Nephrol Dial Transplant (2012) 27: 627–632
doi: 10.1093/ndt/gfr327
Advance Access publication 18 July 2011
Effects of concomitant hepatitis C virus infection in patients with
underlying lupus nephritis on long-term renal outcome
Ahmed H. Mitwalli, Ashik Hayat, Jamal Alwakeel and Durdana Hammad
Department of Medicine, Division of Nephrology, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia
Correspondence and offprint requests to: Ashik Hayat; E-mail: ashikhayat@hotmail.com
Abstract
Background. Despite recent advances in the management
of lupus nephritis (LN), these unfortunate patients are at a
higher risk of developing chronic kidney disease (CKD).
Concomitant chronic hepatitis C virus (HCV) infection is
associated with adverse outcome in patients with LN and
further compounds the risk as some of these patients
choose to undergo kidney transplantation in the near future.
Objectives. The aim of the present study is to evaluate the
long-term impact of chronic HCV infection in patients with
underlying Class IV LN on renal function, progression to
end-stage renal disease (ESRD) and patient survival.
Methods. Retrospective analysis of the medical records of
134 nondialysis-dependent patients with biopsy-proven
World Health Organization Class IV LN with chronic HCV
infection was done from January 1995 to January 2008 at King
Khalid University Hospital, Riyadh, Saudi Arabia. Primary
and the secondary end points were death or the development
of ESRD. The patients were followed over a period of 6.7 6
3.3 (1–14.4) years.
Results. From a total of 134 biopsy-proven Class IV LN
patients, 15 (11.2%) patients were HCV positive of which 2
(13.3%) patients were male and 13 (86.7%) patients were fe-
male. One hundred and nineteen (88.8%) patients were HCV
negative of which 17 (14.3%) were male and 102 (85.7%) were
female. The mean age was 32.47 6 11.8 years. Eight (53.3%)
patients in the HCV-positive group versus 19 (22.6%) patients
in the HCV-negative group progressed to severe renal impair-
ment with serum creatinine >350 lmol/L (P ¼ 0.024). A total
of 8 (53.3%) patients in the HCV-positive group versus 18
(17.3%) in HCV-negative group progressed to ESRD
(P ¼ 0.005). The mean creatinine clearance was higher
(43.3 6 33 mL/min) in the HCV-negative LN group at last
follow-up than in the HCV-positive patients (25 6 34.9 mL/
min) with a statistically significant P-value of 0.0463. Five
patients (33.3%) with HCV-positive LN died in comparison
to eight (7.6%) patients who were HCV negative P ¼ 0.03;
however, the cause of hospital mortality was mainly cardio-
vascular disease (CVD) and infection and none of the patients
died of chronic liver disease, although there was significant
deterioration of the liver function at the end of the study. Ka-
plan–Meier survival estimates showed a significantly inferior
renal function and rapid deterioration to ESRD in LN patients

