bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO1031: Burnout Syndrome Among Paediatric Nephrologists—Report on its Prevalence, Severity and Predisposing Factors
Authors: Pawlowicz-Szlarska Ewa , Skrzypczyk Piotr , Stańczyk Małgorzata , Pańczyk-Tomaszewska Małgorzata , Nowicki Michał 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Burnout is an occupational-related syndrome comprising emotional exhaustion, depersonalization and reduced feelings of work-related personal accomplishments. Addressing and mitigating burnout is essential for avoiding high workforce turnover, patient dissatisfaction and a lower quality of care. There are some reports on burnout among adult nephrologists and general paediatricians, but little has been known about burnout among paediatric nephrologists. The aim of our study was to assess the prevalence and severity of burnout syndrome among Polish paediatric nephrologists.

METHOD
A 25-items online survey consisting of abbreviated Maslach Burnout Inventory and additional self-created questions about work-related factors was completed by 97 physicians affiliated with the Polish Society of Paediatric Nephrology. 75.3% of them were women, the median time of professional experience in the study group was 15 years.

RESULTS
High level of emotional exhaustion, depersonalization and reduced feeling of personal accomplishments was observed in 39.2%, 38.1% and 21.6% of participants, respectively. 26.8% of participants presented at least a medium level of burnout in all three dimensions and 8.2% of them presented high three-dimensional burnout. No associations of burnout intensity and gender, job seniority and the use of holiday leave were found. 41.2% of participants stated, that they would like to take part in burnout prevention and support programme. According to the study participants, excessive bureaucracy in healthcare systems, rush and working overtime were the main job-related problems that can influence burnout intensity.

CONCLUSION
Burnout is an important factor in the professional landscape of paediatric nephrology. Actions aiming at reducing the risk of occupational burnout among paediatric nephrologists should be applied both at personal and institutional levels.
FC009: Women in Nephrology Leadership: A survey by the SFNDT
Authors: Karam Sabine , Hocine Aldjia , Hourmant Maryvonne 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The percentage of women in nephrology has been increasing over the years but remains suboptimal.(1) Likewise, women are still under-represented at the leadership level. Multiple factors have been evoked to explain this gap such as the constraints of motherhood and the lack of adequate culture for women advancement.(2)

METHOD
A 13-question questionnaire was sent to all the members of the Societe Francophone De Dialyse et Transplantation (SFNDT) inquiring about their gender, country, setting of practice and assessing their views about the representation of women in nephrology in general and in leadership positions in particular. Participants were also asked to voice their opinion about the potential barriers impeding women advancement in nephrology and about potential solutions to remediate to the gap.

RESULTS
A total of 237 participants responded to the survey with 17.7% of men. About 45.6% practiced in a public setting and 29% in a university setting. About 52% of the participants deemed that the number of women in nephrology was sufficient and 6.75% also thought that this number was more than sufficient; however only 14.7% thought that the number of women occupying leadership positions was enough. Regarding potential factors limiting women advancement in nephrology, 56.17% thought that there was a lack of incentive from the society to promote women, 55.3% thought that there was a bias toward promoting men, 40.4% thought that the lack of adequate child support played a role and 35.7% thought that the lack of or an insufficient paternity leave had an impact. Regarding potential solutions that could be offered 90.7% of the participants agreed that there was need to encourage a life–work balance and 60% deemed necessary to establish an adequate support system for working women such as daycares, lactation rooms etc.

CONCLUSION
Despite the continuous increase in the number of women in nephrology, their involvement in leadership role remains minimal and needs to be improved by optimizing their work conditions and by providing adequate support for the right work–life balance.
FC012: Urinary Lithogenic Profile in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Bargagli Matteo , Liguori Antonio , Baroni Silvia , D'amato Donato , Tomasello Lidia , Pizzolante Fabrizio , De Matthaeis Nicoletta , Miele Luca , Manuel Ferraro Pietro 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Several epidemiological studies have observed an increased risk for nephrolithiasis in patients affected by non-alcoholic fatty liver disease (NAFLD). However, the urinary lithogenic risk profile for patients with NAFLD is currently unknown.

