The Effects of Oral Vitamin D Supplementation on the Prevention of Peritoneal Dialysis-related Peritonitis
Phase: PHASE2
Conditions: Peritoneal Dialysis-associated Peritonitis, Vitamin D Deficiency
Sponsor: Peking University First Hospital

STUDY PROTOCOL
Open Access
The effects of oral vitamin D
supplementation on the prevention of
peritoneal dialysis-related peritonitis: study
protocol for a randomized controlled
clinical trial
Yu-hui Zhang1,2,3,4†, Xiao Xu1,2,3,4†, Hai-chen Pi5, Zhi-kai Yang1,2,3,4, David W. Johnson6,7,8 and Jie Dong1,2,3,4*
Abstract
Background: Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related
peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled
trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who
have already experienced an episode of peritonitis.
Methods: This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine
the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related
peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be
randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D
supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis
guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The
primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity
(change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to
determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include
time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-
related death (defined as death within 30 days of peritonitis onset).
Discussion: This is the first randomized controlled trail investigating the effects of vitamin D supplementation on
the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine
the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for
preventing PD-related peritonitis among PD patients.
Trial registration: Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.
Keywords: Natural vitamin D3, Peritoneal dialysis, Peritonitis, Serum 25-hydroxyvitamin D, Randomized controlled
trial
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: jie.dong@bjmu.edu.cn
†Yu-hui Zhang and Xiao Xu contributed equally to this work.
1Renal Division, Department of Medicine, Peking University First Hospital,
Beijing, China
2Institute of Nephrology, Peking University, Beijing, China
Full list of author information is available at the end of the article
Zhang et al. Trials          (2019) 20:657 
https://doi.org/10.1186/s13063-019-3784-7

Background
Peritoneal dialysis (PD)-related peritonitis is the most
common infectious complication for patients on PD, and
is a major contributor to treatment failure, hospitalization,
and death [1]. Indeed, PD-related infection is considered
the top, most critical research priority in PD by patients,
caregivers, and clinicians [2, 3]. Almost 40% of patients
will experience one or more episodes of peritonitis during
extended follow-up on PD [4]. Furthermore, once patients
experience an initial peritonitis episode, they are at in-
creased risk of a subsequent, more serious peritonitis
event after a median time interval of 8 months [5, 6]. Key
risk factors for the development of peritonitis include in-
nate and adaptive immune dysfunction, inflammation, and
malnutrition [7–10].
Vitamin D deficiency is commonly associated with
malnutrition [6] and is observed in the majority of dialy-
sis patients [11, 12]. In addition to playing a role in the
regulation of both the innate and adaptive immune sys-
tems [13, 14], vitamin D deficiency has been found to be
independently predictive of increased risks of a variety of
infectious diseases in the general population [15–17].
Previous observational cohort studies have also reported
that vitamin D deficiency is associated with an increased
risk of PD-related peritonitis, even after adjusting for co-
morbidities, nutritional status, and physical performance
[6]. Interventional studies also demonstrated that oral
supplementation of vitamin D may reduce respiratory
infection rates [18, 19].
Therefore, we plan to conduct a pilot study to examine
the feasibility for a future, full-scale randomized con-
trolled trial (RCT) exploring the effect of oral vitamin D
(liquid natural vitamin D3, cholecalciferol; 2000 IU, 0.08
ml) on the risk of PD-related peritonitis in patients who
have already experienced an episode of peritonitis. Our
hypothesis is that oral supplementation of vitamin D
could reduce the risk of subsequent peritonitis.
Methods
Trial design and setting
This is a pilot, single-center, randomized, open-label,
controlled
trial
with
balanced
randomization
(1:1)
among patients on PD. The protocol of this study was
reported adhering to the ‘Standard Protocol Items:
Recommendations for Interventional Trials’ statement
[20] (Additional file 1). After informed consent, all eli-
gible participants will be randomized to the intervention
group with vitamin D supplementation or the control
group. Participants will be followed for 12 months.
Figure 1 shows the schema of the trial.
The study is being conducted in the PD center of
Peking University First Hospital.
