bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in mortality between emergency and elective valve exchange surgeries in a tertiary hospital between 2010 and 2021
Authors: Mazetto A , Garcia R , Stein J , Cinesio H , Goncalves R , Boer B , Tarasoutchi F , Lavitola P
Published: May 2022

Funding Acknowledgements

Type of funding sources: None. Main funding source(s): Public institutions.

Introduction

The natural history of valvular heart disease is very heterogeneous and varies according to the etiology and valve affected. It is well established that the presence of symptoms or some alarm signs indicates interventions to improve the patient’s prognosis. In some cases, the patient is subjected to at a late time of the natural history of his disease, sometimes during clinical instability and this can get a much worse prognosis. Therefore, follow-up of the valvopathic patient is essential to indicate the best moment of intervention. The aim of this study was to analyze the difference in mortality in patients submitted to valve replacement in an elective and in a tertiary hospital.

Objectives

The aim of this study was to evaluate the risk of morbidity and mortality when comparators the use of biological and metallic prostheses in elective surgeries and emergencies.

Methods

Medical records were reviewed of patients undergoing valve replacement surgery in an aortic and mitral position in an emergency and elective character between 2010 and 2021.

Results

A total of 5,340 valve replacement surgeries were performed in an aortic and mitral position, of which 945 were emergency surgical and 4395 in an elective scenario. Among the emergency procedures, there were a total of 270 deaths (28.57%). While in elective procedures mortality was 535 deaths (12.17%). Regarding the nature of the prosthesis, 91.57% were placed biological, where 874 (17.87%) of these procedures were emergency and of these, 255 deaths (29.17%) were recorded. In elective nature, 4,016 prostheses (82.12%) were, among these cases, 499 deaths (12.42%). In relation to mechanical prostheses, the total was 8.42%, 71 of which were placed as an emergency with 15 deaths (21.12%). Valve surgery with mechanical prosthesis was performed in 379 patients and 36 deaths were recorded (9.49%).

Conclusion

Valve replacement in an emergency context has mortality 2.34 times higher than when performed electively. This data reflects that the intervention at a late stage of the natural history of valvopathies, especially in situations of clinical instability brings the patient a worse prognosis and this shows us the importance of accompanying the valvopathic patient appropriately in an outpatient context to indicate the most opportune moment of valve replacement if the procedure is necessary.
Clinical outcomes of mitral valve repair for degenerative mitral regurgitation in elderly patients
Authors: Kawajiri Hidetake , Schaff Hartzell V , Dearani Joseph A , Daly Richard C , Greason Kevin L , Arghami Arman , Rowse Philip G , Viehman Jason K , Lahr Brian D , Gallego-Navarro Carlos , Crestanello Juan A
Published: May 2022

OBJECTIVES

This study analyzes the safety and outcomes of mitral valve repair for degenerative mitral valve regurgitation in patients 75 years of age or older.

METHODS

We retrospectively reviewed the clinical results of 343 patients aged ≥75 years who underwent mitral valve repair for degenerative mitral valve regurgitation as a primary indication between January 1998 and June 2017.

RESULTS

The median (interquartile range) age of the patients was 79.4 (76.9, 82.9) years, and 132 (38.5%) patients were women. Concomitant procedures were performed in 123 patients: tricuspid surgery in 68 (19.8%) and a maze procedure or pulmonary vein isolation in 55 (16.0%). Operative mortality was 1.2%. Operative complications included atrial fibrillation in 37.9%, prolonged ventilation in 7.0%, pacemaker implantation in 3.8, renal failure requiring dialysis in 1.5 and stroke in 3 (0.9%). The median follow-up was 7.4 years (interquartile range, 3.5–14.1 years). The cumulative incidence rates of mitral valve reoperation were 2.2%, 3.2% and 3.2% at 1, 5 and 10 years, respectively. Overall survival at 1, 5 and 10 years were 95%, 83% and 51%, respectively. Older age, smoking and over and underweight were associated with increased risk of mortality, while higher left ventricular ejection fraction and hypertension were associated with reduced risk.

CONCLUSIONS

Mitral valve repair in elderly patients can be accomplished with low operative mortality and complications. Mitral valve repair in the elderly remains the preferred treatment for degenerative mitral regurgitation.
Cardiovascular risk and protective factors in adults with and without diabetes mellitus (Italy, 2016–19)
Authors: Baldissera Sandro , Minardi Valentina , Masocco Maria , Ferrante Gianluigi
Published: May 2022

Background

Cardiovascular (CV) diseases are a major cause of the disease burden worldwide and contribute substantially to health care costs, in particular in people with diabetes. Their incidence can be reduced by multi-factorial interventions. This study intends to describe the occurrence of CV risk and protective/preventive factors in the adult population resident in Italy, to better target public health interventions.

Methods

Data collected in 2016–19 from adults aged 18–69 years, participating in the Italian Behavioural Risk Factor Surveillance System (PASSI) based on a cross-sectional design, were used. The frequency of CV risk/protective factors was estimated in people with and without diabetes. The contribution of socioeconomic level (SEL) to CV risk was also explored.

