bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0402TACROLIMUS PLUS LOW DOSE PREDNISOLONE THERAPY IS MORE EFFECTIVE IN PLA2R -VE MEMBRANOUS NEPHROPATHY PATIENTS
Authors: Jaiswal Akhilesh Kumar , Prasad Narayan , Agarwal Vikas , Singh Mantabya 
Published: June 2020

Abstract

Background and Aims
Idiopathic Membranous Nephropathy (IMN); an autoimmune concomitant nephrotic syndrome of the adult is mainly associated with PLA2R antibody expressed on podocytes. The lack of exact mechanisms involved in the pathogenesis of IMN is transmitted to its therapeutic management. There is no standard therapy for patients with frequent relapsing or steroid-dependent IMN.
We propose the efficacy of low dose Tacrolimus (Tac) plus prednisolone and associated changes in anti-PLA2R in adult IMN.

Method
Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients; 15 diabetic; 7 lupus; 1HBV and 1 ankylosing spondylitis patients were excluded. Finally; 77 Patients were followed and evaluated for the anti-PLA2R level at baseline; 3M; 6M; 12M and end of follow-up (17-61 ; median 38 months). CR; PR; relapse; and side-effects were recorded.Of the 77 patients; at 3M 60(77.92%; CR-37; PR-23); at 6M 61(79.22%; CR-53; PR-8); at 12M 53(68.86%; CR-47; PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up; out of 54 responsive patients 37(68.51%; CR-36; PR-1) remained in remission and 17(31.48%) patients relapsed.

Results
Out of 77 patients; 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M; (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively. There were significant correlations between PLA2R level and 24h proteinuria at baseline; 3M and at 6M. During therapy 4 patients develop cutaneous tenia; 1 osteonecrosis of the femur head; 1 corpus tunnel syndrome; 4 onset diabetes; 3 tremor; and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac; and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note; 4 females had pregnancy and successful delivery in our cohort of patients.

Conclusion
PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.
P0404B CELLS FROM PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS FAIL TO REGULATE T CELL INTERFERON GAMMA RELEASE BUT DO REGULATE OTHER ASPECTS OF T CELL ACTIVATION
Authors: Puli Srinivas , Appelgren Daniel , Hellmark Thomas , Segelmark Mårten 
Published: June 2020

Abstract

Background and Aims
Regulatory features of B-cells have gained increased attention in patients with systemic vasculitis, including granulomatosis with polyangiitis (GPA). The aim with this study was to investigate the frequencies and phenotypes of two putative regulatory B (Breg) cell populations and assess the capacity of B-cells from GPA patients to regulate T-cell activation.

Method
37 GPA patients (22 remission and 15 active) and 31 healthy controls (HC) were included for measurement of CD19+CD24highCD27+ (memory) and CD19+CD24highCD38high (transitional) Breg cells, and 11 GPA patients in remission and 12 HC for the functional studies of B-cells. HC were matched for age and gender.

Results
Memory Breg cells were reduced in GPA both during active disease and remission compared with HC, whereas transitional Breg cells did not differ between the groups. Memory Breg cells consisted of less CD25+ cells during both active disease and remission but expressed more PD-L1 and CD86 during remission compared with active disease and HC. B-cells from GPA patients regulated T-cell proliferation and IL-17a production but failed to regulate IFN-γ production (Fig 1). The levels of IFN-γ and the IFN-γ regulated cytokine CXCL10 were elevated in patient plasma.

Conclusion
Despite reduced levels and altered phenotypes of memory Breg cells, the capacity of GPA patient B-cells to regulate T-cell proliferation and IL-17a production was unaffected. However, we found a profound inability of patient B-cells to regulate T-cell IFN-γ production. This alteration could be important for the persistent inflammation that continues during remission and results in the chronic relapsing nature of the disease
P0407THE INVESTIGATION OF SYNAPTOPODIN EXPRESSION OF PODOCYTES IN GLOMERONEPHRITIS
Authors: Zhang Zhigang 
Published: June 2020

Abstract

Background and Aims
Synaptopodin, a proline-rich actin-associated protein, plays an important role in the regulation of podocytes processes structures and dynamics. The mutation or lack of synaptopodin may lead to the changes of podocytes structures and functions and cause the occurrence of proteinuria. But the underlying molecular mechanisms remain primarily elusive.