Ethical approval, trial registration, and dissemination
The study was approved by the Peking University First
Hospital
Research
Ethics
Committee
(Project-ID:
2016[1149]), and was registered at Clinicaltrails.gov [21]
on 29 August 2017 (NCT03264625 [22]). The results
Fig. 1 Trial schema. HD hemodialysis, 25(OH)D 25-hydroxyvitamin D, PD peritoneal dialysis
Zhang et al. Trials          (2019) 20:657 
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will be disseminated in peer-reviewed journals, and lay
summaries will be presented in “ScienceOpen” [23].
Study population
All patients who have recovered from a PD-related peri-
tonitis at 1 month after the episode will be screened for
eligibility. Patients will be recruited if they meet all of
the following criteria: aged at least 18 years; undergoing
PD for ≥1 month and clinically stable; weekly Kt/V ≥1.5
and no clinical uremic symptoms; and serum 25-
hydroxyvitamin D (25(OH)D) < 75 nmol/l (30 ng/ml).
Patients will be excluded if they have any of the follow-
ing: received vitamin D2/D3 or drugs known to alter
serum 25(OH)D levels during the previous 12 months;
have a history of allergic reaction to cholecalciferol; have
current or past malignant disease, active hepatitis or
hepatic failure, acute systemic infection, active auto-
immune diseases, severe digestive malabsorption or eat-
ing
disorder,
or
human
immunodeficiency
virus
infection or
acquired
immune
deficiency
syndrome
(HIV/AIDS); have a high probability (assessed by the
recruiting physician) of receiving a kidney transplant or
transition to hemodialysis (HD) or dropout due to socio-
economic causes within 6 months; or women who were
pregnant or lactating.
Written informed consent will be required from all
study participants before their involvement in the trial.
Participants can choose to withdraw from the study at
any time without affecting their future treatment. Rea-
sons for non-inclusion and withdrawal will be recorded
in detail.
Randomization and blinding
All consenting patients will be registered in the trial and
randomized 1:1 to either the vitamin D intervention
group or the control group by a computer-generated
random number list. An independent medical staff
member is responsible for participant enrollment and al-
location assignment. The sample size for this pilot study
will be 30 patients for both groups (Fig. 1). Due to the
nature of the medication intervention, neither partici-
pants nor researchers can be blinded. However, both the
primary outcome (the assessment of feasibility and fidel-
ity) and the key secondary outcome (time to peritonitis
occurrence, recovery of peritonitis, peritonitis-related
transition to hemodialysis, and peritonitis-related death)
will be evaluated by independent medical staff who are
blinded to participants’ allocations. In addition, all la-
boratory parameters for all participants will be measured
by laboratory staff who are also blinded to treatment
assignment.
The primary outcome is the assessment of feasibility
(recruitment success, retention, adherence, safety) and
fidelity (change in serum 25(OH)D level during follow-
up) for a large, powered randomized controlled trial to
determine the effects of vitamin D on the risk of PD-
related peritonitis in the future. Secondary outcomes in-
clude time to peritonitis occurrence, recovery of periton-
itis, peritonitis-related transition to hemodialysis, and
peritonitis-related death (defined as death within 30 days
of peritonitis onset).
Intervention
Participants in the intervention group will receive add-
itional vitamin D (liquid natural vitamin D3, cholecalcif-
erol; 2000 IU) in a dose of 0.08 ml orally per day for 12
months following randomization. In order to assess
medication adherence, participants will be asked to take
the study medication that is left over for weighing at
each clinical visit.
Control
Participants in the control group will not receive any
study drug and will be asked to not take any form of
vitamin D supplementation.
Concomitant treatment
For both the intervention and control groups, all dialysis
and other medication prescriptions will be in accordance
with routine clinical care and International Society for
Peritoneal Dialysis (ISPD) guideline recommendations.
Baseline evaluation and follow-up
Data collection for this study is composed of two phases:
baseline evaluation and follow-up. All of the data will be
recorded by the responsible physician on a uniform case
report form (CRF). Detailed information collected in
each phase is described in the following. Table 1 pre-
sents an overview of the data collection schedule during
baseline evaluation and follow-up. All participant infor-
mation will be collected and maintained by trained
medical staff to protect confidentiality.
