bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO1050ACCESS TO DIALYSIS IN PUBLIC HOSPITALS FOR CHRONIC KIDNEY DISEASE PATIENTS: RESULTS FROM THE HEMODIALYSIS REGISTRY WAITING LIST AT ARISTIDE LE DANTEC HOSPITAL IN SENEGAL
Authors: Faye Moustapha , Keita Niakhaleen , Lemrabott Ahmed Tall , Faye Maria , Ba Bacary , Dieng Ameth , Ba Mamadou Aw , Niang Abdou , Ka Elhadji Fary 
Published: May 2021

Abstract

Background and Aims
The lethality and cost of chronic kidney disease (CKD) management are high in Senegal. The aim of this study was to evaluate the access in dialysis at Senegalese public’s hospitals.

Method
This was a retrospective cohort during 4 years (2014-2018) from the hemodialysis registry waiting list at Aristide Le Dantec University Hospital. This registry is composed by: a registration form (social survey and doctor's visa); a written letter addressed to hospital director and the national identity card. From this registry, telephone calls were made to collect data relating to mortality and access to dialysis.

Results
seven hundred fifty-one (751) files were collected. The mean age of the patients was 48.12 ± 15.28 years with a sex ratio of 1.02. The socioeconomic level was low in 85.40% (521/610) and average in 13.61% (83/610). The geographic origin was rural in 11.15%, semi-urban in 07.54% and urban in 81.31%. Ten patients (1.64%) had medical care coverage. On call, 49.70% (373/751) were died before accessing to public dialysis, 29.70% (223/751) had accessed public dialysis and 04.00% (30/751) didn’t yet need dialysis. Hundred twenty-one (16.10%) were unreachable and 0.50% (4/751) was unknown.

Conclusion
The lethality of CKD was high. Access to dialysis in public hospital remains problematic in Senegal despite its democratization. Additional efforts are needed for effective management of all patients at dialysis stage.
FC 046INCIDENCE OF NOSOCOMIAL ACUTE KIDNEY INJURY (AKI) IN A COHORT OF COMMUNITY-DWELLING OLDER ADULTS OVER 8 YEARS OF OBSERVATION
Authors: Ebert Natalie , Schneider Alice , Balabanova Yanina , Brobert Gunnar , Huscher Dörte , Mielke Nina , Schaeffner Elke 
Published: May 2021

Abstract

Background and Aims
Acute kidney injury (AKI) is amongst the most common in-hospital complications especially in old age. Epidemiological data on incidence rates (IR) of nosocomial AKI in individuals aged 70+ years, stratified by age, gender and pre-existing diseases are scarce because older adults are usually underrepresented in clinical research.

Method
We used data from the Berlin Initiative Study (BIS), a longitudinal, population-based cohort of adults aged ≥70 with biennial follow-up visits (including blood and urine tests) in combination with claims data from the AOK Nordost insurance fund to complement information on diagnoses and in-hospital procedures (based on ICD-10 and OPS coding). Nosocomial AKI was defined as documented in-hospital diagnosis (ICD-10: N17.xx) excluding cases with AKI as admission diagnosis. Incidence rates (IR) and 95% confidence intervals (CI) of the first nosocomial AKI were calculated with the number of incident cases during observation divided by the total person-years of follow-up, for AKI cases truncated at the first incidence of nosocomial AKI. IR are reported by age strata, sex and preexisting diseases (diabetes, arterial hypertension, atrial fibrillation, heart failure, angina pectoris, peripheral artery disease and impaired kidney function).

Results
In 2020 individuals (mean age 80.5 years; 52.6% women), 383 developed nosocomial AKI over the median [IQR] follow up time of 8.8 [5.9-9.3] years (Fig.1). The IR of nosocomial AKI was 26.8 (95%CI 24.1-29.6) per 1000 person years among all patients, with higher IR in men compared to women, and - when stratified by age - lowest IR in age category 70-75 versus the highest IR in age category of ≥ 90 years (Fig.1).