Method
we used cellular and pathological experiments to observe the expression changes synaptopodin in vivo and vitrio.

Results
The results showed that the reduction expression of synaptopodin and RhoA were found in the podocytes in different nephriris of human renal biopsy as well as in rat adriamycin nephropathy. The cultured cells treated with inflammatory cytokins such as TNF, IL-1 also showed decreased synaptopodin level in podocyte, which led to low RhoA level and disarrange the actin cytoskeleton assembly, result in the abnormal changes of podocyte morphology.

Conclusion
These data preliminarily proved that synaptopodin loss in podocyte injury plays an important role in the regulation of podocyte morphology and function through RhoA signaling pathway, and further researches are required to clarify the more mechanism, which may provide new strategies and methods for the prevention and treatment of glomerular diseases.
P0409CHARACTERISTICS AND OUTCOME OF ONE HUNDRED EGYPTIAN PATIENTS OF LUPUS NEPHRITIS: A SINGLE TERTIARY CARE CENTER STUDY
Authors: Saleh Mohammed , Nassar Mohammed Kamal , Awad Ehab 
Published: June 2020

Abstract

Background and Aims
Renal biopsy is the “gold standard” for diagnosis of lupus nephritis (LN). It is necessary for classification and is the basis for treatment strategy decisions. This study was carried out in order to analyse the results of renal biopsy in LN patients, its effect on treatment and predictors for remission in an Egyptian cohort.

Method
The results of renal biopsies of LN patients undergoing regular follow up in the outpatient clinic of Mansoura Nephrology and Dialysis Unit (MNDU), Mansoura University Hospital, Egypt in the period between October 2017 and September 2019 were reviewed. The histopathological data were analyzed and correlated to the clinical data of the study group.

Results
A total of 100 LN patients with documented renal biopsy were enrolled in this study. The median age of the patients was 29 years. Most of the patients were females (n=89). Serum creatinine at presentation ranged from 0.57 to 13.5 mg/dl (median 1.3 mg/dl). Class IV (diffuse proliferative) LN was the most frequently encountered class, followed by Classes III, V, II and VI respectively, while class I was detected in only one patient. In proliferative classes (III and IV), the total score of activity indices, ranged from 0 to 16 (minimum–maximum). Mesangial hypercellularity was the most frequent encountered active lesions. Total score of chronicity indices ranged from 0 to 10 (minimum-maximum). Interstitial fibrosis was the most frequent chronicity index. Remission was achieved in 73 patients. Patients who achieved remission had lower serum creatinine and lower pathological chronicity score. In a multivariate logistic regression analysis, serum creatinine at presentation was the strongest predictor for renal remission in this cohort and chronicity index was the strongest predictor in proliferative classes (III and IV). Receiver operating characteristic curve (ROC curve) was done to identify the cutoff point of serum creatinine which can indicate the probability of renal recovery in proliferative and non-proliferative classes (n=100) and in proliferative classes only (n=73). A serum creatinine value of 1.65 mg/dl or less identifies the probability of renal recovery with 76% sensitivity and 71% specificity in proliferative and non-proliferative classes . A chronicity index value of 6 or less identifies the probability of renal recovery with 93% sensitivity and 58% specificity.

Conclusion
Renal biopsy is a must in LN to guide treatment and prognosis. In this Egyptian cohort, serum creatinine at presentation and pathological chronicity index score are the strongest predictors of renal response in LN patients.
P0413THE ICOS+ TREG/ICOS+ TRESP BALANCE HAS A DECISIVE ROLE REGARDING THE PRESERVATION OF THE REMISSION PHASE IN SLE PATIENTS
Authors: Schaier Matthias , Gottschalk Claudius , Kälble Florian , Zeier Martin , Steinborn Andrea 
Published: June 2020

Abstract

Background and Aims
An imbalance between CD4+-regulatory T-cells (Tregs) and CD4+-responder T-cells (Tresps) correlates with active disease flares in Systemic Lupus Erythematosus (SLE) patients. Both cell subsets consist of highly proliferative inducible T-cell co-stimulatory molecule expressing (ICOS+-) and less proliferating ICOS--Treg/Tresp cells.

