Nephrol Dial Transplant (2014) 29: 698–705
doi: 10.1093/ndt/gft377
Advance Access publication 5 September 2013
Original Articles
Divided dosing reduces prednisolone-induced hyperglycaemia
and glycaemic variability: a randomized trial after kidney
transplantation
Christopher J. Yates1,2, Spiros Fourlanos1,2, Peter G. Colman1,2 and Solomon J. Cohney3,4
Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, VIC, Australia, 2Department of Diabetes and
Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, Australia, 3Department of Nephrology, Royal Melbourne Hospital, Melbourne,
VIC, Australia and 4Department of Medicine, NorthWest Academic Centre, University of Melbourne, St Albans, VIC, Australia
Correspondence and offprint requests to: Christopher Yates; E-mail: [email protected]
1.0 versus 1.2, P = 0.039), CONGA-2 (1.2 versus 1.4, P = 0.008)
and J-index (25 versus 31, P = 0.003).
Conclusions. Split prednisolone dosing reduces glycaemic
variability and hyperglycaemia early post-kidney transplant.
A B S T R AC T
Background. Prednisolone is a major risk factor for hyperglycaemia and new-onset diabetes after transplantation. Uncontrolled observational data suggest that divided dosing may
reduce requirements for hypoglycaemic agents. This study
aims to compare the glycaemic effects of divided twice daily
(BD) and once daily (QD) prednisolone.
Methods. Twenty-two kidney transplant recipients without
diabetes were randomized to BD or QD prednisolone. Three
weeks post-transplant, a continuous glucose monitor (iPro2®
Medtronic) was applied for 5 days with subjects continuing
their initial prednisolone regimen (Days 1–2) before crossover
to the alternative regimen. Mean glucose, peak glucose, nadir
glucose, exposure to hyperglycaemia (glucose ≥7.8 mmol/L)
and glycaemic variability were assessed.
Results. The mean ± standard deviation (SD) age of subjects
was 50 ± 10 years and 77% were male. Median (interquartile
range) daily prednisolone dose was 25 (20, 25) mg. BD prednisolone was associated with decreased mean glucose (mean
7.9 ± 1.7 versus 8.1 ± 2.3 mmol/L, P < 0.001), peak glucose
[median 10.4 (9.5, 11.4) versus 11.4 (10.3, 13.4) mmol/L, P <
0.001] and exposure to hyperglycaemia [median 25.5 (14.6,
30.3) versus 40.4 (33.2, 51.2) mmol/L/h, P = 0.003]. Median
glucose peaked between 14:55–15.05 h with BD and 15:25–
15:30 h with QD. Median glycaemic variability scores were decreased with BD: SD (1.1 versus 1.9, P < 0.001), mean amplitude of glycaemic excursion (1.5 versus 2.2, P = 0.001),
continuous overlapping net glycaemic action-1 (CONGA-1;
© The Author 2013. Published by Oxford University Press
on behalf of ERA-EDTA. All rights reserved.
Keywords: hyperglycaemia, new-onset diabetes, prednisolone, transplant
INTRODUCTION
Since the advent of solid organ transplantation, glucocorticoids have been a core component of immunosuppressive regimens [1, 2]. The short elimination half-life of prednisolone (3
h) dictates that daily dosing cannot achieve steady-state
plasma levels, and is likely to be exerting little or no effect in
the second half of the day [3, 4]. An uncontrolled observational study in 16 kidney transplant recipients suggested that
divided daily dosing may produce superior immunosuppressive efficacy with less requirement for diabetes medication [5].
Divided daily dosing may also reduce glycaemic variability, a
factor linked with increased oxidative stress and β-cell dysfunction [6]. The preference for daily (or even alternate daily)
dosing of prednisolone stems largely from a desire to reduce
the suppression of the hypothalamic–pituitary–adrenal axis
and the development of Cushing’s syndrome [7]. However,
even prolonged use of low dose morning prednisolone (5–10
mg) has been associated with inadequate adrenal response to
synacthen, indicating that suppression of the hypothalamic–
pituitary–adrenal axis should be anticipated in all kidney
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1
transplant patients on maintenance doses of ≥5 mg [8–10].
