Pediatr Nephrol (2018) 33:111–116
DOI 10.1007/s00467-017-3767-4
ORIGINAL ARTICLE
Combination therapy of rituximab and mycophenolate
mofetil in childhood lupus nephritis
Julien Hogan 1 & Astrid Godron 2 & Véronique Baudouin 1 & Theresa Kwon 1 &
Jérôme Harambat 2 & Georges Deschênes 1 & Olivier Niel 1
Received: 23 January 2017 / Revised: 8 July 2017 / Accepted: 10 July 2017 / Published online: 5 August 2017
# IPNA 2017
Abstract
Background In clinical trials, the addition of rituximab (RTX)
to the combination therapeutic regimen of mycophenolate mo-
fetil (MMF) and corticosteroids failed to improve outcome in
lupus nephritis (LN). However, recent data suggest that RTX
may have steroid-sparing beneficial effects with an efficacy
similar to that of conventional regimens. We report our expe-
rience with RTX in the treatment of children with LN.
Methods Patients treated with RTX for first occurrence of LN
class III to V were enrolled in the study. Treatment consisted
of methylprednisolone pulse (500 mg/m2) followed by RTX
(1000 mg/1.73 m2) at days 1 and 15, and MMF (1200 mg/m2/
day). Prednisolone tapering and withdrawal was left to the
physician’s discretion. Complete remission (CR) was defined
as a urine protein-to-creatinine ratio (U Pr/Cr) of <5 mg/mg
and normal serum creatinine, and partial remission (PR) as a U
Pr/Cr of <30 mg/mg and a <15% rise in serum creatinine over
baseline.
Results Twelve patients were included in the study, with me-
dian follow-up of 23.7 [interquartile range (IQR) 12.8–33.5]
months. Median age of the patients was 13.6 [12.3–15.1]
years, median proteinuria was 32 [19–67] mg/mg and median
estimated glomerular filtration rate was 76.1 [59.3–97.7] mL/
min/1.73 m2. Median CD20 depletion duration was 10 [6.8–
* Julien Hogan
julien.hogan@aphp.fr
1
Pediatric Nephrology Department, Robert Debré Hospital,
Assistance publique–Hôpitaux de Paris (APHP), Paris, France
2
Pediatric Nephrology Unit, Pellegrin-Enfants Hospital–Bordeaux
University, Bordeaux, France
11.0] months. Prednisolone was rapidly tapered, with median
dose of 0.3 [0.15–0.41], 0.10 [0.09–0.16] and 0.0 [0.0–0.04]
mg/kg/day at 3, 6 and 12 months respectively. At 3 months,
three and seven patients achieved CR and PR, respectively; at
6 and 12 months all patients achieved remission (9 CR, 3 PR)
and none relapsed during follow-up. Five infectious compli-
cations were observed, including three varicella-zoster virus
(VZV) infections.
Conclusions In our pediatric patients with LN, therapy with
RTX + MMF combined with a rapid decrease in steroid ap-
pears to have been an efficacious treatment for severe LN but
was associated with high rate of VZV infection. The potential
of RTX to allow complete steroid avoidance warrants further
investigation in children.
Keywords Lupus nephritis . Children . Rituximab . Steroid
minimization
Introduction
Lupus nephritis (LN) is a rare condition in pediatric patients,
with an estimated annual incidence of 0.32 patients per
100,000 children younger than 16 years [1]. Evidence for
the optimal management of pediatric LN is lacking.
Currently, the usual management regimen of LN in adults
includes an induction therapy with steroids and either cyclo-
phosphamide (CYC) or mycophenolate mofetil (MMF) [2],
and a maintenance therapy with steroids in association with
MMF [3]. Among pediatric patients, CYC has been shown
to be effective both for induction and maintenance therapy
[4], but it is associated with major side effects, such as
myelotoxicity, gonadotoxicity and an increased risk of sec-
ondary malignancy. Sundel et al. reported in a pediatric ran-
domized controlled trial that induction and maintenance
112
therapy with MMF was as effective as intravenous CYC
followed by maintenance therapy with azathioprine [5].
However, all protocols reported to date include prolonged
treatment with steroids, which is associated with numerous
side effects and which especially affects growth in the pediat-
ric population. Recently, many authors have emphasized the
issue of cardiovascular complications in patients treated for
juvenile-onset LN as being the major cause of decreased
life-expectancy [6]. Intima-media thickness and left ventricu-
lar mass were found to be increased in children with LN when
compared with healthy controls [7], with the major risk factor
being steroid exposure [8]. Abnormal bone mineralization [9]
and impaired statural growth are also major issues in pediatric
LN patients that are worsened by steroid treatment. Thus,
strategies aimed at decreasing the dosing and duration of ste-
roid treatment need to be evaluated.
During the last decade, an increasing number of case re-
ports and small case series have reported rituximab (RTX)
treatment outcomes in LN patients, including children
