bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO771A DEDICATED INTERVENTIONAL NEPHROLOGY SERVICE LEADS TO BETTER RENAL SERVICE PROVISION
Authors: Clark Rauri , Ahmed Saeed , Andrews James , Srivastava Shalabh 
Published: May 2021

Abstract

Background and Aims
Interventional Nephrology is a renal procedural sub-speciality that provides procedures the following procedures necessary for the maintenance of dialysis access and renal diagnostics:
In most centres regionally and nationally, these procedures are performed by a mix of nephrologists, radiologists and surgeons. In many centres haemodialysis catheter procedures are performed by nephrologists but without fluoroscopic guidance, with only those procedures which fail to be completed being escalated to interventional radiology. Access to real time imaging improves safety and quality of patient experience by reducing the rate of procedural failure and can the rate of serious complications.
The Sunderland Diagnostic and Interventional Nephrology (SDIN) service was launched in 2018. Briefly, this is a ‘one stop shop’ for all of the above procedures with pre-procedural assessment and post-procedural recovery provided in a dedicated renal day-case area. Procedure lists run Monday to Friday, 52 weeks per year, and are provided by four interventional nephrologists.

Method
Data was collected retrospectively on all activity under the Sunderland Diagnostic and Interventional Nephrology service.

Results
The service has delivered the following benefits:

Conclusion
A dedicated interventional Nephrology service leads to significant benefits for the providing unit and leads to efficiency savings. Most importantly, patients receive safe and efficient care leading to improved experience and in the long term improved clinical outcomes.
MO253A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-RANGING STUDY (LUMINA-1 STUDY) TO EVALUATE THE SAFETY AND EFFICACY OF CCX140 IN SUBJECTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROISS (FSGS)*
Authors: Cortazar Frank , Niles John L , Schall Thomas J , Staehr Peter 
Published: May 2021

Abstract

Background and Aims
Primary Focal Segmental Glomerulosclerosis (FSGS) is the most common primary glomerular disease in patients with end stage renal disease in the United States. Current treatment regimens target reduction in proteinuria, but may have limited response or exhibit disease recurrence. CCX140 is an orally-administered selective small molecule inhibitor of the C-C chemokine receptor 2 (CCR2) under investigation for the treatment reduction of proteinuria in patients with FSGS.
The primary objectives of this study were to evaluate the safety and efficacy of CCX140 in patients with FSGS and a urine protein to creatinine ratio (UPCR) of ≥1 g/g. Efficacy was assessed by the change in UPCR.

Method
Forty-six adult patients with primary or genetic FSGS were randomized into a double-blind, placebo-controlled Phase 2 dose-ranging study designed to evaluate the safety and efficacy of CCX140. Changes of urinary protein excretion estimation (UPCR) from baseline to Week 12 were measured in four blinded treatment groups (three active CCX140 doses of 5 mg once daily, 10 mg and 15 mg twice-daily (BID) vs placebo). Starting at Week 12, all subjects including those in the placebo group received the CCX140, 15 mg BID for an additional 12 weeks, and UPCR changes from Week 12 to Week 24 were assessed. There was a 4-week follow-up period from Week 24 to Week 28 where no CCX140 was administered.

Results
In the intent to treat (ITT) analysis of UPCR changes at Week 12 relative to baseline, the 15 mg BID CCX140 group exhibited the greatest reduction of UPCR (median reduction from baseline 0.9 g/g or approximately 30%, and approximately 25% reduction from baseline for the geometric mean), but that did not differ significantly from the placebo group (median reduction from baseline 0.45 g/g; or approximately 22%, and approximately 23% reduction from baseline for the geometric mean). Also, after crossover of the blinded portion of the trial to 15 mg BID active dosing, the previous placebo group did not appear to exhibit an additional reduction of UPCR. CCX140 at all doses was well-tolerated, with no serious adverse events (SAEs) during the blinded trial and a numerically lower rate of treatment-emergent adverse events in the CCX140 treatment groups.