This prospective randomized crossover study used continuous
glucose monitoring (CGM) to compare glycaemic profiles of
kidney transplant recipients taking divided twice daily (BD)
versus once daily (QD) prednisolone and to determine
whether BD reduces hyperglycaemia and glycaemic variability
compared with QD dosing.
M AT E R I A L S A N D M E T H O D S
This study was undertaken in consenting subjects receiving a
kidney transplant at the Royal Melbourne Hospital between
October 2011 and August 2012. The study was approved by
the Melbourne Health Human Research Ethics Committee.
Glucose monitoring
The Medtronic iPro™ 2 CGM system was used with Medtronic Enlite™ glucose sensors placed on the abdomen (Medtronic, Northridge, CA, USA). This system records an average
interstitial fluid glucose measurement every 5 min for 6 days.
The measurements were blinded to patient and at study
Glycaemic end points
The predetermined study outcomes were mean interstitial
fluid glucose, the time and magnitude of peak and nadir interstitial fluid glucose, glycaemic variability and exposure to hyperglycaemia. The latter was defined as the area under the
concentration–time curve (AUC) where glucose concentration
exceeded 7.8 mmol/L, corresponding with the consensus
American Diabetes Association and World Health Organization definition for impaired glucose tolerance after transplantation [12]. Glycaemic variability was assessed using standard
deviation (SD), mean amplitude of glycaemic excursion
(MAGE), continuous overlapping net glycaemic action
(CONGA-1 and -2) and the J-index.
Sleep disturbance
As a subjective increase in wakefulness is frequently reported by subjects taking glucocorticoids, the validated Athens
F I G U R E 1 : Study protocol. Subjects remained on their randomized prednisolone dosing regimen for Days 1 and 2 before crossover on Day 3
to the alternative dosing regimen. CGM was commenced on Day 1 and removed after Day 5. Day 3 was disregarded as a wash-out period.
BD steroid improves post-transplant glycaemia
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ORIGINAL ARTICLE
Crossover study design
Using sequentially numbered opaque sealed envelopes generated by a third party, subjects were randomized by study
investigators to QD (8:00 h) or BD (50% of total daily dose at
8:00 h and 50% at 20:00 h) prednisolone dosing regimens at
the time of transplantation. Prednisolone doses were then adjusted by the transplant team until Week 3 when the total
daily dose was fixed for a 5-day study period. Dietary and exercise habits were recorded in a diary. Subjects remained on
their initial dosing regimen for Days 1 and 2 before crossover
on Day 3 to the alternate dosing regimen, i.e. BD to QD or QD
to BD (Figure 1). Glucose levels from the ‘wash-out period’ on
Day 3 were disregarded. The Medtronic iPro™2 CGM system
was placed on Day 1 prior to the morning prednisolone dose
at 8:00 h and removed after 8:00 h on Day 6. Therefore, 2 days
of CGM on each dosing regimen were available for comparison (Days 1–2 versus 4–5).
Immunosuppression
Subjects received basiliximab induction and an initial dose
of 500 mg of methylprednisolone prior to kidney transplantation. Maintenance immunosuppression comprised of tacrolimus, mycophenolate and prednisolone, with recipients of
living donor transplants commencing treatment 2–3 days
prior to surgery. Prednisolone was maintained at 20–25 mg
daily during the first 4 weeks post-transplant. Target tacrolimus trough levels were 8–12 ng/mL for the first 2 weeks and
5–8 ng/mL by 4 weeks post-transplant.
