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Nephrology Dialysis Transplantation
granul and an antigen for anti-neutophil cytoplasmic antibody (ACNA). However,
function of PTX3 in MPO-ANCA production has been unrevealed.
METHODS: We used aluminium gel (Alum) that is able to induce NETosis, as an
adjuvant for producing anti MPO-Ig. Alum and recombinant MPO (rMPO) were
intraperitoneally (i.p.) immunized in 12-16 weeks old MPO-deficient mice at day 0 and
day 14, and then rMPO was injected at day 21 for boost. After immunization and boost,
concentration of anti-MPO IgG in their serum was examined by ELISA. To show the
involvement of extracellular PTX3 in this model, protein level of PTX and quantitative
double strand DNA in their peritoneal fluid after Alum i.p. immunization.
Furthermore, we simultaneously administrated recombinant PTX3 in addition to
rMPO + Alum immunization to examine the function of PTX3 in producing antiMPO Ig in vivo.
RESULTS: (1) Anti-MPO IgG was produced by Alum + rMPO immunization model
in MPO-deficient mice, but not wild type mice. (2) I.p. injection of Alum induced
extracellular release of PTX3 as well as double strand DNA and dead cells. (3)
Simultaneous injection of recombinant PTX3 attenuated production of anti-MPO IgG
(Control: 617627 vs. +PTX3: 416622).
CONCLUSIONS: A evidence for regulation by PTX3 in production of murine antiMPO IgG was demonstrated.
Eunjin Bae1, Jung Pyo Lee3, Jung Tak Park4, Se-Ho Chang2
Internal Medicine Gyeongsang National University Changwon Hospital Changwon
Korea, Republic of, 2Internal Medicine Gyeongsang National University Hospital Jinju
Korea, Republic of, 3Internal Medicine Seoul National University Boramae Medical
Center Seoul Korea, Republic of and 4Internal Medicine Yonsei University College of
Medicine Seoul Korea, Republic of
and 72.2% in P group, respectively. Baseline urine protein-to-Cr ratio (PCR), serum
albumin and creatinine concentrations were 5.9063.47 g/gCr, 2.0560.56 g/dl,
0.9160.22 mg/dl in MP group, and 6.7963.51 g/gCr, 2.0360.65 g/dl, 0.9360.21 mg/
dl, respectively. The response to the therapy was evaluated following Japanese guideline
for nephrotic syndrome, which defines complete remission (CR): PCR<0.3, type-1 partial remission (PR1): 0.3<PCR<1.0, type-2 partial remission (PR2): 1.0<PCR<3.5, no
response (NR): PCR3.5 g/day or g/gCr.
RESULTS: In results, concomitant use of MZB seemed to be more advantageous than
solely use of PSL in the early phase of therapeutic period (PCR at 3M: 2.7962.30 g/gCr
(47% of baseline value) in MP vs 3.4563.42 g/gCr (51%) in P), however, there was no
difference in both groups in the latter phase (12M). At 3M, the ratio of high responder
(CR+PR1) in MP group was 35.3% whereas that in P group was 26.7%. Logistic
analysis showed estimated odds ratio of the high responder in MP group was 1.50 (95%
CI was 0.33-6.83), suggesting that the concomitant use of MZB might expedite the
remission. In the group of qualitatively negative PLA2R antibody, the odds ratio of
high responder group was 2.67 (95% CI: 0.28-25.64) in MP group vs 1.00 in P group
whereas the ratio was 0.33 and 0.40 in MP and P groups respectively in cases showing
qualitatively positive PLA2R antibody, suggesting that concomitant use of MZB might
be more effective in PLA2R antibody negative cases.
CONCLUSIONS: In conclusion, although MZB is considered to be a gentle
immunosuppressant, its concomitant use might be considerable therapeutic strategy in
the management of MN-induced NS in the elderly.