Results

Among 129 989 respondents, 4.7% received a diagnosis of diabetes. Many CV risk factors were significantly more frequent in people with diabetes, who often presented multiple risk factors. At the same time, they adopted protective behaviours and received treatments and preventive interventions more often than those without diabetes. Relevant disparities were observed between SEL groups in diabetic people, with the least advantaged showing a worse risk profile.

Conclusions

Adults resident in Italy with diabetes are exposed to CV risk factors more often than those without diabetes. However, they show an increased attention to control these factors and receive more frequent health care, although less than ideal in absolute terms. There is an opportunity to reduce the important CV disease burden in the population through preventive/health promotion targeted interventions, prioritizing people with diabetes and of lower SEL.
Screening and management of tobacco, alcohol, and unhealthy drug use in Saudi Arabia: uptake and practices from primary care physicians’ perspective
Authors: AlShamlan Nouf A
Published: May 2022

Background

Screening and management of tobacco, alcohol, and unhealthy drug use by primary care physicians are crucial because a minority of individuals seek medical advice. However, data regarding this practice are limited. The study objective was to assess the screening practices of primary care physicians in Saudi Arabia for tobacco, alcohol, and unhealthy drug use, barriers to screening, and management of such cases.

Methods

In this cross-sectional study, an online survey was sent to primary care physicians in Saudi Arabia.

Results

A total of 952 physicians participated in the study. Most did not use validated screening tools. A significant proportion of physicians believed that the patient could not answer accurately about using alcohol or drugs and considered it socially unacceptable to ask about these substances. Family physicians screened their patients more frequently for smoking than general practitioners (P < 0.05). More years of experience and practice in the Northern Province of Saudi Arabia were predictors of frequent screening for alcohol and drug use (P < 0.05 and P < 0.01, respectively). Providing information about the risks of these behaviours and brief motivational interviews were the most reported practices.

Conclusions

Most physicians did not utilize validated screening tools. Addressing these barriers is a crucial step in initiating effective screening programmes. Several barriers have been reported from the physicians’ perspective; further study to explore these issues from patients’ perspectives is suggested. Moreover, raising physicians’ awareness about using validated screening tools and locally available services is recommended.
Gestational and childhood urinary iodine concentrations and children’s cognitive function in a longitudinal mother-child cohort in rural Bangladesh
Authors: Kampouri Mariza , Tofail Fahmida , Rahman Syed Moshfiqur , Gustin Klara , Vahter Marie , Kippler Maria
Published: May 2022

Background

Severe iodine deficiency adversely affects neurodevelopment; however, evidence regarding the association of non-severe deficiency and child cognitive functioning is inconclusive.

Methods

This prospective mother-child cohort study was nested in a population-based nutritional supplementation trial in Bangladesh (Maternal and Infant Nutrition Interventions in Matlab [MINIMat]). Participants with data on cognitive abilities at 5 and 10 years of age (n = 1530) and at least one measurement of urinary iodine concentration (UIC) (gestational week 8, 5, and 10 years) were selected. Cognitive abilities were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Wechsler Intelligence Scale for Children (WISC-IV). UICs were measured with inductively coupled plasma mass spectrometry and thereafter adjusted for specific gravity.

Results

Median UICs in our population: (282 μg/L [pregnancy]; 406 μg/L [5 years]; 294 μg/L [10 years]) indicated that iodine intake corresponded to above ‘adequate’ or even ‘excessive’, according to the WHO classification. Maternal ‘UIC <150 μg/L’ was associated with lower full-scale and verbal scores at 5 and 10 years, although the associations were weakened in the fully adjusted models. A tendency of decreased verbal scores was also observed for maternal ‘UIC ≥500 μg/L’ but not for the corresponding child iodine category (≥300 μg/L). Child ‘UIC <100 μg/L’ was associated with lower processing speed (B=-3.1, 95% CI [-6.2, -0.1]; P-value = 0.041) compared with the reference group (100 μg/L≤ UIC <300 μg/L).

Conclusions

Current findings add to the growing evidence of a causal association of early-life iodine intake with cognitive development, indicating that low iodine intake during childhood is associated with reduced processing speed and non-optimal gestational iodine intake is weakly associated with slightly poorer verbal development outcomes.
Chyloabdomen in critically ill patient after Hartmann’s procedure
Authors: Torres-Rey A , Soler-Bernardini H , Bolaños-Avila G
Published: May 2022

Post-surgical chylous ascites (CA) is extremely rare in colon surgery, known as the extravasation of creamy fluid rich in triglycerides accumulating in the peritoneal cavity. The incidence of CA after colorectal surgery remains between 1 and 6.5%. A 71-year-old female presented to the Emergency Department complaining of generalized abdominal pain, weakness and anorexia for several days ago and episodes of hematochezia which started the day before admission. Biopsy from colonoscopy revealed mucinous adenocarcinoma. Rectal mass resection with Hartmann’s procedure was performed due to obstructive recto-colonic mass. Pathology report confirmed pT4aN0M0 tumor invading through the visceral peritoneum. On post-operative Day number 4, drainage output increased, changing appearance to a whitish color. The diagnosis of CA was confirmed by obtaining >550 mg per dL of triglycerides. Changes to a high-protein, low-fat with medium chain fatty acids were made to her enteral diet. After 48 hours of diet adjustment, the drainage output of CA resolved.
An unusual variant of lipoma: case report
Authors: Elouarith Ihssan , Elmajoudi Salma , Habiba Kadiri , Ech-charif Soumaya , Mahdi Youssef , Khmou Mouna , El khannoussi Basma
Published: May 2022