METHOD
We systematically analysed the urinary metabolic profile of patients affected by NAFLD and liver cirrhosis (LC), followed at the hepatology outpatient clinic of our institution, compared to healthy individuals. A complete metabolic work-up for kidney stone disease was performed in all subjects. Multivariable linear regression models adjusted for age, sex, body mass index, eGFR and diabetes, were applied to assess differences in urinary lithogenic risk factors between healthy individuals and patients affected by NAFLD and LC.

RESULTS
A total of 42 patients and 12 healthy individuals were included in the analysis. No differences in age, sex and BMI were found among patients affected by NAFLD and LC, whereas the latter were more diabetic (71.4% versus 14.3%). After adjusting for multiple confounders, patients with NAFLD and LC had lower urinary magnesium (−55 mg/24 h; 95% CI −104, −6; P = 0.03 and −63 mg/24 h; 95% CI −121, −6; P = 0.03, respectively) and borderline oxalate (−1.21 mg/24 h; 95% CI −2.42, −0.01; P = 0.05 and −1.42 mg/24 h; 95% CI −2.79, −0.04; P = 0.04, respectively) excretions, compared with healthy controls. Compared with LC patients, NAFLD patients showed higher urinary ammonia (539 mEq/24 h; 95% CI 245, 833; P &lt; 0.01), ammonia/net acid excretion ratio (0.40; 95% CI 0.18, 0.62; P &lt; 0.01), urine pH (1.16; 95% CI 0.44, 1.88; P = 0.05) and lower urinary uric acid excretion (−210 mg/24 h; 95% CI −419, −0.29; P &lt; 0.01) and titratable acidity (−9.7 mEq/24 h; 95% CI −19.0, −0.4; P = 0.04).

CONCLUSION
Altered urinary ammonia and magnesium excretions seems to be involved in the higher risk for stone formation found in patients with NAFLD. More studies are needed to investigate stone phenotypes and renal handling of ammonia in this setting.
FC035: Exome Sequencing of the Israeli Dialysis-Treated Pediatric Population Reveals Monogenic Etiology in ∼44% of Cases
Authors: Kagan Maayan , Ben Moshe Yishay , Shlomovitz Omer , Atias-Varon Danit , Haskin Orly , Ben-Shalom Efrat , Magen Daniella , Schreiber Ruth , Volovelsky Oded , Shasha-Lavsky Hadas , Davidovits Miriam , Borovitz Yael , Mor Nofar , Khavkin Yulia , Tzvi Behr Shimrit , Pollack Shirley , Geylis Michael , Schnapp Aviad , Weissman Irith , Barel Ortal , Vivante Asaf 
Published: May 2022

Abstract

BACKGROUND
Chronic kidney disease in children is estimated to be secondary to a monogenic etiology in ∼20% of patients and can arise from mutations in a multitude of different single-gene causes. Still, data are lacking on the true prevalence of genetic etiologies dates from a large scale unbiased population screen of children with advanced kidney disease.

METHOD
In order to provide comprehensive real-world evidence for monogenic etiologies of childhood end-stage kidney disease—on a national level—we initiated a nation-wide multicenter study of all pediatric Israeli dialysis units. Specifically, between 2020 and 2021, we recruited ∼90% (n = 66) of children on dialysis from all six dialysis units treating children in Israel. We conducted exome sequencing and diagnostic analysis for all patients. We assessed the diagnostic yield of genetic analysis and its relation to baseline clinical phenotypes.

RESULTS
Overall, the cohort comprises 66 individuals from different families with a first-degree consanguinity rate of 47%. Participants' mean age at renal replacement therapy initiation was 8.1 years (range 1-month to 20-years). Using exome sequencing we identified a genetic etiology in 29 out of 66 (44%) participants. The most common subgroup of diagnostic variants was in genes causing renal cystic ciliopathies (e.g. NPHP1, NPHP4, PKHD1 and BBS9), which together explain 31% of all monogenic etiologies. This was followed by mutations in genes causing CAKUT (e.g. EYA1, HNF1B, PAX2, COL4A1 and GREB1L), steroid-resistant nephrotic syndrome (e.g. LAGE3, NPHS1, NPHS2, LMX1B, SMARCAL1 and CRB2) and tubulopathies (e.g. CTNS, AQP2), which explain 21%, 21% and 17% of all genetic etiologies, respectively. The yield of exome sequencing was higher among non-Jewish compared with Jewish individuals (52% versus 29%) and in children from consanguineous families compared with non-consanguineous families (56% versus 31%). The final molecular diagnosis did not correspond with the pre-exome clinical diagnosis in 17% of cases.

