bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0332DIAGNOSTIC, THERAPEUTIC AND EVOLUTIONARY FEATURES OF KIDNEY DISEASE IN MULTIPLE MYELOMA
Authors: Breik Nessrine , Samia Barbouch , Najjar Mariem , Fattoum Safa , Ben Nsira Sawsen , Azaiez Seif , Harzallah Amel , Karoui Syrine , Gorsane Imen , Benhmida Fethi , Ounissi Monther , Benabdallah Taieb 
Published: June 2020

Abstract

Background and Aims
Multiple myeloma (MM) is a malignant disease of plasma cells. It’s is characterized by clonal proliferation of malignant plasma cells producing monoclonal proteins and causing organ damage. Kidney injury is a common complication of multiple myeloma. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal immunoglobulin and some of which are independent of paraprotein deposition.

Method
We conducted a retrospective study, from January 1974 to June 2019, including all cases of multiple myeloma with renal impairment treated in our Department. The objective of this study is to analyze the epidemiological and clinico-biological characteristics of MM with renal impairment and to identify the predictive factors of mortality.

Results
We collected 196 cases. The average age was 63.47 years (31-86 years) with a male predominance (sex ratio 1.27). The circumstances of discovery was dominated by asthenia, anorexia and weight loss in 150 cases (76.5%). Renal involvement was present at the time of diagnosis of myeloma in 138 patients (70.4%) with an average serum creatinine level of 686.42 μmol/l (92-2960 μmol/L). The average hemoglobin level was 8.05 ± 2.4 g/dl. The average 24-hour proteinuria was 2.62 ± 2.11 g/24h. The renal biopsy puncture was performed in 48 patients (24.4%), revealing myelomatous tubulopathy in 16.32% of cases, AL amyloidosis in 5.1% of patients, Randall disease in 3.06% of patients, nodular glomerulosclerosis in 1% of cases and membranous nephropathy in one patient. In our series, 170 patients received chemotherapy. Of the patients, 25.5% required hemodialysis at the time of diagnosis of MM. In our series, 66.83% progressed to the end stage renal disease, 25.5% were in partial remission and 2.05% in total remission. The causes of death were dominated by infectious complications (14.97%). The average renal survival was 4 months. The prognostic factors correlated with poor renal survival were tobacco (p = 0.01), serum uric acid&gt; 600 μmol/l (p = 0.04) and 24-hour proteinuria&gt; 5g/24h (p = 0.009).

Conclusion
Renal involvement is frequent in multiple myeloma. The spectrum of renal lesions is heterogeneous, and it determines the management and prognosis of MM so the factors associated with renal recovery should be studied further.
P0334HEMOLYTIC UREMIC SYNDROME: CLINICAL PRESENTATION, LABORATORY FINDINGS, MANAGEMENT AND OUTCOMES
Authors: Al Salmi Issa , Metry AbdelMasiah , Hannawi SUAD 
Published: June 2020

Abstract

Background and Aims
Hemolytic-uremic syndrome (HUS) is a disease that has been described as a triad of hemolytic anemia, thrombocytopenia and renal impairment. There are two types of HUS, typical and atypical. HUS remains a leading cause of acute renal injury in children and is increasingly recognized as a cause of renal failure in adults. In our study we evaluated the demographic features, clinical characteristics, management and outcome of HUS.

Method
This is a descriptive study evaluating all cases of Hemolytic Uremic Syndrome (HUS) that have been admitted at Royal Hospital (RH) Oman in the period between 2008 and 2017.