Osteo-lipoma is a very rare benign tumor with a good prognosis. It is composed mainly of mature fatty tissue with a bony component. The diagnosis is based on the histological study, given the clinical and radiological characters that can simulate other benign or malignant pathologies. Osteosarcoma is the main differential diagnosis. The distinction between these two neoplasms is essential as the basis of the treatment is different. We report the case of a patient with a giant ossifying lipoma independent of bone tissue located in the thigh.
Testing the third-body hypothesis in the cataclysmic variables LU Camelopardalis, QZ Serpentis, V1007 Herculis and BK Lyncis
Authors: Chavez Carlos E , Georgakarakos Nikolaos , Aviles Andres , Aceves Hector , Tovmassian Gagik , Zharikov Sergey , Perez–Leon J E , Tamayo Francisco
Published: May 2022

Some cataclysmic variables (CVs) exhibit a very long photometric period (VLPP). We calculate the properties of a hypothetical third body, initially assumed to be on a circular–planar orbit, by matching the modelled VLPP to the observed one of four CVs studied here: LU Camelopardalis, QZ Serpentis, V1007 Herculis and BK Lyncis. The eccentric and low inclination orbits for a third body are considered using analytical results. The chosen parameters of the binary components are based on the orbital period of each CV. We also calculate the smallest corresponding semimajor axis permitted before the third body’s orbit becomes unstable. A first-order analytical post-Newtonian correction is applied, and the rate of precession of the pericentre is found, but it cannot explain any of the observed VLPP. For the first time, we also estimate the effect of secular perturbations by this hypothetical third body on the mass transfer rate of such CVs. We made sure that the observed and calculated amplitude of variability was also comparable. The mass of the third body satisfying all constraints ranges from 0.63 to 97 Jupiter masses. Our results show further evidence supporting the hypothesis of a third body in three of these CVs, but only marginally in V1007 Herculis.
Gamma-ray observation towards the young massive star cluster NGC 6618 in the M17 region
Authors: Liu Bing , Yang Rui-zhi , Chen Zhiwei
Published: May 2022

Young massive clusters have been established as a new population of gamma-ray sources and potential cosmic ray (CR) accelerators. In this paper, we report the detection of gamma-ray emissions near the young star cluster NGC 6618, which is one of the youngest star clusters in our Galaxy. The detected gamma-ray emissions can be divided into two components. One component is point-like and reveals harder spectrum, while the other is extended and with softer spectrum. Such spectral features are significantly different from other young massive clusters and may be due to the propagation effects of CRs accelerated in NGC 6618.
TOI-2046b, TOI-1181b, and TOI-1516b, three new hot Jupiters from TESS: planets orbiting a young star, a subgiant, and a normal star
Authors: Kabáth Petr , Chaturvedi Priyanka , MacQueen Phillip J , Skarka Marek , Šubjak Ján , Esposito Massimilliano , Cochran William D , Bellomo Salvatore E , Karjalainen Raine , Guenther Eike W , Endl Michael , Csizmadia Szilárd , Karjalainen Marie , Hatzes Artie , Žák Jiří , Gandolfi Davide , Boffin Henri M J , Vines Jose I , Livingston John H , García Rafael A , Mathur Savita , González-Cuesta Lucía , Blažek Martin , Caldwell Douglas A , Colón Knicole D , Deeg Hans , Erikson Anders , Van Eylen Vincent , Fong William , Fridlund Malcolm , Fukui Akihiko , Fűrész Gábor , Goeke Robert F , Goffo Elisa , Howell Steve , Jenkins Jon M , Klagyivik Peter , Korth Judith , Latham David W , Luque Rafael , Moldovan Dan , Murgas Felipe , Narita Norio , Orell-Miquel Jaume , Palle Enric , Parviainen Hannu , Persson Carina M , Reed Phillip A , Redfield Seth , Ricker George R , Seager Sara , Serrano Luisa Maria , Shporer Avi , Smith Alexis M S , Watanabe Noriharu , Winn Joshua N ,   the KESPRINT team
Published: May 2022