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Subjects
Subjects were aged between 18 and 75 years old and had a
fasting plasma glucose assessment prior to transplantation to
exclude those with pre-existing diabetes.
conclusion these were downloaded using the Medtronic CareLink® iPro™ software. The CGM was calibrated with four fingerstick capillary glucose tests per day ( prior to meals and at
bedtime) using the Abbott Optium Xceed™ blood glucose
monitoring system (Abbott Laboratories, Abbott Park, IL,
USA). The subjects documented capillary blood glucose test
results were verified using the Optium Xceed™ device
memory. Clarke error grid analysis of Enlite sensor glucose
versus gold standard plasma glucose indicates that, over a
range of 4.5–22.2 mmol/L, >97% of Enlite sensor readings are
within the clinically accurate A + B zones [11]. Between 2.2
and 4.4 mmol/L, over 80% of Enlite sensor readings are within
the clinically accurate A + B zones. The sensor is robust and
accurate over 6 days of continuous use, and mean time lag
compared with plasma glucose is 7.94 ± 6.48 min (95% confidence interval 6.38, 9.50 min) [11].
Power calculation
There were no prior trials comparing glycaemia with QD
and BD prednisolone on which to base power calculations. We
therefore extrapolated from data reported by the UK Prospective Diabetes Study, which indicated that a reduction in
HbA1c of 0.9% was associated with a 12% reduction in any
diabetes-related end point and a 25% reduction in microvascular complications [14]. The A1c-Derived Average Glucose
(ADAG) study confirmed that a linear relationship exists
between estimated average daily glucose and HbA1c [15]. Applying the ADAG equation, a difference in HbA1c of 0.9%
correlates with that in blood glucose of 1.4 mmol/L. For power
calculations in this pilot study, a clinically important difference in mean glucose was therefore considered to be 1.4
mmol/L; and in the absence superior data, this was also considered to represent a clinically important difference in peak
glucose. Assuming this and estimating a SD of 2 mmol/L on
changing regimens, 22 subjects were needed for this study
(based on 90% power and two-sided α = 0.05).
Data analysis
Descriptive statistics used were percentages for categorical
data, mean ± SD for normally distributed continuous data and
median (interquartile range, IQR) for non-normally distributed continuous or ordinal data. Paired and unpaired t-tests
were used to detect the differences in glycaemia and glycaemic
variability between BD and QD dosing regimens. The Wilcoxon rank test was used to detect differences in ordinal data
between dosing regimens. Area under the glucose concentration-–time curve was measured using the trapezoidal rule.
Results were calculated using GraphPad Prism version 6.0a for
Mac OS X, GraphPad Software (La Jolla, CA, USA). P–values
of <0.05 were considered statistically significant.
R E S U LT S
Thirty-four subjects were randomized at the time of transplantation to commence BD (n = 17) or QD prednisolone (n = 17),
with 22 (11 in each arm) completing the study (Figure 2). All
subjects were Caucasian, 77% were male and median (IQR)
age was 49 (46, 57) years (Table 1). The median prednisolone
F I G U R E 2 : Participant flow.
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C.J. Yates et al.
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ORIGINAL ARTICLE
Insomnia Scale was used to assess sleep disturbance after two
nights on each dosing regimen for all subjects [13]. This scale
includes five questions in the domains of sleep induction, nocturnal awakenings, final awakening, total sleep duration and
overall quality of sleep. Each question has four possible
answers scored between 0 and 3, producing a score range
between 0 for no insomnia and 15 for severe insomnia.
Table 1. Characteristics of kidney transplant recipients studied (N = 22)
Age (years)
Male, n (%)
Prednisolone dose (mg/day)
Body weight at transplantation (kg)
Body weight at study commencement (kg)
Caucasian, n (%)
Aetiology of kidney failure
Glomerulonephritis, n (%)
Polycystic kidney disease, n (%)
Vesicoureteric reflux, n (%)
Others, n (%)
Transplant number
1, n (%)
Transplant type
Cadaveric donor, n (%)
Living donor, n (%)
Tacrolimus level (BD prednisolone) (ng/mL)
Tacrolimus level (QD prednisolone) (ng/mL)
Serum creatinine (μmol/L)
49 (46, 57)
17 (77)
25 (20, 25)
75 (64, 86)
75 (62, 85)
22 (100)
10 (45)
6 (27)
4 (18)
2 (9)
22 (100)
17 (77)
5 (23)
10.5 (8.4, 11.3)
10.5 (6.7, 12.5)
141 (101, 195)
Values are median (IQR).