Results
Thirty-six patients identified. The mean age (SD) of 10.68 (14.07) years.
Eighteen (50%) presented with abdominal pain, nausea, vomiting and diarrhea, 9 (25 %) with hypertension, 23 (64 %) with acute kidney injury (AKI), 6 (16.67%) with seizure, 2 (5.56%) with confusion and 1 (2.78%) with cerebrovascular accident (CVA).
Twenty-one (58.33 %) diagnosed as typical HUS of which 19 with Shiga toxin producing Escherichia Coli (STEC) HUS and 2 had post Streptococal HUS.
Six (16.67%) diagnosed with aHUS, 2 (5.56%) with HELLP, 2 (5.56%) with G6PD, 3 (8.33%) with Autoimmune hemolytic anemia (AIHA ), one (2.78%) with congenital TTP and 1 (2.78%) with post partum HUS.
Twenty three (63.89%) needed renal replacement therapy (RRT), while remaining 13 (36.11%) did not require RRT.
Eleven (30.56%) received plasma exchange, 5 (13.89%) received Eculizumab while 2 (5.56%) received plasma infusion and 1 (2.78%) patient received Rituximab.
The majority 22 (61.11%) had partial recovery after treatment, 5 (13.89 %) had compelte recovery and 3 (8.33% ) ended with end stage kidney disease (ESKD) and 1 (2.78%) died from hypertensive crises.

Conclusion
The study results showed that HUS population were mostly due to Shiga toxin producing Escherichia Coli (STEC). It showed that HUS population were young, mostly male and only 25% have known medical comorbidities at time of presentation. Also, the majority presented with AKI requiring dialysis, of which PD was main stay of therapy. The duration of RRT and recovery time was almost a month period.
P0356QUANTITATIVE ASSESSMENT OF GALNAC NUMBER IN THE HINGE REGION OF IGA1 IN IGA NEPHROPATHY WITH CRESCENTS FORMING
Authors: Yu Guizhen , Zhang Yong , Xie Xinfang , Meng Bo , Ying Wantao , Lv Jicheng , Zhang Hong 
Published: June 2020

Abstract

Background and Aims
Aberrant IgA1 O-linked glycosylation of IgA1 hinge region (HR) has been shown playing an important role in the pathogenesis of IgA nephropathy (IgAN). Serum levels of galactose-deficient IgA1 (Gd-IgA1) was associated with the development and progression in IgAN, however variations in the composition of IgA1 HR glycoforms are unknown. In this study we aim to quantitative assessment of GalNAc number in the hinge region of IgA1 in IgAN with crescents forming using mass spectrometry.

Method
Plasma polymeric IgA1 (pIgA1) was purified from a discovery cohort including crescentic IgAN (n=11) non-crescentic IgAN (n=10) and healthy controls (HC, n=10) and a validation cohort (crescentic IgAN, n=10; non-crescentic IgAN, n=10 and healthy controls, n=11). After denaturation, reduction, alkylation and trypsin digestion, liquid chromatography-high-resolution mass spectrometry (LC-MS) was used to analyse the IgA1 HR glycans. The intensity of the identified IgA1 O-glycopeptide was calculated and expressed as the relative abundance for each glycopeptide. The molecular weight (MW) of intact O-glycopeptide was calculated as the formula following:
MW = HR + x GalNAc + y Gal + z NeuAc + H+
(x, y and z represent the number of GalNAc, galactose and NeuAc which bind to one HR in IgA1 O-linked glycopeptides respectively)
Glycopeptide content ratio = (glycopeptide peak intensity/ total glycopeptide intensity) ×100%.

Results
In the discovery cohort population, the level of Gd-IgA1 was highest in patients with crescentic IgAN, middle in patients with non-crescentic IgAN and lowest in healthy controls (347.69±57.89 U/ml vs 336.32±38.44 U/ml vs 330.14±33.22 U/ml), albeit that didn’t reach the statistical significance. There were significantly difference in GalNAc number of IgA1 HR among patients with IgAN and healthy controls. Overall the numbers of GalNAc bound to one HR was much lower in the patients than healthy controls. As shown in the Figure 1, the proportion of GalNAc 3, defined as O-glycans that were bound to one HR at 3 sites, were highest in patients with crescentic IgAN, then the non-crescentic IgAN and lowest in the healthy controls (9.92%±3.37% vs 6.65%±1.53% vs 4.05%±1.24%; p-value for the trend&lt;0.001). Similar results were observed in GalNAc 4 (45.91%±4.75% vs 41.13%±2.95% vs 40.98%±2.95%; P=0.004. However regarding the GalNAc 5 and GalNAc 6, crescentic IgAN was lowest, then non-crescentic IgAN and highest in the healthy control (GalNAc 5: 45.17%±5.46% vs 46.90%±2.78% vs 48.05%±3.02%, P=0.001 GalNAc 6:1.62%±1.60% vs 3.95%±1.92% vs 5.39%±2.38%; P&lt;0.001). These results were consistent in the validation cohort (Figure 1).