We present the confirmation and characterization of three hot Jupiters, TOI-1181b, TOI-1516b, and TOI-2046b, discovered by the TESS space mission. The reported hot Jupiters have orbital periods between 1.4 and 2.05 d. The masses of the three planets are 1.18 ± 0.14 MJ, 3.16 ± 0.12 MJ, and 2.30 ± 0.28 MJ, for TOI-1181b, TOI-1516b, and TOI-2046b, respectively. The stellar host of TOI-1181b is a F9IV star, whereas TOI-1516b and TOI-2046b orbit F main sequence host stars. The ages of the first two systems are in the range of 2–5 Gyrs. However, TOI-2046 is among the few youngest known planetary systems hosting a hot Jupiter, with an age estimate of 100–400 Myrs. The main instruments used for the radial velocity follow-up of these three planets are located at Ondřejov, Tautenburg, and McDonald Observatory, and all three are mounted on 2–3 m aperture telescopes, demonstrating that mid-aperture telescope networks can play a substantial role in the follow-up of gas giants discovered by TESS and in the future by PLATO.
Polycyclic Aromatic Hydrocarbon emission model in photodissociation regions – I. Application to the 3.3, 6.2, and 11.2 μm bands
Authors: Sidhu Ameek , Tielens A G G M , Peeters Els , Cami Jan
Published: May 2022

We present a charge distribution based model that computes the infrared spectrum of polycyclic aromatic hydrocarbon (PAH) molecules using recent measurements or quantum chemical calculations of specific PAHs. The model is applied to a sample of well-studied photodissociation regions (PDRs) with well-determined physical conditions (the radiation field strength, G0, electron density ne, and the gas temperature, Tgas). Specifically, we modelled the emission of five PAHs ranging in size from 18 to 96 carbon atoms, over a range of physical conditions characterized by the ionization parameter $\gamma = G_{0}\times T_{\rm gas}^{1/2}/n_{e}$. The anions emerge as the dominant charge carriers in low γ (<2 × 102) environments, neutrals in the intermediate γ (103 – 104) environments, and cations in the high γ (>105) environments. Furthermore, the PAH anions and cations exhibit similar spectral characteristics. The similarity in the cationic and anionic spectra translates into the interpretation of the 6.2/(11.0+11.2) band ratio, with high values of this ratio associated with large contributions from either cations or anions. The model’s predicted values of 6.2/(11.0+11.2) and 3.3/6.2 compared well to the observations in the PDRs NGC 7023, NGC 2023, the horsehead nebula, the Orion bar, and the diffuse interstellar medium, demonstrating that changes in the charge state can account for the variations in the observed PAH emission. We also reassess the diagnostic potential of the 6.2/(11.0+11.2) versus 3.3/(11.0+11.2) ratios and show that without any prior knowledge about γ, the 3.3/(11.0+11.2) can predict the PAH size, but the 6.2/(11.0 + 11.2) cannot predict the γ of the astrophysical environment.
MO003: Upregulation of NADH/NADPH Oxidase 4 by Angiotensin II Induces Podocyte Apoptosis
Authors: Ha Tae-Sun , Ha Dong-Soo
Published: May 2022

BACKGROUND AND AIMS

Oxidative stress induced by non-hemodynamic effects of angiotensin II in podocytes participates in the development of glomerular injury and proteinuria. We studied the pathophysiologic roles of oxidative stress in angiotensin II-induced podocyte apoptosis.

METHOD

Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and transfected by Nox4 or AT1R siRNAs or negative control scrambled siRNA for 24 h. The changes of podocyte oxidative stress and apoptosis were observed by confocal imaging, western blotting, real-time PCR, FACS and TUNEL assays according to the presence of angiotensin II.

RESULTS

Angiotensin II increased the generation of mitochondrial superoxide anions and reactive oxygen species levels but suppressed superoxide dismutase activity that was reversed by probucol, an antioxidant. Angiotensin II also increased NADH/NADPH oxidase 4 protein and expression in a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of NADH/NADPH oxidase 4 by siRNA reduced the oxidative stress induced by angiotensin II. Furthermore, angiotensin II promoted podocyte apoptosis that was reduced significantly by probucol and NADH/NADPH oxidase 4 siRNA, and also recovered by angiotensin II type 1 receptor siRNA. In sum, angiotensin II induced podocyte oxidative stress and apoptosis through NADH/NADPH oxidase 4 and angiotensin II type 1 receptor.

CONCLUSION

These findings suggest that angiotensin II promotes podocyte mitochondrial oxidative stress, resulting in apoptosis via the upregulation of NADH/NADPH oxidase 4 and angiotensin II type 1 receptor, which could be prevented by NADH/NADPH oxidase 4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as antioxidants.
MO004: Hidden Patterns of T Cell and B Cell Phenotypes seen Through Machine Learning Algorithms in End-Stage Renal Disease
Authors: Lioulios Georgios , Fylaktou Asimina , Xochelli Aliki , Sampani Erasmia , Tsouchnikas Ioannis , Giamalis Panagiotis , Vasileia Daikidou Dimitra , Nikolaidou Vasiliki , Papagianni Aikaterini , Theodorou Ioannis , Stangou Maria
Published: May 2022

BACKGROUND AND AIMS

End-stage renal disease (ESRD) is essentially a chronic inflammatory state and, consequently, it engenders detrimental effects on the immune system. Due to the specific uremic environment, multiple phenotypic lymphocyte alterations are described, similar but not identical to ageing. We aimed to evaluate these changes through simple unsupervised dimensionality reduction algorithms in order to reveal unique phenotypical lymphocyte patterns in ESRD patients.