In the early period after kidney transplantation, acute hyperglycaemia may lead to osmotic symptoms, dehydration and
acute renal impairment [16–20], while new-onset diabetes has
been associated with a 1.8-fold increase in cardiovascular mortality and a 1.5-fold increase in overall mortality [21]. Prednisolone is a major risk factor for hyperglycaemia and new-onset
diabetes after transplantation [12]. The pharmacokinetics of
prednisolone are notable for a short elimination half-life (3.0 h),
suggesting that divided daily dosing may be more appropriate
[3]. To explore this premise, patients without diabetes 3–4
weeks post-kidney transplant participated in a crossover study
of BD versus QD prednisolone dosing, with assessment of glycaemic profiles obtained by CGM. BD prednisolone dosing was
associated with a lower peak and mean interstitial fluid glucose,
a lower exposure to hyperglycaemia (AUC ≥7.8 mmol/L or
140 mg/dL) and less glycaemic variability.
Given the short half-life of prednisolone, it is somewhat
surprising that divided daily dosing has not been subjected to
more clinical trials. An uncontrolled observational study of
patients receiving prednisolone for glomerulonephritis
(n = 35) or renal transplantation (n = 16) reported equivalent
renal outcomes and a lower total daily dose in patients receiving BD dosing compared with a single morning dose (P =
0.008). Additional findings included the use of less concurrent
immunosuppression (mycophenolate and/or cyclosporine, P
= 0.017) and a reduced requirement for diabetes medication
(P = 0.032) [5]. Although the mean glucose level in our study
was only 0.2 mmol/L (3 mg/dL) lower with BD dosing, the
glycaemic profiles differed significantly between regimens
(Figures 3 and 4). Peak interstitial fluid glucose (median) was
1 mmol/L (18 mg/dL) greater with daily prednisolone administration and the majority of subjects (82%) developed diabetic
range results (≥11.1 mmol/L or 200 mg/dL) with this regimen,
compared with 50% with BD. Following daily administration
at 8:00 h, peak interstitial fluid glucose (median) was detected
∼7.5 h later. This is consistent with a study of 40 subjects
without diabetes receiving 30 mg prednisolone daily at 8:00 h
for an exacerbation of chronic obstructive airways disease,
where peak glucose of 11.3 mmol/L (204 mg/dL) occurred at
15:30 h [22]. In contrast, BD prednisolone dosing in the
current study (8:00 and 20:00 h) resulted in a peak interstitial
fluid glucose (median) at ∼15:00 h. Although nadir interstitial
fluid glucose (median) was 0.7 mmol/L lower with QD compared with BD prednisolone, overall exposure to glucose levels
within an abnormal range (AUC of ≥7.8 mmol/L or 140 mg/
dL) was 1.6-fold higher. Following 8:00 h prednisolone administration, median glucose levels were ≥7.8 mmol/L between
10:15 and 23:00 h.
Glycaemic variability has been associated with adverse outcomes and was significantly lower with BD compared with
daily prednisolone administration using all indices—SD,
MAGE, CONGA-1, CONGA-2 and J-index [23–25]. This may
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BD steroid improves post-transplant glycaemia
DISCUSSION
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dose at the time of the 5-day crossover study was 25 (20, 25)
mg, with 14 taking 25 mg/day and 8 taking 20 mg/day. The
median tacrolimus levels were equivalent during QD and BD
prednisolone dosing periods [QD 10.5 (6.7, 12.5) ng/mL, BD
10.5 (8.4, 11.3) ng/mL, P = 0.88]. During the study period, no
extraordinary dietary or exercise habits were noted.