Conclusion
GalNAc numbers in IgA1 HR was lower in patients with IgAN especially in crescentic IgAN. These results suggest that the O-glycans of IgA1 were associated with the severe phenotype in IgA nephropathy.
P0358HYDROXYCHLOROQUINE PREVENTS ANTI-GBM GLOMERULONEPHRITIS IN RATS
Authors: Torigoe Miki , Obata Yoko , Inoue Hiro , Torigoe Kenta , Kinoshita Akira , Koji Takehiko , Nishino Tomoya 
Published: June 2020

Abstract

Background and Aims
Anti-glomerular basement membrane (GBM) glomerulonephritis (GN), characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is a well-known antimalarial drug. In addition, it has immunomodulatory, anti-inflammatory, and autophagy inhibitory effects and its recognized in the treatment of autoimmune disease such as SLE. However, its effect for anti-GBM GN is unknown. In this study, we investigated the effect of HCQ against anti-GBM GN in rats.

Method
7 week old male, WKY rats were induced by the administration of anti-GBM serum (50μg/rat). We administered either HCQ (50mg/kg) or vehicle (Phosphate-buffered saline) from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, hematuria. Urine was collected for 24 hours on day 1, 3, 5, and 7. Rats were sacrificed on day 7 after induction of anti-GBM GN. Renal histological changes were assessed by PAS staining, and Masson trichrome stain, and macrophage was assessed by ED-1 stain. Mitogen-Activated Protein Kinase (MAPK) was evaluated by western blotting (WB) and inflammatory cytokines were evaluated by ELISA using urine.

Results
HCQ treatment suppressed renal function decline. Histologically, extracellular and intracellular cells were increased from day 1, fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM GN had high levels of interferon-α, interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α. These changes were significantly suppressed by HCQ. In addition, HCQ suppressed phosphorylation of JNK/p38 MAPK.

Conclusion
Our study showed that HCQ could attenuate anti-GBM GN and have an anti-inflammatory effect by inhibiting JNK/p38 MAPK activation. HCQ may have therapeutic potential in anti-GBM GN.
P0373MEPOLIZUMAB THERAPY FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) - ONE YEAR FOLLOW-UP STUDY USING ANTI-IL5 AS A STEROID SPARING THERAPEUTIC APPROACH
Authors: Egan Allyson , Sivasothy Pasupathy , Gore Robin , MartinezDel-Pero Marcos , Willcocks Lisa , Smith Rona , Burns Stella , Owen Caroline , Jones Rachel B , Jayne David 
Published: June 2020

Abstract

Background and Aims
EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophilia, necrotising vasculitis and granulomatous inflammation1. Typically, a prodromal asthmatic phase, leads to an eosinophilic stage, which can evolve to include the presence of vasculitis with renal manifestations. In the recent randomised, placebo-controlled MIRRA trial for relapsing and refractory EGPA, adjuvant therapy with anti-IL5 mAB Mepolizumab [MEPO] at 300mg s/c monthly, accrued longer times in remission, reduced steroid exposure and reduced relapse rates2. The aim of our study was to analyse the response and outcome for EGPA patients who received 100mg s/c of MEPO monthly for a minimum of 52 weeks, with particular focus on the steroid minimisation benefits.