[10–12], ultimately leading to the LUNAR trial that compared
the combination therapy of high-dose steroids + MMF with
that of high-dose steroids + MMF + RTX [13]. Add-on RTX
treatment did not significantly improve the response rates at
1 year, which were selected as the primary endpoint, even
though it tended to increase the overall response rate and
allowed a statistically significant improvement in serum com-
plement C3 and C4, as well as a reduction in anti-double-
stranded DNA levels that was associated with reduced pro-
teinuria. Thus, the results of the trial are still being debated,
and a recent meta-analysis focusing on RTX in patients with
refractory LN suggest that RTX effectively induces remission
of LN in patients who do not achieve remission with standard
therapies [14].
Pepper et al. reported on a cohort of patients initially treated
with steroids before the development of LN class III/IV/V
who were subsequently treated with RTX and MMF followed
by MMF maintenance therapy and steroid reduction or with-
drawal. The addition of RTX to the treatment regimen allowed
steroid withdrawal or reduction in one-third of patients [15].
These authors subsequently treated 50 patients in a prospec-
tive observational study with two doses of RTX and methyl-
prednisolone on days 1 and 15 and maintenance therapy with
MMF without steroids, with an excellent response rate of 90%
of patients achieving complete remission (CR) or partial re-
mission (PR) [16]. Therefore, the major interest in using RTX
in the treatment of LN might be to avoid steroid therapy—a
feature which is of high importance for pediatric patients.
Based on those findings, we started to use RTX in our
patients with pediatric LN in order to allow a rapid decrease
and withdrawal of steroids. We retrospectively reviewed pe-
diatric patients treated in two French centers who received
RTX and MMF with the aim to shorten treatment with
steroids.
Pediatr Nephrol (2018) 33:111–116
Methods
The study cohort comprised incident patients with a first oc-
currence of LN stage III, IV or V on kidney biopsy and who
had received RTX treatment in the pediatric nephrology de-
partments of Robert Debré Hospital (Paris) and Bordeaux
University Hospital, respectively, between 2006 and 2015.
Treatment involved a methylprednisolone pulse (500 mg/
1.73 m2) followed by RTX (1000 mg/1.73m2) at days 1 and
15, and MMF at a dose of 1200 mg/m2/day, as previously
described [15]. Tapering and withdrawal of prednisolone
was left to the discretion of each treating physician. CR was
defined as a urine protein-to-creatinine ratio (U Pr/Cr) of
<5 mg/mg and estimated glomerular filtration rate (eGFR) of
≥70 mL/min/1.73 m2, and PR as a U Pr/Cr of <30 mg/mg and
no increase in serum creatinine level of >15% of baseline. B-
cells were considered to be depleted when the CD20 count
was <10/mm3. Antibiotic prophylaxis with sulfametoxazol–
trimethoprine was given during B-cell depletion. Clinical and
biological parameters are reported as the median and inter-
quartile range (IQR) for continuous variables and absolute
number and percentage for binary variables. Daily protein
excretion was estimated using U Pr/Cr on a random urine
sample and eGFR was estimated using the recently published
Full Age Spectrum formula, which allows a continuous esti-
mation of GFR from childhood into adulthood and has been
found to be more accurate in patients with higher GFR [17].
The study protocol was approved by the Ethics committee of
our institution.
Results
Twelve patients were treated with RTX (10 girls and 2 boys)
with a median age of 13.6 [IQR 12.3–15.1] years and a medi-
an follow-up time of 23.7 [12.8–33.5] months. In terms of
ethnicity of the patient cohort, four were Caucasian, three
were Asian, three were Caribbean, one was north African
and one was black African. Renal presentation involved pro-
teinuria (median 32 [19–67] mg/mg) and hematuria; seven of
the 12 patients had impaired renal function (mean GFR 76.1
[59.3–97.7] ml/min/1.73 m2). Renal biopsy revealed that five,
one, one, two and three patients had LN stage IV III, V, IV + V
and III + V, respectively. Nine patients presented with extra-
renal involvement (6 with skin eruptions, 6 with arthritis, 6
with hematological signs and 2 with pericardial effusions).
The median Systemic Lupus Erythematosus Disease
Activity Index (SLEDAI) score was 16 [14–18] at baseline.
Patient characteristics at baseline are presented in Table 1.
Median duration of CD20 depletion was 10 [6.8–11.0]
months. One patient required a third RTX injection at 1 month
to enter full depletion. At 6 months, five patients had a detect-
able CD20 count, of whom four received an additional
Pediatr Nephrol (2018) 33:111–116 113