IR per 1000 person years were higher in patients with diabetes mellitus (IR: 39.3 vs 22.7), arterial hypertension (IR: 31.1 vs 12.2), chronic heart failure (IR: 41.9 vs 22.3), angina pectoris (IR: 37.6 vs 25.7), peripheral artery disease (IR: 55.0 vs 25.1) and impaired kidney function (IR: 43.3 vs 12.4), respectively (Fig.2).

Conclusion
Nosocomial AKI is an in-hospital complication common in older adults with IRs rising continuously with age above the age of 70 years. IR of AKI are considerably higher in patients with cardiovascular comorbidities. A better understanding of the patient population at risk is of great clinical relevance when aiming to improve prevention strategies.
FC 047COMPARISON OF THE CHARACTERISTICS AND MORTALITY OF ACUTE KIDNEY INJURY IN PATIENTS WITH COVID-19 AND OTHER RESPIRATORY INFECTIONS: A PROSPECTIVE COHORT STUDY
Authors: Diebold Matthias , Zimmermann Tobias , Dickenmann Michael , Schaub Stefan , Bassetti Stefano , Siegemund Martin , Breidthardt Tobias , Twerenbold Raphael 
Published: May 2021

Abstract

Background and Aims
Previous studies have indicated a coherency between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI), indicating poor outcomes. However, most studies only included patients with COVID-19 and lacked a control group. Therefore, the aim of this study was to investigate the prevalence and prognostic impact of AKI in patients with COVID-19 in comparison with other respiratory tract infections.

Method
The prospective single-center observational case-control COronaVIrus surviVAl (COVIVA, clinicaltrials.gov NCT04366765) study performed at the University Hospital Basel Switzerland consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March 23 and May 31, 2020. The final diagnosis that led to the inclusion in the study was adjudicated by physicians after reviewing all available medical data including laboratory test results 30 days after discharge. For this analysis, we compared patients tested positive for SARS-CoV-2 with patients tested negative but with an adjudicated diagnosis of upper or lower respiratory tract infection including pneumonia. Primary outcome measure was death at 30 days, secondary outcomes were AKI incidence, renal recovery and need for renal replacement therapy. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline.

Results
Of the 1086 patients included, 507 had a final adjudicated diagnosis of respiratory tract infection and were eligible for this analysis. Of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. Baseline characteristics were comparable between patients with and without COVID-19.
AKI occurred in 95 patients (19%) with a higher incidence (30%, 95%CI 24-37 versus 12%, 95%CI 9-17, p&lt;0.001) and a higher severity (KDIGO stage 3, 22% versus 10%, p=0.003) in patients with COVID-19 as compared to controls, respectively. Need for intensive care (22% versus 6%, p&lt;0.001) and requirement for RRT were higher in patients with COVID-19 (8 patients (4.4%) versus 2 patients (0.62%); p=0.01). Renal recovery at discharge in survivors was similar in patients with (64%) and without COVID-19 (48%, p=0.175). Survival analysis identified AKI as a predictor of 30-day mortality independent of COVID-19 status (adjusted hazard ratio (aHR) 3.44, 95% confidence interval (CI) 1.55-7.63, p=0.002), but COVID-19 patients with AKI carried the highest risk (aHR 4.24, 95%CI 1,82-9.88, p&lt;0.001). (Figure 1)

Conclusion
AKI occurs more frequently and more severely in patients with COVID-19 compared to other respiratory tract infections. It is associated with an increased risk for death, with the highest risk observed in COVID-19 patients. This underlines the augmented burden of AKI during the COVID-19 pandemic.
FC 042IRF8 IN CDC1 IS PROTECTIVE IN POST-ISCHEMIC ACUTE KIDNEY INJURY
Authors: Na Li , Steiger Stefanie , Fei Lingyan , Li Chenyu , Shi Chongxu , Salei Natallia , Schraml Barbara U , Zheng Zhihua , Anders Hans-Joachim , Lichtnekert Julia 
Published: May 2021

Abstract

Background and Aims
Post-ischemic acute tubular necrosis is a common cause of acute kidney disease (AKD) and subsequent chronic kidney disease. In AKD, mononuclear phagocytes (MPCs) including conventional dendritic cells (cDCs) are present during the different phases of kidney injury, repair and regeneration. The contribution of cDCs to AKD is still poorly understood. Hence, we hypothesized that transcription factor interferon regulatory factor 8 (IRF8)-specific cDCs regulate the immune response in AKD.