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with concomitant HCV infection, with a dialysis free survival
of 95 and 80% for the HCV-negative group and 90 and 65% for
the HCV-positive groups at the end of 5 and 10 years respec-
tively, with a highly significant P-value of <0.05 at the end of
10 years.
Conclusion. The present study highlights that concomitant
HCV infection in patients with LN is associated with worse
renal outcome, higher rate of progression to ESRD and
reduced patient survival.
Keywords: end-stage renal disease; hepatitis C virus infection; lupus
nephritis; renal outcome
Introduction
Chronic hepatitis C virus (HCV) infection is a global health
problem affecting >170 million people all over the world and
is responsible for >1 million deaths due to cirrhosis and
hepatocellular carcinoma [1, 2]. Multiple extra hepatic man-
ifestations including kidney disease can be caused by HCV
infection [3]. Both chronic HCV infection and chronic kidney
disease (CKD) are common and are potentially serious med-
ical health problems throughout the world and in recent years,
it has become clear that these two conditions are linked in
several important ways [4–7]. HCV infection is said to be a
silent killer and is associated with increased cardiovascular
mortality in end-stage renal disease (ESRD) patients on he-
modialysis (HD) [8–11]. In a large study of 448 renal trans-
plant patients, Mitwalli et al. [12] found that HCV infection
was a major predictor of adverse renal outcome and nega-
tively influenced graft and patient survival.
Despite improvements in the management of lupus
nephritis (LN), these patients remain at a high risk of
developing ESRD with an estimated incidence of 15%
[13–16]. Since some immunosuppressive medications used
for treating the LN patients inhibits cell-mediated immun-
ity, these patients are prone to viral infection and in turn
viral proliferation and liver damage. The Kidney Disease:
Improving Global Outcomes guidelines recommend that all
patients with CKD and those initiating HD should be rou-
tinely screened for HCV infection [17]. Although clinical
guidelines regarding the management of chronic HCV
628
infections in patients with systemic lupus erythematosus
have been published in 2009, there is still a lack of data
regarding the long-term impact of HCV infection in pa-
tients with underlying LN [18, 19].
Materials and methods
Study design and study population
This retrospective observational study was carried at the King Khalid
University hospital affiliated with the King Saud University, Riyadh,
between January 1995 and January 2008.
Inclusion criteria
New incident biopsy proven Class IV LN patients aged >18 years were
included into the study, all patients who had previously received dialysis or
were currently on dialysis were excluded from the study. Complete history
including age, sex, ethnicity and comorbidities e.g. hypertension, diabetes
mellitus, chronic obstructive pulmonary disease, stroke or history of coro-
nary artery disease were recorded at the time of enrollment into the study. A
complete physical examination including pulse, blood pressure (BP) with
postural drop, peripheral edema, body mass index and systemic examination
were also recorded at the time of enrollment into the study. The laboratory
parameters including complete hemogram, renal function tests like blood
urea, serum creatinine, serum calcium, serum phosphate, serum sodium,
serum potassium, serum magnesium, complete liver profile including serum
bilirubin, serum alanine aminotransferase (ALT), serum aspartate amino-
transferase (AST), alkaline phosphatase, parathyroid hormone level, hepa-
titis B surface antigen and 24-h urine protein measurement were recorded at
baseline and then every 3 months thereafter. All patients were screened for
HCV infection at the time of enrollment into the study and were classified
into HCV-positive and HCV-negative groups. Assessment of HCV status
was done by using enzyme-linked immunosorbent assay (ELISA) test fol-
lowed by recombinant immunoblot assay in all patients. Those patients who
were detected to be positive for either test underwent polymerase chain
reaction (PCR) testing using an amplicor amplification kit (Roche diagnos-
tic, Neuilly, France) according to the manufacturer’s instructions [20]. High-
risk patients such as those who had received a blood transfusion, healthcare
workers or other high-risk groups underwent PCR even when they were
ELISA negative. The patients were followed up over a period of 6.7
3
years, range of 1–14.4 years. The primary and secondary outcomes meas-
ures studied were death or the development of ESRD.
Treatment for LN
Both groups of patients received induction therapy with intravenous meth-
ylprednisolone 1 g daily for 3 days followed by oral prednisolone 1 mg/kg
body weight which was progressively tapered to ~10 mg daily at the end of
6 months and intravenous cyclophosphamide 1 g/1.73 m2 monthly for 6
months and then was replaced by oral azathioprine 2 mg/kg daily there-
after for a period of at least 2 years after the last relapse as per the standard
hospital protocol, in addition to supportive therapy for BP and lipid ab-
normalities based on the physicians discretion. None of the HCV-positive
patients were treated with antiviral therapy for HCV infection either with
interferon alpha or ribavirin.
Statistical analysis
Cumulative probability of patients deteriorating to ESRD was estimated ac-
cording to Kaplan–Meier Survival Analysis [21]. Comparison between the
survival curves obtained from HCV-positive LN patients and HCV-negative
LN patients was performed by means of log-rank test. The variables were age,
gender, BP, baseline kidney function, serum creatinine, urinary protein and
hepatitis status. Frequency analysis was used to grade the renal impairment.
Descriptive statistics was calculated for quantitative variables. Means of the
quantitative variables were compared by Student’s t-test taking P < 0.05 as the
level of statistical significance. SPSS statistical package (SPSS Inc., Chicago,
IL) version 12 was used for survival curves and statistical analysis.
Results
One hundred and thirty-four patients fulfilled the criteria for
enrollment into the study. Fifteen (11.2%) patients were
A.H. Mitwalli et al.
HCV positive of which 2 (13.3%) were male and 13
(86.7%) were female. One hundred and nineteen (88.8%)
were HCV negative of which 17 (14.3%) were male and
102 (85.7%) were female. The mean age was 32.47

