bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO273A NOVEL APPROACH TO ASSESS THE DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF IMMUNOGLOBULIN A NEPHROPATHY (IGAN) PATIENTS IN A US REAL-WORLD SETTING
Authors: Przybysz Raymond , Mehta Rina , Rovira Tomas Gisela , Aldworth Carolina , Doherty Jim , Studer Rachel 
Published: May 2021

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAN) is a chronic glomerular disease that affects approximately 100,000-200,000 people in the US. Approximately 15-40% of IgAN patients will eventually progress to end stage kidney disease (ESKD) within 10-20 years of diagnosis, and there is currently no targeted therapy for this disease. Decreased kidney function, persistent proteinuria and hypertension are some of the clinical manifestations of IgAN, and with demographic aspects (e.g. ethnicity) are considered as predictors of disease progression. The aim of this study is to better understand the demographic and clinical characteristics of IgAN patients in the US identified via physician notes.

Method
This is a descriptive, retrospective study of adult (≥ 18 years) IgAN patients in Optum® Electronic Health Records (EHRs), between January 2007 and December 2019. Optum® EHRs contain de-identified clinical and medical administrative data from 96 million people in 50 states that come from more than 140,000 providers at 740 hospitals and over 7,000 clinics. Identification of IgAN patients is challenging because there are no specific ICD codes for this disease so we used natural language processing of physician notes and chose patients with at least two IgAN records with the first one considered to be the index date, and no negative mention, as well as a biopsy procedure. Here, we present the baseline demographic and clinical characteristics of the identified patients up to 12 months before and at the index date.

Results
A total of 1803 patients with a biopsy record (22% of all patients with at least two IgAN records in their EHRs in our study) were included in this analysis; results are presented in Table 1. The mean age was 48 years, and the majority of patients were male (60.9%) and white (75.7%). Proteinuria levels of ≥1 g/day were found in 34% of patients. The mean eGFR was 45 ml/min/1.73m2 and 21.6% of patients had severe deterioration of kidney function (eGFR &lt;15). The mean creatinine level was 3 mg/dL. Pain, edema and fatigue/tiredness were reported in 39.6%, 18.1% and 13.4% of patients, respectively. Hypertension was reported in 73% of patients. Based on the ICD 9 (585.6) and ICD-10 (N18.6) codes for diagnosis, 17.5% of patients had ESKD in our study.

Conclusion
In our cohort, a significant proportion of patients were found to have high proteinuria levels and severe deterioration of kidney function or ESKD. Moreover, edema and fatigue were recorded for a noticeable proportion of patients. In addition to the commonly reported symptoms, our study also found that pain was reported in a high proportion of patients. These findings highlight the clinical and symptom burden to patients with IgAN, suggesting that future targeted interventions are needed to reduce the burden and delay the progression of this disease.
MO274EVALUATION OF SERUM C3 LEVELS AND C3 IMMUNOFLUORESCENCE IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT STUDY
Authors: Chalkia Aglaia , Thomas Konstantinos , Giannou Panagiota , Panagiotopoulos Alexandros , Hadziyannis Emilia , Kapota Athanasia , Gakiopoulou Harikleia , Vasilopoulos Dimitrios , Petras Dimitrios 
Published: May 2021

Abstract

Background and Aims
The role of complement activation, mainly alternative system, has been recently proposed to play an important role in the pathogenesis of ANCA associated vasculitis (AAV). Real life data assessing its predictive role in renal outcomes are limited. In this study, we evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in patients with AAV.

Method
In this retrospective study, patients with AAV were categorized according to their baseline serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Clinical, serologic, treatment and histopathologic characteristics, as well as prognosis between the 2 groups were compared.

