Persistent lupus activity in systemic lupus erythematosus dialyisis patients of Chinese
origin
Jessica Choi Ang
Division of Nephrology, Department of Medicine, Kuang Tien General Hospital ,
Taiwan.
Corresponding author: Jessica Choi Ang, MD.
Address: Division of Nephrology, Department of Medicine, Kuang Tien General
Hospital , 286, Kuang Tien Road, Taichung 403, Taiwan.
Tel: 886-4-23425045
Fax: 886-4-23425099
E-mail: jchang1964@hotmail.com
Running Title: Persistent lupus activity in SLE Dialysis Patients
Abstract
Aims: To assess whether serological lupus activity is reduced in systemic lupus
erythematosus(SLE) dialyisis patients of Chinese origin.
Methods: This was a retrospective analysis of Chinese patients with SLE who are
followed in a single hospital, Taiwan. The serological lupus activity of SLE were
studied during end-stage renal disease(ESRD) before and after the institution of dialysis.
Controls consisted of fifty-four age and sex matched patients in the clinic with lupus
nephritis who had not developed renal insufficiency. We measured anti-nuclear antibody,
serum complement 3 , and anti-double-stranded DNA levels. Patients were followed for
at least 1 year after the institution of dialysis therapy or until their death.
Results: We collected twenty-seven patients, 8 males and 19 females. The mean age was
36.1±2.3 years. Seven patients were undergoing peritoneal dialysis, the others
hemodialysis. There was a significant decrease of serological lupus activity in ESRD
with respect to controls. However, the serological lupus activity did not decrease
significantly after dialysis. Five patients died during the followup period, most of them
of sepsis. The mortality rate was 5/27( 18.5%)
Conclusion: Chinese Patients with SLE who develop ESRD may exhibit a fall in
serological lupus activity, although this continues after dialysis.
Key Words: Systemic lupus erythematosus, end-stage renal diseases, dialysis, Lupus
autoimmunity, Chinese
Introduction
Whether lupus activity decreases in lupus patients who reach end-stage renal
disease (ESRD) has been investigated by many researchers.[1-10] Most reports
suggested that the clinical activity of systemic lupus erythematousus (SLE) was
quiescent in most patients with ERSD under regular dialysis.[1-7] However, there are
different reports indicating that a moderate degree of extrarenal disease activity does
persist in these patients. [8-11] The literature reports mainly Caucasians. Recently
Krane et al [11] reported that SLE did not always burn out in patients who reached
ESRD, although not all patients with SLE leading to ESRD continue to manifest active
lupus. The data from their series of lupus patients who underwent dialysis suggested
that black race was an important independent variable in the renal and overall prognosis
of patients with lupus nephritis.[11] Besides, most studies assessed the lupus activity by
the flare of clinical manifestations of SLE, although some
clinical events could be
misleading. For example, pericarditis or pleuritis may have occurred because of uremia
or dialysis rather than the lupus flares. Fever could have been erroneously attributed to
lupus rather than infection. On the contrary, serological data such as level of
anti-nuclear antibody(ANA), serum complement 3 (C3 ), and anti-double-stranded DNA
(anti-dsDNA) may provide better evidence of lupus activity in these patients. In order to
evaluate the possibility that there might be a subgroup of patients in whom SLE does
not burn out when they develop ESRD, a single center without the confounding effects
of racial diversity is necessary. Therefore, a retrospective study to evaluate the
serological lupus activity before and after the dialysis in Chinese end-stage lupus
nephritis patients was performed.
Patients and Methods
Patients selection
The medical records of all patients with SLE and ESRD who received Dialysis
(defined as Group I) at Veteran General Hospital, Kaohsiung, Taiwan, from Oct 1, 1990
to Sep. 30 2001, were selected by a computer base registration system. The lupus
nephritis controls (Group II) were selected as the age and sex matched patients in the
clinic with a history of lupus nephritis who had not developed renal insufficiency. In
these control , lupus nephritis had been documented by renal biopsy. Thorough review
of medical records was undertaken in each patient. Twenty-seven patients, all of whom
met at least four criteria of the American Rheumatism Association for SLE [12], form
the cohort of this report. All patients of this study had been receiving dialysis for at least
six months.