METHOD

A wide panel of senescent and exhaustion-related lymphocyte markers, including CD45RA, CCR7, CD31, CD28, CD57, and PD1 on T cells and CD27 and IgD on B cells, was assessed by flow cytometry in 30 ESRD patients and 20 healthy controls of similar age, sex and ethnicity. The resulting immunological multidimensional phenotype was projected at lower dimensions using two algorithms: principal component analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP).

RESULTS

The plane defined by the two first eigenvectors of PCA showed two clusters, patients and controls, with PCA variable loadings of non-senescent markers pointing towards the controls' centroid. Indeed, ‘naïve’ lymphocytes were reduced in ESRD patients compared with controls [CD4+CD45RA+CCR7+200(150–328) versus 426(260–585) cells/μL, respectively; P = .001] and [CD19+IgD+CD27–54(26–85) versus 130(83–262) cells/μL, respectively; P < .0001]. Also, PCA projections of the multidimensional ESRD immune phenotype suggested a more senescent phenotype in haemodialysis compared with haemodiafiltration treated patients.

Finally, clustering based on UMAP projections revealed three distinct patients groups (UMAP 1–3), exhibiting gradual changes for naive, senescent and exhausted lymphocyte markers. Out of these, the UMAP 1 group was characterized by a predominance of CD8 senescent T cell subsets, in contrast, to groups UMAP 2 and 3, which showed a gradual decrease of all T cell subsets, in comparison to healthy controls. These groups were found to differ in the type of dialyzer used, with polysulfone or derivatives alone more often prescribed in UMAP 2–3 patients (13 out of 17) compared with 4 out of 13 in UMAP 1, P = .012.

CONCLUSION

Simple machine learning algorithms may help to unravel hidden lymphocyte markers and define patterns characteristic of ESRD. Moreover, significant connections of immune changes with dialysis methods and dialyzers were revealed and described.
MO005: RPTEC/TERT1 Cells Cultured in Monolayer are not Suitable for Assessing Apolipoprotein A-I uptake due to the Lack of Cubilin–Amnionless (CUBAM) Complex
Authors: Llorens Cebrià Carmen , Durán Monica , Molina Van den Bosch Mireia , Dominguez Pamela , Villena Yolanda , Cantero Recasens Gerard , José Soler Romeo Maria , Hellín Joan López , Jacobs Cachá Conxita
Published: May 2022

BACKGROUND AND AIMS

Renal proximal tubule epithelial cells (RPTECs) are responsible for solute and protein reabsorption. It has been described that the human RPTEC/TERT1 cell line expresses several transporters, including the cubilin–amnionless–megalin complex that is responsible for the uptake of a broad range of filtered proteins. Therefore, this cell line is considered a gold standard to perform receptor-mediated protein endocytosis assays. All lipoproteins interact with megalin to be reabsorbed except for apolipoprotein A-I (ApoA-I), which is dependent on cubilin–amnionless (CubAm) presence. Here, we aimed to confirm whether megalin and CubAm were correctly expressed and located at the cell membrane of RPTEC/TERT1 cells to later perform ApoA-I uptake assays.

METHOD

We first tested the specificity of the antibodies against cubilin, amnionless and megalin by immunofluorescence using histological sections of healthy human kidney tissue. Afterwards, RPTEC/TERT1 cells (purchased at ATCC, passage 1) were cultured using conventional culture plates for 7 days and also in transwells for 3 weeks to induce cell polarization. In these conditions, we studied cubilin, amnionless and megalin gene expression by RT-PCR and protein expression by immunofluorescence after fixation with 4% PFA.

RESULTS

As expected, in human kidney tissue, cubilin, amnionless and megalin were located at the brush border of the proximal tubular cells confirming the specificity of the tested antibodies. Although cubilin, amnionless and megalin were present at the RNA level in RPTEC/TERT1 cells cultured in conventional culture plates, immunocytochemistry analysis revealed that only megalin was located at the cell membrane in a few cells, cubilin was not expressed and amnionless was found in the nucleus (see Figure 1). When the RPTEC/TERT1 cells were cultured in transwells, even though the cells were clearly polarized, cubilin and megalin were not expressed, and amnionless was still not found at the correct location.

CONCLUSION

RPTEC/TERT1 cell line when cultured in monolayer expresses cubilin, amnionless and megalin at the RNA level, but only megalin could be located at the cell membrane of the cells. Although further research is needed, our results suggest that this cell model is not suitable for performing ApoA-I endocytosis assays as it lacks the CubAm complex at the cell membrane in the tested conditions.
MO007: Clinical and Laboratory Profile of Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Authors: Gkika Vasiliki , Louka Michaela , Kanellopoulou Konstantina , Fokas Stavros , Tigka Eirini , Tsagkatakis Mihail , Kostopoulou Myrto , Koutsogianni Anastasia , Lymperopoulos Konstantinos , Tsirpanlis George
Published: May 2022

BACKGROUND AND AIMS

Recent advances in the treatment of autosomal dominant polycystic kidney disease (ADPKD) highlight the interplay between the clinical and laboratory profile of the disease. This study aims to present the baseline characteristics of patients followed in a large ADPKD cohort from a single center and explore possible associations between demographic, clinical and laboratory parameters.