Method
AKD was induced by unilateral ischemia reperfusion injury in IRF8-deficient Clec9a-specific DCs (IRF8fl/fl Clec9acre/cre or cre/wt) and wild type C57BL/6 mice. Immune phenotyping of leukocytes in kidney and spleen and mRNA expression profiling were performed, as well as kidney function evaluated. For in vitro studies, IRF8 small interfering RNA transfection technology on bone marrow-derived DCs was used.

Results
In the healthy kidney and lymphoid organ (e.g., spleen and kidney draining lymph node), we identified four MPC subsets according to the diverse expression patterns of CD11b and CD11c. Of which, IRF8 was specifically expressed in the CD11blow CD11chigh R4 subset (containing mainly cDC1). During AKD, IRF8 deficiency in cDCs reduced the number of MHCII+ DCs accumulating among tubulointerstium space without affecting cDC2 or CD64+ DCs, while completely abolished cDC1 in post-ischemic kidney (See Figure). This was accompanied with a decrease in the surface expression of chemokine receptor CCR7 and CCR9, reduction in the number of kidney CD4- CD8+ T cells and Tregs, but a moderate increase in TH1-related and pro-inflammatory cytokines and infiltrating neutrophils in the kidney of mice with IRF8-deficient cDCs. This was in line with reduced kidney function, marked by aggravated GFR loss, elevated plasma BUN level, kidney atrophy, pathological tubular injury and living proximal tubule loss. In vitro, bone marrow-derived IRF8-deficient DCs showed an impaired ability to repair “artificially injured” tubular epithelial cells (TECs), accompanied with less phagocytosis capacity and maturation capacity under necrotic TECs soup or histone stimulation.

Conclusion
Our data show that the restricted depletion of IRF8 in cDCs reduces the number of infiltrating kidney cDC1, which drives tissue inflammation and damage, and ultimately aggravates post-ischemic AKD. Thus, cDC1s are having a protective role in AKD.
FC 029PODOCYTE AND GLOMERULAR ENDOTHELIAL CELL DERIVED MICRORNAS REGULATE PODOCYTE NEPHRONECTIN IN MEMBRANOUS GLOMERULONEPHRITIS
Authors: Müller-Deile Janina , Sopel Nina , Ohs Alexandra , Kotb Ahmed , Marwin Groener , Daniel Christoph , Amann Kerstin , Schiffer Mario 
Published: May 2021

Abstract

Background and Aims
Autoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because the glomerular filtration barrier is normally size selective and impermeable for antibodies.

Method
Kidney biopsies from patients with MGN, cell culture, zebrafish and mice models were used to investigate the role of nephronectin (NPNT) regulating microRNAs (miRs) for the glomerular filtration barrier.

Results
We found that endothelial cell-derived miR-192-5p and podocyte-derived miR-378a-3p are upregulated in patients with anti-phospholipase A2 receptor antibody positive (PLA2R-ab+) iMGN and regulate glomerular NPNT expression (Fig. 1). Overexpression of miR-378a-3p and miR-192-5p as well as morpholino mediated npnt knockdown in zebrafish induced edema, proteinuria, loss of podocyte markers and podocyte effacement. The most prominent phenotype however were structural changes of the glomerular basement membrane (GBM) with increased lucidity, slicing and lamellation especially of the lamina rara interna (Fig. 2, Fig. 3). The phenotype was comparable to ultrastructural findings seen in iMGN. IgG sized nanoparticles accumulated in lucidity areas of the lamina rara interna and lamina densa of the GBM in npnt knockdown zebrafish models. Loss of slit diaphragm proteins and severe structural impairment of the GBM were further confirmed in podocyte specific Npnt knockout mice (Fig. 4).