Results:
Forty-seven patients (51% men) were enrolled with a mean age at diagnosis of 65 years and were followed up for a median period of 56 months. At baseline, 23% (11/47) of the patients were hypocomplementemic (C3 &lt;75 mg/dL). These patients were older (74 vs. 65 years,p=0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p=0.006), were more often hemodialysis dependent (64% vs. 19%, p=0.009) and progressed more often to ESRD (55% vs .11%,p=0.01) compared to normo-complementemic patients (n=36). On multivariate analysis, serum Cr at diagnosis (HR=16.8, 95%CI: 1.354-208.62,p=0.028) and low serum C3 (HR=2.492; 95% CI: 1.537-11.567,p=0.044) were independent predictors for ESRD. Among 25 patients with kidney biopsy data, those with positive IF staining for C3 (56%, n=14) had more often a mixed histological pattern (72% vs. 27%,p=0.033), low serum C3 levels (42% vs. 18%,p&lt;0.001) and serious infections during follow-up (57% vs. 18%,p=0.047) compared to those with negative (n=11) IF staining.

Conclusion
Low serum C3 levels at diagnosis may be an independent prognostic factor for ESRD progression in patients with AAV. This should be taken into account in therapeutic and monitoring strategies.
MO275RARE VARIANTS OF COMPLEMENT FACTOR H AND THROMBOMODULIN ARE OVER-REPRESENTED IN A COHORT OF SEVERE IGA NEPHROPATHY PATIENTS
Authors: Maillard Nicolas , Fremeaux Bacchi Veronique , Vieira-Martins Paula , Jullien Perrine , Alamartine Eric , Mariat Christophe 
Published: May 2021

Abstract

Background and Aims
IgA nephropathy is the most frequent primary glomerulonephritis leading to end stage renal disease (ESRD) in about 30% of cases within 20 years after diagnosis. Complement activation through alternative and lectin pathways has been described to impact the pathogeny of the disease. We hypothesized in this study that rare variants of alternative pathways regulatory genes could be overrepresented and could play a role at initiating the disease and could harm the prognosis of IgA Nephropathy.

Method
Patients with biopsy proven IgA nephropathy with markers of severity comprising an evolution through ESRD and/or a proteinuria &gt;0.5g/day with available DNA sample were included. All coding sequences of CFH, CFI, MCP, C3, Factor B THBD and CFHR5 genes were analyzed by next generation sequencing. We defined a variant as rare when its minor allele frequency was below 0.1% in the general population. Frequencies were compared to a French volonteers cohort (n=80) and a European large cohort (n=503)

Results
We screened 128 patients with IgA N, with following characteristics at diagnosis: median age 42.4 yo, proteinuria (median) 1.4g/day, hypertension 66%, median eGFR 48.7 mL/min/1.73m². The median follow-up was 99 months and 58% of patients progressed to ESRD.
We identified rare variants with MAF&lt;0.1% in 10.2 % (n=13) including 1 patient with two rare variants. The functional consequences of the 12 out the 14 variants are unknown. Two variants in CFH are located in function domains and are pathogenic.
Patients with IgA N have high rates of rare variants in CFH (n=9/128 ; 7 %) versus normal controls (n=9/503 ; 1.8%) (p=0.004); Pathogenic Variants with minor allele frequency &lt;0.1% in CFH were found in 2 IgA N (2 out of 128, 1.5%) versus 1 European controls (1 out of 503)
In total, 11 % (14/128), 3.8 % (5/128) and 0.8 % (1/128) of the 128 patients were homozygous for the at-risk haplotype MCP ggaac, CFH tgtgt or both, respectively (versus 6.2 % (5/80), 3.8 % (3/80) and 0% in the controls)
6 patients carried the pathogenic variant in THDM gene p.Ala43Thr (6/128) versus 5 in 508 controls population (p=0.01).
No difference in term of hypertension, proteinuria, eGFR, Oxford classification, vascular score at diagnosis was noticed between patients without any rare variant compared to patients with at least one rare variant. The progression through ESRD was not different between groups.

Conclusion
In this cohort of Caucasian IgA nephropathy patients, rare variants of CFH and THBD were found significantly overrepresented compared to a French and European control cohort. Rare variants of alternative pathway regulatory genes were not associated with particular severity or prognosis.
MO280VALIDATION OF AN ANCA ASSOCIATED VASCULITIS RENAL RISK SCORE IN THE SOUTH WEST OF ENGLAND
Authors: Nimmo Ailish , Singh Arvind , Hopkins Jena , Rixon Anna , Sreerama Spoorthy , Tran Christina , Risdale Saira 
Published: May 2021

Abstract

Background and Aims
Determining the renal prognosis for patients with ANCA associated vasculitis (AAV) is important in guiding treatment decisions, including balancing the risks and benefits of aggressive immunosuppression, and informing patients of their likely trajectory. We examined the performance of the clinicopathologic risk stratification tool developed by Brix et al. 1 in determining renal outcomes in a cohort of AAV patients in the South West of England.