Method
This retrospective, descriptive study analysed 13 patients with EGPA, who received 100mg s/m monthly MEPO therapy under the eosinophilic asthma care-pathway. Time points of assessment included MEPO commencement [M0] and 12 [M12] months.

Results
One patient had MEPO switched to Rituximab to treat both EGPA and new onset rheumatoid arthritis

Conclusion
The relapsing nature of EGPA places a potential dependency of therapy on steroids for asthmatic and vasculitic flares. This underscores the importance of targeted pathway specific biologic therapy to minimise steroid exposure, prevent tissue damage and ensure early response to therapy. This study demonstrates that anti-IL5 serves as a favourable model with steroid minimisation, improvement in asthma control questionnaire, reduction in BVAS and eosinophil counts at the 100mg s/c dosage. ANCA positive serology normalised in all four patients, independent of subtype. Well tolerated, it demonstrated considerable clinical benefit, with 12 patients [92.3%] continuing anti-IL5 therapy beyond 12 months. Adjuvant therapy with conventional immunosuppressants was well tolerated and renal function was preserved.
ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. J.C.Jenette, et al Revised International Chapel Hil Consensus Conference Nomenclature of Vasculitides. 65, 1–11 (2013).
2. Wechsler, M. E. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N. Engl. J. Med. 376, 1921–1932 (2017).
P0379BION-1301, A FULLY BLOCKING ANTIBODY TARGETING APRIL FOR THE TREATMENT OF IGA NEPHROPATHY: ASSESSMENT OF SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS IN LONG-TERM NONCLINICAL STUDIES
Authors: Kreijtz Joost , Van Zandvoort Peter , Van de Crommert Jos , Friesen Maarten , Lo Jeannette , Endsley Aaron , Lauriault Veronique , Mueller Thomas , Van Elsas Andrea 
Published: June 2020

Abstract

Background and Aims
IgA Nephropathy (IgAN) is a common form of glomerulonephritis and its pathogenesis is thought to consist of sequential pathogenic hits, including the production of auto-antigen galactose-deficient IgA1 (Gd-IgA1) and auto-antibody formation ultimately resulting in immune complex deposition, inflammation and functional deterioration of the kidney. Serum levels of APRIL (A PRoliferation Inducing Ligand, TNFSF13) and levels of Gd-IgA1 are correlated with severity of disease (Zhao et al, 2012). As a ligand for the receptors BCMA and TACI, APRIL is thought to regulate differentiation and proliferation of B cells and plasma cells and IgA class switching. BION-1301 is a humanized antibody neutralizing APRIL. In nonhuman primates, BION-1301 reduced serum levels of IgA, IgM, and IgG with no drug-related toxicity (Dulos J, et al. ASN Annual Meeting. 2018). Here we describe the nonclinical safety assessment of BION-1301, to support its continued clinical development for the treatment of IgA Nephropathy.

Method
A 14-week repeat-dose toxicity and toxicokinetic/pharmacodynamic (TK/PD) study in non-human primates (NHP) was performed by biweekly intravenous bolus (IV) administration of BION-1301 at three different dose levels. To support a potential change in route of administration, a 4-week repeat-dose NHP bridging study was conducted with weekly subcutaneous (SC) administration of BION-1301 at three different dose levels.

Results
In both the 14-week IV study and the 4-week SC study, BION-1301 was evaluated for safety, TK and PD. For TK and PD, BION-1301 levels, uncomplexed APRIL levels and immunoglobulin levels (IgA, IgG, IgM) were quantified in serum. Immunophenotyping was performed on peripheral blood to assess the impact of BION-1301 on the B cell compartment. In both studies BION-1301 was well tolerated with no test-article related findings. 14-week IV dosing as well as 4-week SC dosing of BION-1301 reduced serum APRIL levels as well as serum immunoglobulin levels.