The average glucose was lower with BD dosing compared
with daily dosing, mean 7.9 ± 1.7 versus 8.1 ± 2.3 mmol/L (P <
0.001) (Figure 3A). Peak glucose was lower with BD than daily
dosing, median 10.4 (9.5, 11.4) versus 11.4 (10.3, 13.4) mmol/
L (P < 0.001) (Figure 3B). Glucose levels of ≥11.1 mmol/L
(200 mg/dL) occurred in 18 of 22 (82%) subjects while taking
daily prednisolone, compared with 11 of 22 (50%) subjects
while taking BD prednisolone (P = 0.055). Nadir glucose was
lower with daily prednisolone, median 5.5 (4.7, 6.2) versus 6.2
(5.4, 6.7) mmol/L (P = 0.006) (Figure 3C). Exposure to glucose
concentrations of ≥7.8 mmol/L was lower with BD than daily
dosing, median 25.5 (14.6, 30.3) versus 40.4 (33.2, 51.2)
mmol/L/h (P = 0.003) (Figure 3D). Subgroup analyses of glycaemic end points limited to those initially commenced on
QD prednisolone and those initially commenced on BD prednisolone were consistent with the results of the entire cohort
(Table 2). Three cases of acute rejection occurred in the first
year post-transplant (in two subjects initially randomized to
QD and one initially randomized to BD prednisolone).
The median 24-h glycaemic profiles for BD and daily prednisolone dosing are illustrated in Figure 4. Following a single
dose of prednisolone at 8:00 h, median interstitial fluid glucose
increased to a peak of 10.4 mmol/L between 15:25 and 15:30 h
and decreased gradually to a nadir of 6.2 mmol/L between
06:20 and 06:30 h. In contrast, BD prednisolone dosing (8:00
and 20:00 h) produced a lower peak median interstitial fluid
glucose of 8.6 mmol/L between 14:55 and 15:05 h, with a
nadir of 7.0 mmol/L between 06:30 and 06:50 h. Glycaemic
variability was significantly lower with BD compared with
daily dosing as assessed by SD, MAGE, CONGA-1, CONGA2 and J-index (Table 3). Median (IQR) Athens insomnia scale
scores were not significantly different [BD 4.5 (2.0, 8.3) versus
QD 3.5 (0.8, 7.3), P = 0.129].
ORIGINAL ARTICLE
Table 2. Subgroup analyses of glycaemic end points
QD prednisolone
BD prednisolone
Pvalue
Subjects initially commenced on QD prednisolone (n = 11)
Mean glucose
8.1 ± 2.2
8.0 ± 1.7
0.946
(mmol/L/h)
Peak glucose
11.9 (10.7, 13.6)
10.5 (9.8, 12.0)
0.030
(mmol/L)
Nadir glucose
5.4 (4.9, 6.3)
6.2 (5.6, 7.0)
0.053
(mmol/L)
Glucose ≥ 7.8
34.9 (33.3, 55.5)
25.7 (13.1, 34.9) 0.042
(mmol/L)
Subjects initially commenced on BD prednisolone (n = 11)
Mean glucose
8.1 ± 2.4
7.9 ± 1.6
<0.001
(mmol/L/h)
Peak glucose
11.4 (10.1, 12.6)
9.9 (8.5, 11.3)
0.001
(mmol/L)
Nadir glucose
5.8 (4.6, 6.2)
6.2 (4.7, 6.7)
0.029
(mmol/L)
Glucose ≥ 7.8
42.6 (32.8, 50.1)
24.6 (18.6, 28.8) 0.005
(mmol/L)
Results are median (IQR) except mean glucose (mean ± SD).
be important, as glycaemic variability has been associated with
adverse outcomes. Both in vivo and in vitro studies have
suggested that glycaemic variability induces oxidative stress to
a greater extent than sustained hyperglycaemia, and this may
exacerbate chronic β-cell dysfunction [6]. Although not replicated in all studies, glycaemic variability has also been associated with complications of diabetes, including accelerated
atherogenesis and microalbuminuria [26–29].
