Pediatric Nephrology (2019) 34:685–688

https://doi.org/10.1007/s00467-018-4127-8

ORIGINAL ARTICLE

Equations to estimate prednisone dose using body weight

Francesco Emma 1 & Giovanni Montini 2,3 & Antonio Gargiulo 1

Received: 19 July 2018 / Revised: 14 October 2018 / Accepted: 19 October 2018 / Published online: 27 October 2018
# IPNA 2018

Abstract
Background In the clinical practice, prednisone (PDN) dose in children is often prescribed using the patient weight, despite dose
calculation using body surface area (BSA) is assumed to be preferable, because it parallels better with PDN metabolism in human
subjects.
Methods Calculations based on body weight (W) carry the risk of underdosing, particularly in young children. Conversely, BSA
estimation requires knowing the patient height, which is not always available, and more complex calculations.
Results To overcome these limitations, we have developed linear equations allowing approximating the BSA-based dose using
only the patient weight in kilogram. To this end, we have used anthropomorphic data from 754 pediatric patients and have
validated the proposed equations with a prospective cohort of 77 children with steroid sensitive nephrotic syndrome. The
equation estimating a dose of 60 mg/m2 was [2 × W + 8] and the equation estimating a dose of 40 mg/m2 was [W + 11].
Conclusions Both equations performed very well and predicted reliably the BSA-based dose with an average error of 3.4% and
2.2%, respectively.