Conclusion
Podocyte NPNT is important for proper glomerular filter function and GBM structure and is regulated by podocyte and glomerular endothelial cell derived miRs. We hypothesize that loss of NPNT in the GBM is part of the pathophysiology of iMGN and enables subepithelial immune complex deposition in iMGN.
FC 030CONTACTIN-1 IS A NOVEL ANTIGEN IN IDIOPATHIC MEMBRANOUS GLOMERULONEPHRITIS AND IN CIDP- ASSOCIATED GLOMERULONEPHRITIS
Authors: Salama Alan , Fehmi Janev , Antonelou Marilina , Barratt Jonathan , Ashman Neil , Carr Aisling , Reilly Mary , Keddie Stephen , Querol Luis , Pikkuoeura Sonja , Cortese Andrea , Delmont Emilien , Persson Staffan , Radunovic Aleksandar , Roberts Ian Simon David , Davies Alexander , Rinaldi Simon 
Published: May 2021

Abstract

Background and Aims
Recently a number of antigens have been identified as pathogenic antibody targets in cases of primary membranous glomerulonephritis(MGN), including phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain containing 7A(THSD7A), and NELL-1, while exostosin is found in secondary (lupus associated) MGN. However, other as yet undiscovered antigens are thought to exist. Although rare, there is a recognised association between chronic inflammatory demyelinating polyneuriopathy (CIDP) and nephrotic syndrome.

Method
We investigated the link between CICP and MGN and the associations with Contactin-1(CNTN1), a node of Ranvier neuronal protein, as a potential common autoantigen, by immunohistochemistry, RT-PCR and proteomic analysis of isolated glomeruli. We tested sera from 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 210 disease controls, for CNTN1 antibodies.

Results
We describe a series of 16 patients, all presenting with CIDP, nephrotic syndrome due to MGN, and with circulating and deposited anti-contactin-1 (CNTN1) antibodies (IgG4 predominant in those tested) in the kidney. The onset and resolution of both disorders had a close temporal relationship, and the majority of cases were resistant to first-line therapies typically employed for inflammatory neuropathies, but achieved a good outcome with non-standard treatment. Importantly, four (1.4%) further patients with isolated MGN identified from a serum bank of 295 idiopathic MGN patients with no CIDP were also positive for anti-CNTN1 antibodies. CNTN1 protein was detected by mass spectroscopy within glomeruli from patients with CNTN1 antibodies, but not in healthy kidney or anti-PLA2R associated MGN. CNTN1 mRNA was found in renal cortical tissue.

Conclusion
These data provide evidence that CNTN1 antibodies precipitate both autoimmune neuropathy and MGN. The temporal correlation of these disorders, as well as the presence of CNTN1 protein and antibodies in both peripheral nerve and diseased glomeruli, supports a common antibody-mediated pathological process, and defines a new antigenic target in MGN. CNTN1 antibodies have diagnostic and therapeutic relevance, and may additionally serve as a means of monitoring disease activity in both conditions. Other factors may explain presentation with isolated neurological disease or MGN.
FC 031LARGE SCALE VALIDATION OF THE NEW INTERNATIONAL PROGNOSTIC SCORE OF IGA NEPHROPATHY ON A FRENCH COHORT WITH PROLONGED FOLLOW-UP
Authors: Bon Grégoire , Jullien Perrine , Mariat Christophe , Alamartine Eric , Maillard Nicolas 
Published: May 2021

Abstract

Background and Aims
IgA Nephropathy is the most frequent primary glomerulonephritis worldwide, with a progression to End Stage Renal Disease in up to 30% of cases within 20 years after diagnosis. The severity of this disease is nevertheless extremely heterogenous with a majority of slow progression to late stages of Chronic Kidney Disease. The early stratification of risk to progress to ESRD is crucial. In this aim, International IgA Nephropathy Network recently developped a risk prediction tool (IINN tool) to allow an estimation of the probability to progress. The objective of our study was to validate this prediction tool (i) in our French Caucasien retrospective cohort (ii) on long term prognosis.