Conclusion
Results of these nonclinical toxicity studies with toxicology, TK and PD endpoints demonstrate that BION-1301 is well tolerated for up to 14 weeks of dosing, corroborates pharmacodynamic proof-of-mechanism and support prolonged dosing and SC administration of BION-1301 in patients with IgA Nephropathy.
P0382“FALSE” POSITIVITY OF SERUM ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY (ANTI-PLA2R AB) IN PATIENTS WITH NON MEMBRANOUS GLOMERULAR DISEASE
Authors: Mok Irene , Choo Jason 
Published: June 2020

Abstract

Background and Aims
Phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN) and the detection of circulating autoantibodies to PLA2R (Anti-PLA2R Ab) is a major advance in understanding this disease. In this study, we aimed to determine if Anti-PLA2R Ab serves as a specific marker for PMN in our multi-ethnic Southeast Asian cohort.

Method
This was a prospective cohort study of all adults with glomerular disease undergoing biopsy between 1st January 2015 and 30th June 2018. Anti-PLA2R antibody levels were quantitatively determined by IgG ELISA (Euroimmun). Results are expressed as RU/ml. We considered a value of &gt;20RU/ml to represent a positive result, value of &lt;14RU/ml to be negative and values between 14-20 RU/ml to be indeterminate.

Results
Out of the cohort of 192 patients, there were 27 patients with Membranous Nephropathy (MN), with 12 PMN and 15 with secondary MN (SMN). Secondary causes were Hepatitis (1), Malignancy (1), Lupus (13). In our analyses, 10 (83.3%) PMN pts were positive for Anti-PLA2R Ab, with 7(58.3%) strongly positive with titres &gt;200RU/ml and 2(16.7%) negative. For SMN, the majority, 12 out of 14 patients (85.7%) tested negative and the remaining 2 (7.7%) yielded values of indeterminate levels.
Of note, among the 165 patients with non membranous glomerular disease, there were 15 patients (9.1%) with indeterminate Anti-PLA2R Ab levels and 31 patients (18.9%) tested positive for Anti-PLA2R antibody, with levels &gt;20 RU/ml. Of these 31 patients, the majority of the patients had low levels of Anti-PLA2R Ab of &lt;50 RU/ml. However there were 5 patients who had considerably high levels of Anti-PLA2R Ab of &gt;50 RU/ml and their characteristics are tabled below (Table 1)

Conclusion
Consistent with other published studies, positive Anti-PLA2R antibody levels were highly specific for PMN in our multi-ethnic Southeast Asian population and our centre has since been consistently using this test for differentiating between PMN and SMN. What is most striking in our study is that we have found high-titre Anti-PLA2R antibody positivity in non-MN patients, which has not been frequently reported in literature. The unifying feature amongst these patients appear to be the presence of arterial and arteriolar sclerosis which is usually non-specific. Though we would not normally do the Anti-PLA2R antibody test in a patient with low suspicion of MN, our study findings warrants further investigation and may indicate the limited usefulness of Anti-PLA2R antibody levels as a screening tool for glomerulonephritis.
P0393NEPHROTIC SYNDROME IN POST HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS-20 YEARS' EXPERIENCE IN A SINGLE CENTER
Authors: Ha Myung Ah , Yang Chul-Woo , Kim Yong-Soo , Park Cheol Whee 
Published: June 2020

Abstract

Background and Aims
Nephrotic syndrome (NS) is an extremely rare complication of hematopoietic stem cell transplantation(HCT) that usually occurs in association with chronic graft-versus-host disease. The etiology and pathogenesis of NS in HCT recipients remain unclear. There are only a few case reports and case series of NS following HCT that have been published.

Method
We reviewed the records of kidney biopsy in Seoul St. Mary’s Hospital between January, 2008 and January, 2019, and identified 32 kidney biopsy specimens from patients obtained after HCT. All patients underwent kidney biopsy for proteinuria or increased creatinine. Patient demographic data and laboratory data were collected for analysis. Responses to treatment were categorized as complete remission (CR), partial remission (PR), or non-response. The CR and PR were defined as a reduction of urine protein/creatinine ratio to &lt;0.3g/day and urine protein/creatinine ratio between 0.31g/day and 3.4g/day, respectively.