It is believed that most prednisolone effects are mediated
through intracellular glucocorticoid receptor binding and
genomic signalling [3]. The glucocorticoid receptor–
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prednisolone complex is localized to the nucleus where dimerization is necessary for interaction with DNA sequences,
known as glucocorticoid response elements. Subsequent alterations in gene expression occur slowly (i.e. hours) and are
thought to explain some of the metabolic and anti-inflammatory effects of glucocorticoids, including hyperglycaemia [30,
31]. Our data suggest that these glycaemic effects occur predominantly within the initial 12 h after prednisolone dosing and
are greater with larger prednisolone doses.
While our study has focused on the reduction in hyperglycaemia obtained with divided dosing of prednisolone, small
studies have suggested that this may also enhance immunosuppressive effects [4, 32]. As daily dosing is associated with
the absence of measureable drug in the circulation for approximately half of the day, this could reduce its immunosuppressive and anti-inflammatory effects. Both Uhl et al. [32] and
Czock et al. [3] found that divided BD methylprednisolone
provided more sustained suppression of CD4+, CD8+ and
CD3+ lymphocytes in healthy volunteers. A study by Keller
and colleagues highlighted the potential importance of sustained exposure to prednisolone in controlling the alloimmune
response. Studying 40 kidney transplant recipients on daily
prednisolone, Keller and colleagues observed an association
between measured half-life of methylprednisolone and prevention of rejection. In the 18 patients with a rejection episode in
the first 6 months post-transplant, they noted a significantly
shorter half-life for methylprednisolone compared with the 22
who remained rejection free (2.5 versus 2.9 h, P = 0.03) [4].
Further studies are required examining both the therapeutic
and adverse effects of divided dosing of prednisolone compared with QD dosing, with a potential outcome being a
reduction in total daily dose [5].
C.J. Yates et al.
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F I G U R E 3 : Glycaemic end points: mean glucose (A), peak glucose (B), nadir glucose (C) and exposure to glucose ≥7.8 mmol/L (≥140 mg/dL)
(D) for QD prednisolone dosing and divided BD prednisolone dosing. Boxes indicate median (IQR) and error bars indicate range.
ORIGINAL ARTICLE
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F I G U R E 4 : Median 24-hour glycemic profiles for alternative prednisolone dosing regimens: daily at 08:00 (A), divided twice daily at 08:00 and
20:00 (B) and both profiles superimposed together (C), IQR indicated (shading).
The differing glycaemic profiles demonstrated with the two
prednisolone regimens has implications for strategies to screen
for hyperglycaemia in kidney transplant recipients receiving
BD steroid improves post-transplant glycaemia
prednisolone, and for the selection of hypoglycaemic therapies
in these patients. The diurnal impact of prednisolone on glycaemia, with morning nadir and afternoon peak, indicates that
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Table 3. Glycaemic variability with alternative prednisolone dosing
regimens
Test
QD prednisolone
BD prednisolone
P-value
Standard deviation
MAGE
CONGA-1
CONGA-2
J-index
1.9 (1.6, 2.0)
2.2 (1.9, 2.7)
1.2 (0.9, 1.3)
1.4 (1.3, 1.8)
31 (24, 38)
1.1 (0.8, 1.6)
1.5 (1.2, 1.9)
1.0 (0.8, 1.2)
1.2 (1.0, 1.5)
25 (22, 31)
<0.001
0.001
0.039
0.008
0.003
prednisolone doses, afternoon blood glucose would be a highly
sensitive screening test for hyperglycaemia. Dividing the prednisolone into morning and evening doses reduced peak
glucose, mean glucose, exposure to hyperglycaemia and glycaemic variability in the early period following kidney transplantation. The magnitude of these differences warrants the
performance of further studies in the future.
