bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0354MATRIX ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY IN PROTEIN ALTERATIONS ASSOCIATED WITH THE PROGRESSION OF IGA NEPHROPATHY DISCOVERY
Authors: Ivanova Mariia , Dyadyk Olena , Ivanov Dmytro , Clerici Francesca , Smith Andrew , Magni Fulvio 
Published: June 2020

Abstract

Background and Aims
IgA nephropathy (IgAN) is one of the most diffuse glomerulonephrites worldwide, but there are still many issues regarding its prognosis and pathogenesis understanding. Although the diagnosis is established by renal biopsy examination, there are still remaining pitfalls in primary origin discrimination, and therefore for prognosis and outcome for the patient.

Method
In this pilot study we performed matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) with a high spatial resolution (raster sampling of 20 μm) on formalin fixed paraffin embedded renal biopsies obtained from patients with IgAN (n=11) and other mesangioproliferative glomerulonephrites (MesPGN, n=6) attempting to enlighten proteomic alterations that may be associated with the progression of IgAN. The patients in both disease groups were separated according to their CKD stage (CKDI, CKDII, CKDIII and more). After MALDI-MSI analysis, all biopsies were stained with hematoxylin and eosin, scanned and overlaid with molecular image in order to verify the signals’ spatial distribution.

Results
Using MALDI-MSI we detected clear differences in the proteomic profiles of IgAN and other MesPGN tissues. Fourteen signals (AUC ≥ 0.8) were observed to have an altered intensity among the different CKD stages within the IgAN group. In particular, large increases in the intensity of these signals could be observed at CKD stages II and above. Putatively identified, these signals primarily corresponded to proteins involved in inflammatory and healing pathways and their increased intensity was localised within regions of tissue with large amounts of inflammatory cells or sclerosis (Figure 1), verified by immunohistochemical staining (Figure 2).

Conclusion
The capability of MALDI-MSI to provide highly spatially resolved proteomics analysis of complex renal tissue demonstrates it a useful additional diagnostic and prognostic tool and a promising approach in the search for prognostic or predictive markers in glomerular diseases.
P0355FAMILY HISTORY OF COMPLEX TRAITS IN THE CUREGN COHORT: ASSOCIATIONS WITH RENAL FUNCTION, COMORBIDITY BURDEN AND DISEASE PROGRESSION
Authors: Zanoni Francesca , Verbitsky Miguel , Carlassara Lucrezia , Marasa Maddalena , Kiryluk Krzysztof , Gharavi Ali 
Published: June 2020

Abstract

Background and Aims
Family history (FHx) of complex traits may reflect shared genetic/environmental risk. Few studies suggest associations with increased risk of comorbidities and worsening renal function, but this has not been examined in primary glomerulopathies (GNs). Herein, we studied the association of FHx of complex traits with presentation patterns, comorbidities and disease progression in a prospective cohort of patients with primary GN.

Method
The Cure Glomerulopathy Networ (CureGN) is a prospective multi-center observational study of GN patients (N=2474) affected by biopsy-proven Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN) and IgA Nephropathy/Vasculitis (IgAN/V). Associations of self-reported FHx of diabetes (DM), coronary artery disease (CAD), cancer (C), clotting disorders (CD), and autoimmune diseases (AD) with eGFR, UPCR at diagnosis, and comorbidities prevalence were studied using linear and logistic regression models adjusted for age, sex, ethnicity, race, BMI and other relevant clinical covariates. Associations between FHx and ESRD/40%eGFR reduction were investigated with multivariate Cox models.

Results
FHx of DM was associated with lower eGFR and higher UPCR at diagnosis in the entire cohort (p=0.006 and p=0.03), lower eGFR in FSGS (p=0.02) and higher UPCR in IgAN/V (p=0.01). Regarding comorbidity burden (Table 1), FHx of DM was associated with higher prevalence of DM, heart failure and infections requiring hospitalization, FHx of C with cancer, FHx of CD with higher prevalence of thrombosis and FHx of AD with inflammatory bowel, celiac diseases, asthma and drug allergies. At the survival analysis adjusted for age, sex, ethnicity, race, BMI, diagnosis group, eGFR and UPCR at diagnosis, DM, hypertension, use of immunosuppressants and RAAS-inhibitors, FHx of DM was associated with higher risk of the composite outcome of ESRD/40%eGFR reduction in the entire cohort (HR 1.39, 95%CI 1.07-1.81, p=0.01), and specifically in FSGS (HR 1.76, 95%CI 1.08-2.85, p=0.02) and in the paediatric subgroup (HR 1.98, 95%CI 1.04-3.80, p=0.04).

