bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO030PATIENT SAFETY IN A LARGE MULTINATIONAL RENAL SERVICES PROVIDER NETWORK
Authors: Marrón Belén , Silva Israel , Wollheim Charlotta , Lucas Carlos , Torok Marietta , Akdeniz Filiz , Pearce Suzanne , Westesson Ulf , Macário Fernando 
Published: June 2020

Abstract

Background and Aims
Patient safety is considered of paramount importance under any qualified provision of care, but results from routine tracking of incidents have scarcely been reported, even when that may negatively impact survival.
To analyze all types of incidents in a multinational renal service provider network from Jan.1st to Sept. 30th, 2019.

Method
For the last 10 years, our institution has tracked all incidents under a structured process program, as well as, educated our staff in the importance of proactively reporting and analyzing incidents in a quarterly basis at the clinic, by country and globally. Incidents are categorized in 4 different types: A-Patient related; B-Staff and visitors; C-Products and D-Equipment. Different incident codes are assigned to each type.

Results
A total of 68.399 incidents (2.7 incidents/patient/year) have been reported during Q1-Q3 2019 (higher than in 2018: 2.2). This means an increase of 20% in the total number of reported incidents. Total incidents/1000 treatments was 17.1 (12.1 patient-related incidents). Reporting follows a heterogeneous pattern among countries, being lowest in Argentina and highest in the UK. Top 5 reported incidents were as follows: Codes A15 (voluntarily shortened treatment) and A14 (Patient did not show up), both related to patient adherence to treatment, accounted for 36% of total incidents, vascular access (VA) complications (A4) for 10.5%, change of dialyzer and/or blood lines due to clotting (A2) for 8.6% and recurrent minor monitor malfunction (D1) for 6.7% of incidents. Codes related with unexpected death or cardiorespiratory arrest are not present among the total global top 10 incidents.

Conclusion
Detailed tracking of incidents and comparison between countries have potential to increase quality of care. Room for improvement recently made the Corporate Medical Office to launch new strategies on VA management, anticoagulation and patient compliance, among others. This large series may help other institutions to better monitor and standardize patient safety.
MO034ANALYSIS OF A MOUSE MODEL FOR MCTO DUE TO THE MUTATION OF MAFB TRANSACTIVATION DOMAIN
Authors: Usui Toshiaki , Morito Naoki , Tsunakawa Yuki , JEON Hyojung , Hamada Michito , Mizuno Seiya , Takahashi Satoru , Yamagata Kunihiro 
Published: June 2020

Abstract

Background and Aims
Transcription factor MafB in podocytes is essential for podocyte differentiation and maintenance. Previous works identified a missense mutation in the transactivation domain of MAFB as the cause of multicentric carpotarsal osteolysis (MCTO). MCTO is a condition involving progressive osteolysis of the carpal and tarsal bones. MCTO patients also develop with focal segmental glomerulosclerosis (FSGS) and renal failure (MCTO nephropathy). However, the pathogenesis of MCTO in vivo is unclear.

Method
In order to address this question, we generated an MCTO mouse model using the CRISPR/Cas9-mediated genome editing. This mouse has a human MCTO mutation c.176C&gt;T, (p.Pro59Leu). Mafb MCTO/ MCTO mice were obtained by crossing Mafb MCTO/WT mice. Control animals were Mafb WT/WT mice. Sequencing analysis was performed to confirm the integration of the MCTO mutation on F2 generations. We checked urine of these mice every 4 weeks, and biochemical and histological analysis were performed at 26 weeks-ages. RNA-seq analysis of the isolated glomeruli of these mice was performed at 10 weeks-ages.