Values are median (IQR).
afternoon blood glucose testing would have greater sensitivity
than fasting blood glucose testing for the detection of hyperglycaemia during the early post-transplant period (Figure 4).
For patients requiring insulin, the glycaemic effects of daily
prednisolone dosing may be best managed with morning
administration of intermediate acting insulin (e.g. isophane),
while the glycaemic profile associated with BD prednisolone
would be best matched with a long-acting insulin, such as glargine or detemir [33–35]. Clearly, specific studies examining
the effects of divided dosing in transplant recipients with preexisting diabetes are required.
Insomnia is frequently reported among patients receiving
moderate-to-high dose glucocorticoids, and a single polysomnography study has demonstrated a very small increase in
Stage 2 sleep with slight rapid eye movement sleep suppression
[36]. There was some concern that taking a portion of prednisolone nocturnally may further aggravate sleep disturbance.
Despite this, we found no significant difference in Athens insomnia scale scores, although the study was insufficiently
powered to identify small differences.
We have demonstrated the effects of adopting divided prednisolone dosing over a relatively short period. While the
results are strictly applicable only to a Caucasian kidney transplant population on a calcineurin inhibitor-based immunosuppression regimen, they have significant implications for the
management of inflammatory diseases where higher doses of
prednisolone are often employed over a period of many weeks.
Interestingly, split dosing of prednisolone has been effective in
systemic vasculitis, rheumatoid arthritis, nephrotic syndrome,
temporal arteritis and Bell’s palsy [2, 37–39]. While blinding
in this study was limited by both clinicians and patients
needing to know dosages, bias was minimized by using the
blinded-to-patient iPro2 CGM device, and by asking subjects
to maintain usual dietary and exercise habits during the 5-day
study period, recording these in a diary. Clearly, further
studies are needed within and beyond the transplant setting.
Future studies examining glucocorticoid-based immunosuppression may also include the evaluation of preparations with
a more prolonged action. These may be able to deliver a more
sustained immunosuppression, with less glycaemic variability
despite infrequent dosing [40].
In conclusion, kidney transplant recipients receiving maintenance prednisolone as part of a calcineurin inhibitor-based
regimen experience peak glucose ∼7–8 h after morning prednisolone administration, with interstitial fluid glucose levels
often ≥11.1 mmol/L (200 mg/dL). This pharmacodynamic
pattern suggests that, in patients receiving moderate
704
C.J.Y. was involved in all aspects of this research. S.F., P.G.C.
and S.J.C. contributed to study design, data analysis and
manuscript writing. C.J.Y. is the guarantor of this manuscript.
AC K N O W L E D G E M E N T S
We sincerely thank to Alexandra Gorelik and the MelbEpiCentre for assistance with power calculations and data analysis.
Australian New Zealand Clinical Trials Registry:
ACTRN12612001302842.
FUNDING
This project was funded by a Royal Melbourne Hospital Home
Lottery grant-in-aid, a Novo Nordisk Regional Diabetes
Support Scheme grant and an Australian and New Zealand
Society of Nephrology-AMGEN Research grant.
C O N F L I C T O F I N T E R E S T S TAT E M E N T
The authors declare that the results presented in this paper
have not been published previously in whole or part, except in
abstract format. Medtronic provided Enlite glucose sensors for
use in this study. Abbott Diabetes provided Optium Xceed
blood glucose monitoring systems for use in this study. C.J.Y.
received a PhD stipend from an Australian Postgraduate
Award and the Nick Christopher Award, University of Melbourne/Royal Melbourne Hospital.
(See related article by Sever. Transplantation–steroids–
impaired glucose metabolism: a hope for improvement?
Nephrol Dial Transplant 2014; 29: 479–482.)
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ORIGINAL ARTICLE
AUTHORS’ CONTRIBUTION
Received for publication: 9.5.2013; Accepted in revised form: 26.7.2013
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BD steroid improves post-transplant glycaemia
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