Method
In this study we aimed to examine the role of age-dependent differentiation for maintaining the ICOS+-Treg/ICOS+-Tresp or ICOS--Treg/ICOS--Tresp balance in SLE remission patients compared to active disease patients and to evaluate the influence of proliferation inhibitor or glucocorticoid therapy concerning the maintenance of these equilibria.

Results
In 83 healthy volunteers, the ratio of ICOS+-Tregs/ICOS+-Tresps increased significantly with age, while that of ICOS--Tregs/ICOS--Tresps did not change. In 86 SLE remission patients, medication controlled disease activity was associated with an age-independently increased ratio of both ICOS+-Tregs/ICOS+-Tresps and ICOS--Tregs/ICOS--Tresps. In 13 active disease patients this increased ICOS+-Treg/ICOS+-Tresp ratio could not be maintained, due to an age-dependent earlier terminal differentiation of ICOS+-Tregs than of ICOS+-Tresps. The increased ratio of ICOS--Treg/ICOS--Tresp was maintained in active disease patients, but it decreased with age. This was attributable to an age-independent aberrant differentiation of ICOS--Tresps and a resulting loss of age-dependent differentiation of ICOS--Tregs. Especially the administration of proliferation inhibitors (azathioprine or mycophenolic acid) ensured prolonged differentiation and maintenance of functional ICOS+-Tregs with age. There was a similar but weaker effect of this medication on ICOS+-Tresps, causing a significant decrease of these cells with age. The proliferation capacity was neither affected in ICOS+-Tregs/Tresps nor in ICOS--Tregs/Tresps. As a result, the ratio of ICOS+-Tregs/ICOS+-Tresps increased significantly with age and kept the patients in remission. In contrast, glucocorticoids increased the differentiation of ICOS--Tregs especially in younger individuals, but had an adverse effect on their proliferation capacity.

Conclusion
Our data reveal a crucial role of the ICOS+-Treg/ICOS+-Tresp balance for the maintenance of self-tolerance and avoidance of disease flares in SLE. The used immunosuppressive therapy, especially the administration of proliferation inhibitors, has a decisive effect on the preservation of regular differentiation of all Treg/Tresp subsets with age, and most importantly avoids the terminal differentiation and immune senescence of ICOS+-Tregs.
P0414URINARY HEPCIDIN AS A BIOMARKER OF NEPHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
Authors: Saleh Marwa , Eldeep Ahmed , L Abdelsalam Adel , El-baiomy Azza , Awad Ehab 
Published: June 2020

Abstract

Background and Aims
Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that is associated with poor prognosis. The current available urinary biomarkers are neither sensitive nor specific for diagnosing LN. This study was undertaken to investigate whether urinary hepcidin represents a marker of nephritis in SLE patients.

Method
A cross-sectional study was conducted with 3 study groups compromising 30 patients with biopsy proven LN, 30 patients with non-nephritis SLE and 20 healthy control. Spot urinary samples were collected from all participants and the levels of hepcidin in urine were measured by ELISA, 24 h urinary proteins, urinary and serum creatinine were measured.

Results
Urinary hepcidin was significantly higher in LN patients than in non-nephritis SLE and control (470, 258, 43.0 ng/mg creatinine respectively) (P &lt; 0.001) as shown in figure 1. Urinary hepcidin was significantly correlated with serum creatinine (P 0.017) and 24 hours urinary proteins (P 0.003). ROC curve cut-off values of urinary hepcidin were 4.3000, Area under curve (AUC) of hepcidin was 0.553, with sensitivity (SN) of 63.3%, specificity (SP) of 60%, Positive predictive value (PPV) 70.4, negative predictive value (NPV) 52.2 in SLE patients as shown in table 1 and figure 2.

Conclusion
Although urinary hepcidin level was significantly higher in LN patients than in non-nephritis SLE and control, it failed to discriminate patients with LN from those without. Further studies are still needed before considering urinary hepcidin as a non-invasive diagnostic marker of LN.
P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION
Authors: Rabasco Cristina , Martínez Ana , Ortega Rosa , Espinosa Mario 
Published: June 2020

Abstract

Background and Aims
Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes.