Baseline evaluation
For all eligible and consenting patients, information re-
garding demographic data (age, gender, body mass index
(BMI), education, marital status, occupation, income,
health insurance), dialysis duration, primary disease, co-
morbidities, current medication, and history of PD-
related peritonitis will be recorded. Baseline biochemis-
try indices (including blood routine, serum creatinine,
albumin, alanine transaminase, lipids, electrolytes, para-
thyroid hormone, and serum 25(OH)D levels), dialysis
adequacy (including the urea clearance index (Kt/V) and
creatinine clearance rate (CCr)), and inflammatory bio-
markers (interleukin-6, plasminogen activator inhibitor
1) will be evaluated. After randomization, the assigned
treatment should be recorded in detail.
Zhang et al. Trials          (2019) 20:657 
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Follow-up and outcome evaluation
All participants are planned to be followed-up for 12
months, with clinic visits every month. During the
follow-up, clinical information including self-reported
symptoms and physical examination will be gathered.
Biochemistry indices (including blood routine, serum
creatinine, albumin, alanine transaminase, lipids, electro-
lytes, parathyroid hormone, and serum 25(OH)D levels)
and dialysis adequacy will be evaluated every 3 months.
Participants will be evaluated for compliance by weigh-
ing residual liquid vitamin D3 every month. All out-
comes and adverse events will be recorded. Please refer
to the following sections for detailed outcomes and
adverse events.
The primary outcome is assessment of feasibility (re-
cruitment success, retention of participants for 12
months, patient adherence, and safety) and fidelity
(change in serum 25(OH)D level between baseline and
12 months). Secondary outcomes include time to peri-
tonitis occurrence, recovery of peritonitis, peritonitis-
related transition to HD, and peritonitis-related death
(defined as death within 30 days of peritonitis onset).
Death not associated with peritonitis, transition to HD
not associated with peritonitis, and receiving a kidney
transplant will be recorded as competing outcomes.
Recruitment will be determined as the proportion
(percentage) of potentially eligible patients recruited into
the trial: the numerator would be the number of patients
recruited in the trial; the denominator would be the
number of patients diagnosed with PD-related related
peritonitis during the recruitment period. Successful re-
cruitment will be defined as greater than 40%, the 95%
CI (confidence interval) for this cutoff point is 28–52%.
Reasons for non-participation from those who were di-
agnosed with peritonitis but were not recruited will be
recorded. Retention will be evaluated by measuring attri-
tion during the follow-up at each clinic visit. The reten-
tion rate will be calculated as the percentage of patients
who completed the trial among patients recruited in the
trial. Successful retention will be defined as > 80% at the
end of the 12-month follow-up period. Adherence to
taking vitamin D will be evaluated by weighing the vita-
min D that is left over at each clinical visit. The adher-
ence rate will be calculated as the percentage of patients
who are adherent to the dosing regimen among patients
recruited in the intervention group. Participants taking
an average dose over 70% of the required dose are con-
sidered adherent to the dosing regimen. Acceptable ad-
herence will be defined as greater than 70%. Fidelity will
be measured by the difference of change in the serum
25(OH)D level over time between the interventional
group and the control group.
For the assessment of safety, both severe and non-
severe prespecified adverse events during the study
course, including allergic reaction to vitamin D, hyper-
calcemia, and hyperphosphatemia, will be recorded.
Severe adverse events include an AE which fulfils at
least one of the following: life-threatening, requires
hospitalization, results in disability or congenital ab-
normality, or requires medical intervention to prevent
one of the aforementioned outcomes.
The recovery of peritonitis was defined as complete
resolution
of
peritonitis
(normalization
of
body
temperature, resolution of abdominal pain, clearing of
dialysate, and PD effluent white blood cell count < 100
cells/μl with < 50% polymorphonuclear cells using anti-
biotics alone without relapse within 4 weeks of comple-
tion of therapy).
Biochemical testing methods
Blood samples will be analyzed at Peking University First
Hospital, Beijing. Biochemical profiles will be tested
using an automatic Hitachi chemistry analyzer. Serum
25(OH)D levels will be measured using an electrochemi-
luminescence
method
(E601;
Roche
Diagnostics,
Germany).