Results
Interestingly, MafbMCTO/MCTO newborn mice exhibited a 10% lower body weight than control mice. The differences were still observed at 2 weeks, with Mafb MCTO/MCTO mice presenting a 23% lower body weight than control animals. The length of femoral bones in Mafb MCTO/MCTO mice was shorter than that of control. MCTO model mice exhibit growth deficiency. In addition, Mafb MCTO/ MCTO mice resulted in albuminuria at 4 weeks-ages from postnatal periods and became persistent. Renal histological analysis in adult stage revealed FSGS-like glomerular lesions in Mafb MCTO/ MCTO mice. In electron microscope analysis, microvillous transformation of the foot processes of podocytes in Bowman’s space and foot processes effacements were seen in Mafb MCTO/ MCTO mice. These phenotypes are similar to that seen in MCTO nephropathy patients. Subsequently, we performed RNA-seq analysis of isolated glomeruli to gain insight into the molecular mechanism of the MCTO mutation. We found Cldn1, gene expression in mature podocytes caused profound proteinuria, was significantly increased in Mafb MCTO/ MCTO glomeruli.

Conclusion
This study is significant for revealing the mechanism of MCTO and contributes to the development of an alternative treatment against MCTO nephropathy by providing model mice for use.
MO045MITOCHONDRIAL DYSFUNCTION AND MUSCLE ENERGETICS IN CKD PATIENTS
Authors: Gamboa Jorge , Ikizler Alp , Yu Chang , Damon Bruce , Brown Nancy , Towse Theodore 
Published: June 2020

Abstract

Background and Aims
Patients with chronic kidney disease (CKD) suffer from frailty and sarcopenia. Skeletal muscle mitochondria are important for physical function and could be a target to prevent frailty and sarcopenia.

Method
We tested the hypothesis that mitochondrial function worsens with the progression of CKD. We evaluated the interaction between mitochondrial function and co-existing comorbidities such as impaired physical performance, intermuscular adipose tissue (IMAT) infiltration, inflammation, and oxidative stress. We evaluated in-vivo thigh mitochondrial function using 31-phosphorus magnetic resonance spectroscopy to obtain the phosphocreatine (PCr) recovery constant, a measure of mitochondrial function. We measured physical performance using the six-minute walk test, IMAT infiltration and markers of inflammation in plasma.

Results
Sixty-three participants were studied including controls (n=21), patients with CKD not on maintenance hemodialysis (MHD; n=20), and patients on MHD (n=22). We found a prolonged PCr recovery constant in patients on MHD (53.3 (43.4, 70.1) seconds) and with CKD not on MHD (46.3 (40,0, 49.9) seconds) compared to controls (34.2 (28.8, 43.7) seconds) (p&lt;0.001 between groups), Figure 1A-C. Mitochondrial dysfunction was associated with poor physical performance, greater IMAT, and increased markers of inflammation Figure 2A-C.

Conclusion
Mitochondrial function worsens with the progression of CKD and correlates with physical function, IMAT, inflammation, and oxidative stress. These data suggest that therapeutic approaches targeted at mitochondrial dysfunction and dynamics could prevent or treat frailty and sarcopenia in patients CKD.
MO051EFFECTS OF SEMAGLUTIDE ON CHRONIC KIDNEY DISEASE OUTCOMES: A POST HOC POOLED ANALYSIS FROM THE SUSTAIN 6 AND PIONEER 6 TRIALS
Authors: Tuttle Katherine , Cherney David , Hadjadj Samy , Idorn Thomas , Mosenzon Ofri , Perkovic Vlado , Rasmussen Søren , Wolthers Benjamin , Bain Stephen C 
Published: June 2020

Abstract

Background and Aims
The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a renal benefit with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo. The PIONEER 6 CVOT reported cardiovascular safety with oral semaglutide in a similar cohort using a similar trial design. In the present post hoc study, eGFR data from the SUSTAIN 6 and PIONEER 6 trials were pooled to evaluate the potential benefit of semaglutide (s.c. or oral) vs placebo on chronic kidney disease (CKD) outcomes.