Conclusion
In the study, CCX140 did not demonstrate a therapeutically meaningful reduction in proteinuria relative to the control group after 12 weeks of blinded treatment. The study provides insights into the natural disease progression of patients with primary or genetic FSGS as part of a clinical trial setting.
MO255LONG-TERM MAINTENANCE TREATMENT WITH RITUXIMAB IN ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT STUDY
Authors: Chalkia Aglaia , Thomas Konstantinos , Kourniotis Dimitrios , Panagiotopoulos Alexandros , Alexakou Zoe , Mpora Margarita , Aggelis George , Vasilopoulos Dimitrios , Petras Dimitrios 
Published: May 2021

Abstract

Background and Aims
There is limited guidance and evidence for the ideal duration of maintenance treatment in ANCA-associated vasculitis (AAV) with rituximab (RTX). This study aimed to describe the efficacy and safety of long-term maintenance treatment with RTX, in a cohort of patients with AAV.

Method
Retrospective, descriptive study of 62 patients with AAV. We included 42 patients, who received RTX maintenance treatment in a newly diagnosed or a relapsed disease. We recorded the duration, dosage, and adverse events (infections, infusion-related events, relapses, late onset leukopenia, malignancy and hypogammaglobulinemia).

Results
43 patients (average age 60.33 years, 49% women) received fixed interval dosing with RTX maintenance 1000 mg every 6 months. The most frequent organ involvement (74%) was lung and/or kidney. 33% (14/43) of the patients received RTX maintenance in a relapsed disease. The RTX regimen was followed after induction treatment with rituximab (47%), cyclophosphamide (33%), combination cyclophosphamide and rituximab (14%) or methotrexate/MMF (6%). Median total duration of maintenance treatment was 24 months (range 6-72 months). The most frequent adverse event was serious infections in 23% of the patients, including SARS-CoV-2 in two patients, while four of these patients died. We also recorded: hypogammaglobulinemia in 14%, malignancy in 5% and infusion-related events in 2%. The rate of the major relapses in our cohort during RTX maintenance was quite low at 7% (3/43), the time between 24-60 months, and the rate of the major relapses dependent on the induction treatment was quite the same: cyclophosphamide group vs rituximab group (7 vs 10%, p=0.786).

Conclusion
In our cohort long-term maintenance treatment in AAV with rituximab maintains remission for longer time, with a quiet safety profile. This could suggest that in selected patients, extended periods of rituximab treatment might be safe.
MO261LUPUS NEPHRITIS AND COVID-19 INFECTION
Authors: Valentinova Monova Daniela , Monov Simeon 
Published: May 2021

Abstract

Background and Aims
Covid-19 infection poses a serious challenge for immune-compromised patients with autoimmune systemic diseases. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities.
The aim of this study is to describe clinical characteristics of patients with lupus nephritis (LN) and Coronavirus disease 2019 (COVID-19), and to identify baseline variables associated with a severe infection requiring hospitalization.

Method
A telephone survey investigating the impact of COVID-19 on patients with biopsy - proven LN was administered. Data extraction included diagnosis, disease activity status, demographics, occupational exposure, adherence to social distancing advise, therapy, comorbidities, and laboratory tests. Covid-19 was classified as definite diagnosis of Covid-19 disease (presence of symptomatic Covid-19 infection, confirmed by a nasopharyngeal SARS-CoV-2 polymerase chain reaction test). Comparisons between patients with or without hospitalization were performed.

Results
114 patients (median age 34,9 ± 12,4 years) with LN were included in the study. All were on different doses glucocorticoids, 82 were taking hydroxychloroquine and 30 took immunosuppressants. 31 patients (26 women, 5 men) developed symptomatic COVID-19 infection - they have at least one symptom (chest pain, fever, asthenia, chills, cough, sore throat, dyspnea, headache, arthralgia, myalgia, odynophagia, diarrhea, conjunctivitis, hypo-, ageusia, hypo-, anosmia) of COVID-19 and were PCR test positive. These 31 patients prior to their COVID-19 illness were treated with methylprednisolone, 16 - with cyclophosphamide, 8 - with azathioprine, 3 – with hydroxychloroquine. Six patients (4 men, 2 women) required hospitalization - these were more frequently older and with comorbidities (cardio-respiratory illness, hypertension and other) and active LN (3 –class IV LN, 2-class V LN, 1 class III LN and 1 Class II LN, according the 2003 ISN/RPS classification). Adherence to therapy and to social distancing advise was high. The median time from onset of symptoms to hospital admission was 6 (3-11) days. The median length of stay was 12 days (8-20) days. No deaths occurred.