Method
All biopsy-proven IgA Nephropathy patients from Saint Etienne retrospective cohort for whom proteinuria, mean arterial pressure, CKD-EPI based GFR estimate and adequate Oxford classification at diagnosis were available have been included for analysis. For each patient the estimate of risk to progress to ESRD and/or 50% GFR decline was computed at 5, 10 and 15 years according to the IINN tool. For each time of follow-up, risks were grouped and ranked by deciles, and the median observed rate of event was compared to the median of predicted risk by decile, at 5, 10 and 15 years of follow-up. Correlation between observed and predicted risk was expressed as a Pearson correlation coefficient. A R²&gt;0.8 was considered adequate to validate the prognosis tool.

Results
A total of 468 patients have been included for analysis, with a median age of 38.9 years old, a median proteinuria of 0.5g/day, a mean CKD-EPI of 81,6 mL/min/1,73m² and mean arterial pressure of 96.9mmHg at diagnosis. The cumulative number of events at 5,10, 15 years were respectively of 34, 54, 68. The median follow-up was 12 years. The correlations between observed/predicted risks were R² =0,990 [0,959 ; 0,998] at 5 years, R² = 0,984 [0,930 ;0,996] at 10 years and 0,964 [0,851 ;0,992] at 15 years after diagnosis.

Conclusion
In our study we validated the IINN tool to predict the risk to progress to ESRD and/or 50% eGFR decline (i) in a French Caucasian cohort and (ii) even after 5, 10 and 15 years after diagnosis, allowed by a particularly long follow-up.
FC 035VOCLOSPORIN INCREASES RENAL RESPONSE AT COMMONLY USED UPCR THRESHOLDS IN PATIENTS WITH LUPUS NEPHRITIS
Authors: Dall'Era Maria , Mina-Osorio Paola , Birardi Vanessa , Randhawa Simrat 
Published: May 2021

Abstract

Background and Aims
Voclosporin is a novel calcineurin inhibitor with a favorable metabolic profile and a consistent dose-concentration relationship, potentially eliminating the need for therapeutic drug monitoring.
We have previously reported the primary endpoint of the Phase 3 AURORA trial showing the addition of voclosporin to mycophenolate mofetil (MMF) and a low-dose glucocorticoid regimen results in significantly higher renal response (RR) rates at one year of treatment compared to MMF and low-dose glucocorticoids alone in patients with lupus nephritis (LN). For the primary endpoint, RR was defined as ≤0.5 mg/mg UPCR with stable renal function in the presence of low-dose glucocorticoids and no use of rescue medication.
Several studies have demonstrated that proteinuria represents the best single predictor for long-term renal outcomes.1,2 Given the efficacy of voclosporin in terms of proteinuria reduction, we conducted a sensitivity analysis evaluating RR with additional UPCR targets.

Method
A total of 179 participants in the voclosporin (23.7 mg BID) arm and 178 participants in the control arm from the AURORA trial were included in this analysis. All participants received MMF (target 1 g BID) and low-dose oral glucocorticoids (initiated at 20-25 mg/day and tapered to 2.5 mg/day at 16 weeks).
For this post hoc analysis, the UPCR component of RR was revised to include UPCR targets at 0.2 mg/mg intervals above and below the original ≤0.5 target used for the primary endpoint in AURORA (i.e., ≤0.7 mg/mg or ≤0.3 mg/mg, respectively). Odds ratios for RR at six months and one year of treatment were analyzed using a logistic regression model with terms for treatment, baseline UPCR, biopsy class, and MMF use at baseline and region.