Methods of assessment
The demographic data including sex, age at the time of study, age at the time of
SLE diagnosis and ESRD was collected by chart review. The evidence of laboratory
markers of lupus activity included levels of ANA, serum C3 , and anti-dsDNA before
the institution of dialysis therapy. The serum C3 were checked by nephelometry (Dade
Behring, Marburg, Germany). The anti-dsDNA antibodies were detected by
enzyme-linked immunosorbent assay. Hypocomplementemia was defined as serum C3
lower than 72 µg/dL The serological lupus activity was also assessed over a 3-month
period after the institution of dialysis. Patients were followed for at least 1 year after the
institution of dialysis therapy or until their death. Fifty four lupus nephritis patients
were selected as controls and assessed in the same way ( serological lupus activity).
Statistical analysis
To detect any difference in baseline characteristics between those ESRD patients
before dialysis and those without renal insufficiency (lupus nephritis controls), Fisher’s
exact test was used for categorical variables, while the nonparametric Mann-Whitney
test was used for continuous variables. The paired and unpaired Student’s t-test were
used to compare paired data and between groups, respectively. All numerical variables
were expressed as meanone standard deviation(SD). A P-value of less than 0.05 was
considered statistically significant. Analysis was performed using SPSS software.
Results
There were twenty-seven patients with SLE and ESRD, 8 males and19 females.
(Group I, n=27). Seven patients were undergoing peritoneal dialysis, the other patients
were undergoing hemodialysis. Fifty four lupus nephritis patients without renal
insufficiency were selected as controls (Group II, n=54). Pertinent demographic data are
listed in Table 1. There were no significant differences between groups concerning sex,
age at the time SLE diagnosis and at the time of study, and duration of disease. An
average time of 6 years elapsed from the diagnosis of lupus nephritis and the
development of ERSD. These patients had a mean age of 31 years when dialysis was
initiated, and they were studied, on average, two years later. The serological lupus
activity between SLE in ESRD patients and lupus nephritis controls are shown in table
2. There was a significant decrease of serological lupus activity in ESRD as compared
to controls. The serological lupus activity in the period before and after the institution of
dialysis therapy are shown in table 3. Serological lupus activity continued in the
majority of patients. There was no significant difference in serum C3 level or
anti-dsDNA titer before and after dialysis. Five out of twenty-seven patients with SLE
in ESRD died during the Follow-up period, one male and four females. Their age
ranged from 19 to 42 years. The duration of dialysis ranged from 12 months to 8 years.
The serological lupus activity was elevated. Four of them died of sepsis, one died of a
cardiovascular event. The mortality rate was 5/27( 18.5%)
Discussion
ESRD is a major contributing factor to morbidity and mortality in patients
with SLE. As dialysis therapy became routine for all patients with ESRD, their
survival improved significantly. With prolonged survival, it was observed that lupus
activity decreased despite reduced immunosuppressive treatment. Fries et al [1] were
the first to call attention on the effects of ESRD on the clinical course of SLE. A
comparison of early (near-normal renal function with lupus nephritis) and late (initiation
of dialysis therapy) specific lupus symptoms in 13 SLE patients revealed marked
clinical and serological improvement, such that the diagnosis of SLE could not be made,
at the time of dialysis, without knowing prior history. Since that time, there have been
authors reporting minimal lupus activity in SLE patients undergoing chronic dialysis.
[2-7] Jarrett et al[2] reported minimal lupus activity in their 14 patients undergoing
hemodialysis, most of whom had reduced lupus activity after beginning dialysis.
Five-year survival, however, was lower in their lupus patients compared with the
general dialysis population, and this was attributed to infectious and vascular-access
complications. However, there are conflicting reports demonstrating that a moderate
degree of extrarenal disease activity does persist [9-10]. Nossent et al [10] reported,
from the Dutch SLE Registry, the Dutch experience with 55 patients treated with either
hemodialysis or peritoneal dialysis. Both the need for immunosuppression and overall
extrarenal disease activity were reduced, but not abolished, after initiation of dialysis.
The hypothesis of there may be a subgroup of patients in whom SLE does not burn out
when they develop ESRD prompted our study.