Method
Data from 6,480 subjects from SUSTAIN 6 (N=3,297; median follow-up, 2.1 years; mean baseline eGFR, 76 mL/min/1.73 m2) and PIONEER 6 (N=3,183; median follow-up, 1.3 years; mean baseline eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 mg s.c. OW, 1.0 mg s.c. OW or 14 mg oral once daily) or placebo. We evaluated time to onset of persistent eGFR reduction (thresholds of ≥30%, ≥40%, ≥50% and ≥57% [57% corresponds to a doubling of serum creatinine]) from baseline in the overall pooled population and by baseline CKD subgroups (≥30–&lt;60 mL/min/1.73 m2, n=1,699; ≥60 mL/min/1.73 m2, n=4,762; data were missing for 19 subjects). Analyses were performed using a Cox proportional-hazards model with treatment group (semaglutide vs placebo) and CKD subgroup as fixed factors and the interaction between both stratified by trial.

Results
In the overall population, the hazard ratios (HRs) for time to onset of persistent eGFR reductions with semaglutide vs placebo were &lt;1.0, but did not achieve statistical significance. In subjects with baseline eGFR ≥30–&lt;60 mL/min/1.73 m2, HRs for semaglutide vs placebo were consistently lower compared with the overall population and, in this subgroup, semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs placebo (Figure; p=0.03). Numerically larger effects were seen with increasing eGFR reduction thresholds in this subgroup, with the exception of the 57% eGFR reduction threshold. No statistically different interactions between treatment and CKD subgroup were observed.

Conclusion
The findings of this post hoc analysis of pooled data from SUSTAIN 6 and PIONEER 6 on clinically relevant outcomes for CKD support a smaller magnitude of eGFR decline with semaglutide vs placebo, despite relatively short follow-up times. The small number of events at both the 50% and 57% thresholds, and the associated broad confidence intervals, limit the interpretability of the results. In line with previous findings, the data suggest a renal benefit of semaglutide vs placebo in subjects with established CKD. The FLOW trial (ClinicalTrials.gov Identifier: NCT03819153), which is dedicated to exploring CKD outcomes with semaglutide treatment, is ongoing to test this hypothesis in patients with CKD at baseline.
MO073ACCELERATION OF KIDNEY FUNCTION DECLINE AFTER INCIDENT HOSPITALIZATION WITH CARDIOVASCULAR DISEASE: THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT
Authors: Ishigami Junichi , Trevisan Marco , Lund Lars , Jernberg Tomas , Coresh Josef , Matsushita Kunihiro , Carrero Juan Jesus 
Published: June 2020

Abstract

Background and Aims
The cardiorenal syndrome refers to a bidirectional relationship between the kidney and the heart. However, epidemiological evidence of cardiovascular disease (CVD) as a risk factor for chronic kidney disease (CKD) progression is actually scarce. We here quantified slopes of kidney function decline before and after the incidence of major CVD.

Method
We examined the slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before vs. after an incident hospitalization with heart failure (HF) (n=20,420), coronary heart disease (CHD) (n=18,152), or stroke (n=1,808) using data from a complete laboratory data collection in Stockholm, Sweden between 2006 and 2011. We used mixed-effect models with unstructured residual correlation matrix and stratified by index eGFR (≥60, 30-59, &lt;30 ml/min/1.73m2).

Results
Overall, patients who had HF were older, and had more comorbidities (e.g., diabetes, hypertension) and lower eGFR compared to those who had CHD or stroke. Incident hospitalization with HF and CHD, but not stroke, was significantly associated with a subsequent accelerated decline in eGFR, with a faster eGFR decline and greater slope change after HF than CHD. In the overall population, the pre-event vs. post-event eGFR slopes (ml/min/1.73m2 per year) were -1.67 (-1.77 to -1.57) vs. -2.76 (-2.82 to -2.71), with a Δslope of -1.09 (-1.16 to -1.02) for HF; -1.09 (-1.20 to -0.98) vs. -1.87 (-1.92 to -1.81), with a Δslope of -0.78 (-0.85 to -0.70) for CHD; and -1.00 (-1.37 to -0.63) vs. -0.99 (-1.19 to -0.78), with a Δslope of 0.02 (-0.24 to 0.27) for stroke (Figure 1A). The accelerated declines in eGFR after HF and CHD were consistent across the spectrum of eGFR, although pre-event eGFR slopes were steeper in lower eGFR (e.g., pre-event eGFR slope for HF -0.64 (-0.76 to -0.53) for eGFR ≥60, -1.43 (-1.57 to -1.30) for eGFR 30-59, and -2.42 (-2.71 to -2.12) for eGFR &lt;30 ml/min/1.73m2) (Figure B-D).