Conclusion
FHx of complex traits are associated with higher prevalence of specific comorbidities. FHx of DM identifies patients with lower eGFR at diagnosis, higher prevalence of infections and higher risk of renal disease progression. These findings, which need to be confirmed in other cohorts, suggest that FHx could be an additional useful parameter for risk stratification and management of primary GN.
P0369MINOR GLOMERULAR ABNORMALITIES ARE ASSOCIATED WITH DETERIORATION OF LONG-TERM KIDNEY FUNCTION AND MITOCHONDRIAL INJURY
Authors: Park Mooyong , Yu Byung Chul , Park Su Jung , Park Jin Hoon , Lee Kyung Ho , Moon Ahrim , Choi Soo Jeong , Kim Jin Kuk , Hwang Seung Duk 
Published: June 2020

Abstract

Background and Aims
Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers.

Method
We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with IgA nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time×group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers.

Results
Compared to the MHC group, the MGA and IgAN groups displayed differences in the time×group effects of eGFR (Figure 1), higher mean annual rates of eGFR decline (Table), and higher urinary mtDNA copy numbers (Figure 2); however, these groups did not significantly differ from each other.

Conclusion
The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.
P0375URINARY DICKKOPF-3 PREDICTS RENAL SURVIVAL IN ANCA-ASSOCIATED VASCULITIS
Authors: Diaz Enamorado Yunayka , Shabaka Amir , Garcia Iñigo Francisco Jose , Villacorta Javier , Cases Corona Clara Maria , Dominguez Torres Patricia , Fernandez Juarez Gema Maria 
Published: June 2020

Abstract

Background and Aims
Urinary Dickkopf-related protein-3 (DKK3), a stress-induced renal tubular glycoprotein, has been identified as a novel biomarker for chronic kidney disease patients at risk of kidney disease progression. The aim of our study was to assess urinary DKK3 as a diagnostic biomarker for predicting GFR loss and renal survival in a cohort of patients with ANCA-associated vasculitis

Method
We measured baseline urinary DKK3 levels in a cohort of patients diagnosed with ANCA-associated vasculitis (AAV), and repeated measurements at 1 and 3 months of diagnosis. Urinary DKK3 levels were normalized to urinary creatinine concentrations to account for dilution of the urine. The association between baseline uDKK3/creatinine levels and the rate of GFR loss was measured. The primary composite outcome was defined as an increase of &gt;50% in baseline serum creatinine, initiation of renal replacement therapy or death.

Results
We included 36 AAV patients with a mean age 71.2 ±12.0 years, 55.6% males, with baseline eGFR at diagnosis 22.3 ±14.1 ml/min. There was a correlation between baseline DKK3-creatinine levels and age (r=0.48, p=0.003) and baseline eGFR (r=-0.327, p=0.051). Ten patients (27.8%) reached the primary composite outcome. Patients were then stratified into two groups according to baseline uDKK3 levels. The group of patients with baseline uDKK3-Creatinine &gt;16000 pg/mg were older (76±12.5 vs 66.4 years, p=0.014), presented a lower baseline eGFR (16.2±10.8 vs 28.5±14.5 ml/min, p=0.007) and had higher baseline uCD163 levels (1135.1 [312.4-2537.5] vs 397.2 [146-809.4], p=0.089]). There were no differences in baseline proteinuria, microhematuria or histological class across the groups. After a median follow-up of three years, 44.4% of the patients in the highest DKK3 group reached the primary composite outcome, whereas only 11.1% of those with lower DKK3 levels reached the endpoint at the end of follow-up (p=0.026) . The area under the time-dependent curve for predicting the primary composite outcome according to uDKK3 was 0,677, with a sensibility of 80% and specificity of 61.5% at the cutoff 16056 pg/mg. Additionally, patients who had a &gt;30% increase in uDKK3 levels after one month reached the primary composite outcome more often (40%) than those who remained with a stable or decreasing DKK3 levels (0%, p=0.04). There were no differences in the rate of change in DKK3 and the different treatment regimens.