Table 1 Data collection schedule
Baseline Week
4
Week
8
Week
12
Week
16
Week
20
Week
24
Week
28
Week
32
Week
36
Week
40
Week
44
Week
48
Demographic data, PMH, and
medications
X
Clinical symptoms and adverse
events
X
X
X
X
X
X
X
X
X
X
X
X
X
Biochemical
indices
Blood routine
X
X
X
X
X
Blood
biochemistry
X
X
X
X
X
Serum 25(OH)D
X
X
X
X
X
Dialysis
adequacy
Weekly Kt/V
X
X
X
X
X
Weekly CCr
X
X
X
X
X
Adherence
24-h recall
X
X
X
X
X
X
X
X
X
X
X
X
X
CCr creatinine clearance rate, Kt/V urea clearance index, 25(OH)D 25-hydroxyvitamin D, PMH past medical history
Zhang et al. Trials          (2019) 20:657 
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Statistical analysis
Statistical analysis will be conducted using SPSS software
(version 22.0; SPSS Inc.) and SAS software (version 9.4;
SAS Institute). Continuous variables will be expressed as
the mean ± standard deviation, median with interquartile
range, and percentage. Student’s t test, the Mann–
Whitney U test, and the chi-square test will be used to
compare differences in baseline characteristics between
the intervention and control groups.
The recruitment rate, retention rate, and adherence
rate will be reported as percentages and associated 95%
CI. Adverse events will be recorded as the event rate per
patient-year. Linear mixed-effects regression models will
be used to analyze the change in serum 25(OH)D levels
between the two groups. Competing risks Cox regression
models will be used to compare the time to peritonitis
between the two groups. Logistic regression models will
be applied to compare the short-term outcome of
subsequent peritonitis.
For all statistical analysis, the level of significance will
be set at 0.05.
Discussion
The present pilot RCT aims to evaluate the feasibility of
oral vitamin D supplementation among PD patients and
to explore its effects on the risk of PD-related peritonitis.
Few interventional studies have been done exploring the
effects of vitamin D on preventing infection, especially
among PD patients. Therefore, obtaining data on the
evaluation of feasibility is the priority in this study. The
findings of this pilot study will be used to inform the de-
sign and methodology of a definitive study evaluating
the efficacy and safety of vitamin D supplementation in
the prevention of PD-related peritonitis among patients
on PD.
In the general population, there are many RCTs ex-
ploring the effects of vitamin D in preventing infections,
such as respiratory infections in vitamin D-deficient pa-
tients with chronic obstructive pulmonary disease [19],
and in children [18]. However, no such study has been
undertaken in patients with end-stage kidney disease
even though vitamin D deficiency has been shown to be
independently associated with PD-related peritonitis [6].
Our study has applied a rigorous design in choosing
the time point for patient enrollment. According to pre-
vious cohort studies, patients having experienced a peri-
tonitis episode tend to develop a subsequent one after a
median time interval of 8 months [5]. Therefore, we fo-
cused our attention on the prevention of a subsequent
peritonitis episode during a 12-month period among PD
patients who have recently recovered from peritonitis,
given that this is expected to provide an enriched cohort
of patients with a high peritonitis event rate. Based on
current data, more than 20% of participants have
developed one or more subsequent episodes of periton-
itis during a 1-year observation period. As ISPD guide-
lines recommend a standardized treatment period of 2–
3 weeks for PD-related peritonitis [24], we chose to
enroll patients into the present study 1 month after the
onset of a PD-related peritonitis, as antibiotic treatment
would be expected to be completed by this time.
We have adopted a study design using vitamin D and
blank control for included patients with vitamin D defi-
ciency. The study design is similar to most previously
published randomized controlled trials of vitamin D
among the general population [19, 25], CKD patients
[26], and the dialysis population [27]. Although recent
KDIGO guidelines suggest that vitamin D deficiency be
corrected, the level of recommendation is 2C, and
whether
natural
vitamin
D
supplementation
could
improve clinical outcomes remains a question that needs
further exploration [28], which justifies the ethics of our
study.
