Rheumatology, 2024, 63, 906–907
https://doi.org/10.1093/rheumatology/kead554
Advance access publication 17 October 2023
Editorial
Editorial
Outcome of lupus nephritis in children
This editorial refers to ‘Renal relapse in children and adoles-
cents with childhood-onset lupus nephritis: a 20-year study’,
by Chan et al. 2024;63:953–61.
Chan et al. [1] present, in this issue of Rheumatology, the
incidence of renal relapses in children with LN. They show
that relapses are common and importantly that they predict
the development of both end-stage kidney disease (ESKD) and
advanced kidney disease, defined as chronic kidney disease
(CKD) stages 3–5. Also importantly, achieving complete remis-
sion and the use of mycophenolate mofetil seemed to reduce the
chance of relapse.
This study is important, as our knowledge on how to best
treat children with LN is still scarce. The goal is to help chil-
dren to live normal productive lives with normal lifespans.
There is a balance between giving enough treatment to achieve
those goals and at the same time avoiding treatment-related
morbidity and mortality. It is thus important to define which
treatment goals are needed for long-term protection of the kid-
neys and the lives of these children. Is the goal of low disease
activity enough or do we need to achieve complete renal remis-
sion? And how do we define complete renal remission?
As a start, let us remind ourselves that LN class III–V in
children is a very serious condition. In untreated children, the
short- to moderate-term mortality is at least 50% [2]. The
prognosis was drastically changed when >50 years ago treat-
ment with steroids and CYC became available.
Important studies by Cameron et al. [3] at Guy’s Hospital in
London showed that children diagnosed during the 1960s and
1970s still had a 20% chance of dying during a 20-year follow-
up. The chance of ESKD was similarly high, with one in five
children needing dialysis or transplantation after 20 years [3].
This prognosis has gradually changed and both the mortal-
ity risk and renal survival have continued to improve. Data
from a renowned centre did, some 20 years ago, still show a
6% mortality and that 9% of the surviving children had devel-
oped ESKD. This was after a mean follow-up of 11 years [4].
Tektonidou et al. [5] studied the change in survival of chil-
dren with lupus between 1950 and 2016. They found, as
expected, major differences between high- and middle-/low-
income countries. At the end of that time period, the 10-year
chance of death was 3% and 21%, respectively [5].
Data on really long-term kidney survival in children is
much more scarce, if not non-existent. Oni et al. [6] summa-
rized five studies from the last 20 years. These studies all had
relatively short follow-up, with a mean between 3 and
20 years. ESKD was found in 1–15% of the children. A study
from north and central India showed an 8.2% mortality and
Accepted: 6 October 2023
C The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
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84% renal survival during 15 years of follow-up. Chan et al.
[7], from Hong Kong, reported on 92 children with a median
follow-up of 10.3 years. Two patients died, 3.2% developed
ESKD and further 5.4% advanced CKD.
What are the factors that can predict
long-term renal outcome?
We do not fully have that knowledge in children with renal lu-
pus. From the study in this issue of Rheumatology, complete
renal remission seemed to be of importance [1]. This makes a
lot of nephrological sense, as the degree of impairment of kid-
ney function and the degree of proteinuria in virtually all kid-
ney conditions strongly predicts the rate of further decline of
kidney function [8]. This seems to be true in both inflamma-
tory kidney diseases and in other kidney conditions where the
underlying condition in itself is stable. A typical example are
children with kidney malformations who gradually develop
worsening kidney function during their lives. Inherent mecha-
nisms mainly related to glomerular hyperfiltration seem to in-
dependently cause further impairment of kidney function
unrelated to the initial offending factor [8].
How do we define complete renal remission?
The definition of renal remission is far from uniform. We
used in a previous publication seven different previously used
definitions of renal remission in a cohort of 248 children [9].
Between 50 and 78.8% of the children were defined to be in
complete remission depending on the definition used.
We, and other recent studies by paediatric nephrologists,
have chosen to use an even stricter definition. With the aim of
achieving long-term kidney survival, we want the child to ob-
tain normal kidney function, defined as normal estimated glo-
merular filtration rate (eGFR), and to be free of proteinuria.
With this definition, only 25% of 382 children in an interna-
tional cohort achieved complete remission lasting >12 months
[10]. Similarly strong recommendations have also been advo-
cated for adult patients [11].
However, there is a problem with using this strict defini-
tion of complete remission. Proteinuria and/or impaired
eGFR can, in a child free of lupus symptoms, also signify
CKD. There is no other way than a repeat kidney biopsy to
differentiate ongoing renal lupus from kidneys scarred
from the, at that point, well-controlled LN. Per-protocol bi-
opsies have been advocated to reduce the number of renal
relapses.
Editorial
In summary, we need more long-term follow-up studies of
children with LN. We need to know the prognosis of children
who have had lupus for >10–20 years. This will give us fur-
ther knowledge on how strict the definition of complete re-
mission needs to be. The default paediatric nephrology
hypothesis, to be tested, is that our treatment goal should be a
child with normal kidney function free from proteinuria.
Data availability
All data are available in the article.
Authors’ contributions
K.T. and C.d.M. both conceptualized and wrote the editorial.
Funding
No specific funding was received from any bodies in the pub-
lic, commercial or not-for-profit sectors to carry out the work
described in this article.
Disclosure statement: The authors have declared no conflicts
of interest.
1, 2 cents with lupus nephritis. Rheumatology (Oxford) 2022;61:
Kjell Tullus * and Chiara De Mutiis
1
Paediatric Nephrology, Great Ormond Street Hospital for Children,
NHS Foundation Trust, London, UK
2
Paediatric Unit, Maggiore Hospital, Azienda USL, Bologna, Italy
*Correspondence to: Kjell Tullus, Paediatric Nephrology, Great
Ormond Street Hospital for Children, NHS Foundation Trust,
London WC1N 3JH, UK. E-mail: kjell.tullus@gosh.nhs.uk
907
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