Method
A retrospective review of case notes of patients diagnosed with AAV between 2010 and 2020 from two renal units (Bristol and Plymouth) was performed. Patients were followed up until 1st August 2020. Demographic details, kidney function at presentation and initial treatment regime were collected alongside kidney biopsy data.
The renal risk score divides patients into three groups determined as being at low, medium and high risk of adverse renal outcomes based on (1) the percentage of normal glomeruli on kidney biopsy, (2) the percentage of tubular atrophy and interstitial fibrosis on kidney biopsy and (3) eGFR at diagnosis.
The outcome of interest was the development of end stage kidney disease (ESKD), defined as a dialysis requirement &gt;3months or kidney transplantation. Patients were censored for death.

Results
In total 93 individuals were diagnosed with AAV over the study period; 51% were female and the median age at diagnosis was 69 years [IQR 60-78]. ANCA subclass was MPO positive in 73% of cases, PR3 positive in 19% and ANCA negative in 8%. At presentation, 42% had an eGFR below 15ml/min/1.73m2. With respect to risk scores, 17% of individuals were low risk (n=16), 52% were medium risk (n=48) and 31% were high risk (n=29).
Median follow up was 3.2 years [IQR 1.3-5.9], over which time 18% of patients developed ESKD (1 in the low risk group, 7 in the medium risk group and 9 in the high risk group). A further 20% of patients died. A Kaplan-Meier survival curve (Figure 1) demonstrated worsening renal survival with rising risk group (Log-rank test, p=0.05). At 1 year, 74 patients (80%) were alive and in these individuals renal survival was 100% in the low risk group, 91% in medium risk group and 75% in the high risk group.

Conclusion
Overall, 18% of patients developed ESKD over a median follow up of 3.2 years. The renal risk score developed by Brix et al. helps prognosticate renal survival and may assist in shared decision making with patients regarding treatment options. The score demonstrates the importance of the degree of chronicity in determining renal survival. Further work in larger cohorts to compare the performance of the risk score in different subgroups of patients with AAV would be informative.
MO281THE EVALUATION OF TEST EFFICIENCY ON LOW TITER SERUM PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Authors: Cui Haoyuan , Li Chao , Li Hang , Duan Lin , Li Yan , Chen Limeng , Li Xuemei 
Published: May 2021

Abstract

Background and Aims
Antibody to phospholipase A2 receptor (PLA2R) was widely detected for a decade as a diagnostic marker of idiopathic membranous nephropathy. Recently, several studies reported that a lower cut-off of serum PLA2R antibody (PLA2RsAb) could improve diagnostic efficacy. The recommend cut-off ranged from 2.0 to 2.7 RU/ml which was considered largely improving the sensitivity of the assay. Other reported that although sensitivity of the measurement might loss to some extent cut-off at 14 RU/ml might of the best clinical performance. However, the lower cut-off was slightly higher than the minimum detection limit, that was 2.0 RU/ml. There was no study evaluated the test efficiency of low titer antibody of the measurement.

Method
The reference range of PLA2RsAb was validated by testing 40 serum from health volunteer, male/female ratio was 20/20. The samples for intra and inter-batch precision test were prepared by mixing low titer PLA2RsAb serum. The intra-batch precision was performed by repeating six times of the validation sample in one plate. The inter-batch precision was performed by repeating four times of validation samples in one plate on five days.

Results
The medium age of male was 34 (31, 53) and 46 (31, 54) for female, respectively. PLA2RsAb was ranged from 2.0 to 4.3 RU/ml for male and 2.0 to 4.0 RU/ml for female. The average of intra-batch validation sample was 8.1 ± 1.2 RU/ml. The intra-batch precision was presented by coefficient of variation, that was 15%. The average of inter-batch validation samples were 4.0 ± 0.4 RU/ml and 5.2 ± 0.5 RU/ml, respectively. The inter-batch precision was 10% for both validation serum.