METHOD

This study enrolled patients who were being followed in a specialized outpatient ADPKD clinic from December 2018 to December 2021. At enrollment, demographics, medical and family history, and laboratory data were recorded using a standardized form. Estimated glomerular filtration rate (eGFR) was calculated and magnetic resonance imaging for total kidney volume (TKV) measurement was performed.

RESULTS

Three hundred (162 women and 138 men) ADPKD patients at a mean age ± SD of 40.87 ± 12.9 years were enrolled in the study. Overall, 67.3% of them were classified as chronic kidney disease, stage 1 and stage 2. The ADPKD was diagnosed at a mean age ± SD of 27.2 ± 11.65 years. Twenty-six % of 300 patients were diagnosed before the age of 20. A positive family history was present in 89.75% of patients. In this subgroup, the median age of the affected parent who reached end-stage renal disease was 55 (range 28–87) years. Hypertension was diagnosed in 88% of the patients at a mean ± SD age of 35.89 ± 11 years. Hepatic cysts were present in 78% of them, urinary tract infections, nephrolithiasis, macroscopic hematuria and pain in 44.87%, 43%, 24.71% and 54.23%, respectively. In 31% of the cases, there was a family history of intracranial bleeding. In multivariable analysis, lower eGFR was associated with older age (P < 0.001), younger age at the time of ADPKD diagnosis (P < 0.012) and greater values of the height-adjusted TKV (P < 0.001) and body mass index (BMI, P = 0.11).

CONCLUSION

In this study, patients with ADPKD were diagnosed at a young age and hypertension developed in the majority of them early in the course of the disease. Renal function was influenced by age, height-adjusted cyst renal volume, early diagnosis of ADPKD and BMI.
MO027: Clinical efficacy of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease
Authors: Martins Muñoz Judith , Tarragon Blanca , De Lorenzo Alberto , Espinel Laura , Teresa Naya Maria , Cubas Alfonso
Published: May 2022

BACKGROUND AND AIMS

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. The only treatment approved today to slow its progression is tolvaptan (vasopressin antagonist). However, there is no clinical efficacy parameter for follow-up during treatment.

To assess the clinical efficacy of treatment based on analytical (Fg) and radiological parameters: total kidney volume adjusted to height (TKV h).

METHOD

Retrospective observational study was undertaken of patients with ADPKD on treatment with tolvaptan after its approval in Spain in 2017.

RESULTS

Of the 182 ADPKD, 18% (n = 33) started treatment. The mean follow-up time of patients was 39.85 ± 10.04 months. Of the patients included; 60.6% (n = 20) were male, age 47.64 ± 8.64 years, a baseline glomerular filtration rate of 65.24 ± 20.14 mL/min and a height-adjusted total baseline renal volume of 1137.45 ± 667.58 mL. Baseline Mayo Clinic classification: 1C (72.7%), 1D (15.2%) and 1E (12.1%). Baseline CKD stages were as follows: 1: 15.2% (n = 5), 2:48.5% (n = 16), 3a:18.2% (n = 6), a 12.1% (n = 4) and 6.1% stage 4 (n = 2). The variation of Fg (mL/min), with respect to baseline was as follows: 1, 3, 6, 12, 24 and 36 months: (−4.26 ± 5.65; −3.54 ± 4.52; −1.68 ± 5.71, −10.89 ± 21.65, −10.54 ± 12.64, −8.08 ± 7.5). Fg decreased at months 1, 3, 6, 12, 12, 24 and 36 by 72.7%, 67.7%, 44.8%, 70.8%, 70.8%, 85% and 85.7%, the latter follow-up period being reached in 14 patients of the sample studied. Despite the decrease in Fg, 100% of the patients at 36 months had a higher Fg than expected according to the Mayo Clinic Fg prediction model, in accordance with their TKV at baseline.

A mean decrease in TKVh was observed in annual control periods, the mean being as follows: −80.8 ± 290, −14.7 ± 187 and −82.8 ± 415.8 mL. In 100% of the patients with control at the third year (17 patients of the total sample), the percentage increase in TKV was lower than expected according to the Mayo Clinic model.

CONCLUSION

Although there is no efficacy parameter in the follow-up of treatment with tolvaptan in patients with ADPKD, our study shows an improvement in the expected value of both Fg and TKV; therefore, it could be considered an effective drug.
MO035: Education needs in diagnosing rare renal diseases: a clinician survey
Authors: Rohani-Montez Christy
Published: May 2022

BACKGROUND AND AIMS

There are approximately 300 inherited, congenital or acquired rare kidney diseases known. However, there is a significant delay in their diagnosis, which may result in inappropriate and potentially harmful testing or treatment due to misdiagnosis, or other adverse outcomes due to missed diagnosis.