INTRODUCTION AND AIMS: Idiopathic membranous nephropathy (MN) is most
common in elderly patients showing nephrotic syndrome. However, little is known
about treatment option and outcome of the elderly MN patients with long term follow
METHODS: We retrospectively enrolled patients with biopsy proven MN between
April 1990 and December 2015 from eight tertiary hospitals in Korea. Among them, we
excluded patients who had secondary causes of the MN and had subnephrotic range
proteinuria. We evaluated presenting features, clinical outcomes and analyzed the allcause mortality, infection, renal outcome and remission with respect to age or treatment option.
RESULTS: 198 younger patients (<65 years) and 133 elderly patients ( 65 years)
were enrolled. Median follow up was 95.4 months (range, 3.2-393.1 months). Mortality
rate and infection rate were significantly higher in elderly group than younger group.
In elderly patients, use of ACEi or ARB and achievement of remission were associated
with lower mortality rate and renal outcome. Achievement of remission was
significantly related with male gender, higher estimated glomerular filtration rate and
use of ACEi or ARB. The treatment option was not significantly with achievement of
remission. However, the immunosuppressant therapy was significantly associated with
higher renal outcome and infection compared with conservative therapy. In addition,
steroid monotherapy was independent predictor of higher renal outcome and infection
than steroid plus other immunosuppressant therapy.
CONCLUSIONS: This study showed conservative treatment could be a better
treatment option in elderly MN patients in aspect of infection and renal outcome.
Hajime Hasegawa1,2, Tetsuya Mitarai2,1, Yasuhiko Tomino2, Hitoshi Yokoyama2,
Kunihiro Yamagata2, Masayuki Iwano2, Kaori Takayanagi1
Dept of Nephrol and Hypertens, Faculty of Blood Purification Saitama Medical Center,
Saitama Medical University Kawagoe Japan and 2Study group for nephrotic syndrome
in the elderly Study group for nephrotic syndrome in the elderly Kawagoe Japan
INTRODUCTION AND AIMS: Membranous nephropathy (MN) often causes
prednisolone (PSL)-resistant nephrotic syndrome (NS) in the elderly, and forces to use
immunosuppressant which shows multiple adverse effects. Mizoribine (MZB) is an
immunosuppressant eliciting its action through the inhibition of nucleic acid
metabolism, and known to show lesser adverse effects comparing to cyclophosphamide
or cyclosporine. In this multi-centered cohort study, we investigated the clinical
advantage of MZB in the elderly with MN-induced NS.
METHODS: Thirty-six patients with biopsy-proven primary MN showing NS were
enrolled from 24 independent facilities in Japan. Enrolled patients, being older than 65
of age and preliminary obtained none of therapy, were randomly assigned to two therapeutic groups, solely administered 30 mg of PSL (P group, n=18), or concomitantly
administered 150 mg of MZB (MP group, n=18). Withdrawing procedure of PSL was
controlled by the study protocol. Measurement of urine protein and blood test was
scheduled at 0, 3, 6, 9 and 12 M after administration of medications. In a part of cases,
qualitative analysis of anti-phospholipase A2 receptor (PLA2R) titer was performed.
Averaged ages and ratio of male in both groups were 73.3 and 66.7% in MP and 72.8
Ondrej Derner1, Satu Pesickova1, Zdenka Hruskova1, Barbora Svobodova1,
Jakub Zavada3, Martin Lenicek2, Romana Rysava1, Vladimir Tesar1
Department of Nephrology General University Hospital and First Faculty of Medicine,
Charles University in Prague Prague Czech Republic, 2Department of laboratory diagnostics Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of
Medicine, Charles University in Prague Prague Czech Republic and 3Institute of
Rheumatology Institute of Rheumatology, First Faculty of Medicine, Charles University
in Prague Prague Czech Republic
INTRODUCTION AND AIMS: Lupus nephritis (LN) is one of the most severe organ
manifestations of systemic lupus erythematosus and despite great progress in the
treatment of LN in past decades, it remains a significant cause of morbidity and mortality.
The aim of this retrospective study was to compare different types of initial treatment in
terms of long-term outcome and to assess short term response after initial therapy.