Keywords Idiopathic nephrotic syndrome . Body surface area

Introduction
Prednisone (PDN) remains the mainstay of treatment of the
first episode and for relapses of idiopathic nephrotic syndrome
(INS) in children. The first significant effort to define appro-
priate dosing of PDN for the treatment of the first episode of
INS is represented by the International Study of Kidney
Disease in Children (ISKDC) that proposed in 1979 to treat
all patients with 60 mg/m2/day of PDN for a period of 4 weeks,
followed by 4 weeks of treatment with 40 mg/m2 on alternate
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00467-018-4127-8) contains supplementary
material, which is available to authorized users.
* Francesco Emma
francesco.emma@opbg.net
1 trial to test two different PDN schemes for the treatment of
Department of Pediatric Subspecialties, Division of Nephrology,
Bambino Gesù Children’s Hospital – IRCCS, Piazza S. Onofrio 4,
00165 Rome, Italy
2
Department of Clinical Sciences and Community Health, University
of Milan, Milan, Italy
3
Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione
IRCCS Ca’Granda - Ospedale Maggiore Policlinico, Milan, Italy
days [1]. Since then, alternative schemes have been proposed
using different tapering modalities [2–4]. Similarly, protocols
have been proposed for the treatment of relapses [2–4]. In
principle, these patients should be seen by a healthcare pro-
vider before starting high-dose PDN. In most cases, PDN dose
is calculated using body surface area (BSA). In the clinical
practice, however, PDN is often prescribed based on body
weight, in particular if the patient cannot be seen in the med-
ical office to measure height. This often results in the prescrip-
tion of a lower dose of PDN, especially in young children [5]
and in children that are lean. Conversely, since BSA formulas
combine both height and weight to estimate surface area, the
impact of weight changes on BSA is reduced and the dose per
kilogram is often similar to the dose per square meter in obese
children. A similar remark applies to severely nephrotic chil-
dren, when doses are not calculated using dry weight.
Recently, the Italian Medicine Agency (AIFA) has sponsored
a nationwide multicentric open-label prospective randomized
relapses of INS (PROPINE study—EudraCT 2012-004326-
16). Due to protocol restrictions, PDN had to be prescribed by
phone immediately after relapse, before seeing the patient in
the medical office, using the patient weight that was measured
at home by parents. We developed therefore equations to ap-
proximate the BSA-based dose using only the patient weight.
686
In the month following randomization, patients were checked
by their referring physicians and BSA was calculated,
allowing comparing retrospectively the two dose calculations.
Methods
Overview
Patient weight, height, and age were obtained from several
Italian cohorts of children with renal diseases that had re-
ceived steroid treatment. These include 471 patients with
INS that have been collected at the Bambino Gesù
Children’s Hospital and in the NefroKid study, 203 children
with lupus nephritis or full-house nephropathy, and 80 chil-
dren with IgA nephropathy. The latter cohorts were used to
enrich the population with children of older age; some of these
cohorts have already been described [6–8]. The total number
of patients was 754, including 430 boys (67.5%) and 324 girls
(32.5%), with a mean age of 7.1 ± 2.3 years. In the majority of
cases, patients had no edema when their weight was mea-
sured. The validation cohort was represented by 77 patients
with nephrotic syndrome randomized in the PROPINE study.
Since proteinuria was detected by dipstick before significant
fluid accumulation, no patient had edema.
Calculation of the steroid dose
Steroid dose was first estimated based on BSA. BSA
(expressed in m2) was calculated using the following formulas,
where weight is expressed in kilogram and height in centimeter:
Mosteller formula [9]: BSA = ([H × W]/3600 )0.5
DuBois formula [10]: BSA = 0.20247 × (H/100)0.725 ×
W0.425
DuBois II formula [10]: BSA = 0.007184 × H0.725 ×
W0.425
Haycock formula [11]: BSA = 0.024265 × H0.3964 ×
W0.5378
Gehan and George formula [12]: BSA = 0.0235 ×
H0.42246 × W0.51456
Boyd formula [13]: BSA = 0.0003207 × H0.3 × (1000 ×
W)(0.7285 − ( 0.0188 × LOG(1000 × W))
As previously described [5], results were very similar be-
tween most formulas (supplementary figure 1). Therefore, the
commonly used Mosteller formula was used in the remaining
of the study.
In addition, steroid doses were also calculated based on
weight, using common approximations, namely 2 mg/kg,
which approximates a dose of 60 mg/m2 and two third of
the 2 mg/kg dose (i.e., 1.33 mg/kg), which approximates a
dose of 40 mg/m2.
Pediatr Nephrol (2019) 34:685–688
All weight and height values of this report are expressed in
kilograms and in centimeters, respectively.
Statistical analysis
Data were analyzed with SPSS 21.0.0.2 for windows. Data
distribution was assessed with the Kolmogorov-Smirnov test.
If a normal distribution was observed, data were compared
using the t test and are reported in the text as mean ± SD. If
not, data were compared with the Mann-Whitney U test and
are reported in the text as median and interquartile range. All
tests are two-sided and considered significant for p values <
0.05.
Results
New equations based on weight
Several equations were tested using linear and curvilinear
models to approximate steroid dose using the patient weight.
Linear equations were selected because of their simplicity,
which is particularly important in the clinical setting, and be-
cause the observed distribution was linear (see below).
Two equations were obtained to approximate a dose of
60 mg/m2 and 40 mg/m2 of PDN. The maximal PDN dose
was set to 70 mg for the 60 mg/m2 equation and to 60 mg for
the 40 mg/m2 equation. This led to exclude 278 and 122 chil-
dren for each of these two calculations, respectively, because
the calculated dose exceeded the maximal dose.
The final equations were as follows:
60mg=m2 ¼ 2  W þ 8
40mg=m2 ¼ W þ 11
Figure 1a, d shows scattered plots comparing the BSA-
based dose with the above formulas or with the 2 mg/kg and
1.33 mg/kg formulas. As expected, the latter equations under-
estimate the BSA-based dose, particularly in young children.
Conversely, the newly proposed equations provide a nearly
perfect estimate of the BSA-based dose, with a slight overes-
timation in older children for the 60 mg/m2 equation and for
younger children for the 40 mg/m2 equation.
The Bland-Altman plots in Fig. 1 c and f illustrate differ-
ences expressed as percent of the BSA-based dose. As shown,
the [2 × W + 8] equation, which approximates a dose of
60 mg/m2, overestimates on average the BSA-based dose by
3.4%. Overestimation rarely exceeded 11% (95th percentile).
For the [W + 11] formula, which approximates a dose of
40 mg/m2, the average overestimation was 2.2%, with a sim-
ilar error margin. Both formulas performed very well in
preventing dose underestimation. This is further illustrated in
panels b and f, which show the average dose of the entire
Pediatr Nephrol (2019) 34:685–688 687