11.8 years; 19 (14.2%) were male and 115 (85.8%) were
female. Fifteen patients (11.2%) were HCV positive of
which 2 (13.3%) were male and 13 (86.7%) were female.
One hundred and nineteen (88.8%) were HCV negative of
which 17 (14.3%) were male and 102 (85.7%) were female.
There was no predilection for gender in the incidence of
HCV infection. Thirteen percent of the males were positive
for HCV infection in comparison to 14.3% of males who
were negative for HCV infection. The probable reasons for
the acquisition of the HCV infection in these patients were
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blood transfusions, dental procedures, sharing blades at the
barber shops and bloodletting (blood shedding using a tool
shared by many people for relieving high BP).
The mean age of patients in the HCV-positive group was
32.47
11.8 years, while in the HCV-negative group it was
34.6
12.3 without any statistical significance. Mean follow-
up period was 6.7
3.3 years with a range of (1–14.4 years).
Fifteen patients were lost to follow-up in the HCV-negative
group; however, none of the patients was lost to follow-up in
the HCV-positive group. The baseline demographics and clin-
ical characteristics of the LN patients are shown in Table 1.
There was no statistically significant difference between
mean systolic and diastolic BP between HCV-positive and
HCV-negative patients. Systolic and diastolic BP was 140.1

20.1 and 84
11 mmHg in the HCV-positive patients and
145.2
12.3 and 86.2
7.4 mmHg in the HCV-negative
patients, respectively, (P ¼ 0.77 and 0.31, respectively).
Nine (60%) patients were hypertensive with BP >130/90
mmHg HCV-positive group in comparison to 74 (62%) in
HCV-negative group (P ¼ 0.86). The mean 24-h urinary
protein level was higher in the HCV-positive patients of
3.4
3.8 g in comparison to HCV-negative patients of
2.24
2.26 g; however, the values did not reach the stat-
istical significance (P ¼ 0.88), there was no difference in
serum albumin levels between HCV-positive patients of
32.8
8.4 g/L and negative patients 32.2
7.1 g/L
(P ¼ 0.76) at the baseline. The blood urea and serum crea-
tinine levels were 7.5
5 mmol/L and 108
53 lmol/L in
HCV-positive patients and 7.5
48 mmol/L and 103
67.6
lmol/L in HCV-negative patients (P ¼ 0.98 and 0.78, re-
spectively). The mean total cholesterol in HCV-positive pa-
tients was 4.87
1.9 mmol/L, while in HCV-negative
patients it was 5.1
1.3 mmol/L (P ¼ 0.542). There was
no statistically significant difference between AST and ALT
levels between HCV positive and negative patients at the
baseline with values of 20.2
4.6 and 18.5
4.7 IU/L for
former and 18.2
4 and 21.1
3.9 IU/L for later with
P ¼ 0.07 and 0.18, respectively. We did not find any differ-
ence in the immunological profile like ANA and dsDNA
levels between HCV positive and negative patients, the
ANA and dsDNA levels in the former were 822.54
908
and 598
597.8, while in the latter, the levels were 1011.49