Conclusion
Elevated urinary DKK3 levels help identify those patients who are at a higher risk of kidney disease progression and dialysis dependency over the next three years in ANCA-associated vasculitis. DKK3 monitoring could be considered in the follow-up of these patients to assess the effect of treatment and predict the long-term response.
P0381THE UTILITY OF LOW DOSE RITUXIMAB FOR INDUCTION AND MAINTENANCE TREATMENT IN ELDERLY PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A SINGLE CENTRE EXPERIENCE
Authors: Metraiah El Hakem , Dospinescu Paula , Fluck Nicholas , Basu Neil , Kidder Dana 
Published: June 2020

Abstract

Background and Aims
Elderly patients with Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) tend to have higher rates of mortality and treatment-related adverse events. Rituximab is now widely used in the treatment of patients with AAV based on the results of remission induction (RITUXVAS and RAVE) and remission maintenance (MAINRITSAN) randomized controlled trials. Elderly patients were relatively under-represented in these trials. In this observational study we aimed to examine the outcome of elderly patients who received Rituximab (either as low dose Rituximab (LDR) or standard dose Rituximab (SDR)) for remission induction and maintenance.

Method
We investigated the outcome of three treatment strategies in elderly (age&gt;65 years) patients who presented with AAV to our Vasculitis clinic from 1 July 2007 to 9 of July 2017. These strategies included: LDR (17 patients), SDR (14 patients) and Cyclophosphamide/Azathioprine (Cyc/A) 26 patients. LDR patients received two dose of 500mg Rituximab fortnightly followed by six monthly 500mg doses for 2 years. SDR patients received 1g Rituximab fortnightly followed by six monthly 1g doses for 2 years. Cyc/A patients received 1.5mg/kg oral Cyclophosphamide for 3 months followed by 18 months of Azathioprine.

Results
Among 57 AAV patients, 56% were females and mean age of 79.6 +/- 4 (LDR), 72.4 +/- 7.2 (SDR), and 71.1 +/- 5 (Cyc/A) (p=0.001). The distribution of MPA and GPA was 11/6 in LDR, 7/7 in SDR and 18/8 in Cyc, respectively. Relapsing GPA was significantly higher in SDR 12/2 compared to LDR 3/14, and Cyc/A 0/26 (p=0.0001). There were no significant differences in serum creatinine, BVAS scores or CRP between groups at initiation of treatment. Patients survival at 24 months was 88% (LDR), 92% (SDR), and 77% (Cyc), p=0.3. The mean corticosteroids dose at 3 months from onset of treatment was significantly lower in the LDR (7.6 +/- 1.7) and SDR (8.6 +/- 3.1) compared with Cyc/A (12.5 +/- 3.6), p=0.001. 1 patients relapsed in the SDR group and 4 patients in the Cyc/A group. Hospitalization for infections were significantly lower in the LDR (3 episodes) compared to Cyc/A (17 episodes), p=0.004. The number of patients with hypogammaglobulinemia was not significantly different between LDR and SDR.

Conclusion
In this single centre observational study, we found that low dose Rituximab for remission induction and maintenance associated with similar patient outcome to SDR. The findings of this study needs to be replicated with longer duration of follow-up.
P0385CLINICAL DIFFERENCES OF MEMBRANOPROLIFERATIVE GLOMERULONEPHROPATHY (MPGN) ACCORDING TO PRESENCE OF HEPATITIS B VIRUS INFECTION
Authors: Kim Hea Eun , CHIN HO JUN 
Published: June 2020

Abstract

Background and Aims
Traditional definition of MPGN by morphologic changes on light microscopic examination was reclassified into MPGN caused by immunoglobulin/immune complex injury and C3 glomerulopathy (C3G) with alternative complement pathway abnormality based on immunofluorescence staining. MPGN might be caused by various causes such as malignancy, infection, autoimmune diseases, etc. It was rarely known the clinical characteristics of MPGN according to the possible causes excluding C3G.

Method
We enrolled 20,481 adult patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, there were 553 patients with MPGN whom we reclassified into 18 patients with C3G and 535 MPGN patients. We excluded patients with cancer, autoimmune disease, hepatitis C virus infection, C3G, or combined pathologic diagnosis other than MPGN. Finally, we enrolled 156 patients without hepatitis B surface antigen (HBsAg)[MPGN] and 48 patients with HBsAg [MPGN_HBV]. The final outcomes were incidences of end stage renal disease (ESRD) and death.

