bluuebunny/crossref_metadata_2025_split huggingface dataset:
#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France
Authors: Bataille Pierre , Durel Cécile-Audrey , Thervet Eric , Chauveau Dominique , Maillet Serge , Schmidt Aurélie , Terrier Benjamin 
Published: May 2024

Abstract

Background and Aims
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2).

Method
All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers &gt;97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations.

Results
The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable.

Conclusion
According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.
#1000 Living alone and prognosis in elderly patients with chronic kidney disease: a nationwide study from Denmark
Authors: Thomsen Mette K , Jensen Simon Kok , Heide-Jørgensen Uffe , Slot Matilde , von Heymann Annika , Lauritzen Kira , Johansen Christoffer , Christiansen Christian Fynbo 
Published: May 2024

Abstract

Background and Aims
Patient care is increasingly relying upon involvement of patient relatives, including for patients with chronic kidney disease (CKD). However, patients living alone may be disadvantaged due to a lack of support. We aimed to assess the difference in prognosis after incident CKD in elderly patients between patients living alone versus living with others in a nationwide cohort study.

Method
We identified all patients aged 65 years or older with incident CKD from January 1, 2016, to December 31, 2020, with follow-up until December 31, 2021. We used data from national registries to identify CKD from out-patient creatinine measurements and linked these data to hospital treatment procedures and information from the Civil Person Registration system by the universal and unique personal identification number assigned to all Danish residents at birth or immigration.
We defined incident CKD as having two or more estimated glomerular filtration rate (eGFR) values below 60 ml/min/1.73 m2 registered at least 90 days apart. We categorized eGFR according to “Kidney Disease: Improving Global Outcomes” (KDIGO) CKD stages into 45-59 ml/min/1.73 m2 (mildly/moderately decreased), 30-44 ml/min/1.73 m2 (moderately/severely decreased), 15-29 ml/min/1.73 m2 (severely decreased), &lt;15 ml/min/1.73 m2 (kidney failure).
We assessed cohabitation (living alone, or living with others), also in national registry data. We described the population by age group, sex and stage of CKD. Analyzing mortality, we followed patients from date of CKD to death or end of follow-up, whichever came first. We calculated the median time to death, using age as the time scale and reported these by cohabitation status with 95% confidence intervals (CIs).
In further analyses, we will estimate the cumulated proportion who experienced a rapid decline in kidney function, as a measure of prognosis, and model the association between cohabitation and prognosis/mortality in regression models.

Results
We identified 204 662 elderly patients with CKD from 2016 to 2020, with 55% women and 38% 80 years or older. For severity, 84% had mildly/moderately decreased kidney function, 13% had moderately/severely decreased kidney function, 2% had severely decreased kidney function and only less than 1% (457 patients) presented with kidney failure.
At index, 55% lived with others and 45% lived alone. Overall, 53 715 died during follow-up, and median age at death was 82 (95% CI: 82;82) for CKD patients living together with someone, but 78 (95% CI: 77;78) for those living alone.

Conclusion
The results are preliminary, and further analyses, including age adjustment, mortality estimates and information on adult children, will be available for presentation at the ERA conference 2024.
#1447 Calcimimetics improve impaired cardiac function and contractility in chronic phosphate loading by activating the CaSR/cAMP signaling cascade
Authors: Grund Andrea , Haffner Dieter , Leifheit-Nestler Maren 
Published: May 2024

Abstract

Background and Aims
High phosphate loading stimulate the synthesis of PTH and FGF23 and is associated with increased cardiovascular (CV) mortality. In hemodialysis patients, the administration of calcimimetics led to reductions in PTH and FGF23 and the latter was associated with a lower rate of CV events. We have previously shown that mice with a high dietary phosphate load show elevated PTH and FGF23 levels and develop impaired systolic cardiac function, which could be improved by calcimimetics. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR). Phosphate (Pi) was shown to inactivate the parathyroid CaSR at concentrations &gt;1.4 mM Pi. Whether calcimimetics contribute to CV event reduction indirectly via lowering PTH and FGF23 or directly via activation of the cardiac CaSR is unknown.

Method
Wild-type mice were fed a high phosphate diet (HPD) ± etelcalcetide (Etl) or a normal phosphate diet (NPD), cardiac function was assessed by echocardiography and Millar catheterization, and cardiac tissue was harvested for histology and RNAseq analyses. In addition, isolated adult mouse cardiomyocytes (AMCM) were stimulated ex vivo with PTH, FGF23 or Pi, contractility and calcium handling were measured with the addition of Etl and activity analyses were performed.