Conclusion
Healthy population showed low titer PLA2RsAb positive according to a lower cut-off. The validation showed relative high coefficient of variation on intra and inter-batch precision of low titer PLA2RsAb.
MO246ESTIMATING DELAY IN TIME TO ESKD FOR TREATMENT EFFECTS ON PROTEINURIA IN IGA NEPHROPATHY AND FSGS*
Authors: Carroll Kevin , Conley Leah , Mercer Alex , Saleem Moin A , Barratt Jonathan 
Published: May 2021

Abstract

Background and Aims
Reduction in proteinuria is associated with lower risk of end-stage kidney disease (ESKD) in IgA nephropathy (Thompson et al, 2019) and focal segmental glomerulosclerosis (FSGS) (Troost et al, 2017). Sparsentan, a dual endothelin receptor and angiotensin II receptor antagonist, is in phase 3 clinical trials in IgA nephropathy (PROTECT) and FSGS (DUPLEX), that are powered to detect a treatment benefit on proteinuria-based endpoints versus standard of care angiotensin receptor blockade (irbesartan). In this study, we aim to estimate the delay in time to ESKD conferred by the hypothesized treatment effect of sparsentan on proteinuria in these phase 3 trials; for PROTECT, a 30% reduction in urine protein to creatine ratio (UP/C) vs irbesartan in IgA nephropathy patients, and for DUPLEX, 30% more patients achieving the new FSGS Partial Remission Endpoint (UP/C &lt;1.5 g/g associated with a 40% reduction in UP/C) versus irbesartan.

Methods
We analysed individual patient level data from two UK registries: the first is provided by Leicester General Hospital, UK and consists of IgAN patients, and the second is the UK National Registry of Rare Kidney Disease (RaDaR) Nephrotic Syndrome cohort, with access provided by the University of Bristol, UK, including FSGS patients. IgAN patients with urine total protein value ≥1.0 g/day or UP/C ≥1.0 g/g and eGFR &gt;30 mL/min at the initiation of renin-angiotensin system blockade (RASB) were identified, as were patients with primary or genetic FSGS with UP/C ≥1.5 g/g and eGFR ≥30 mL/min. The time to ESKD (eGFR &lt;15 mL/min, initiation of dialysis, transplantation) or death from any cause over the patient follow-up period was analysed using accelerated failure time modelling; Weibull, Log Logistic and Log Normal distributions were applied with the fitted survivor function reported from the model with the lowest AIC. The time gained for a given reduction in risk in ESKD/death and 5-year survival was estimated under proportional hazards.

Results
A 30% reduction in proteinuria in IgAN patients confers a 50% lower risk of ESKD, extending the median time to ESKD by 10.7 years, from 12.4 to 23.1 years; 5-year ESKD free survival rate is also increased, from 77.7% to 88.1%. Similarly, ongoing analysis in FSGS patients indicates 30% more patients achieving the FSGS Partial Remission Endpoint confers lower risk for ESKD and increase in 5-year ESKD free survival.

Conclusion
The data from the Leicester General Hospital, UK and RaDaR provide invaluable insight into the longer-term natural history of IgAN and FSGS patients and time to ESKD. Therapeutic interventions that reduce proteinuria and the risk of ESKD can confer important and clinically meaningful extensions in the time patients are alive and free from ESKD.
MO282EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI IMMUNE GLOMERULONEPHRITIS
Authors: Zaworski Jeremy , Vandenbussche Cyrille , Bataille Pierre , Hachulla Eric , Glowacki Francois , Gibier Jean baptiste , Daroux Maïté , Rastimbazafy Anderson , Bitton Laura , Humez Sarah , Guincestre Thomas , Azar Raymond , Hoffmann Maxime , Bourdon Franck , Lemoine Corinne , Cardon Gerard , Behal Helene , Gnemmi Viviane , Quemeneur Thomas 
Published: May 2021

Abstract

Background and Aims
Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis.

Methods
This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype).

Results
One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p &lt; 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up.