Conclusion
Incident hospitalization with cardiac diseases (i.e., HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline.
MO074RENAL FUNCTION DECLINE IN OLDER MEN AND WOMEN WITH ADVANCED CKD - RESULTS FROM THE EQUAL STUDY
Authors: Chesnaye Nicholas , Dekker Friedo W , Evans Marie , Caskey Fergus , Torino Claudia , Postorino Maurizio , Szymczak Maciej , Ramspek Chava , Drechsler Christiane , Wanner Christoph , Jager Kitty J 
Published: June 2020

Abstract

Background and Aims
Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in CKD 4-5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation.

Method
The EQUAL study is an observational prospective cohort study in stage 4-5 CKD patients ≥65 years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 to December 2018. eGFR was calculated using the CKD-EPI equation. Linear mixed models were used to model the eGFR trajectory by sex, and joint models were applied to deal with informative censoring.

Results
We included 7801 eGFR measurements in 1682 patients over 2911 years of follow-up. Renal function declined 14.0% (95% CI 12.9%-15.1%) on average each year. Renal function declined faster in men (16.2% per year, 95% CI 15.9%-17.1%) compared with women (9.6% per year, 95% CI 6.3%-12.1%), which remained largely unchanged after accounting for various mediators, and for informative censoring due to mortality and dialysis initiation. We identified effect modification by diabetes, with faster declines in renal function found especially in women with diabetes.

Conclusion
In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators, and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women.
MO075DNA METHYLATION AND RESPONSE TO STEROIDS IN CHILDREN WITH NEPHROTIC SYNDROME
Authors: Hayward Samantha , Suderman Matthew , Bierzynska Agnieszka , Welsh Gavin I , Saleem Moin A 
Published: June 2020

Abstract

Background and Aims
Historically, paediatric patients with nephrotic syndrome (NS) have been crudely categorised by their response to steroids: steroid resistant (SRNS), steroid sensitive (SSNS) and secondary SRNS. However, growing evidence that these categories do not correspond to single diseases has led to a demand that they be re-defined based on biological mechanisms involved in the disease process. Indeed, next generation sequencing has identified causative mutations in up to 30% of paediatric NS patients (‘monogenic’ NS); however, specific disease mechanisms in the remaining patients remain unknown.
We propose that the remaining phenotype variation in NS may be explained by DNA methylation, the reversible but heritable addition of methyl groups to DNA that change how the underlying DNA sequence is interpreted.
MO076LONGITUDINAL CHANGES AND OUTCOME OF HIGH BLOOD PRESSURE IN EUROPEAN CHILDREN ON RENAL REPLACEMENT THERAPY
Authors: Vidal Enrico , Bonthuis Marjolein , Jager Kitty J , Harambat Jerome 
Published: June 2020

Abstract

Background and Aims
Few studies have focused on trends of hypertension (HTN) and status of blood pressure (BP) control over time in children on renal replacement therapy (RRT). In this study, we aimed to evaluate the 5-year trend in BP antihypertensive medications (AHs) use, as well as the association between HTN and mortality among RRT patients enrolled within the ESPN/ERA-EDTA Registry.