1556 and 564.37
705.4, respectively, with a P-value of
0.64 and 0.84, respectively. There was also no significant
difference between fasting blood glucose (FBG) level
in HCV positive and negative patients at the baseline
with the FBG level in the HCV-positive patients being
HCV, LN, renal outcome 629
a
Table 1. The baseline demographic and clinical characteristics of the LN patients with and without HCV infection

Patient characteristics HCV-positive LN, N ¼ 15 HCV-negative LN, N ¼ 119 P-value

Age (years) (mean 6 SD) 32.47 6 11.8 34.6 6 12.3 0.52

Gender
Male (%) 2 (13) 17 (14) 0.91
Female (%) 13 (87) 102 (86) 0.91
Hypertension (%) 9 (60) 74 (62.2) 0.86
Diabetes mellitus (%) 3 (20) 23 (19.8) 0.98
Systolic BP (mmHg) (mean 6 SD) 140.1 6 20.1 145.2 6 12.3 0.77
Diastolic BP (mmHg) (mean 6 SD) 84 6 11 86.2 6 7.4 0.31
24-h urinary protein (g/day) (mean 6 SD) 3.4 6 3.8 2.24 6 2.26 0.88
ANA (mean 6 SD) 822.54 6 908 1011.49 6 1556 0.64
dsDNA (mean 6 SD) 598 6 597.8 564.37 6 705.4 0.85
Blood urea (mmol/L) (mean 6 SD) 7.5 6 5 7.48 6 5 0.98
Serum creatinine (lmol/L) (mean 6 SD) 108 6 53 103 6 67.6 0.78

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Total cholesterol (mmol/L) (mean 6 SD) 4.87 6 1.9 5.1 6 1.3 0.54
FBS (mmol/L) (mean 6 SD) 5.62 6 1.93 5.86 6 2.75 0.15
Serum albumin (g/L) (mean 6 SD) 32.8 6 8.4 32.2 6 7.1 0.76
AST (IU/L) (mean 6 SD) 20.2 6 4.6 18.2 6 4 0.07
ALT (IU/L) (mean 6 SD) 18.5 6 4.7 21.1 6 3.9 0.18
PT 12.8 6 1.5 12.3 6 1.07 0.10
C 3 at baseline g/L 0.809 6 0.384 0.811 6 0.40 0.92
Activity index 3.26 6 1.94 3.4 6 1.59 0.63
Chronicity index 10.06 6 2.6 10.9 6 2,44 0.21
Cumulative cyclophosphamide dose 7225.3 6 2344 74126 6 1623 0.69
(mg) (mean 6 SD)
Number of patients on ACE-I (%) 13 (86) 101 (85) 0.831
a
ACE-I, angiotensin-converting enzyme inhibitors.

5.62
1.93, while as the FBG level in the HCV-negative

patients being 5.86
2.75 with a P-value of 0.15.
The baseline kidney biopsy of all the LN patients was
evaluated for activity and chronicity index by the Interna-
tional Society of Nephrology renal pathological association
(ISN-RPA) 2004 classification. The activity and chronicity
index in HCV positive and negative LN patients was 3.26

1.94 and 10.06
2.6, while as activity and chronicity
index in HCV-negative patients were 3.4
1.59 and 10.09

2.44, respectively, with a P-value of 0.63 and 0.21,
respectively.
We did not find any difference in the usage of the angio-
tensin-converting enzyme inhibitors or angiotensin recep-
tor blockers in the HCV-positive or the HCV-negative
patients. There was also no difference in the cumulative
dosage of cyclophosphamide or prednisolone received by
the two groups, Figure 1.
We stratified our patients into three groups according to the
serum creatinine levels, Group 1 serum creatinine <120
lmol/L, Group 2 serum creatinine 121–350 lmol/L and
Group 3 serum creatinine >350 lmol/L. Of the 15 patients
in the HCV-positive group, 5 (35%) were in Group 1, 2
(14.3%) were in Group 2 and 8 (53.3%) were in Group 3,
while in the HCV-negative group of 119 patients, 33 (39.3%)
were in Group 1, 32 (38.1%) were in Group 2 and 19 (22.6%)
were in Group 3. The P-value was highly significant (P 0.02)
in Group 3 between the HCV positive and the negative pa-
tients at the last follow-up, Figures 2 and 3.
There was no statistically significant difference between
serum creatinine levels at enrollment in HCV-positive and
HCV-negative patients with values of 108
53 and 103