Results
In addition to the positive effect on HPD-induced systolic cardiac dysfunction, Etl improved impaired LV contractility and reduced fibrosis. RNAseq analyses revealed reduced Ca, PKA and cAMP signaling by HPD. Ex vivo stimulation of AMCM with PTH and FGF23 had no functional effects. In contrast, Pi significantly worsened contractility and Ca handling, which was blunted by Etl co-stimulation. Downstream of cardiac CaSR, Pi reduced the formation of cAMP, which led to PKA-dependent dephosphorylation of PLN and subsequently to lower Serca2a activity, which was ultimately responsible for the reduced contractility. Etl led to improved cardiomyocyte contractility via increased cAMP synthesis and increased PLN phosphorylation and Serca2a activity.

Conclusion
Our data suggest that Etl ameliorates the Pi-induced pathologic cardiac phenotype associated with high phosphate load via direct activation of CaSR/cAMP signaling cascade, resulting in improvement of cardiomyocyte contractility.
#2255 Impact and interest of using the EKFC formula instead of CKD-EPI in estimating GFR in the laboratory on clinical practice
Authors: Derain-Dubourg Laurence , Lemoine Sandrine , Letourneau Pierre , Cabezas Lara , De Mul Aurelie , Chardon Laurence 
Published: May 2024

Abstract

Background and Aims
Early diagnosing Chronic Kidney Disease (CKD) is of major importance in daily practice, and the automatic reporting of the estimated glomerular filtration rate (eGFR) for all plasma creatinine (Pcr) determinations is mandatory. The CKD-EPI 2009 formula [1] is considered the most accurate creatinine-based GFR estimating formula in adults in Europe and is currently utilized by laboratories. However, CKD-EPI equation is inadequate in young adults &lt; 25 years and CKD-EPI equation is debated in the elderly over 75 years, with the BIS1 equation [2] showing better performance in this age group. The creatinine-based European Kidney Function Consortium (EKFC) equation [3] provides continuous GFR estimation from 2 years to adulthood and the elderly, presenting itself as a potential alternative to both the CKD-EPI and BIS1 equations. Our objective was to assess the impact of using the EKFC equation (and/or BIS1 in the elderly) compared to CKD-EPI in daily practice in identifying patients with a GFR &lt; 60 or &lt; 30 ml/min/1.73 m2, which represents the threshold for referring to a nephrologist and adjusting drug dosage, respectively.

Method
We retrieved data from the laboratory database, including gender, age, and the lowest measurement of Pcr for all patients over 18 years who underwent Pcr determination in November 2023. eGFR was calculated for all patients using the CKD-EPI and the EKFC equation. For patients over 70 years, eGFR was also estimated with the BIS1 equation. Pcr was assessed using an enzymatic method traceable to IDMS (Architect c®, Abbott Diagnostics). Results were expressed as the mean bias between EKFC and BIS1, and CKD-EPI (considered as the reference) according to age groups, and as the number of patients misclassified as &lt; 60 or &lt; 30 ml/min/1.73 m2.

Results
10 066 patients (50.5% females, mean age 56.0 ± 21.2 years [18.0-106.7]) underwent Pcr determination (mean 84.7 ± 72.3 µmol/L) with 1 706 (16.9%) and 405 (4.0%) having a GFR &lt; 60 or &lt; 30 ml/min/1.73 m2, respectively.
EKFC and BIS underestimated CKD-EPI eGFR in all groups, but especially in the groups of young adults and the elderly. However, the number of misclassified patients is small, except in the elderly when CKD-EPI is considered less accurate.

Conclusion
The use of EKFC in laboratories to estimate eGFR offers continuous GFR estimation from 2 years to adulthood and elderly and could be an alternative to both CKD-EPI and BIS1. The automatic reporting of eGFR with EKFC by laboratories in Europe could allow for an earlier diagnosis of CKD and initiation of nephroprotection in young adults, in addition to providing better nephrological care for the elderly.
#321 Hemodiafiltration for ESRD patients
Authors: Zhang Fan , Bai Yan , Wang Weiqiong , Zhong Yifei 
Published: May 2024

Abstract

Background and Aims
This systematic review and meta-analysis were designed to determine the effect of hemodiafiltration (HDF), or hemofiltration (HF) compared to hemodialysis on the prognosis of end-stage renal disease (ESRD) patients.

Method
PubMed, Embase, and Web of Science were searched for published studies from reception to 18 September 2023, and updated search on October 15, 2023. Randomized clinical trials (RCTs) or cohort studies evaluated prognosis of hemodiafiltration, or hemofiltration compared to hemodialysis in patients with ESRD were included. Data was synthesized based on heterogeneity with corresponding model selected, and trial sequential analyses were conducted. The primary outcome was all-cause mortality, and secondary outcome was cardiovascular mortality and dialysis adequacy. Outcomes were reported as relative risk (RR), hazard ratio (HR), or mean difference (MD) with a 95% confidence interval (95% CI).