Fig. 1 Comparison between

different methods for calculating
prednisone (PDN) dose. The left
(a, b, c) and right (d, e, f) panels
show results to approximate a
PDN dose of 60 mg/m2 and
40 mg/m2, respectively. Panels a
and d show the correspondence
between the body surface area
(BSA)-based dose and the
commonly used equations (gray
symbols) or the newly proposed
equations (black symbols). Panels
b and e show doses calculated for
each patient with the three
different methods; BMosteller^
indicate the BSA-based dose
using the Mosteller formula.
Panels c and f show the
Bland-Altman plots analyzing the
performance of the new equations

study population. There were no significant differences be- dose corresponding to 40 mg/m2 was 33 mg [29–42] when
tween doses calculated using patient’s BSA and doses estimat- calculated with the new formulas and 33 mg [28–43] when
ed with the new equations, contrary to doses calculated with calculated based on BSA (p = 0.84).
the common equations based on weight.

Validation cohort Simplified formulas

Further to the above results, an additional simplification can

The above data were prospectively validated in a cohort of
77 patients with relapses of nephrotic syndrome in which
the maximal daily induction dose was 60 mg, followed by
a maximal dose of 50 mg on alternate days. The break-
down by age was similar to the discovery cohort
(supplementary figure 2). The median dose of PDN for
an induction treatment of 60 mg/m2 was 51 mg [44–60]
when calculated with the new formulas, and 50 mg [42–60]
when calculated based on BSA (p = 0.65). The median
also be proposed:
60mg=m2 ¼ 2  W þ 10
40mg=m2 ¼ W þ 10
Using these latter equations, patients will receive an addi-
tional 2 mg of PDN when estimating the 60 mg/m2 dose and
1 mg less PDN when estimating the 40 mg/m2 of PDN, which
in the clinical practice could be acceptable.
688
Discussion
Most guidelines for the treatment of the first episode or for
relapses of INS recommend an initial dose of PDN of 60 mg/
m2 or, alternatively, 2 mg/kg of body weight. After achieving
remission, the dose is often lowered to 40 mg/m2 on alternate
days, or, alternatively, two third of the 2 mg/kg dose (i.e.,
1.33 mg/kg) on alternate days. Most schemes are adaptations
of the initial ISKDC proposal, in which PDN dose was calcu-
lated based on BSA. After intestinal absorption, a large pro-
portion of PDN is retained in the plasma, depending on pro-
tein levels, while the remaining diffuses in tissues to exert its
actions at the intracellular level [14]. The pharmacokinetics of
PDN varies considerably according to individual patient char-
acteristics, pathological states, and patient age [15, 16]. The
best method for calculating PDN dose in children with INS
has not been established yet. No significant differences were
observed in the remission rate at 6 months in an open-label
trial that randomized patients with newly onset or with relaps-
ing INS to receive either 2 mg/kg/day or 60 mg/m2/day of
prednisolone for 6 weeks, followed by 6 weeks of either
1.5 mg/kg or 40 mg/m2 on alternate days [17].
In the clinical practice, as well as in some clinical trials, the
initial dose of PDN for treating INS is frequently calculated as
2 mg/kg. In the recent Cochrane systematic review on corti-
costeroid therapy for INS in children for example, studies
using an initial PDN doses of 60 mg/m2/day and studies using
a dose of 2 mg/kg/day were pooled together in the same meta-
analysis [2].
Nonetheless, BSA- and weight-based doses are not entirely
equivalent, especially in small children [5, 18], which could
potentially require a higher dose to obtain the same biological
effect. The newly proposed equations represent a quick and
reliable method to calculate PDN dose using only the patient
weight, without the risk of underdosing in patients that have
normal or lean body mass.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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