Conclusions
Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.
MO284UTILITY OF SERUM IGA/C3 RATIO IN PREDICTING RENAL DISEASE PROGRESSION IN IGA NEPHROPATHY
Authors: Mohammed Sophia , Chinnadurai Rajkumar , Ponnusamy Arvind 
Published: May 2021

Abstract

Background and Aims:
IgA nephropathy is the most prevalent and predominantly slow progressing glomerular disease. Risk prediction tools like the international IgAN help to guide the prognosis in this group of patients. The IgA/C3 ratio has been shown to be a useful predictor of poor outcomes in Chinese cohort but such a study is lacking in the Caucasians. The study aims to investigate the utility of IgA/C3 score in predicting renal outcome in 5 years (50% decline in five years or reaching ESRD) in a Caucasian cohort.

Method
All available patients with biopsy-proven IgA nephropathy in our centre between January 2001 and December 2013 were included in this observational study (115 patients). Baseline (biopsy date) data relevant to the scores including demographics, laboratory and the histopathological features were collated at the time of biopsy. Follow up data on renal functions and renal outcome (50% decline in eGFR at 5 years) were collected until an arbitrary end date 31/12/2018. IgA/C3 ratio was available in 46 (40%) of the patients and this cohort wase split into two groups based on IgA/C3 ratio (A- ratio &lt;/=3 and B- ratio &gt;3) and analysed.

Results
We had a total of 115 patients recorded over this 13-year period. The median age of our cohort at time of biopsy was 41 years with a predominance of male gender (71%). At baseline 84% were hypertensive and 11% diabetic. 77% were on a renin-angiotensin blocker, with 53% being on a statin.
At 2 years follow-up the median decline in estimated glomerular filtration (eGFR) between the groups was similar (Group- A 2.65 ml/min vs Group- B 2 ml/min, p=0.557). At 5 years, the median decline in eGFR was higher in Group B though not statistically significant (9.3ml/min vs 4.6ml/min, p=0.475) (Table-1). At 5 years a higher IGA/C3 ratio was showing appositive corelation to the decline in eGFR (Figure–2).

Conclusion
Patients with higher IgA/C3 ratio had a higher drop in estimated glomerular filtration rate at five years of follow-up. Validation in a larger sample is warranted before this can be used clinically.
MO285CLINICAL PRESENTATION OF IGA NEPHROPATHY AND LONG-TERM RENAL OUTCOME
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Petre Nicoleta , Mircescu Gabriel 
Published: May 2021

Abstract

Background and Aims
There is a wide range of clinical presentation of IgA nephropathy (IgAN), from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. However, there is little epidemiologic data on the relationship between the clinical pattern at diagnosis and long-term renal outcome.

Method
We performed a unicentric retrospective study on 299 consecutive IgAN patients (age 43 [35-56] years, 71% male, eGFR 42.1 [25.2-62.8] mL/min, proteinuria 1.3 [0.6-2.6] g/g creatinine) - kidney biopsy proven - between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018).

Results
Patients were followed for a mean of 41 (95%CI 38, 44) months, and 80 (27%) patients experienced the composite endpoint.
The most frequent clinical presentation at diagnosis regardless of age was nephritic syndrome (68%), followed by asymptomatic urinary abnormalities (AUA) (19%), macroscopic hematuria (15%), acute kidney injury (AKI) (14%) and nephrotic syndrome (10%).
The clinical pattern varied in frequency with age: macroscopic hematuria had a bimodal distribution in the 20- and 60-years groups, AKI was more frequent in the 50 to70 years groups, AUA was more often present in the 30 to 50 years groups (Figure 1).
Mean renal survival time for the entire cohort was 70 (95%CI 65, 75) months; patients with AKI (40 (95%CI 27, 54) vs 75 (95%CI 69, 80) months, p&lt;0.001), nephrotic syndrome (42 (95%CI 26, 57) vs 73 (95%CI 67,78 months, p&lt;0.001)) at diagnosis had significantly shorter renal survival time.
In multivariate Cox regression analysis adjusted for IgAN progression factors, presence of nephritic syndrome at diagnosis was associated with good renal outcome, while clinical presentation as AKI or nephrotic syndrome were associated with poor renal survival (Table 1).

Conclusion
Although AKI and nephrotic syndrome are uncommon in IgAN at diagnosis, their presence seems to be associated with poor renal survival.