Results
There were 26 RCTs, 10 cohort studies, and total of 36 articles included in the meta-analysis. Pooled results of RCTs showed a statistically significant difference in all-cause mortality between HDF/HF group and standard hemodialysis group (RR = 0.86; 95% CI 0.78-0.96; I2 = 29%; Fig. 1). Trial sequence analysis (TSA) showed that the all-cause mortality curve crossed the traditional and TSA boundaries, but it was not yet as informative as desired. Subgroup analysis found that ESRD patients treated with hemodiafiltration had a 13% lower risk of death (RR = 0.87; 95% CI 0.78-0.97; Fig. 1) with no heterogeneity (I2 = 0%). In contrast, the effect of hemofiltration on mortality risk in ESRD patients was not significant (RR = 0.70; 95% CI 0.39-1.29; Fig. 1). A similarly statistically significant difference in cardiovascular mortality (RR = 0.747; 95% CI 0.607-0.917; I2 = 0%; Fig. 2) for RCTs. In addition, HDF/HF treatment was significantly associated with improved dialysis adequacy (Assessed by Kt/V) in ESRD patients (MD: 0.09; 95% CI 0.01-0.17; I2 = 96%). The combined results of cohort studies showed a 28.6% reduction in mortality risk in ESRD patients treated with HDF (HR = 0.714; 95% CI 0.575-0.886; I2 = 84%; Fig. 3), with an HR for cardiovascular mortality of 0.708 (95% CI 0.604-0.829; I2 = 0%; Fig. 4).

Conclusion
Overall, HDF/HF was associated with reduced all-cause mortality and cardiovascular mortality in patients with ESRD and contributed to improved dialysis adequacy.
#1157 Body mass and fluid balance in dialysis: global profiles in Apollo Dial DB
Authors: Croft Kaitlyn , Wolf Melanie , Jiao Yue , Winter Anke , Nikam Milind , Stuard Stefano , Guinsburg Adrian , Koulechov Kirill , Mcguigan Stuart , Usvyat Len , Larkin John , Maddux Frank 
Published: May 2024

Abstract

Background and Aims
Fluid management is a fundamental component of dialysis care. Achieving euvolemia and avoiding fluid overload can be challenging in dialysis. Apollo Dial DB, an anonymised dialysis database from a global kidney care network, was used to gain deeper insights in patterns of patient body mass and fluid balance during dialysis treatments worldwide.

Method
Apollo Dial DB, a global anonymised dialysis database, contains real-world data from patients in 40 countries beginning January 2018 throughout March 2021. Parameters include demographics, diagnoses, laboratories, medications, treatments, quality of life, and outcomes. This analysis assessed body mass and fluid status parameters on patients in Asia-Pacific (AP), Europe, Middle East, and Africa (EMEA), Latin America (LA), Northern America (NA). In addition, bioimpedance for body compositions of patients was assessed as it was available in AP, EMEA, and LA.

Results
The first version of the Apollo Dial DB includes data on 543, 169 patients, with 4.6% from AP, 13.9% from EMEA, 7.0% from LA, and 74.5% from NA countries. EMEA and NA have a higher proportion of patients in the bigger height categories versus the AP and LA regions (Table 1). There is a difference in mean body weight post dialysis of more than 10 kg between regions; the highest weights were observed in EMEA and NA in contrast to the AP and LA regions. Average albumin levels were consistent in all global regions. Intradialytic weight gain is lowest in EMEA at 1.8 kg and highest in NA at 2.2 kg between treatments. While ultrafiltration volume ranged from 2.0 L to 2.4 L, being the highest in AP and NA. Bioimpedance measures defining body compositions were available for the majority of patients in AP (59.3%), EMEA (86.9%), and LA (90.7%). Patient averages in EMEA are slightly higher for ATM, FTM, LTM, TBW than for LA and AP; this is somewhat explained by the differences in body weight between the cohorts (Fig. 1).

Conclusion
A descriptive analysis of the body mass and fluid status across minor and major regions bring to light key profiles and differences in the characteristics of dialysis patients across the world and fluid management practices in dialysis care. Differences in intradialytic weight gain may deserve further analysis considering the impact of dialysis modality on fluid balance, such as potential influences of convective therapies. These findings act as benchmarks for the nephrology community. Apollo Dial DB offers opportunities for investigators to conduct global analytics and advance kidney disease research.
#2502 The CONVINCE randomized trial found positive effects of hemodiafiltration on quality of life in patients with kidney disease on dialysis
Authors: Rose Matthias , Fischer Felix , Hockham Carinna , Vernooij Robin Wm , Barth Claudia , Canaud Bernard , Cromm Krister , Davenport Andrew , Fischer Kathrin I , Jaha Hanna , Schappert Anna , Blankestijn Peter J 
Published: May 2024

Abstract

Background and Aims
Health-related quality of life of ESKD patients is negatively affected by disease-specific symptoms and can additionally be impaired by renal replacement therapy. Previous studies indicate that hemodiafiltration (HDF) may have a positive impact on the patients’ perceived health status compared to hemodialysis (HD), but overall evidence has been inconclusive. We investigated whether HDF is beneficial with respect to the patients’ perceived health status in the CONVINCE Trial.