Results
Of the 32 cases, 21 were male and 11 were female patients. The mean patient age was 43.7(range: 15-68). Average follow-up period was 46.6 months (range: 2-107 months). The mean duration between HCT and renal biopsy was 33.2 months (range: 6–206 months). The underlying diseases resulting in the need for HCT were acute myeloid leukemia, 10 patients; acute lymphoid leukemia, 9 patients; aplastic anemia, 4 patients; myelodysplastic syndrome, 3 patients; multiple myeloma, 3 patients; chronic myeloid leukemia, 1 patient; amyloidosis, 1 patient; and blastic plasmacytoid dendritic cell neoplasm, 1 patient. The most common histopathological finding was membranous glomerulonephritis (N=20). Other glomerular diseases identified were thrombotic microangiopathy, amyloidosis, C1q nephropathy, focal segmental glomerulosclerosis and diabetic nephropathy. During the follow-up period, 25 patients were treated with steroids or cytotoxic agents.18 patients were treated with angiotensin II receptor antagonist. There was no statistically significant difference between the groups in terms of ANOVA of the decrease in proteinuria according to steroids or cytotoxic agents treatment (p = 0.075) and ARB treatment. (p = 0.156)

Conclusion
Based on our result, more case will require discussion of treatment options for NS following HCT.
P0399RELAPSE TREATMENT WITH LOW DOSE OF STEROIDS IN STEROID-SENSITIVE MINIMAL CHANGE DISEASE
Authors: Álvarez Nadal Marta , Martin Irene , Villa Hurtado Daniel Eduardo , Viera Ramírez Elizabeth , Lopes Vanessa , Fernandez Lucas Milagros , Villacorta Javier 
Published: June 2020

Abstract

Background and Aims
Treatment of Minimal change disease (MCD) consists of high dose of steroids (HDS) for several weeks implying significant drug toxicity. On the other hand, renal relapses of steroid-sensitive MCD sometimes respond to lower doses of steroids.

Method
The objective of the study was to analyze weather low dose for steroids (LDS) is effective for treatment MCD relapses among frequently-relapsing steroid-sensitive patients. Since 2019, new relapses of steroid-sensitive patients with MCD within the Nephrology Department of Hospital Ramón y Cajal were treated with LDS. Cumulative dose of steroids, time to remission and time free of relapse were compared between relapse episodes treated with LDS and previous relapses among same patients treated with HDS.

Results
Twenty-six relapses among six steroid-sensitive MCD patients were analyzed. 15 relapses were treated with LDS and compared with 11 previous relapses among same patients treated with HDS. Mean dose of prednisone for initial treatment of the relapse was 0.89 ± 0.1 mg/kg in patients treated with HDS and 0.45 ± 0.1 mg/kg in patients treated with LDS. Mean cumulative dose of prednisone among patients treated with LDS and HSD were 1998.1 ± 1418 mg and 5611.7 ± 2326 mg, respectively. (p=0.001). Mean cumulative dose of prednisone adjusted by body weight among patients treated with LDS and HSD were 23.43 ± 14.27 mg/kg and 68.93 ± 27.05 mg/kg, respectively. (p=0.019). There was no difference in duration of treatment among HDS and LSD groups (163.45 ± 86.43 vs 138.80 ± 108.80, respectively; p = 0.525). All patients achieved complete remission after steroid therapy in both LSD and HSD groups. Mean time to remission was 18.7 days among HSD relapses and 18.4 days among the LSD relapses (p = 0.9). Time free of relapse after therapy among HDS and LDS treated relapses was 9.1 ± 5.3 months and 5.5 ± 3.5 months, respectively (p = 0.1).

Conclusion
Among steroid-sensitive MCD patients, relapse therapy with low dose of steroids (0.5 mg/kg) seems to be effective and allows minimization of steroid cumulative dose and drug toxicity.