METHODS: Patients with most severe forms of lupus nephritis (class III, IV and
combined forms III+V and IV+V) were enrolled into a study (n=157; median age 32.6
years; M/F 25/132), where patients were divided into 3 groups based on the initial
treatment administered: cyclophosphamide (CYC, 70.1 %), cyclosporine A (CsA, 15.9
%) and mycophenolate mophetil (MMF, 13.4 %) group. Renal response (using criteria
as defined by EULAR/ERA-EDTA recommendation 2012) after one year of treatment
was assessed in a sub study counting a total of 102 patients with biopsy proven LN diagnosed between 2007 and 2013 in our centre.
RESULTS: Median time of follow-up was 7.2 years (range 3 - 16 years). At baseline, the
CYC group had significantly higher proteinuria (median 2.3 g/day) compared to MMF
(median 0.8 g/day) (p = 0.0436) while it did not differ from CsA group. There were no
statistically significant differences in renal function among the groups at baseline. At
the end of follow-up, nor renal function neither proteinuria differed in the three
groups. During the follow up, 11/110 (10 %) patients from CYC group, 4/25 (16 %) in
the CsA group and 1/21 (4.7 %) in the MMF group died. There was no difference in the
overall survival (p=0.395). Renal replacement therapy was needed in 7/110 (6.4 %) in
CYC group, 4/25 (16 %) in CsA group and 1/21 (4.7 %) in MMF group, and the renal
survival did not significantly differ between groups. In a sub study of 102 patients, complete response at one year after renal biopsy was achieved in 72 % of patients and partial
response in 23 %, the remaining 5 % of patients were classified as non-responders.
Renal relapse during follow-up occurred in 34 % of patients.
CONCLUSIONS: Our retrospective study of patients with first manifestation of lupus
nephritis did not show any difference in long-term survival comparing three common
types of initial therapy. Short term outcomes were comparable with results of similar
Fadel Alrowaie1, Ali AlFayez1, khalid Almatham1
Medical Specialities Department King Fahad Medical City Riyadh Saudi Arabia
INTRODUCTION AND AIMS: Lupus nephritis (immune complex) is the most
serious complication of systemic lupus erythematosus (SLE) and the strongest
predictor of poor outcome. The spectrum of renal involvement includes
podocytopathies, renal thrombotic microangiopathy, tubulointerstitial nephritis and
amyloidosis. No data about non-immune complex nephritis is published in Saudi
Arabia.This study aimed to better characterize the incidence, clinical and morphological features, and outcomes of SLE patient with non immune complex renal involvement
from large Saudi SLE cohort.
doi:10.1093/ndt/gfx165 | iii509
METHODS: SLE patients were identified using nephrology section glomerulonephritis
(GN) registry. All SLE patients who had renal biopsy between 2006-2014 were
reviewed. The biopsy result were divided into two groups: Immune complex lupus
nephritis (based on ISN/RPS classification from I-VI) and non immune complex (renal
pathology not consistent with ISN/RPS classification).
RESULTS: A total of 78 patients with SLE who had renal biopsies identified. 69 with
lupus nephritis class 1-6 were excluded from the study, and nine (11.5 %) found to
have other forms of renal involvement were included. Mean age is (26 6 7.6), Female :
Male (8:1), laboratory data at presentation (mean); Cr (126 6 126), Hb (10.6 6 2), all
except one had subnephrotic proteinuria. Interestingly antinuclear antibody was
positive in 3 patients while anti-double stranded DNA (anti-dsDNA) and antiphospholipid antibody (APL ) were positive in 7 patients ( 77 % ). Histological diagnoses identified were as follows: three focal segmental glomerulosclerosis (FSGS), two
minimal change nephropathy (MCD), two thrombotic microangiopathic glomerulonephritis (TMA), one membranoproliferative glomerulonephritis (MPGN) 3, and one
fibrillary glomerulonephritis (FGN). Most of the patients achieved remission, while 2
were lost to follow up, and one patient died of sepsis.