Conclusion
Covid-19 is more frequent in the subgroup of LN patients without therapy with hydroxychloroquine, which might play some protective role against the most harmful manifestations of Covid-19. Male sex, previous lung disease, serum creatinine level, proteinuria, glucocorticoids use &gt; 5 mg/day, were associated to hospitalization of patients with LN.
MO263KLOTHO IS PROTECTIVE IN THE CONTEXT OF ACUTE GLOMERULAR INJURY BUT IS NOT EXPRESSED IN PODOCYTES
Authors: Charrin Emmanuelle , Dabaghie Dina , Mencke Rik , Sen Ilke , Möller-Hackbarth Katja , Zambrano Sonia , Olauson Hannes , Patrakka Jaakko 
Published: May 2021

Abstract

Background and Aims
Podocyte integrity is crucial for the maintenance of glomerular function in health and disease. Numerous studies have reported that Klotho overexpression, or treatment with recombinant Klotho, reduces glomerular and tubular damage in mouse models of renal disease. However, the mechanism(s) of action are not fully understood. Several recent studies have also reported that Klotho is expressed in podocytes, where it protects against various types of injury. These findings conflict with previous studies, which have shown that renal Klotho expression is exclusively confined to proximal and distal tubular cells.

Method
To address this discrepancy and enhance our understanding of the putative glomeruloprotective effects mediated by Klotho, we examined the expression pattern of Klotho in human and mouse kidney by several different methods, and explored its protective effects by overexpressing full-length human Klotho directly in podocytes or in a distant organ (i.e. liver).

Results
Data at the mRNA and protein levels all converged towards an absence or very low expression of Klotho in podocytes. The generation of a podocyte-specific Klotho knockout mouse further demonstrated that its deletion did not affect glomerular structure or function. Moreover, Klotho deficiency did not worsen glomerular injury in an experimental model of glomerulonephritis (anti-GBM). However, when Klotho was overexpressed in hepatocytes (Alb-cre;hKlothofl/+ - Alb-hKL), serum Klotho increased drastically with no changes in Fgf23 or phosphate metabolism. In mice challenged with anti-GBM, renal histology and ultrastructure of the filtration barrier was less severely affected in Alb-hKL compared to WT mice. There were also significantly less albuminuria, podocyte loss and interstitial fibrosis in Alb-hKL mice compared to their WT littermates. In contrast, mice which overexpressed Klotho in podocytes (Pod-hKL) were not protected from renal injury.

Conclusion
Taken together, these results strongly suggest that Klotho is not expressed in any substantial amounts in human or mouse podocytes, and that membrane-bound Klotho does not play a role in podocyte biology. Importantly, our results confirm a beneficial role for soluble Klotho in protecting podocytes against injury, and in maintaining glomerular integrity and function.
MO264COMPLEMENT PATHWAY MIGHT HAVE A ROLE IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS: A RETROSPECTIVE SINGLE CENTER STUDY OF 15 YEARS
Authors: Eren Sadioğlu Rezzan , Kiremitçi Saba , Aktar Merve , Şengül Şule , Gokmen Derya , Akturk Serkan , Keven Kenan , Nergizoglu Gökhan , Ertürk Şehsuvar , Ateş Kenan , Ensari Arzu , Kutlay Sim 
Published: May 2021

Abstract

Background and Aims
The role of complement in focal segmental glomerulosclerosis (FSGS) is an area of interest and C4d staining could indicate complement related renal damage. We investigated detailed C4d staining properties in native kidney biopsies and possible relation to clinical features.

Method
We retrospectively evaluated the renal biopsies of 114 patients diagnosed with FSGS within last 15 years. C4d expressions examined in glomeruli (mesangial and/or capillary wall, vascular pole, sclerotic areas), tubular region (basement membrane, adsorbtion droplet) and vascular areas (arteriols and arteries) via immunohistochemistry. A novel glomerular C4d score (G-C4d-S) was achieved on the basis of the localization, pattern, extent and intensity of the C4d expression (min-max, 0-13).