METHOD

A 14-question online survey was developed to assess clinician knowledge, experience and educational needs in rare disease. The survey was launched on 31 March 2021 and closed on 2 August 2021.

RESULTS

A total of 927 physicians specializing in 16 different therapeutic areas participated in the survey. Of those, 60 were nephrologists from the European Union or USA. Approximately 70% of nephrologists considered rare diseases much rarer as compared with standard definitions in the European Union (5 per 10 000) or USA (<200 000). Sixty-seven percent said they never or only rarely (every 6 months to 1 year) see rare disease patients. The majority, 93%, had been involved in a rare disease diagnosis; however, only 20% were mostly or very confident in making such a diagnosis. Barriers differed between US and EU neurologists, with US nephrologists reporting that knowledge of rare disease signs and symptoms, as well as access to diagnostic tests are more often a barrier compared with EU5 nephrologists (Figure 1). When asked about most effective rare disease education, case-based, text-based, and short-format education given by world renowned clinicians were most popular. A comprehensive online learning platform with current, organized education and resources was considered most valuable.

CONCLUSION

This educational research study identifies gaps in diagnosing rare diseases in nephrology practice and supports the need to develop education for nephrologists on recognizing rare kidney diseases earlier, shortening the diagnostic odyssey and enabling earlier referral and treatment.
MO041: Impaired ACE2 glycosylation and protease activity lowers susceptibility to SARS-COV-2 infection in Gitelman/Bartter syndromes
Authors: Bertoldi Giovanni , Ravarotto Verdiana , Sgarabotto Luca , Gobbi Laura , Federica Stefanelli Lucia , Calò Lorenzo
Published: May 2022

BACKGROUND AND AIMS

ACE2, part of the counter-regulatory arm of the renin–angiotensin system, serves both as protective toward oxidative stress and cardiovascular remodeling and as a key entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 has two isoforms, non-glycosylated and glycosylated, the latter being accountable for the binding with SARS-CoV-2. After the binding, viruses use proteases as cathepsin-L (Cat-L) to entry the cells. Both ACE2 glycosylation and Cat-L activity are pH-dependent. Gitelman and Bartter syndromes (GS/BS), rare genetic tubulopathies, are characterized by electrolytic alterations, activation of the renin–angiotensin system, yet normo-hypotension, increased levels of ACE2 and metabolic alkalosis with likely increased intracellular pH. We reported that during the first wave of COVID-19 in early 2020 none of our cohort of 128 GS/BS patients from the major hotspots in Northern Italy had been infected or suffered any major COVID-19 symptoms and in a second survey on the same cohort in 2021, we reported only eight positives, four asymptomatic and four with very light symptoms This study aims to investigate potential mechanisms as ACE2 glycosylation and Cat-L activity related to patients’ metabolic alkalosis and viral entry/infection.

METHOD

Mononuclear cells ACE2 glycosylation (Western blot) and blood Cat-L activity (ELISA) from 20 GS/BS patients have been compared with those from 15 healthy subjects.

RESULTS

Non-glycosylated ACE2 was higher in GS/BS (0.82 ± 0.19 d.u. versus 0.67 ± 0.13, P = 0.01); glycosylated ACE2 was not different (0.85 ± 0.28 in GS/BS versus 0.73 ± 0.23, P = 0.19). Cat-L activity was lower in GS/BS (3.90 ± 1.13 r.f.u. versus 5.31 ± 0.8, P <0 0.001) and inversely correlated with blood bicarbonate (HCO3−), while a negative correlation between glycosylated ACE2 and HCO3− approaches statistical significance (P = 0.08).

CONCLUSION

GS/BS's metabolic alkalosis, likely by increasing intracellular pH, influences the glycosylation of ACE2 and the activity of Cat-L, providing a mechanistic explanation for the near-complete absence of COVID-19 or its symptoms reported in our cohort. These findings provide a rationale for pursuing the identification and/or synthesis of new drugs that specifically target ACE2 glycosylation and/or proteases involved in SARS-CoV-2 infection.
MO065: The Association of Glomerular Neural Cell Adhesion Molecule-1 Expression with Membranous Lupus Nephritis and the Injury of Central Nervous System
Authors: Liu Yang , Zhang Mingchao , Luo Song , Xu Feng , Yang Fan , Chen Dacheng , Xia Wen , Miao Yiqi , Jiao Chenfeng , Chen Xin , Liu Xia , Hu Winxin
Published: May 2022

BACKGROUND AND AIMS

Neural cell adhesion molecule-1 (NCAM-1) has been found to be associated with central nervous system (CNS) injury in patients with lupus nephritis in small case series. This study aimed to explore the relationship between glomerular NCAM-1 expression and CNS injury in patients with membranous lupus nephritis (MLN) and the influence of NCAM-1 expression on the prognosis of MLN.

METHOD

238 patients(47 class V, 132 mixed class V + III/IV, 46 class III/IV, 7 class II, 6 lupus podocytopathy) with SLE-associated CNS injury were screened from the LN cohort between 2009 and 2019. CNS injury was assessed by clinical and brain MRI. Patients without CNS injury were served as the control. The degree of electron-dense subepithelial deposits and proportion of podocyte foot process effacement (FPE) was assessed semi-quantitatively by electron microscopy. Kidney NCAM-1 was stained by immunohistochemistry. The NCAM-1 expression in patients with different classes of LN and its relationship with CNS injury was analyzed.