CONCLUSIONS: Non-immune complex GN contribute to 11.5 % of renal biopsies in
SLE patients, the majority has at least one of APL antibody positive with FSGS as predominant pathology followed by MCD, that may suggest podocytopathies as pathogenesis. Our data consistent with Hertig et al 2001 and Baranowska-Daca et al 1999 data
but none of our FSGS patients were of collapsing variant in comparison to Salvatore et
al 2012 study. Nephrologist and rheumatologist should have low threshold in performing renal biospies in patient with SLE, as not every renal abnormalities is ( immune
complex )lupus nephritis .
Natalia Chebotareva1, Irina Bobkova1, Natalia Neprinzeva1
Nephrology I.M. Sechenov First Moscow State Medical University Moscow Russian
INTRODUCTION AND AIMS: In kidney tissue heat shock proteins are an important
part of the intracellular defense system, that fulfill a range of functions, including
cytoprotection and the intracellular assembly, folding and translocation of proteins.
Moreover, the unique properties of Heat shock protein (HSP)70 provide an important
immunoregulatory function results in differentiation of specific regulatory phenotypes
T cells (FoxP3 positive), producing IL-10. HSPs may play an important role in the
immune diseases, such as CGN. Our study aim was to assess urinary excretion of HSPs
in urine and expression in renal tissue in patients (pts) with different CGN course.
METHODS: Concentrations of HSP27 and HSP70, IL-10 in urine were determined in
70 patients with CGN by using ELISA technique. 30 pts - with proteinuria (PU) 1-3 g/
d, 40 - with nephrotic syndrome (NS), including 10 pts with severe NS (anasarca, PU to
12 g/d, hypoalbuminemia < 20 g/L), and 11 pts - with NS and impaired renal function.
Expression of HSP70 and FoxP3 (a marker of Treg cells) was assessed in renal tissue by
RESULTS: HSP27 and HSP 70 urine levels were significantly elevated in patients
suffering from active courses of chronic glomerulonephritis predominantly in
nephrotic syndrome versus healthy controls (Tab). The urinary HSP-27 and HSP 70 in
pts with active CGN correlated directly with proteinuria (Rs = 0,4, p < 0,05; Rs= 0,34,
p<0,05, respectively) and negatively with the level of serum albumin (Rs = -0,32 p <
0,05, Rs = -0, 2, p = 0,05). In CGN patients with severe NS (anasarca, PU to 12 g/d,
hypoalbuminemia < 20 g/L) urinary HSP27 and HSP-70 level were higher compared
to CGN pts with moderate NS (Tab). HSP70 urinary values were significantly elevated
(0,8 [0,7;3,4]ng/ml) in pts with higher expression of this protein in the renal tissue. Upregulation of HSP70 was detected in tubulointerstitium (tubular cells, infiltrate cells,
myofibroblasts), in podocytes and epithelial parietal cells. But tubulointerstitial expression of HSP70 was pronounced in active nephritis courses with a higher degree of tissue
damage. But the number of positive FoxP3 cells (T regulatory anti-inflammatory cells,
expressing IL-10) in the interstitium by severe nephrotic syndrome significantly
decreased (2,0 [0,44; 4] vs 8,5 [3; 16] positive cells in pts without NS). At the same time
urinary IL-10 levels were decreased to trace values in this pts group (trace vs 0,11 [0;
1,12]ng/ml )
iii510 | Abstracts
Nephrology Dialysis Transplantation
CONCLUSIONS: We provide evidence for elevated HSP27 and HSP70 concentrations
in urine in patients suffering from CGN. Urinary levels of HSP70 corresponding to the
high expression in the renal tubulointerstitium may be used as a marker of
tubulointerstitial injury in CGN.