Results
Of the patients (56 females, mean age 43±14 years) with a median follow-up time of 35±3 months, mean proteinuria, eGFR, and albumin level were 4984 mg/day, 72.2 ml/min/1.73m2, 3.56 g/dL, respectively. Median G-C4d-S was 6 (IQR, 4-7) and it was negatively correlated with serum creatinine at diagnosis (r=-0.21, p=0.02). Glomerular staining (both focal and diffuse, higher than moderate in intensity) was positive in 78 (68.4%) of the patients. C4d on glomerular sclerotic area was positive in 43 (37%) patients and it was associated with lower eGFR at diagnosis.
Forty five patients achieved remission during the follow-up. Among the pathological features only glomerular C4d staining was associated to remission (p=0.02). There were 20 (18.7%) patients who need renal replacement theraphy (RRT) and 7 deaths (6.1%) at the end of the cohort. Lower rate of C4d staining on tubular adsorption droplets and arteriols/arteries were found to be associated need for RRT (p=0.013, p=0.012, respectively). There were no significant relationship between mortality and C4d staining features.

Conclusion
In conclusion, we noted that significant number of patients had positivie C4d on glomeruli, arteiroles and tubular area. We indicated that C4d staining at diagnosis could help to distinguish active glomerulonephritis. Additionally, it seems to be essential to examine non-glomerular area of native kidney biopsies, as well.
MO266URINARY TRANSFERRIN AND IGG EXCRETIONS PREDICT TUBULOINTERSTITIAL LESIONS IN PATIENTS WITH IGA NEPHROPATHY
Authors: Elena Saganova , Galkina Olga , Sipovskii Vasiliy , Smirnov Alexei 
Published: May 2021

Abstract

Background and Aims
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is a frequent cause of end-stage renal disease. The best predictors of progression are histologic parameters. Nevertheless, there is a pressing need to identify suitable noninvasive biomarkers in IgAN, to aid with diagnosis, treatment decisions, and prediction of the disease progression.
Our aim was to assess diagnostic value of urinary excretions of transferrin and IgG in prediction of morphological lesions in patients with IgAN.

Method
37 patients [19 female, age Me 33 (25; 48) years] with biopsy proven IgAN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. 24-hour urinary excretions of transferrin (uTr), IgG (uIgG) were measured by immunoturbidimetric method (Furuno CA-90, Furuno Electric Co., Ltd., Japan). Tubulointerstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3-diffuse tubular and interstitial lesions). All patients consistently were separated into two groups according to the degree of each morphological lesion (TIF or TA): “mild” (TIF or TA grade 0 or 1) and “severe” (TIF/TA grade 2-3).

Results
uTr, uIgG positively correlated (p&lt;0,05) with TIF (r=0,38, r=0,43) and TA (r=0,38, r=0,45), respectively. We did not find correlations between uTr, uIgG and glomerulosclerosis.
Using ROC-analysis all patients were separated in two groups using uTr or uIgG according to the degree of morphological lesions (“mild” or “severe) (Table 1,2; Figure 1).
According to the results of ROC-analysis we also found that all cut-off values of uTr, uIgG corresponded to the level of urinary protein excretion not more than 1,25 g/24hour.

Conclusion
Our results show that uTr and uIgG can be used as markers of early tubulointerstitial lesions in patients with IgA nephropathy with mild protein excretion.
MO270PROGNOSTIC ROLE OF ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY NEGATIVIZATION AT THREE MONTHS IN MEMBRANOUS NEPHROPATHY
Authors: Stefan Gabriel , Stancu Simona , Popa Otilia , Zugravu Adrian Dorin , Petre Nicoleta , Mircescu Gabriel 
Published: May 2021

Abstract

Background and Aims
The predictive value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) levels at three-months from diagnosis in patients with membranous nephropathy (MN) is not proven.

Method
We retrospectively examined the renal outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, serum creatinine 1.0 (0.9, 1.3) mg/dL) who were diagnosed with MN by kidney biopsy and had positive serum anti-PLA2R ab during 2016-2019.
The outcomes were: kidney survival defined as renal replacement therapy (RRT) initiation; partial (proteinuria 0.5 to 3.5g/24h) or complete remission (proteinuria &lt;0.5g/24h and serum albumin ≥3.5g/dL) - whichever came first.
Variables related to renal outcome were further evaluated in univariate and multivariate Cox proportional hazard (CPH) models.