According to the US Dietary Guidelines, the recom-
mended daily dose of vitamin D for older adults is 600–
800 IU per day [29], while a meta-analysis of randomized
controlled trials in the general population showed a
usual dose of 300–2000 IU per day [30]. In non-dialysis
CKD patients, a systemic review indicated that at least
2000 IU vitamin D per day is necessary for ameliorating
vitamin D deficiency [31]. In dialysis patients, a random-
ized controlled trial among maintenance hemodialysis
patients showed that a weekly dose of 10,333 IU chole-
calciferol for 15 weeks could raise vitamin D levels from
13.3 ng/ml to 23.6 ng/ml [32]. Participants in all of these
studies showed an improvement in serum 25(OH)D
level, with low incidences of hypercalcemia and hyper-
phosphatemia. As participants in our study need to take
vitamin D for a whole year, after considering the safety,
efficacy, and feasibility, we chose to set the dose of vita-
min D at 2000 IU. The liquid form of vitamin D was
chosen for the sake of convenience in oral administra-
tion and evaluation of compliance. According to data
from preliminary results of the present study, oral sup-
plementation of vitamin D 2000 IU per day could raise
serum 25(OH)D to adequate levels. Serum levels of
25(OH)D increase significantly once oral supplementa-
tion of vitamin D is started, reaches a plateau around 40
ng/ml by the 6th month, and thereafter remains stable.
The underlying mechanism for the observed associ-
ation between vitamin D deficiency and infection in pre-
vious studies [6, 15–17] may lie in the role of vitamin D
in potentiation of the innate immune system. The
immunoregulatory effect of 1,25(OH)2D is mediated
through the vitamin D receptor, which is present in
most immune cells. Vitamin D would upregulate macro-
phage differentiation, induce the production of anti-
microbial peptide cathelicidin, as well as decrease the
Zhang et al. Trials          (2019) 20:657 
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release of cytokines. Thus, higher levels of vitamin D
may result in an increased anti-infectious ability and
limit the potential inflammatory damage [13].
Vitamin D deficiency has been identified as one of the
common modifiable risk factors for PD-related periton-
itis [33]. Exploring whether supplementation of vitamin
D could lower the risk of subsequent peritonitis would
help identification of a potentially novel and cheap strat-
egy for preventing PD-related peritonitis. Furthermore,
the role of vitamin D supplementation on outcomes of
PD-related peritonitis will also be explored. The result of
this pilot study will determine the feasibility of conduct-
ing a full-scale RCT, which may help to better inform
shared decision-making by patients and clinicians with
respect to the role of vitamin D supplementation regard-
ing
the
prevention
and
mitigation
of
PD-related
peritonitis.
Trial status
This is the first edition of the protocol (September 30,
2016) approved by the ethics committee of Peking Uni-
versity First Hospital. The first participant was enrolled
on September 30, 2017. Currently, 42 patients have been
recruited into the study and the final recruitment target
is 60. Recruitment and follow-up are scheduled to con-
tinue until January 30, 2021.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13063-019-3784-7.
Additional file 1. SPIRIT 2013 Checklist: Recommended items to address
in a clinical trial protocol and related documents.
Abbreviations
25(OH)D: 25-Hydroxyvitamin D; ISPD: International Society for Peritoneal
Dialysis; IU: International unit; PD: Peritoneal dialysis; PROBE: Prospective,
open-label randomized controlled pilot trial with blinded end-points;
RCT: Randomized controlled trial
Acknowledgements
The authors express their appreciation to the patients, doctors, and nursing
staff of the Peritoneal Dialysis Center of Peking University First Hospital.
Authors’ contributions
Research idea and study design: JD, Y-hZ, H-cP, and DWJ; data acquisition:
XX, Y-hZ, Z-kY; data analysis plans: Y-hZ and JD; supervision or mentorship:
JD. Each author has contributed important intellectual content to the con-
ception and design of this study. All authors were involved in drafting the
manuscript or revising it, and accept accountability for the overall work by
ensuring that questions on the accuracy or integrity of any portion of the
work are appropriately resolved. All authors have given final approval of the
version to be published.
Funding
This trial was conducted with no external funding, no internal funding, or
any grants.
Availability of data and materials
The datasets generated during the current study are not publicly available
due to the issue of individual privacy, but are available from the
corresponding author on reasonable request.