Desmond YH Yap1, Paul Lee1, Irene Yam1, Chun Hay Tam2, Sunny Wong2,
Susan Yung1, Tak Mao Chan1
Department of Medicine The University of Hong Kong Hong Kong Hong Kong and
Department of Medicine and Geriatrics United Christian Hospital Hong Kong Hong
INTRODUCTION AND AIMS: Cyclophosphamide (CYC) and mycophenolate
mofetil (MMF) are standard induction treatments for active lupus nephritis (LN). CYC
induction might be associated with more sustained response compared with MMF.
Lymphocyte subsets have been implicated in the pathogenesis of LN, but the impact of
CYC and MMF treatment has not been investigated.
METHODS: Lymphocyte subsets and serum cytokine levels were determined using
flow cytometry and ELISAs respectively in 14 patients with active LN randomized to
receive either CYC or MMF (n=7 in each group), combined with prednisolone, as
induction immunosuppression.
RESULTS: At 24-week after starting induction immunosuppression, CYC treated
patients showed a higher percentage of circulating CD8+ cytotoxic T cells compared
with the MMF group (47.6610.9% vs. 20.363.8%, p=0.015). CYC treated patients also
had a numerically lower percentage of Th1 cells (1.661.2% vs. 6.964.0%, p=0.094) and
a higher percentage of regulatory T cells (3.062.2% vs 1.962.0%, p=0.534). The
percentages of circulating naı̈ve B, memory B and plasma cells were similar in the two
groups. The percentage of circulating memory B cells correlated with anti-dsDNA antibody level in both groups (r=0.964, p=0.036 for the CYC group and r=0.951, p=0.049
for the MMF groups respectively). CYC treated patients had lower serum IFN-gamma
level (83.66136.9 pg/mL vs. 453.16349.1 pg/mL, p=0.032), whereas serum IL-2, IL-4,
IL-6, IL-10, IL-17, IL-18, IL-21, IL-23, BAFF, IFN-alpha and MCP-1 levels were similar
in both groups.
CONCLUSIONS: Induction immunosuppressive treatment with corticosteroids and
CYC or MMF resulted in differences in lymphocyte subsets and serum cytokine profile
in LN patients, which might have clinical implications.
Javier Villacorta2, Mercedes Acevedo3, Teresa Cavero1, Francisco Diaz-Crespo4,
Alfredo Cordon, Beatriz Sanchez Alamo, Manuel Praga1, Gema FernandezJuarez
Nephrology Hospital Universitario Doce de Octubre Madrid Spain, 2Nephrology
Hospital Universitario Fundacion Alcorcon madrid Spain, 3Nephrology Hospital Virgen
de la Salud Toledo Spain and 4Pathology Hospital Virgen de la Salud Toledo Spain
INTRODUCTION AND AIMS: Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study we aimed to assess the
treatment response rates and long-term outcomes of vasculitis patients presenting with
renal failure.
METHODS: This retrospective study included 151 patients with renal vasculitis from
three hospitals who underwent a renal biopsy between 1997-2014. Patients with renal
failure which required dialysis at the onset were compared to those presenting with
more preserved renal function. The primary end point was treatment response and
patient surivival.
RESULTS: Patients with severe renal involvement had a lower response to treatment
compared to those having preserved renal function (26.6% versus 93.4%; p<0.001).
Dialysis dependent patients who received plasmapheresis in addition to immune
suppressants associated a higher rate of renal recovery (41.6% versus 12.5%; p=0.05). A
higher incidence of severe infections was observed among patients withsevere renal
involvement (38.4% versus 18.1%, p=0.01). The mortality rate was significantly higher
among vasculitis patients presenting with renal failure (53.8% versus 22.2%, p=0.001).
Global survival at1 and 5 years was 60% and 47% in patients requiring dialysis
compared with 90% and 80% among those with more preserved renal function
(p<0.001). After multivariate adjustement, the need for dialysis remained as an
independent predictor of death (HR 2.5; 95% CI, 1.1 to 5.7; p=0.03).
CONCLUSIONS: The presence of severe renal dysfunction represents an independent
risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a
lower response rate to immunosuppressive therapy and a higher incidence of severe
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