Method
The CONVINCE Trial is an international multi-center, prospective, randomized, open label, controlled trial, comparing benefits and safety high-dose HDF versus high-flux HD. All-cause mortality was the primary outcome of the trial and a broad range of Patient-Reported Outcomes (PROs) were investigated as secondary outcomes. Eight generic health domains (Physical Function, Pain Intensity, Pain Interference, Fatigue, Sleep Disturbance, Depression, Anxiety, Ability to Participate in Social Roles and Activities) were assessed using the Patient-Reported Outcome Measurement Information System, PROMIS®-29 v2.0 profile, and an additional PROMIS short-form assessing Cognitive Function. PROs were collected every three months over the course of the study. As the perceived health status is likely related to mortality, we estimated the effect of HDF on PROs using a joint modelling approach to account for potential bias by selective dropout due to death.

Results
A total of n = 1 360 patients have been randomized to HD (n = 677) and HDF (n = 683). Both groups were comparable at baseline, with physical function (44.0 on the PROMIS T-score metric) considerably lower than the general population. Median follow-up was 30 months. We could obtain 84% of the planned PRO follow-up assessments on average. Overall, we found a steady decline in Health-Related Quality of Life (HRQoL) over the observation period; with statistically significant group differences for Physical Function (P = .047), Cognitive Function (P = .049), Pain Interference (P = .027) and the Ability to Participate in Social Roles and Activities (P = .023), all favouring HDF over HD.

Conclusion
Within the CONVINCE trial we have applied a comprehensive assessment of PROs comparing HDF with HD. Along with a beneficial effect on survival rates, we observed a slower decline in patients perceived health status when treated with HDF compared to HD. CONVINCE provides further evidence that HDF is beneficial in terms of quality of life.
#1683 Gut permeability, circulating bacterial fragments, and left ventricular strain in peritoneal dialysis
Authors: LI Chuanlei , Szeto Cheuk Chun 
Published: May 2024

Abstract

Background and Aims
There are limited data on the association of gut permeability, circulating bacterial fragment load, left ventricular strain in patients on peritoneal dialysis (PD). We aimed to measure circulating bacterial fragments, NT-proBNP, calprotectin and zonulin levels, and to evaluate their association with gut permeability, circulating bacterial fragment load, left ventricular strain and clinical outcomes on PD patients.

Method
We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. Serum endotoxin, bacterial DNA, NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technical and patient survival, secondary outcomes were hospitalization data.

Results
One hundred and eight patients were recruited. No correlations between circulating bacterial fragments, NT-proBNP, calprotectin and zonulin levels in PD patients. Circulating bacterial fragments, calprotectin and zonulin levels are positively correlated with insulin resistance index (bacterial DNA: P = .002, calprotectin: P = .014, zonulin: P = .006), while NT-proBNP level is associated with volume overload in PD patients (volume of overhydration: P = .000, E:I ratio: P = .000), peritoneal characteristics (D/P4: P = .004, MTAC: P = .048). NT-proBNP level have a negative correlation with nutritional characteristics (albumin: P = .000, hemoglobin: P = .033) and residual GFR (P = .000). In univariate analysis of PD patient survival, NT-proBNP is associated with patient survival (P = .003), but this association become insignificant after multivariate analysis of clinical confounding factors. NT-proBNP is the strongest independent predictor of technical survival rate in PD patients (P = .005). Patients in the highest tertiles of NT-proBNP and calprotectin have lower technical survival rates, but only patients in the highest tertiles of NT-proBNP, not calprotectin, have lower patient survival. NT-proBNP is also correlated with the number of hospitalizations per year (P = .004) and total hospitalization time (P = .012) in PD patients. Endotoxin and bacterial DNA levels in PD patients have no predictive value for PD patient survival, technical survival, number of hospitalizations per year, and total hospitalization time.

Conclusion
There is no correlation between gut permeability, circulating bacterial fragments, and impairment of left ventricular function in PD patients. Circulating bacterial fragments levels and gut permeability are associated with insulin resistance, while impairment of left ventricular function is associated with solution overload. Bacterial fragment levels have no predictive value on survival rate, technical survival rate and hospitalizations data in PD patients. NT-proBNP is the strongest independent predictor of technical survival rate in PD patients.