Ethics approval and consent to participate
The study is approved by the Peking University First Hospital Research Ethics
Committee (Project-ID:2016[1149]). Written informed consent is required
from all study participants before their involvement in the trial.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1Renal Division, Department of Medicine, Peking University First Hospital,
Beijing, China. 2Institute of Nephrology, Peking University, Beijing, China. 3Key
Laboratory of Renal Disease, Key Laboratory of Renal Disease, Ministry of
Health, Beijing, China. 4Key Laboratory of Renal Disease, Ministry of
Education, Beijing, China. 5Department of Emergency Medicine, Peking
University First Hospital, Beijing, China. 6Department of Nephrology, Princess
Alexandra Hospital, Brisbane, Australia. 7Australasian Kidney Trials Network,
University of Queensland, Brisbane, Australia. 8Translational Research Institute,
Brisbane, Australia.
Received: 4 August 2019 Accepted: 9 October 2019
References
1.
Ye H, Zhou Q, Fan L, Guo Q, Mao H, Huang F, Yu X, Yang X. The impact of
peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis
patients. BMC Nephrol. 2017;18(1):186.
2.
Manera KE, Johnson DW, Craig JC, Shen JI, Ruiz L, Wang AY, Yip T, Fung
SKS, Tong M, Lee A, et al. Patient and caregiver priorities for outcomes in
peritoneal dialysis: multinational nominal group technique study. Clin J Am
Soc Nephrol. 2019;14(1):74–83.
3.
Manera KTA, Craig J, Shen J, Jesudason S, Cho Y, Sautenet B, Teixeira-Pinto
A, Howell M, Wang A, Brown E, Brunier G, Perl J, Dong J, Wilkie M, Mehrotra
R, Pecoits-Filho R, Naicker S, Dunning T, Scholes-Robertson N, Johnson DW.
Developing consensus-based outcome domains for trials in peritoneal
dialysis: an international Delphi survey. Kidney Int. 2019;96(3):699–710.
4.
Dong J, Li Z, Xu R, Chen Y, Luo S, Li Y. Disease severity score could not
predict the outcomes in peritoneal dialysis-associated peritonitis. Nephrol
Dial Transplant. 2012;27(6):2496–501.
5.
Xu R, Chen Y, Luo S, Li Y, Dong J. The influence of duration of peritoneal
dialysis therapy on the outcomes of initial and subsequent peritonitis is
different. Perit Dial Int. 2012;32(4):473–6.
6.
Pi HC, Ren YP, Wang Q, Xu R, Dong J. Serum 25-hydroxyvitamin D level
could predict the risk for peritoneal dialysis-associated peritonitis. Perit Dial
Int. 2015;35(7):729–35.
7.
Qin W, Judith B, Beth P, Linda F. Albumin at the start of peritoneal dialysis
predicts the development of peritonitis. Am J Kidney Dis. 2003;41(3):664–9.
8.
Jie D, Yanjun L, Ying X, Rong X. Daily protein intake and survival in patients
on peritoneal dialysis. Nephrol Dial Transplant. 2011;26(11):3715–21.
9.
Dong J, Chen Y, Luo S, Xu R, Xu Y. Peritoneal protein leakage, systemic
inflammation, and peritonitis risk in patients on peritoneal dialysis. Perit Dial
Int. 2013;33(3):273–9.
10.
Kato S, Chmielewski M, Honda H, Pecoits-Filho R, Matsuo S, Yuzawa Y,
Tranaeus A, Stenvinkel P, Lindholm B. Aspects of immune dysfunction in
end-stage renal disease. Clin J Am Soc Nephrol. 2008;3(5):1526–33.
11.
Singer RF. Vitamin D in dialysis: defining deficiency and rationale for
supplementation. Semin Dial. 2013;26(1):40–6.
12.
Mehrotra R, Kermah D, Budoff M, Salusky IB, Mao SS, Gao YL, Takasu J, Adler
S, Norris K. Hypovitaminosis D in chronic kidney disease. Clin J Am Soc
Nephrol. 2008;3(4):1144–51.
13.