Method
We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD).

Results
A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)].
Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008).

Conclusion
Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive.
These results would support the theory that complement activation in this entity can play an important role.
It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.
P0425MEMBRANOUS NEPHROPATHY IN TURKEY: TURKISH SOCIETY OF NEPHROLOGY GLOMERULER DISEASES (TSN-GOLD) DATABASE RESULTS
Authors: Yildiz Abdulmecit , Ulu Memnune Sena , Oruc Aysegul , Ucar Ali Riza , Ozturk Savas , Alagoz Selma , Eren Necmi , Kocyigit Ismail , Koksal Cevher Simal , Haras Ali Burak , Sumnu Abdullah , Arinsoy Turgay , SAHIN Garip , Suleymanlar Gultekin , Cavdar Caner , Kumru Şahin Gizem , Kurultak Ilhan , Unsal Abdulkadir , Manga Sahin Gulizar , Kazan Sinan , Vatansever Bulent , Dikec Mehmet , Dursun Belda , Sayarlioglu Hayriye , Turkmen Kultigin , Artan Ayse Serra , Aktas Nimet , Yilmaz Zulfikar , Behlül Ahmet , Dheir Hamad , Kutlay Sim , Seyahi Nurhan 
Published: June 2020

Abstract

Background and Aims
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in the adult population. The aim of our study is to determine the demographic and clinical characteristics and biopsy findings of the patients diagnosed with MN in our country.

Method
The study included 991 patients with renal biopsy who were followed in 47 nephrology clinics and enrolled in the database of Turkish Nephrology Primary Glomerular Diseases (TSN-GOLD) Working Group between May 1, 2009, and June 1, 2019. The demographic and clinical characteristics and biopsy findings of all patients included in the study were analyzed.

Results
The mean age of patients included in our study was 46±14.8 years and the gender distribution was (M / F, 582/409). 80.3% (n = 796) of the patients had nephrotic proteinuria at the time of diagnosis. Before the biopsy, the PLAR2 antibody was examined in 137 patients and positive in 71.5% (n = 98) patients. Hypertension was present in 34.6% (n = 343) of the patients. Mean estimated glomerular filtration rate was 93.9±32.8 ml/min/1.73 m2, albumin level was 2.7 ± 0.2 mg/dL, proteinuria level in urine was 7,1±6,4 gr/day and total cholesterol level was 295±3.7 mg/dL. On light microscopy, baseline membrane thickening was found in 92% (n=907) and interstitial inflammation in 53% (n=524) specimens. In immunofluorescence staining, 3 (+) IgG accumulation was highest in 578 (58.3%) of the specimen.

Conclusion
This multicentre study is the largest study to analyze clinical, laboratory, and biopsy specimens of MN patients at the time of biopsy in our country. The findings are consistent with the literature. Prospective follow-up results of these patients will help us to understand the renal prognosis and treatment response better.
P0426HISTOLOGICAL PREDICTORS OF RENAL PROGNOSIS IN LUPUS NEPHRITIS: WHICH COMPARTMENT MAKES THE DIFFERENCE?
Authors: Stefan Gabriel , Stancu Simona , Georgescu Carmen , Zugravu Adrian Dorin , Petre Nicoleta , Mircescu Gabriel 
Published: June 2020

Abstract

Background and Aims
Lupus nephritis (LN) encompasses a spectrum of glomerular, tubulointerstitial, and vascular lesions; we aimed to evaluate which compartment injury has renal prognostic value.

Method
We retrospectively examined the renal outcome at 31 December 2015 of 66 patients (age 36 [28-52] years; 76% female; eGFR at baseline 60.8 [24.4-78.1] mL/min) who were diagnosed with lupus nephritis by kidney biopsy during 2010-2015. Data regarding the clinical presentation, renal function, histology (presence/absence of lesions - Table 1; ISN/RPS classification) and treatment were retrieved from the electronic patients’ files. We used a composite endpoint in the survival analysis (Cox proportional hazard models, CPH): renal replacement therapy initiation, doubling of serum creatinine and death, whichever came first.