Results
RR with UPCR ≤0.7 mg/mg was achieved by 46.9% of participants in the voclosporin arm vs 32.0% of participants in the control arm at one year of treatment (OR 2.07, p&lt;0.0014) and 39.1% of participants in the voclosporin arm vs 24.7% of participants in the control arm at six months of treatment (OR 2.10, p=0.0020). RR with UPCR ≤0.3 mg/mg was achieved by 28.5% of participants in the voclosporin arm vs 15.7% of participants in the control arm at one year (OR 2.27, p=0.0023 and 22.9% of participants in the voclosporin arm vs 14.0% of participants in the control arm at six months of treatment (OR 1.90, p=0.0238; Table 1).

Conclusion
Participants treated with voclosporin in addition to MMF and low-dose glucocorticoids achieved statistically significantly increased renal response rates regardless of the level of UPCR used, including at an even more stringent ≤0.3 mg/mg target. This analysis further supports the efficacy observed with voclosporin in the Phase 3 AURORA and the prior Phase 2 AURA-LV global trials.
FC 068QUALITY OF LIFE OVER TIME IN OLDER MEN AND WOMEN WITH ADVANCED CKD - RESULTS FROM THE EQUAL STUDY
Authors: Chesnaye Nicholas , Meuleman Yvette , De Rooij Esther , Dekker Friedo W , Evans Marie , Caskey Fergus , Torino Claudia , Szymczak Maciej , Drechsler Christiane , Wanner Christoph , Jager Kitty J 
Published: May 2021

Abstract

Background and Aims
Differences between the sexes are apparent in the epidemiology of CKD. Cross-sectional studies show that women consistently report a poorer health-related quality of life (QoL) than men, however, longitudinal studies are lacking. Here we investigate the sex-specific evolution of QoL over time in advanced CKD. As a secondary aim, we explore the sex-specific determinants of QoL.

Method
EQUAL is an observational prospective cohort study in stages 4 and 5 CKD patients ≥65 years not on dialysis with an incident estimated glomerular filtration rate (eGFR) &lt; 20 ml/min/1.73m². Data on QoL (measured using the RAND-36), clinical and demographic patient characteristics were collected between April 2012 and September 2020. QoL trajectories were modelled by sex using linear mixed models, and joint models were applied to deal with informative censoring. We followed patients until death or dialysis initiation.

Results
We included 5151 QoL measurements in 1416 patients over a total of 1986 person years of follow-up. Overall, the physical component summary (PCS) declined with 2.0 (95% CI 1.4-2.6) points and the mental component summary (MCS) by 2.4 (95% CI 1.8-3.0) points per year. Although women had overall lower QoL scores, figure 1 demonstrates that PCS and MCS declined more than twice as fast in men (PCS: 2.4 per year, 95% CI 1.7 – 3.1, MCS: 2.9 per year, 95% CI 2.2 – 3.6) compared with women (PCS: 1.1 per year, 95% CI -0.2 – 2.0, MCS: 1.5 per year, 95% CI 0.5 – 2.4). We identified a non-linear interaction effect between sex and eGFR levels on QoL, demonstrating a stronger negative effect of decreased eGFR on both PCS (p=0.02) and MCS (p=0.04) in men compared with women. Subsequent adjustment for renal decline attenuated the difference in rate of QoL decline between men and women (difference after adjustment; PCS: 1.1, 95% CI -0.1 – 2.2, MCS: 1.2, 95% 0.0 – 2.3). In univariable analyses, higher serum haemoglobin was more beneficial to QoL in men compared to women (p-value for interaction; PCS: p=0.03, MCS: p=0.01). Higher serum phosphate had a strong harmful effect on both PCS and MCS in men, but not in women (PCS & MCS: p&lt;0.001). The presence of pre-existing diabetes had a negative effect on PCS and MCS in men, but to a lesser extent in women (PCS: p=0.02, MCS: p=0.01).

Conclusion
Despite the higher overall QoL reported by men, both their physical and mental QoL declined approximately twice as fast compared with women. The faster decline in men was mediated in part by their lower levels of renal function, which had a stronger impact on their QoL as compared with women. Furthermore, in exploratory analyses we identified that high levels of phosphate, low levels of haemoglobin, and pre-existing diabetes were more detrimental to QoL in men than in women.