Sterling KA, Eftekhari P, Girndt M, Kimmel PL, Raj DS. The immunoregulatory
function of vitamin D: implications in chronic kidney disease. Nat Rev
Nephrol. 2012;8(7):403–12.
Zhang et al. Trials          (2019) 20:657 
Page 6 of 7

14.
Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011;7(8):
337–45.
15.
Lang PO, Samaras N, Samaras D, Aspinall R. How important is vitamin D in
preventing infections? Osteoporos Int. 2013;24(5):1537–53.
16.
Jat KR. Vitamin D deficiency and lower respiratory tract infections in
children: a systematic review and meta-analysis of observational studies.
Trop Dr. 2017;47(1):77–84.
17.
Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-
hydroxyvitamin D level and upper respiratory tract infection in the Third
National Health and Nutrition Examination Survey. Arch Intern Med. 2009;
169(4):384–90.
18.
Camargo CA Jr, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K,
Sumberzul N, Rich-Edwards JW. Randomized trial of vitamin D
supplementation and risk of acute respiratory infection in Mongolia.
Pediatrics. 2012;130(3):e561–7.
19.
Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J,
Decallonne B, Bouillon R, Decramer M, Janssens W. High doses of vitamin D
to reduce exacerbations in chronic obstructive pulmonary disease: a
randomized trial. Ann Intern Med. 2012;156(2):105–14.
20.
Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K,
Hrobjartsson A, Mann H, Dickersin K, Berlin JA, et al. SPIRIT 2013 statement:
defining standard protocol items for clinical trials. Ann Intern Med. 2013;
158(3):200–7.
21.
ClinicalTrials.gov [https://www.clinicaltrials.gov/ Accessed 1 July 2019].
22.
The effects of oral vitamin D supplementation on the prevention of
peritoneal dialysis-related peritonitis [https://www.clinicaltrials.gov/ct2/
show/NCT03264625?term=NCT03264625&rank=1 Accessed 1 July 2019].
23.
ScienceOpen [https://www.scienceopen.com Accessed 1 July 2019].
24.
Li PK, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, Johnson
DW, Kuijper EJ, Lye WC, Salzer W, et al. Peritoneal dialysis-related infections
recommendations: 2010 update. Perit Dial Int. 2010;30(4):393–423.
25.
Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, Suzana S,
Jeyaseelan L, Christopher DJ, Smieja M, et al. Adjunctive vitamin D for
treatment of active tuberculosis in India: a randomised, double-blind,
placebo-controlled trial. Lancet Infect Dis. 2015;15(5):528–34.
26.
Levin A, Tang M, Perry T, Zalunardo N, Beaulieu M, Dubland JA, Zerr K,
Djurdjev O. Randomized controlled trial for the effect of vitamin D
supplementation on vascular stiffness in CKD. Clin J Am Soc Nephrol. 2017;
12(9):1447–60.
27.
Bhan I, Dobens D, Tamez H, Deferio JJ, Li YC, Warren HS, Ankers E, Wenger
J, Tucker JK, Trottier C, et al. Nutritional vitamin D supplementation in
dialysis: a randomized trial. Clin J Am Soc Nephrol. 2015;10(4):611–9.
28.
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.
29.
McGuire S. U.S. Department of Agriculture and U.S. Department of Health
and Human Services, Dietary Guidelines for Americans, 2010. 7th Edition,
Washington, DC: U.S. Government Printing Office, January 2011. Adv Nutr.
2011;2(3):293–4.
30.
Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-
analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):
1730–7.
31.
Alvarez J, Wasse H, Tangpricha V. Vitamin D supplementation in pre-dialysis
chronic kidney disease: a systematic review. Dermatoendocrinology. 2012;
4(2):118–27.
32.
Armas LA, Andukuri R, Barger-Lux J, Heaney RP, Lund R. 25-Hydroxyvitamin
D response to cholecalciferol supplementation in hemodialysis. Clin J Am
Soc Nephrol. 2012;7(9):1428–34.
33.
Rudnicki M, Kerschbaum J, Hausdorfer J, Mayer G, Konig P. Risk factors for
peritoneal dialysis-associated peritonitis: the role of oral active vitamin D.
Perit Dial Int. 2010;30(5):541–8.
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