Table 1 Patient characteristics at baseline

Patient Age (years) Gender LN U P/Cr (mg/ Serum albumin Creatininemia eGFR (mL/min/
number classification mg) (g/L) (μmol/L) 1.73 m2)

P1 10.4 Female IV + V 71 19.6 53 91.1

P2 13.5 Male III + V 8 24.6 43 129.8
P3 12.4 Female V 24 24.7 68 78.9
P4 13.7 Female III + V 115 29.1 49 113.9
P5 12.0 Female IV 5 31.1 75 71.5
P6 17.4 Male IV + V 12 27.5 79 97.8
P7 15.1 Female IV 25 24.2 99 61.8
P8 10.8 Female IV 107 26.1 66 73.2
P9 12.6 Female IV 66 14.0 104 51.6
P10 15.3 Female IV 21 25.9 136 45.0
P11 18.1 Female III + V 47 25.1 67 97.7
P12 14.8 Female III 38 29.0 120 48.3
Median [IQR] 13.6 32 [19–67] 25.5 [24.5–27.9] 71.5 [61.7–100.3] 76.1 [59.3–97.7]
[12.3–15.1]

LN, Lupus nephritis; U P/Cr, urine protein-to-creatinine ratio; eGFR, estimated glomerular filtration rate; IQR, interquartile range

injection of RTX. Prednisolone was rapidly tapered so that the
median dose was 0.3 [0.15–0.41], 0.10 [0.09–0.16], 0.0 [0.0–
0.04] mg/kg/day at 3, 6 and 12 months, respectively. Seven
patients were off steroids at 12 months. MMF treatment was
ongoing in all patients at the last follow-up.
At 3 months, three patients had achieved CR and 7 PR. The
remaining two patients who had not achieved remission still
had nephrotic range proteinuria but no renal failure, and biop-
sy revealed that one of these patients also had LN class V. At 6
and 12 months all patients had achieved remission (9 CR and
3 PR) (Table 2). Three patients had a control biopsy that
showed an improvement of the lesion, but with some remain-
ing immunoglobulin G (IgG) subepithelial staining in patients
with associated LN class V. Among the 12 patients, seven still
had detectable anti-DNA antibodies and five still had some
complement activation at 12 months. One patient with nega-
tive anti-DNA at 12 months had a reappearance of anti-DNA
at last-follow-up without clinical relapse. Median SLEDAI
score at 12 months decreased to 3 [0–4]. Seven patients had
a follow-up of longer than 2 years, none experienced renal
relapse. Overall, the patients maintained their statural growth,
with a median change in height of 0 [−0.5 to 0] standard
deviation over the 1-year treatment period. Five infectious
complications were observed: one patient with septic shock,
one patient with pneumonia and patients with 3 varicella-
zoster virus (VZV) infections. Considering the bacterial infec-
tions, the septic shock occurred 1 month after starting
the treatment, and the patient presented a low CD4 level of
316/mm 3 , no detectable CD20 cells and a persistent
hypergammaglobulinemia (37 g/L), while the patient with
pneumonia presented 2 years after treatment initiation with
normal CD4, CD20 counts and IgG levels. Considering the
three patients with VZV-related infections, two occurred early
in the course of the disease, with a varicella 3 weeks after
treatment initiation in which the CD4 count was 670/mm3,
and a zoster 8 weeks after treatment initiation where the
CD4 count was 310/mm3. One zoster infection was observed
14 months after treatment initiation where the CD4 count was
412/mm3 and the CD20 count was 51/mm3. All these patients
had previously presented varicella during childhood or had a
positive serology; none had hypogammaglobulinemia.
Finally, one patient presented a pancreatitis likely secondary
to sulfametoxazol–trimethoprine treatment that was reversible
after drug withdrawal. No other extra renal complications
were noted.
Discussion
We report a successful strategy of treatment that avoids long-
term steroid therapy in pediatric patients with LN. All 12
patients treated achieved at least PR at 6 months and 1 year.
Although the low number of patients precludes statistical
comparisons, our results are at least as good as the results
found in the Italian pediatric Systemic Lupus Erythematosus
(SLE) cohort by Ruggiero et al. who reported a 70.1% remis-
sion rate, including 30.8% in CR at 6 months, and an 83.2%
remission rate, including 53.3% in CR at 12 months [18].
Moreover, we only included patients with severe LN (stage
III to IV), and mean GFR at baseline was lower in our patients
than in the Italian cohort (76 vs. 104 mL/min/1.73 m2,
respectively).
Despite the course of the disease generally being more
severe in children than in adults, the outcome of children with
114 Pediatr Nephrol (2018) 33:111–116