CONCLUSION
Exome sequencing in an unbiased pediatric cohort with end-stage kidney disease yields a genetic diagnosis in 44% of cases and reveals many underappreciated monogenic etiologies. Surprisingly, renal cystic ciliopathies causing-genes were more common than CAKUT genes in our cohort. These results emphasize the importance of genetic testing among children with advanced chronic kidney disease and validate the role of exome sequencing as a standard routine diagnostic tool.
FC038: Efficacy of Levamisole for Maintaining Remission after the First Flare of Steroid Sensitive Nephrotic Syndrome in Children: The Nephrovir-3 Randomized Controlled Trial
Authors: Dossier Claire , Kwon Theresa , Nekrouf Celia , Bensaid Philippe , Parmentier Cyrielle , Galerne Aurelien , Chace Anne , Gobet Sophie , Nathanson Sylvie , Mahdi Fouad , Zenkhri Ferielle , Rouget Sebastien , Boyer Olivia , Berard Laurence , Rousseau Alexandra , Hogan Julien , Deschenes Georges 
Published: May 2022

Abstract

BACKGROUND AND AIMS
In children with Steroid Sensitive Nephrotic Syndrome (SSNS), relapse after the first flare occurs in 80% of cases, whatever the dosage or duration of initial steroid therapy. Therefore, there is an unmet need for early interventions to reduce the incidence of relapse and subsequent steroids and immunosuppressive drug exposure. Levamisole is an antihelmintic drug with an immunomodulatory action that reduces relapses in children with frequent relapses or steroid-dependant NS. NEPHROVIR-3 is the first trial to assess the efficacy of levamisole in increasing duration of initial remission after the diagnosis of INS.

METHOD
NEPHROVIR-3 is a multicentric placebo-controlled randomized trial (1:1), in 38 centres of the Paris area, France. Patients were included at INS diagnosis and randomized, when steroid sensitive within 4 weeks, to receive either levamisole 2.5 mg/kg/48 h or placebo for 6 months, in addition to the French steroid protocol (18 weeks-3990 mg/m2). Primary outcome was the relapse-free survival at 1 year. The effect of the study drug was analysed by a Cox proportional hazard model stratified on centre.

RESULTS
Between September 2017 and February 2020, 86 patients were included, median age at INS onset was 5 years (IQ 3–7), with 69% of boys. At 4 weeks, 68 of them were randomized. Median time to remission was 8.5 days (IQ 6–12). Relapse-free survival at 12 months was 53.8% [95 confidence interval (95% CI) 34.7–69.5] in the levamisole group versus 20.9% (7.2–39.4) in the placebo group (P = .007). The risk of relapse associated with levamisole was HR = 0.37 (95% CI 0.15–0.89).

CONCLUSION
Early treatment with levamisole at the first flare of childhood SSNS significantly improves relapse-free survival at 1 year.
FC044: Heterozygous Variants in Kinase Domain of NEK8 cause an Autosomal-Dominant Ciliopathy
Authors: Claus Laura , Stallworth Jennifer , van Jaarsveld Richard , Turner Joshu , Hawks Alexandra , May Melanie , Flanagan-Steet Heather , Louie Raymond , Silver Josh , Lerner-Ellise Jordan , Morel Chantal , Mighton Chloe , Ziegler Alban , Barakat Stefan , Dahan Karin , Demoulin Nathalie , Jean Goffin Eric , Larsen Martin , Michael Hertz Jens , Lilien Marc , Olinger Eric , Sayer John , Obeidová Lena , Seeman Tomas , Senum Sarah , Hanna Christian , Rogers Curtis , Duran Karen , Peters Edith , Harris Peter , Mason Jennifer , van Haaften Gijs , M. Van Eerde Albertien , Steet Richard 
Published: May 2022

Abstract

BACKGROUND AND AIMS
NEK8/NPHP9 encodes a protein that localizes to the primary cilium. Biallelic NEK8 variants are known to cause multiorgan developmental defects, including kidney cystic dysplasia and extensive extra-renal defects, with heterozygous carrier parents being asymptomatic [1]. This autosomal recessive inheritance is the most common inheritance mode for ciliopathies. Complementary to this, we now propose a dominant negative effect for specific heterozygous NEK8 missense variants in the kinase domain resulting in an autosomal-dominant ciliopathy.