Method
25.223 BP measurements from 5.032 patients who started RRT before 20 years of age, between 2007-2016, were included. Mixed models were used to analyse trends of BP, the JointPoint regression to assess prevalence of uncontrolled HTN (uHTN) over time, and multivariable Cox proportional hazard models to evaluate association of BP with mortality.

Results
Mean systolic BP (SBP) at RRT initiation was 1.66(+0.15), 1.05(+0.15) and 1.09(+0.08) SDS in HD, PD and transplanted (Tx) patients, respectively, while it was 1.41(+0.19), 1.12(+0.18), and 0.79(+0.06) SDS in the corresponding RRT categories after 5 years. Patients on HD showed a significant decrease in the prevalence of uHTN over time (57.1% at dialysis start vs 41.4% after 5 years; annual percentage change [APC] -4%; 95% CI: -5.7;-2.2; p&lt;0.05), coupled with a significant reduction in AHs use (APC -3.5%; 95% CI: -6.7;-0.2). PD patients showed a similar reduction in uHTN prevalence (APC -4.9%; 95% CI: -7.2;-2.6; p&lt;0.05), but a significant increase in AHs use (APC +3.6%; 95% CI: 0.6;6.6; p&lt;0.05). After 5 years, Tx patients showed a significant reduction in both prevalence of uHTN (APC -4.8%; 95% CI: -7.8;-1.7; p&lt;0.05) and use of AHs (APC -2.2%; 95% CI: -4.1;-0.3%; p&lt;0.05). Having uHTN was not associated with mortality (HR 0.95; 95% CI: 0.68-1.33).

Conclusion
A more adequate control of BP over time seemed to be obtained in children on RRT. Findings in PD patients suggest that this requires a progressive increase in the use of AHs.
TO004IMPACT OF RENAL TRANSPLANT ON COGNITIVE FUNCTION AMONG ESRD PATIENTS ON DIALYSIS
Authors: Kaul Anupma , Bhaduria Dharmendra , Prasad Narayan , Gupta Amit 
Published: June 2020

Abstract

Background and Aims
Kidney transplantation can help in mitigating neuropsychological (NP) impairments in end-stage renal disease (ESRD). Evidences have shown mixed responses on the the nature of cognitive function in patients who have undergone renal transplantation.Present study looked into the factors impacting cognitive domains and impact post transplant.

Method
43 patients who were stable ESRD on thrice a week hemodialysis were investigated 6 months pre and post transplant using a battery of neurophysiological testing assessing attention–concentration, psychomotor ability and memory.
Formal kinetic modelling of dialysis delivery ensured adequate renal replacement therapy. Transplant function was assessed on regular interval and following a stable graft function and on stable doses of immunosuppressive medication 6 months post transplant were reassessed

Results
Within-subject comparisons showed statistically significant improvement in memory performance after kidney transplant. Other NP measures (attention– concentration and psychomotor abilities) showed non-significant improvements. Normative comparisons showed NP impairments on dialysis, which were not apparent after transplant

Conclusion
These data demonstrate improvements in cognition following kidney TX and emphasize the reversibility of the memory problems evidenced in dialysis
TO018ACUTE KIDNEY INJURY IDENTIFICATION: USE OF ELECTRONIC AKI ALERTS VERSUS ELECTRONIC HEALTH RECORDS IN HOSPITAL EPISODE STATISTICS
Authors: Savino Manuela , Casula Anna , Wong Esther , Kolhe Nitin , Medcalf James , Nitsch Dorothea 
Published: June 2020

Abstract

Background and Aims
Acute kidney injury (AKI) refers to an abrupt decline in the glomerular filtration rate (GFR) which may be associated with significant morbidity and mortality. Since April 2015, an automated real-time electronic alert system for AKI has been introduced and progressively implemented in England, with alert data being sent to the UK Renal Registry (UKRR) for collection into a master patient index (MPI). Historically, the only way to routinely measure AKI incidence in hospital was to analyse the Hospital Episode Statistics (HES). The introduction of the MPI allows for the first time a comparison between warning-test score defined AKI and clinical coding. This project aims to determine whether episodes of AKI identified in the UKRR MPI correspond to coded diagnoses on the discharge record held in HES.