Results
Forty (69%) patients had negative anti-PLA2R ab at 3 months; there were no differences regarding age, serum creatinine, serum albumin, proteinuria and treatment when compared to the group with positive ab at 3 months.
Fifty-seven (97%) patients received immunosuppressive treatment, cyclophosphamide-based regimens were the most frequent (87%), followed by cyclosporine (10%).
Overall, 64% of the patients reached a form of remission. Cumulative remission rates were 34% after 6 months, 54% after 12 months, 68% after 18 months and 73% after 24 months. Only five patients (9%) relapsed during the study period. Median time to cumulative remission was 12.0 (95%CI 8.2, 15.7) months.
In the CPH models, negativization of the anti-PLA2R antibodies at three months was an independent predictor for remission, however lower serum albumin was also retained as a risk factor for absence of remission (Table 1).
During the follow up period 6 (10%) patients died. Cardiovascular disease and infections were the main causes of death. A total of 5 (9%) patients started RRT during the study period. The mean renal survival time was 50.3 (95%CI 46.5, 54.0) months. We found no difference in renal survival regarding anti-PLA2R Ab titer or negativization.

Conclusion
Negativization of anti-PLA2R antibodies in the first three months from diagnosis was a predictor for remission in patients with membranous nephropathy.
MO272CLINICOPATHOLOGICAL CORRELATION OF APRIL AND BAFF IN IG A NEPHROPATHY- A SINGLE CENTER LONGITUDINAL OBSERVATIONAL STUDY
Authors: Gopal Anjana , Gracious Noble 
Published: May 2021

Abstract

Background and Aims
Aberrantly glycosylated IgA1 molecules are important in the pathogenesis of IgA nephropathy. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are cytokines involved in immunoglobulin class switching and production of galactose deficient IgA1(Gd IgA1). We aimed to study the association of serum levels of APRIL and BAFF with the clinical severity and pathological grading of IgA nephropathy (IgAN) and to assess the strength of the association by studying the clinicopathological correlation.

Method
The research study was conducted as a single-center longitudinal observational study. The study subjects were recruited based on the pathological diagnosis of primary IgA nephropathy. The plasma levels of APRIL, BAFF and Gd IgA1 were estimated using enzyme-linked immunosorbent assay (ELISA). All the study subjects were followed up for one year to study the renal outcome.

Results
In our study group of thirty-eight patients, the median estimated glomerular filtration rate(eGFR) was 33.9(15.9,79.4) ml/minute/1.73m2. The median levels of the cytokines APRIL and BAFF were 170.81(82.45, 550.61) ng/L and 6.66(3.39,16.33) ng/ml respectively. The baseline characteristics of the study group is given in table 1. APRIL levels had significant positive correlation with Gd IgA1 levels (correlation coefficient 0.556, p=0.003) in patients with IgAN. We also observed that patients with elevated APRIL levels had elevated BAFF levels also (correlation coefficient 0.657, p &lt;0.001). Patients who had crescents, mesangial hypercellularity and endocapillary proliferation in biopsy had elevated APRIL and BAFF levels whereas patients with segmental sclerosis and tubular atrophy had low levels of APRIL(Table 2). However, the levels of APRIL and BAFF did not show any significant correlation with eGFR and proteinuria at time of presentation. At the end of one year, 12(31.5%) patients reached end stage renal disease (ESRD) and these patients had lower levels of APRIL, BAFF, and Gd IgA1. It was also seen that eighty-three percent of those who reached ESRD had chronic changes in biopsy like tubular atrophy and interstitial fibrosis(p=0.05). Hence the severity of tubulointerstitial fibrosis in histology correlated well with progression to end stage renal disease as seen in most glomerular diseases. But we did not find any association between APRIL, BAFF, and Gd IgA1 levels and the decline in eGFR over one year.

Conclusion
We conclude that levels of APRIL and BAFF are associated with elevated levels of Gd IgA1 in patients with IgAN and had a significant association with proliferative lesions in renal biopsy. But these cytokines levels did not have any association with the eGFR at time of presentation nor decline in eGFR over one year.