METHOD
We performed genetic testing in patients from several medical centers. To explore the consequences of the identified NEK8 variants, we are performing cilia staining assays in patients' skin fibroblast and kidney cells, as well as in mIMCD3 cells overexpressing the identified variants. Furthermore, we are examining the impact of the NEK8 variants on replication stress response.

RESULTS
We identified three distinct heterozygous NEK8 variants in 12 families (Table 1), all leading to missense alterations in the kinase domain. Interestingly the p.Arg45Trp variant is a recurrent variant we detected in 10 unrelated families. All patients have a kidney phenotype that varies from mild focal segmental glomerulosclerosis to prenatal presentation with polycystic kidneys. Most patients have kidney failure needing kidney replacement therapy at varying ages of onset. In all patients, we thoroughly checked whether a second variant could be found. Furthermore, the large symptomatic family and de novo occurrences favor a dominant inheritance mode. Our preliminary results from functional studies show abnormal primary cilia formation in serum-starved cells as well as increased replication stress.

CONCLUSION
We present the first evidence for a pathogenic effect of heterozygous NEK8 variants. Remarkably our patients present with a kidney limited phenotype as compared to the multiorgan defects found in patients with biallelic variants. This reveals a new mode of inheritance for NEK8 variants and expands genotype-phenotype correlations for this gene.
FC068: Association of PLA2R Antibody Exposure and EGFR Slope in PLA2R-Related Membranous Nephrology: Results from a Cohort of 3982 Adult Chinese Patients
Authors: Le Wei-Bo , Shi Jingsong , Hu Weixin , Zhi-Hong Liu 
Published: May 2022

Abstract

BACKGROUND AND AIMS
PLA2R antibody level could be used in the risk stratification for patients with Membranous Nephrology (MN). However, the association of PLA2R antibody level and glomerular filtration rate slope in PLA2R-related MN and what specific PLA2R antibody level should be used to predict the risk of disease progression remains unclear.

METHOD
A total of 11 628 patients who had at least one positive serum PLA2R antibody test (&gt;20 RU/mL) were screened from July 2016 through June 2021 in our kidney center. The baseline was defined as the first time of PLA2R antibody test. PLA2R exposure level was defined as area under the curve of the antibodies divided by the time of follow-up. The eGFR slope for each individual was calculated using mixed-effects models. The association between PLA2R exposure level and eGFR slope was analyzed using locally weighted linear regression. The candidate cutoff level of PLA2R antibody used to predict the risk of disease progression were defined as the value corresponding to the lower quartile (25th percentile) of the eGFR slope.

RESULTS
A total of 3982 PLA2R-related MN patients were finally included in this study. The median follow-up (IQR) was 3.7 (2.7–4.6) years. The participants had a median (IQR) proteinuria exposure of 1.7 (0.94–3.4) g/24 h and a median (IQR) PLA2R antibodies exposure level of 27.7 (11.9–67.0) RU/mL during follow-up. The median eGFR slope (IQR) was –1.5 (–5.2 to –0.02) mL/min/1.73 m2 per year in the mixed model. The relationship between eGFR slope and PLA2R antibody exposure is linear in the square root scale of PLA2R antibodies, but is obvious non-linear in the linear scale and in the log scale of PLA2R antibodies. One unit increase of PLA2R antibodies exposure in square root scale is associated with a –0.61 ± 0.02 mL/min/1.73 m2 per year faster decline in eGFR (P &lt; 0.001). The level of PLA2R antibody exposure corresponding to the lower quartile of the eGFR slope (–5.2 ml/min/1.73 m2 per year) is 8.7 RU/mL in square root scale (75 RU/mL in linear scale).

