showed a steady

increase in the relative risk of death in dialysis patients with

increasing Ca 9 P product. It was hypothesized that

increased Ca 9 P product may contribute to vascular calci-

fication and lead to cardiovascular disease [28].

Total serum ALP activity was inversely correlated with

bone mineral density in CKD patients [29]. There is a

direct correlation between bone-specific ALP and total

ALP activity and iPTH in HD patients [29]. In our study,

both treatment groups showed a significant reduction in

serum ALP across visits. These reductions in ALP coin-

cided with the hypercalcemic episodes reflecting the

slowing down of bone mineral turnover. Earlier studies

revealed that more paricalcitol subjects experienced nor-

malization of their high bone-specific ALP compared to

placebo subjects [21, 30].

In our previous study, we noted that all our CKD patients

had a significant vitamin D deficiency with a mean level of

serum 25(OH)D of 15.3 ± 4.2 ng/mL [31]. Many studies

confirmed the benefits of anti-inflammatory properties of

paricalcitol and calcitriol [32–34]. We found that CKD

patients receiving replacement therapy with low vitamin D

levels not only had reduced interleukin-6 levels but also

appeared to have stable renal functions [35]. As inflam-

mation played a role in peritoneal functions [36], we

expected changes in PFT with the replacement of vitamin D

in CAPD patients. Unfortunately, in this study, there were

no significant effects from either drug on peritoneal mem-

brane function and Kt/V in our study population. This result

may be due to the fact that we did not have their baseline

vitamin D levels and only a small number of patients were

enrolled in the study. However, further evaluation of these

effects would require a longer follow-up time.

hsCRP is a marker of inflammation which correlates

well with cardiovascular risk and mortality. In the Fra-

mingham study, three biomarkers (CRP, PAI-1, and

UACR) predicted hypertension and all biomarkers were

dysregulated by reduced vitamin D receptor activation

[37]. Unfortunately, we did not see any significant reduc-

tion of hsCRP in either the paricalcitol or calcitriol group.

Our study had several limitations. There is limited

experience in using the introduced dose-calculated regi-

mens for paricalcitol dosing and only one study had

reported on the use of oral paricalcitol in 26 CAPD patients

[21]. Thus, dose calculations were performed by the prin-

cipal investigator personally. Frequency of dosing for both

treatment groups also differed as paricalcitol capsules were

given as an alternate-day dosing and calcitriol as a daily

dose. The timing of administration was similar in both

treatment groups. The study conclusion was also limited by

the small number of patients. On the plus side, however,

the randomized controlled nature of the study and the

completeness of follow-up added strength to our results.

Conclusions

We concluded from this study that both oral paricalcitol

and oral calcitriol were equally efficacious in reducing

serum iPTH in the treatment of CAPD patients with SHPT

and had similar rates of hypercalcemic events. On the other

hand, serum Ca 9 P product was significantly higher in the

paricalcitol group and lower in the calcitriol group at the

end of the study period. We recommend a more gradual

control of serum iPTH by reducing the initiation dose of

vitamin D so as to minimize hypercalcemic events. There

were no differences in hsCRP level and PFTs between the

groups. A larger randomized controlled trial is necessary to

confirm these preliminary findings.

Acknowledgments This study was supported by the Faculty of

Medicine UKM Research Grant FF-262-2010.

Conflict of interest The authors have declared that no conflict of

interest exists.

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