Method
The UKRR MPI of all AKI electronic alerts (AKI stages 1, 2 and 3) in patients ≥18 years of age, between 01/01/2017 and 31/12/2017 were linked to HES data to identify a hospitalised AKI population. Descriptive analyses were conducted to describe the demographics and to investigate whether those with electronic AKI alert also had an International Classification of Diseases (ICD)-10 code for AKI (N17) in HES.

Results
From 01/01/2017 to 31/12/2017, 301,504 hospitalised adults received an AKI electronic alert. AKI severity was positively associated with the percentage of AKI alerts which were coded in HES. There was also a significant variation in HES coding between hospitals, but generally, variation was most pronounced for AKI stage 1, with a mean of 48.2% [SD 14], versus AKI stage 3, with a mean of 83.3 % [SD 7.3] (figures 1, 2 and 3). There was an inverse trend with age in that younger adults AKI staging warning scores were less often coded in HES and this was true for all the three AKI stages (33% of AKI episodes coded in HES for people aged 18-29 versus 64% for people ≥ 85 years old) (Table 1).

Conclusion
In 2017, earlier stages AKI warning scores were poorly coded in HES. There was also high degree of inter-hospital variability, particularly for AKI warning score 1, reflecting potentially poor clinical recognition and documentation in medical record and subsequent clinical coding. AKI warning scores were poorly captured in HES for younger adults in comparison to those of older age; reasons for which need to be identified. Use of HES to identify cases of AKI is likely to underestimate the incidence of AKI, especially for AKI stage 1, though a high proportion of the most severe cases will be captured.
TO021LONG-TERM OUTCOMES OF COMMUNITY- VERSUS HOSPITAL-AQUIRED ACUTE KIDNEY INJURY: A RETROSPECTIVE ANALYSIS OF A LARGE COHORT IN A GERMAN TERTIARY CARE CENTER
Authors: Khadzhynov Dmytro , Schmidt Danilo , Eckardt Kai-Uwe , Schmidt-Ott Kai M 
Published: June 2020

Abstract

Background and Aims
This study compared epidemiology, short- and long-term outcomes for patients with community-acquired (CA) and hospital-acquired (HA) acute kidney injury (AKI).

Method
We retrospectively analyzed all episodes of AKI over a period of 3.5 years (2014–2017) on the basis of routinely obtained serum creatinine measurements in 103,161 patients whose creatinine had been measured at least twice and who had been in the hospital for at least two days. We used the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria for AKI and analyzed the first hospital admission. A total of 103161 were admitted in hospital and fulfilled the inclusion criteria. Average observation period per patient was 248 days.

Results
The incidence of CA-AKI among included hospital admissions was 9.7% compared with an incidence of 8.6% of HA-AKI, giving an overall AKI incidence of 18,3%. Patients with CA-AKI were younger than patients with HAAKI (64 vs 66,2y) and had significantly less comorbidities, including preexisting cardiac failure, ischemic heart disease, hypertension, diabetes. Patients with CA-AKI were more likely to have stage 1 AKI (69,3 vs 58,4%, p&lt;0.001) and had significantly shorter lengths of hospital stay than patients with HA-AKI (14 vs 24d, p&lt;0.001).
Those with CA-AKI had better survival than patients with HA-AKI (Figure 1; p&lt;0.001). Patiens with CA-AKI were less likely dialysis dependent before discharge (1,9 vs 4,8% in HA-AKI; p&lt;0.001) Patients with HA-AKI received more often administrative coding of AKI (29,3% vs 26,5% in CA-AKI patients; p&lt;0.001)

Conclusion
Patients with CA-AKI sustain less severe AKI than patients with HA-AKI, accordigly showing better short- and long-term outcomes. However, patiens with CA-AKI are at risk of inadequate clinical perception of AKI.