CONCLUSION
A linear relationship was observed between eGFR slope and PLA2R antibodies exposure in square root scale. It would be more helpful to report PLA2R antibodies test in square root scale than in linear scale. Our data suggest that 8.7 RU/mL in square root scale (75 RU/mL in linear scale) could be used as one of the candidate cutoff values of PLA2R antibody level to predict the risk of MN progression.
FC082: Effects of Dapagliflozin in Patients with Chronic Kidney Disease According to Background Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Dose
Authors: Lambers Heerspink Hiddo , Jong Niels , Stefansson Bergur , Chertow Glenn , Maria Langkilde Anna , Mcmurray John , Correa-Rotter Ricardo , Rossing Peter , Toto Robert , Wheeler David 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Treatment guidelines for patients with chronic kidney disease (CKD) recommend renin–angiotensin system inhibition (RASi) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) to reduce the risk of kidney failure. However, patients with more advanced CKD do not always tolerate RASi. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of kidney failure in patients with CKD in the DAPA-CKD trial. We performed a post hoc analysis of this trial to assess the efficacy of dapagliflozin by baseline dose level of ACEi or ARB.

METHOD
Participants with CKD [estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. Participants were to be treated with the recommended target dose, or a stable tolerated dose of ACEi or ARB, unless medically contraindicated, for ≥4 weeks prior to inclusion. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease or death from a kidney or cardiovascular cause. A prespecified kidney-specific secondary outcome was the same as the primary endpoint, but without cardiovascular death. A composite cardiovascular outcome (heart failure hospitalization or cardiovascular death), and all-cause mortality were other secondary endpoints. Time-to-event analyses were performed to assess the effects of dapagliflozin versus placebo according to baseline prescription and dose of ACEi or ARB treatment.

RESULTS
Of 4296 (99.9%) participants with available data on ACEi/ARB doses, 1231 (28.7%) were using the target dose, 1867 (43.5%) a dose ≥50% to &lt;100% of target, 1068 (24.9%) a dose 0 to &lt;50% of target and 130 (3.0%) were not using an ACEi/ARB. In the placebo group, the event rate for the primary outcome was highest among participants not using ACEi/ARBs compared to the other subgroups (figure 1). The benefit of dapagliflozin on the primary composite outcome was consistent regardless of use or non-use of the target dose of ACEi/ARBs. This consistency was maintained for the secondary outcomes (Figure 1). Dapagliflozin compared to placebo reduced the rate of eGFR decline over the study by –0.93 [95% confidence interval (95% CI) 0.61–1.25] mL/min/1.73 m2. This effect was present regardless of the use or non-use of target doses of ACEi/ARBs (P for interaction 0.877).

CONCLUSION
Dapagliflozin was similarly efficacious in reducing major adverse kidney and cardiovascular outcomes in participants with CKD regardless of the use or dose of ACEi/ARB.
FC086: Improved Immunologic Response to COVID-19 Vaccine with Prolonged Dosing Interval in Hemodialysis Patients
Authors: Haarhaus Mathias , Duhanes Monica , Lesevic Natasa , Matei Bogdan , Ramsauer Bernd , Da Silva Rodrigues Rui , Su Jun , Haase Michael , Santos Carla , Macário Fernando 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Vaccination against coronavirus disease 2019 (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in hemodialysis patients.

METHOD
All patients within a Swedish hemodialysis network, vaccinated with two doses of COVID-19 vaccine 2–8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by the EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included.

RESULTS
Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23.6%). Three patients received combinations of different vaccines. Response rate (antibody titres &gt;7 U/mL) was 89.9%, while 39.3% developed high antibody titres (&gt;204 U/mL), 47 (43–50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres [median (25th–75th percentile) 1558.5 (814.5–3763.8) U/mL versus 87 (26–268) U/mL; P = 0.002], while the time between vaccine doses did not differ between groups (P = 0.7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses, decreasing serum calcium levels and previous COVID-19 (Table 1).

CONCLUSION
In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in hemodialysis patients. While the response rate was good, only a minority developed high antibody titres 47 (43–50) days after the second vaccine dose.