67.6 lmol/L, respectively, with a P-value of 0.783;
however, the serum creatinine levels were significantly higher
Fig. 1. Renal functions in LN patients with and without HCV infection at
the last follow-up. There was highly significant statistical difference be-
tween the Hep C positive and negative patients in Group 3 with P-value of
0.02.
in the HCV positive 523.2
290 lmol/L than in the HCV
negative 260.7
24 lmol/L patients at the end of the study
(P < 0.001). Similarly, there was no difference between glo-
merular filtration rate (GFR) at enrollment between the two
groups 59.2
38.1 mL/min in HCV-positive patients and
58.6
30.02 mL/min in HCV-negative patients (P ¼ 0.943);
however, the GFR was lower in HCV-positive patients 25

34.9 mL/min than HCV-negative patients 43.3
33 mL/min
at last follow-up with a statistically significant P-value of
0.046.
There was no statistically significant difference in the
FBG levels between the HCV positive and the HCV nega-
tive groups at the end of the study, the FBG level in
HCV-positive patients was 6.8
4.1 mmol/L and in
HCV-negative patients was 5.9
3 mmol/L with a P-value
of 0.29.
630 A.H. Mitwalli et al.

a P-value of 0.20 and 0.98, respectively, however, we noticed

that the C3 levels were significantly lower in HCV positive
patients 0.8
0.1 g/L than HCV-negative patients 1.2
0.1
g/L with a P-value of <0.001. We also found a worsening of the
markers of liver function in the HCV-positive patients than
HCV-negative patients at the end of the study. The ALT, serum
albumin and the PT levels were 62.8
13 IU/L, 26.6
8.2 g/L
and 15.0
1.4, respectively, in HCV-positive patients, while as
ALT, serum albumin and the PT levels were 21.6
4 IU/L,
36.3
5.3 g/L and 12.5
1.17 in HCV-negative patients,
respectively, with a P-value of 0.005, 0.001 and 0.001,
respectively.
Five (33.3%) HCV-positive LN patients died in compar-
ison to eight (6.7%) HCV-negative LN patients with a

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Fig. 2. Renal function in patients with LN with HCV positive and neg-
ative at last follow-up. There was highly significant statistical difference
between the Hep C positive and Hep C negative patients at the last follow-
up with a P-value of <0.001.
relatively significant P-value of 0.03. Kaplan–Meier
survival curves for HCV-positive verses HCV-negative pa-
tients are presented in Figure. HCV-positive patients had a
rapid decline renal function leading to ESRD as compared
to HCV-negative patients the difference was statistically
significant (P < 0.05 log-rank test). The renal survival
i.e. dialysis free at the end of 5 and 10 years was 95 and
80% for the HCV-negative group and 90 and 65% for the
HCV-positive group with a highly significant P-value at the
end of 10 years (P < 0.05).