Table 2 Patient outcome at 3, 6 and 12 months of follow-up

Patient At 3 months At 6 months At 12 months

number
U P/Cr eGFR mL/min/ Remission U P/Cr eGFR (mL/min/ Remission U P/Cr eGFR (mL/min/ Remission
mg/mg 1.73 m2 statusa (mg/mg) 1.73 m2) status (mg/mg) 1.73 m2) status

P1 11 126.1 PR 15 120.1 PR 13 105.1 PR

P2 2 126.8 CR 1 123.3 CR 2 159.4 CR
P3 7 99.4 PR 3 88,0 CR 3 83.5 CR
P4 45 136.1 0 7 115.9 PR 23 152.9 PR
P5 1 94.1 CR 1 90.9 CR 1 107.5 CR
P6 4 99 PR 7 92.5 PR 3 97 CR
P7 12 56.1 PR 2 88.6 CR 1 78.9 CR
P8 35 126.1 0 3 136.3 CR 1 111.2 CR
P9 27 114.1 PR 4 97.9 CR 3 112.6 CR
P10 8 92.7 PR 3 97.1 CR 13 121.7 PR
P11 24 139.3 PR 5 163.6 CR 1 131 CR
P12 4 71.1 CR 3 109.2 CR 2 110 CR
Median 1 [4–25] 106.8 3 [3–5] 103.6 2 [1–6] 110.6
[ICR] [93.8–126.3] [92.1–120.9] [103.1–124.0]

CR, Complete remission; PR, partial remission

a
At 3 months, 3 had achieved CR and 7 PR; the remaining 2 patients (0) had not achieved remission at this time point, with nephrotic range proteinuria
but no renal failure