Results
Nephrotic syndrome was the most frequent form of presentation (42%), followed by nephritic (24%) and nephrotic-nephritic (15%). Most of the patients received immunosuppression treatment (97%, 70% cyclophosphamide regimen). Twenty-five patients (38%) reached the composite endpoint. They were older, male more often, had higher mean arterial pressure (MAP), lower serum albumin, decreased eGFR and higher proteinuria. Moreover, they were in class IV LN and had glomerulosclerosis more frequently. Median renal survival for the entire cohort was 4.4 (95%CI, 2.3-6.5) years. In the multivariatle CPH for the histological predictors, only ISN/RPS classification and tubular atrophy were associated with renal survival (Table 1). In a CPH that included clinical, histological and treatment variables, only lower eGFR (0.97 (95%CI, 0.95-0.99)), MAP (1.03 (95%CI, 1.00-1.06)) and tubular atrophy (4.52 (95%CI, 1.50-13.55)) remained as independent predictors of renal survival.

Conclusion
Tubular atrophy seems to be an important prognostic sign in LN; therefore, greater importance should be given to the tubulointerstitial compartment evaluation.
P0438PREDICTORS OF TREATMENT RESPONSE AND LONG-TERM OUTCOME IN PATIENTS WITH PAUCI-IMMUNE GLOMERULONEPHRITIS AND SEVERE RENAL DYSFUNCTION AT DIAGNOSIS
Authors: Lionaki Sophia , Marinaki Smaragdi , Kalogeropoulos Petros , Liapis George , Gakiopoulou Harikleia , Kapsia Helen , Tzioufas Athanasios , Boletis Ioannis 
Published: June 2020

Abstract

Background and Aims
Severe kidney involvement represents a frequent clinical scenario for patients with pauci-immune (PI) vasculitis. We aimed to explore the factors, which are associated with prognosis, in short and long term, following administration of appropriate immunosuppressive therapy.

Method
Patients were included if they had biopsy proven PI glomerulonephritis (GN) with estimated GFR&lt;20 ml/min/1.73 m2 or dialysis requirement at presentation, received standard immunosuppression and were followed for a minimum period of one year. We recorded clinical, laboratory and histopathological parameters at diagnosis, at 3 months, at 1 year and at the end of follow up. Outcomes of interest included response to treatment, end stage kidney disease (ESKD), and death. Treatment response was defined by the ability to come off dialysis with an eGFR&gt;20 ml/min/1.73 m2 with no signs of vasculitis. Histopathological evaluation included arteriosclerosis, % of normal glomeruli, activity index, chronicity index.

Results
A total of 83 patients, with a mean age of 59.6 (15.05) years were included. There were, 45 males (54.2%). After 3 months, 59 patients (71.1%) had responded to immunosuppressive therapy, 16 (19.3%) were dialysis depended, 5(6.02%) died and 2 were lost in follow up. By the end of the 1st year, 59 patients (71.1%) achieved remission, 16(19.3%) ended up in ESKD and 6(7.4%) died. Factors which were associated with treatment response included MPO-ANCA positivity [odds ratio OR:3.9, 95%CI (1.13-13.37) p=0.03], eGFR&gt;10ml/min/1.73m2 at presentation [OR:2.5, 95% CI(0.86-7.30), p=0.009], normal glomeruli &gt;10% [OR:3.8, 95%CI (1.24-12.1), p=0.02], and chronicity index more than 6 [OR:6.2, 95% CI(1.77-22.4), p=0.004]. Risk factors associated with ESKD included non-response to immunosuppressive therapy [Relative Risk RR:0.05, 95%CI (0.01-0.2) p&lt;0.0001)], normal glomeruli&lt;10% in the diagnostic biopsy [RR: 2.9, 95% CI (1.38-6.32), p=0.005] and age&gt;75 years [RR:3.2, 95% CI (0.9-10.6) p=0.055]. Two of the 6 deaths were disease related.

Conclusion
A significant proportion of patients with PI-GN, who presented with severe renal dysfunction, responded to immunosuppressive therapy and recovered renal function approximately 3 months after initiation of therapy. The most important risk factors for ESKD were age&gt;75 years, &lt;10% normal glomeruli in the diagnostic kidney biopsy and non-response to immunosuppressive therapy.