Discussion

Chronic HCV infection is a global health problem with a

prevalence of 0.9–18.1% in the general population all over
the world; however, the prevalence is higher in a subset of
Fig. 3. Creatinine clearance in patients with LN and HCV positive and patients on chronic HD ranging from 5 to 60% [9, 10]. Chronic
negative at enrollment and end of the study. There was highly significant
statistical difference between the Hep C positive and Hep C negative
HCV infection is one of the important risk factors for the
patients at the last follow-up with a P-value of 0.043. development and progression to CKD. The prevalence of both
chronic HCV infection and LN is quite high in Saudi Arabia,
the prevalence of the former has been reported to be around
1.8% in Saudi Arabia [22], while as incidence of LN has been
Table 2. Renal outcome in patients with LN patients with HCV infection
at the end of the study reported to be 47.9% by Al-Arfaj et al. [22]. In the present
study, we report an incidence of chronic HCV infection of
HCV positive, HCV negative, 11.2% in our Class IV LN patients. Since LN predominantly
Parameters N ¼ 15 (%) N ¼ 104 (%) P-value affects females more than males, it is expected that majority of
our patients 86% were females; however, we did not find
FBS (mmol/L) 6.8 6 4.1 5.9 6 3 0.29 any predilection of HCV infection for either gender.
(mean 6 SD)
ANA 1467.8 6 1303 930.7 6 1578 0.20
Chronic HCV infection is one of the most important risk
(mean 6 SD) factor for the long-term deterioration of kidney function,
dsDNA 331.524 6 532 334.94 6 551 0.98 reduced graft survival and patient survival and is associated
(mean 6 SD) with increased incidence of renal allograft rejection [12,
ALT (IU/L) 62.8 6 13 21.6 6 4 0.005 22–24]. We stratified the LN patients depending upon the
(mean 6 SD)
C3 g/L 0.8 6 0.1 1.2 6 0.1 <0.001 severity of the renal failure, majority of our HCV-positive
PT 15.0 6 1.4 12.5 6 1.17 <0.001 patients in comparison to HCV-negative patients had serum
Serum albumin (g) 26.6 6 8.2 36.3 6 5.3 <0.001 creatinine >350 lmol/L at the end of the follow-up 53.3%
(mean 6 SD) versus 22.6%, respectively (P < 0.02); similarly, the serum
Death 5 (33.3%) 8 (7.6) 0.03
ESRD 8 (53%) 18 (17.3) 0.005
creatinine levels and the creatinine clearance were higher and
lower, respectively, at the end of the study in HCV-positive
patients which were statistically significant. The renal
diseases associated with chronic HCV infection include
We did not find any difference in the immunological markers cryoglobulinemia, membranoproliferative glomerulonephri-
like ANA and dsDNA levels between HCV positive and neg- tis and membranous nephropathy and IgA nephropathy
ative patients with a ANA and dsDNA level of 1467.8
1303 whether the deterioration of kidney function is due to the
and 331.524
532 in HCV positive patients and 930.7
1578 superadded renal lesion attributed to HCV infection cannot
and 334.94
551 in HCV negative patients, respectively, with be ascertained since we did not have repeat kidney biopsy
HCV, LN, renal outcome
Fig. 4. Represents the hazards of progression to ESRD over a period of time. The X-axis represents the time in days and the Y- axis represents the
cumulative hazard.
available in these patients and also the cryoglobulin levels
were not regularly monitored, we are not sure of contributions
of cryoglobulinemia in the worsening of renal function in
these patients. Other possible reason we could speculate for
the more severe deterioration of renal function in the HCV-
infected patients may be due to the lesser immunosuppressive
medication exposure in the HCV-positive patients fearing the
flare of the HCV infection; however, we did not find any
difference in the dose and the type of the immunosuppressive
medication exposure between the two groups, both groups
received the hospital protocol-induction therapy with intra-
venous methyl prednisolone and intravenous cyclophospha-
mide followed by maintenance therapy with steroids and the
azathioprine.
In a recent retrospective cohort study involving
>470.000 adult veterans, patients with HCV infection were
more likely to develop ESRD (4.3 per 1000 person-year)
than HCV-seronegative patients (3.1 per 1000 person-year)
[25]. Moreover, in patients with an estimated GFR 30 mL/
min/1.73m2, the presence of HCV was associated with a
nearly 3-fold higher risk of ESRD. These findings were
confirmed by a subsequent cross-sectional study showing
that HCV-positive patients had a 40% higher likelihood for
developing renal insufficiency compared with seronegative
subjects [26]. Beside the risk of renal disease progression,