This study has several unique reasons. First, most studies assessed the lupus
activity by the flare up of clinical manifestations of SLE. There might be some potential
bias when ambiguous clinical events are considered, like pericarditis or pleuritis, which
might have occurred because of uremia or dialysis. There have been no prospective
studies performed to our knowledge. Since serological markers represent a more
objective measurement of disease activity, it seems logical to use lupus serological data
such as level of anti-nuclear antibody (ANA), serum complement 3 (C3 ), and
anti-double-stranded DNA (anti-dsDNA) as unequivocal evidence of lupus activity.
Secondly, the most previous literatures described mainly Caucasian people. Some
researchers proposed there may be a subgroup of patients in whom SLE does not burn
out when they develop ESRD. Is it the racial factors that makes the different prognosis
in patients with lupus nephritis? Krane et al [11] reported that black race was an
important independent variable in the renal and overall prognosis of patients with lupus
nephritis. The data from their series of lupus patients who underwent dialysis suggested
that that lupus activity may persist in patients with ESRD. It is speculated that the study
population, 84% of whom were black women, may represent a subgroup of patients
with lupus in whom the disease remains active, even after they have developed ESRD.
The patients in this study were all Chinese and received regular follow-up at a single
center. Though it is a retrospective study, it can still highlight the serological lupus
activity before and after the dialysis in Chinese end-stage lupus nephritis patients. Last,
our study showed that the major cause of mortality in patients with SLE and ESRD was
represented by infectious complications. Moreover, the serological lupus activity were
high and four of them died of sepsis. Since none of the four patients had received
high-potency cytotoxic drugs or high dose corticosteroid therapy, it is unlikely that the
immunosuppressive therapy predisposed them to serious infection. From the standpoint
of persistent low serum complement level, one might consider the possibility of
immunological trigger activity or exhaustion, that requires further studies.
The limitation of this study included the method of retrospective study, the
abscence of the concomitant clinical activity index, and the small sample size. It would
be ideal to include more patients in a prospective cohort study and correlate
simultaneous symptoms with serological study. More study about the pathogenesis of
different serological and/or clinical lupus activity among different subgroup of SLE
patients are also needed in the future.
In summary, the precise relationship between ESRD and SLE activity remains
incompletely understood, although it is expected that most Western patients with
advancing renal disease may experience a significant decline in SLE activity. Chinese
patients with SLE who develop ESRD continue to display evidence of serological lupus
activity after dialysis, although some degree of reduction is demonstrable. Such patients
require careful long term followup to prevent the possibility of sepsis.
References
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Jarrett MP, Santhanam
S, Del Greco F. The clinical course of end-stage renal
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Rodby RA, Korbet SM, Lewis EJ. Persistence of clinical and serological activity in
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Table 1. Demographic details of SLE on chronic dialysis patients and lupus nephritis
controls
Group I(n=27)
Age at the time of SLE 26.1±2.2
Group II(n=54)
p
25.4  2.2
NS
35.4  2.3
N
diagnosis (years)
Age at the time of study 36.1±2.3
(years)
Male: Female
8:19
16: 38
NS
Disease duration(years)
8.2±2.2
7.8 2.2.5
NS
Age at diagnosis of ESRD 30.8±2.2
Group I: SLE with end-stage renal disease patients
Group II: lupus nephritis controls with a history of lupus nephritis who had not
developed renal insufficiency.
Data are expressed as mean  one SD.
SLE:systemic lupus erythematousus
NS = no statistical significance.
Table 2. Serological lupus activity between SLE in ESRD patients and lupus nephritis
controls
Serological lupus
Lupus
nephritis
controls SLE in ESRD patients
activity
(n=54)
(n=27)
Positive ANA
100%
77.8%*
Mean ANA titer
333
172
Decreased serum C3
100%
37.0*
Elevated anti-ds DNA 100%
29.6*
level
SLE= systemic lupus erythematousus, ESRD = end-stage renal disease
ANA= anti-nuclear antibody, anti-dsDNA = anti-double-stranded DNA
*P-value less than 0.05
Table 3. Serological lupus activity before and after dialysis in 27 SLE patients on
chronic dialysis
Serological lupus activity Before dialysis
After dialysis
Positive ANA
77.8%
74.1%
Mean ANA titer
172
160
Decreased serum C3
37.0
40.7
29.6
26.0
level
Elevated anti-ds DNA
SLE= systemic lupus erythematousus, ANA= anti-nuclear antibody, anti-dsDNA =
anti-double-stranded DNA