Results
Patients with MPGN_HBV are younger than MPGN (45.5 ± 15.8 years vs 54.6 ± 15.7 years, p=0.001) and included more males (43 (89.6%) vs 97 (62.2%), p&lt;0.001). The systolic blood pressure was not different between groups but the diastolic blood pressure was higher in MPGN_HBV (85.4 ± 10.4 mmHg vs 80.7 ± 13.4 mmHg, p=0.018). The level of urine protein to creatinine ratio was not different between groups but the level of glomerular filtration rate (GFR) was higher in patients with MPGN_HBV compared to patients with MPGN (65.8 ± 29.0 ml/min/1.73 m2 vs 57.5 ± 34.8 ml/min/1.73 m2, p=0.039). Mortality was observed in 2 patients with MPGN_HBV (4.2 %) and 9 patients with MPGN (5.8%)(p=1.000) during 64.9 months (median). Incident ESRD was notified in 6 patients with MPGN_HBV (13.3 %) and 39 patients with MPGN (26.5 %)(p=0.067) during 47.8 months (median). HBV positivity was not a risk factor to mortality (p=0.847) and was not a risk factor to incident ESRD (p=0.108), either, by Cox’s hazard proportional model adjusted with related factors to mortality. The most important risk factor was hemoglobin and GFR at renal biopsy.

Conclusion
The clinical characteristics of MPGN according to presence of HBsAg were different, however, the prognosis was not dependent on HBsAg positivity, which suggested the severity of renal injury was more important than the cause of renal injury.
P0388ABC-R ANCA STUDY ESTABLISHMENT OF AN ANATOMOPATHOLOGICAL BIOLOGICAL AND CLINICAL PROGNOSTIC SCORE IN THE MANAGEMENT OF ANCA VASCULITIS WITH RENAL IMPAIRMENT
Authors: HODIQUE Florine , NOUVIER Mathilde , PICARD Cecile , RABEYRIN Maud , Juillard Laurent , DIJOUD Frederique , FABIEN Nicole , Fouque Denis , BARBA Thomas , HOT Arnaud 
Published: June 2020

Abstract

Background and Aims
Glomerulonephritis is common in ANCA associated vasculitis (GN-AAV). There is extensive published data on the renal prognosis of these conditions. However, few authors have described predictive factors for end-stage renal disease (ESRD) in patients with GN-AAV. Many authors suggest that renal biopsy should be abandoned in patients whose diagnosis would be established by antibody positivity alone.
The aim of the study was to establish a prognostic score for renal damage during ANCA vasculitis and demonstrate need for prognostic renal biopsy.

Method
One Hundred and eighteen patients referred to 2 french nephrology departments in Lyon between January 2003 and January 2019 were retrospectively analysed. Patients were randomly divided in 2 cohorts at a ratio of 70/30: training and validation cohorts. ESRD was defined as glomerular filtration rate (eGFR) ≤ 15mL/min/1.73m2,need of chronic dialysis or renal transplantation.

Results
Of the 118 patients, 38 (32.20%) developed ESRD. We identified 3 criteria associated with development of ESRD in patients with GN-AAV. One point was assigned to each criterion according to a threshold value: eGFR at the time of renal biopsy ≤ 15 mL/min; percentage of sclerotic glomeruli ≥ 11% and percentage of normal glomeruli &lt; 20%. A new prognostic renal score was established in patients with GN-AAV. It classifies patients into 3 categories at risk of developing ESRD: low (≤ 1 point), moderate (2 points) and high (3 points).

Conclusion
Two of the three criteria of our score are histological. Biopsy remains, when possible, an essential tool for diagnosis and especially to predict renal prognosis of ANCA vasculitis with renal impairment.
P0396THE NEPHRITIC SYNDROME IN JAPAN AND EUROPE
Authors: Weiner Maria , Fujimoto Shouichi , Suzuki Yusuke , Skrunes Rannveig , Goritschan Anna , Crnogorac Matija , Geddes Colin C , Turkmen Kultigin , Galesic Kresimir , Rosenkranz Alexander , Kaname Shinya , Sugiyama Hitoshi , Segelmark Mårten 
Published: June 2020

Abstract

Background and Aims
The combination of new onset haematuria, proteinuria and declining GFR, often referred to as the nephritic syndrome, constitute a strong indication for renal biopsy. Several different disease entities can underlie these findings, many of them requiring prompt treatment. Epidemiological studies of glomerular diseases are in general hampered by the strong influence of differences in biopsy practices. However, there is reason to believe that such differences are less pronounced in cases of acute/subacute nephritic syndrome. The aim of the present study is to compare the frequencies of diseases causing the nephritic syndrome in Japan and Europe using data from renal biopsy registries.

Method
Data were retrieved from national or regional renal biopsy registries in Japan, Sweden, Norway, Scotland, Austria, Croatia and Turkey from 2007-01-01 to 2018-12-31. Only patients biopsied due to acute or subacute nephritic syndrome, defined as a combination of new onset haematuria, sub-nephrotic proteinuria and reduced GFR, were included. Demographic, clinical and laboratory data were collected from the time of renal biopsy.