LN has greatly improved in the past three decades, with an
increase in the 5-year renal survival from 52% in 1985 to 91%
nowadays [12]. Current guidelines recommend the use of in-
travenous low-dose CYC or oral MMF as induction treatment
followed by an adjunct treatment with either MMF or azathi-
oprine [19]. In terms of the use of steroids, although guidelines
aim at decreasing cumulative glucocorticoid doses, they still
recommend three methylprednisolone pulses of 500–750 mg,
followed by oral prednisone 0.5 mg/kg/day for 4 weeks, ta-
pering to ≤10 mg/day by 4–6 months, followed by low-dose
prednisone (5–7.5 mg/day) as part of the adjunct treatment.
Although guidelines state that gradual drug withdrawal, glu-
cocorticoids first, can then be attempted, there is no agreement
on the timing for withdrawal, and the great majority of patients
remain on glucocorticoid treatment at 1 year. In our study, the
majority of patients were off steroids at 1 year, and the other
patients were receiving lower doses than have been previously
reported in pediatric studies (mean ± standard deviation
0.03 ± 0.04 vs. 0.63 ± 0.36 mg/kg in the Italian cohort).
Prolonged corticosteroid use is associated with increased
risk of premature cardiovascular disease and a two- to fourfold
increased risk of coronary events in SLE [20]. Steroids
also significantly impact statural growth in children, as
underlined by the benefit of steroid-free regimens in pediatric
transplanted patients who display a significant improvement
in growth compared with patients on steroids [21]. Finally,
cosmetic changes associated with prolonged steroid use may
contribute to non-adherence increasing the risk of treatment
failure [22]. These disadvantages of steroid use led Lightstone
and colleagues to use RTX not as an Badd-on^ drug to standard
therapy, but as a steroid-sparing agent [16]. These authors
developed the treatment protocol that we used in our patients,
but without any oral steroid, and treated 50 consecutive adult
patients, who displayed a good outcome with an overall re-
mission rate of 86% (52% with CR and 34% with PR) [16].
They also demonstrated a good safety profile of this treatment,
with only five infectious complications requiring hospitaliza-
tion, all of which responded to treatment [16]. In our patients,
we observed five infectious complications among 12 patients,
of which three were VZV infections, including two
reactivations as zoster and one primary infection as varicella.
Rothwell et al. reported an increased risk of VZV infection in
pediatric renal transplant patients treated with MMF, an in-
creased incidence of VZV infections during the first year
post-transplantation, from 1.4 to 15.8%, after MMF was
added to the treatment regimen [23]. Limited data on the risk
of VZV infections associated with RTX are currently avail-
able. Moreover, all our patients had detectable serum anti-
VZV IgG antibodies or a previous history of varicella in child-
hood, and none of them had hypogammaglobulinemia.
However, cases of varicella have been reported in adult pa-
tients with B-cell lymphoma treated with RTX-containing
chemotherapy [24]. It could be hypothesized that the use of
RTX induces an impaired humoral response against VZV that,
together with the use of MMF, may explain the high rate of
VZV infection found in our cohort. This high rate of infection
Pediatr Nephrol (2018) 33:111–116
has to be taken into account, and further studies in children are
needed to assess the risk of infection associated with this ther-
apeutic strategy.
Our study has a number of limitations due to its retrospec-
tive design and the small sample size that precludes the com-
parison of our results with those found in patients with stan-
dard therapy. Moreover, the relatively short follow-up time
precludes conclusions on the efficiency of this treatment to
prevent relapses later in the course of the disease. However,
our results, obtained using a standardized protocol, seem at
least as good as those published in other cohorts of pediatric
LN on a short-term follow-up. Long-term follow-up of those
patients will also be of great interest in order to assess the
ability of RTX to decrease the rate of relapse.
Conclusion
The addition of RTX to MMF in induction treatment of severe
LN in children may allow the rapid tapering and withdrawal of
steroids with an excellent remission rate. The long-term effect
of this strategy on the risk of relapse and on treatment side
effects, including infections, impaired growth and cardio-
vascular status, remains to be assessed. As the results of the
RITUXILUP trial in adult patients are awaited, further studies
assessing the safety of this strategy and the possibility of oral
steroid avoidance regimens in the treatment of childhood LN
are still needed.
Compliance with ethical standards The study protocol was approved
by the Ethics committees of the participating institutions.
Disclosures None to report.
References
1. Mackie FE, Kainer G, Adib N, Boros C, Elliott EJ, Fahy R, Munro
J, Murray K, Rosenberg A, Wainstein B, Ziegler JB, Singh-Grewal
D (2015) The national incidence and clinical picture of SLE in
children in Australia—a report from the Australian Paediatric sur-
veillance unit. Lupus 24:66–73
2. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill
JT, Petri M, Gilkeson GS, Wallace DJ, Weisman MH, Appel GB