the overall prognosis for patients with HCV-related neph-
ritis is poor because of a high incidence of coinfections and
CVD [27]. Another possible mechanism underlying HCV-
related kidney injury is nonimmunologically mediated.
HCV-positive patients with and without cirrhosis have ele-
vated levels of fasting serum insulin and insulin resistance
and higher prevalence of diabetes [28]. HCV core protein
directly reduces expression of insulin receptor substrate
(IRS) proteins 1 and 2 [29], responsible for metabolic ef-
fects of insulin and promotes activation of IRS-1 and high
expression of tumor necrosis factor at least in hepatic cells
631
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[30]. Insulin resistance and hyperinsulinemia cause excess
intrarenal production of Insulin like growth factor-I and
transforming growth factor-b thus promoting proliferation
of renal cells, and upregulate the expression of angiotensin
II type 1 receptors in mesangial cells, thus enhancing the
deleterious effects of angiotensin II in the kidney. This set-
ting also leads to excess local production of endothelin-1,
reduced endothelial synthesis of nitric oxide and increased
oxidative stress [31]. Although we noticed higher blood
sugars in our HCV-positive patients at the last follow-up,
it was not statistically significant. Our patients were not
routinely monitoring for HbAic levels.
Beside the risk of renal disease progression, the overall
prognosis for patients with HCV-related nephritis is poor be-
cause of a high incidence of coinfections and CVD [27]. We
observed, in our study, that more patients in the HCV group
died than in HCV-negative group; however, none of these
patients died of liver failure or cirrhosis, although there was
significant deterioration in liver function tests as evidenced by
the elevation in the ALT and prothrombin time (PT) and
decrease in the serum albumin level in the HCV-positive pa-
tients at the last follow-up, suggesting that severe immunosup-
pression related to steroids and cyclophosphamide may have a
role in flaring up the proliferation of the virus in these patients
and exacerbating liver damage. We also noticed that the HCV-
positive patients had significantly lower C3 levels in compar-
ison with the HCV-negative patients at the last follow-up
suggesting that these patients may have persistent immunolog-
ical activity related to the LN or even low C3 may have been a
consequence of HCV-related cryoglobulinemia which unfortu-
nately was not evaluated in our study. At this point, it is very
difficult to hypothesise whether the immunosuppression
causes further viral proliferation which in turn leads to deteri-
oration of the liver function and exacerbation of the lupus
activity and hence leads to smoldering kidney damage. We
suggest further studies should be carried out to unravel any still
632
unanswered questions regarding the special relationship be-
tween HCV infection and the kidney in general but particularly
LN and the outcome in these patients which our study could not
do due to many limitations we have encountered.
Limitations
We are still unsure of the cause for the deterioration in
renal function in our patients although we can speculate a
few culprits. We think it would have been quite informative
if a repeat kidney biopsy was available during the course of
the follow-up in these patients with deteriorating renal
function to evaluate whether these renal lesions are related
to underlying LN or some other causes as mentioned
above, particularly immunofixation of the kidney sample
for the HCV antigens would have been very valuable. We
also believe that these patients should have been regularly
monitored for cryoglobulinemia and the HBA1c levels
both of these tests were not, unfortunately, done in these
patients. Another important limitation of our study was
that the follow-up quantitative HCV PCR was not, done
which would have been very useful to asses the effect
of the immunosuppression on viral proliferation in these
patients.
Conclusion
The present study highlights that concomitant HCV infec-
tion in patients with underlying LN is associated with
worse renal outcome, higher rate of progression to ESRD
and reduced patient survival and liver damage. There is no
gender predilection for HCV infection in patients with
underlying LN. More intensive efforts should be made in
the prevention and appropriate treatment of chronic HCV
infection in patients with LN.
Conflict of interest statement. None declared.
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Received for publication: 19.10.10; Accepted in revised form: 9.5.11