Results
A total number of 2789 patients from Japan and 1202 patients from Europe were included. Among the Japanese patients, 46% were women, median age was 67 years (IQR 54-74) and median creatinine concentration at the time of renal biopsy was 198 µmol/L (IQR 109-343). In Europe, 43% were women, median age was 58 years (IQR 42-70) and median creatinine concentration was 210 µmol/L (IQR 127-390). Figures from the different European countries are presented in Table 1. The most common diagnosis in both Japan and Europe was ANCA-associated nephritis (44% in Japan, 34% in Europe), followed by IgA nephritis (8.5% in Japan, 18.6% in Europe) and acute tubulointerstitial nephritis (6.2% in Japan and 7.1% in Europe).

Conclusion
We describe preliminary data from a large multicenter cohort of patients presenting with the nephritic syndrome. This clinical presentation is most often encountered in the 6th and 7th decade of life and the distribution between men and women is fairly equal. The most common underlying cause of the nephritic syndrome in both Japan and Europe is ANCA-associated nephritis.
P0406ASSOCIATION OF MICROHEMATURIA WITH OUTCOMES IN ADULT PATIENTS WITH IGA NEPHROPATHY
Authors: Mirioglu Safak , Gurel Erdem , Guzel-Dirim Merve , Kara Asli , Ozluk Yasemin , Aktar Irem , Dirim Ahmet Burak , Ciftkaya Aylin , Oto Ozgur Akin , Caliskan Yasar Kerem , Kilicaslan Isin , Yazici Halil , Turkmen Aydin , Sever Mehmet Sukru 
Published: June 2020

Abstract

Background and Aims
Although hematuria is the cardinal symptom of IgA nephropathy (IgAN), its effects on the outcome have not been studied extensively. We, therefore, aimed to analyze the association between microhematuria and clinicopathological features as well as outcome parameters in adult patients with IgAN.

Method
129 adults with IgAN, diagnosed by kidney biopsy, and followed up for a median duration of 54.5 (IQR: 24.25-92.75) months, were included in this retrospective study. Urinary sediment analyses during the bouts of macrohematuria were not taken into consideration. For the purpose of this analysis, microhematuria was described as ≥5 red blood cells per high-power field (RBCs/hpf) and classified as mild (5-9 RBCs/hpf), moderate (10-19 RBCs/hpf), or severe (≥20 RBCs/hpf). Study outcome (event) was defined as at least a 50% reduction in baseline eGFR or development of stage 5 chronic kidney disease (eGFR &lt;15 ml/min/1.73 m2). eGFRs of the patients were calculated by using CKD-EPI formula.

Results
Demographic, clinical, laboratory and histopathological features of patients at the time of diagnosis are summarized in the table. Usage of ACEi/ARBs [75/81 (92.5%) vs 45/48 (93.75%), p=0.803], fish oil [30/81 (37%) vs 19/48 (39.5%), p=0.773], azathioprine [16/81 (19.7%) vs 10/48 (20.8%), p=0.882] and mycophenolic acid derivatives [14/81 (17.2%) vs 11/48 (22.9%), p=0.434] were comparable among the patients with and without microhematuria. Corticosteroids were more frequently used in patients with microhematuria [41/81 (50.6%) vs 17/48 (35.4%)], although this difference was not statistically significant (p=0.093). Overall 30 patients (23.2%) reached the study outcome, and there were no differences between patients with (19, 23.4%) and without (11, 22.9%) microhematuria (p=0.944). Kaplan-Meier analysis revealed that event free survival rates were similar across study groups: 77.1% for patients without microhematuria; while 80% for mild, 77.3% for moderate, and 72.7% for severe microhematuria (p=0.436) (Figure). Microhematuria did not predict the study outcome when multivariable Cox regression analyses were performed [HR: 1.847 (95% CI: 0.696-4.904), p=0.218]. Throughout the follow-up, microhematuria disappeared (dropped below 5 RBCs/hpf) in 43 patients (53%), 8 of whom (18.6%) reached the study outcome as compared to 11 patients (28.9%) with persistent microhematuria (p=0.273). Disappearance of microhematuria was not a predictor of study outcome, as well [HR: 0.386 (95% CI: 0.068-2.180), p=0.281].

Conclusion
Microhematuria is not associated with renal outcomes of adult patients with IgAN.