(2005) Mycophenolate mofetil or intravenous cyclophosphamide
for lupus nephritis. N Engl J Med 353:2219–2228
3. Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D,
Eitner F, Appel GB, Contreras G, Lisk L, Solomons N (2011)
Mycophenolate versus azathioprine as maintenance therapy for lu-
pus nephritis. N Engl J Med 365:1886–1895
4. Lehman TJ, Onel K (2000) Intermittent intravenous cyclophospha-
mide arrests progression of the renal chronicity index in childhood
systemic lupus erythematosus. J Pediatr 136:243–247
5. Sundel R, Solomons N, Lisk L (2012) Efficacy of mycophenolate
mofetil in adolescent patients with lupus nephritis: evidence from a
two-phase, prospective randomized trial. Lupus 21:1433–1443
115
6. Quinlan C, Marks SD, Tullus K (2016) Why are kids with lupus at
an increased risk of cardiovascular disease? Pediatr Nephrol 31:
861–883
7. Sozeri B, Deveci M, Dincel N, Mir S (2013) The early cardiovas-
cular changes in pediatric patients with systemic lupus erythemato-
sus. Pediatr Nephrol 28:471–476
8. Quinlan C, Kari J, Pilkington C, Deanfield J, Shroff R, Marks SD,
Tullus K (2015) The vascular phenotype of children with systemic
lupus erythematosus. Pediatr Nephrol 30:1307–1316
9. Alsufyani KA, Ortiz-Alvarez O, Cabral DA, Tucker LB, Petty RE,
Nadel H, Malleson PN (2005) Bone mineral density in children and
adolescents with systemic lupus erythematosus, juvenile dermato-
myositis, and systemic vasculitis: relationship to disease duration,
cumulative corticosteroid dose, calcium intake, and exercise. J
Rheumatol 32:729–733
10. Marks SD, Patey S, Brogan PA, Hasson N, Pilkington C, Woo P,
Tullus K (2005) B lymphocyte depletion therapy in children with
refractory systemic lupus erythematosus. Arthritis Rheum 52:
3168–3174
11. Nwobi O, Abitbol CL, Chandar J, Seeherunvong W, Zilleruelo G
(2008) Rituximab therapy for juvenile-onset systemic lupus erythe-
matosus. Pediatr Nephrol 23:413–419
12. Pereira T, Abitbol CL, Seeherunvong W, Katsoufis C, Chandar J,
Freundlich M, Zilleruelo G (2011) Three decades of progress in
treating childhood-onset lupus nephritis. Clin J Am Soc Nephrol
6:2192–2199
13. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-
Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G
(2012) Efficacy and safety of rituximab in patients with active pro-
liferative lupus nephritis: the lupus nephritis assessment with ritux-
imab study. Arthritis Rheum 64:1215–1226
14. Weidenbusch M, Rommele C, Schrottle A, Anders HJ (2013)
Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus
nephritis. Nephrol Dial Transplant 28:106–111
15. Pepper R, Griffith M, Kirwan C, Levy J, Taube D, Pusey C,
Lightstone L, Cairns T (2009) Rituximab is an effective treatment
for lupus nephritis and allows a reduction in maintenance steroids.
Nephrol Dial Transplant 24:3717–3723
16. Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M,
Cairns TD, Lightstone L (2013) Prospective observational single-
centre cohort study to evaluate the effectiveness of treating lupus
nephritis with rituximab and mycophenolate mofetil but no oral
steroids. Ann Rheum Dis 72:1280–1286
17. Pottel H (2017) Measuring and estimating glomerular filtration rate
in children. Pediatr Nephrol 32:249–263
18. Ruggiero B, Vivarelli M, Gianviti A, Benetti E, Peruzzi L, Barbano
G, Corona F, Ventura G, Pecoraro C, Murer L, Ghiggeri GM,
Pennesi M, Edefonti A, Coppo R, Emma F (2013) Lupus nephritis
in children and adolescents: results of the Italian collaborative
study. Nephrol Dial Transplant 28:1487–1496
19. Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I,
Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F,
Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG,
Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga
M, Schneider M, Starra A, Tesar V, Vasconcelos C, van
Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D,
Boumpas DT (2012) Joint European league against rheumatism
and European renal association-European dialysis and transplant
association (EULAR/ERA-EDTA) recommendations for the man-
agement of adult and paediatric lupus nephritis. Ann Rheum Dis
71:1771–1782
20. Nikpour M, Urowitz MB, Ibanez D, Harvey PJ, Gladman DD
(2011) Importance of cumulative exposure to elevated cholesterol
and blood pressure in development of atherosclerotic coronary ar-
tery disease in systemic lupus erythematosus: a prospective proof-
of-concept cohort study. Arthritis Res Ther 13:R156
116
21. Zhang H, Zheng Y, Liu L, Fu Q, Li J, Huang Q, Liu H, Deng R,
Wang C (2016) Steroid avoidance or withdrawal regimens in
Paediatric kidney transplantation: a meta-analysis of randomised
controlled trials. PLoS One 11:e0146523
22. Masood S, Jayne D, Karim Y (2009) Beyond immunosuppression -
challenges in the clinical management of lupus nephritis. Lupus 18:
106–115
23. Rothwell WS, Gloor JM, Morgenstern BZ, Milliner DS (1999)
Disseminated varicella infection in pediatric renal transplant
Pediatr Nephrol (2018) 33:111–116
recipients treated with mycophenolate mofetil. Transplantation 68:
158–161
24. Okamoto A, Abe A, Okamoto M, Kobayashi T, Inaguma Y, Tokuda
M, Yanada M, Morishima S, Kanie T, Yamamoto Y, Tsuzuki M,
Mizuta S, Akatsuka Y, Yatsuya H, Yoshikawa T, Emi N (2014) A
varicella outbreak in B-cell lymphoma patients receiving rituximab-
containing chemotherapy. J Infect Chemother 20:774–777