RESULTS

In total, positive NCAM-1 staining was found in 59 of 238 (24.8%) LN patients with CNS injury. NCAM-1 positive rates were significant higher in the cases with class V (22/47, 46.8%) and mixed class (35/132, 26.5%) than those with proliferative class (2/46, 4.3%), class II (0/7) and lupus podocytopathy (0/6). NCAM-1 positive rate was significantly higher in class V (46.8% versus 13.3%, P < 0.001) and mixed class (26.5% versus 7.3%, P < 0.001) patients with CNS injury than those patients without CNS injury. Compared with NCAM-1 negative MLN (included class V and mixed class) patients with CNS injury, NCAM-1 positive MLN patients had much higher proportion of nephrotic syndrome (54.4% versus 37.2%, P = 0.03), hypoalbuminemia (66.7% versus 49.2%, P = 0.029), extensive subepithelial immune deposits (56% versus 25.5%, P = 0.009) and proportion of FPE (75.4 ± 10.2% versus 68.1 ± 16.6%, P = 0.038), and significantly lower duration of SLE (12.0 (3.0, 48.0) months versus 26.0 (4.5, 84.0) months, P = 0.046) and renal CI score (2.0 (1.0, 3.0) versus 3.0 (2.0, 4.0), P < 0.001). No significant differences were found between the NCAM-1 positive and NCAM-1 negative MLN patients in the baseline SCr level, imaging features of brain MRI, extrarenal organ involvement and long-term patient and renal outcomes.

CONCLUSION

NCAM-1 is associated with MLN (including class V and mixed class) and CNS injury, and NCAM-1 positive MLN shows special clinicopathological features of renal injury, indicating that NCAM-1 positive MLN could be a subtype of MLN.
MO074: SGLT2 Inhibition Promotes Intrinsic Kidney Regeneration by Cells of the Renin Lineage
Authors: van der Pluijm Loïs , Koudijs Angela , Stam Wendy , Rotmans Joris , Gross Kenneth W , Paul Pieper Michael , Jan van Zonneveld Anton , Bijkerk Roel
Published: May 2022

BACKGROUND AND AIMS

With chronic kidney disease (CKD) prevalence rapidly increasing, the need for novel therapies is rising. Sodium glucose co-transporter-2 (SGLT2) inhibitors were originally developed to treat hyperglycemia in patients with type 2 diabetes mellitus. Clinical trials with the SGLT2 inhibitor empagliflozin revealed a marked attenuation of the slope of kidney function decline, also in patients with non-diabetic CKD. The exact mechanism of this kidney sparing effect still remains to be clarified. Interestingly, cells of renin lineage (CoRL), residing in the juxtaglomerular apparatus to regulate blood pressure and fluid balance, have been demonstrated to harbor a stem cell like potential. CoRL have the ability to replenish glomerular cell number by dedifferentiating, migrating and subsequently replacing various glomerular cell types in different kidney injury mouse models. Considering that empagliflozin treatment affects renin plasma levels and electrolyte balance in patients, we hypothesized that empagliflozin could have an effect on CoRL-induced glomerular regeneration.

METHOD

Experiments were performed in a Ren1cre; tdTomato lineage-trace mouse strain that expresses a tomato fluorescent label in all cells derived from renin lineage. Two kidney injury mouse models were applied; bilateral ischemia reperfusion injury (bIRI) and 5/6 nephrectomy (5/6NTx). Empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days. Subsequently, mice were sacrificed and kidneys were harvested for histological analysis.

RESULTS

In both the bIRI and 5/6NTx model, empagliflozin intake led to an increase (>2-fold) of CoRL found in the intraglomerular regions compared with vehicle control littermates. These CoRL seemed to selectively differentiate towards different glomerular cell types per model: bIRI combined with empagliflozin administration resulted in an increase of claudin- (10-fold) and integrin-α8- (1.5-fold) tomato double positive cells, suggesting favored differentiation from CoRL to respectively a parietal epithelial or mesangial cell type. In contrast, in the empagliflozin treated 5/6NTx model, an increase (1.5-fold) in tomato-podocyn double positive cells was observed, implying more restocking of glomerular podocytes by CoRL in this model.

CONCLUSION

SGLT2 inhibition by empagliflozin treatment leads to increased CoRL-mediated intrinsic regeneration potential and provides the kidney with different replenished cell types in different kidney disease models. Our findings demonstrate a novel mechanism via which SGLT2 inhibition might protect against kidney injury.
MO077: Systemic Therapy with a Single-Dose Kidney-Targeted Bioengineered VEGF Construct Improves Stenotic Kidney Hemodynamics in Experimental Renovascular Disease
Authors: Chade Alejandro , Bidwell Gene
Published: May 2022

BACKGROUND AND AIMS

We recently developed a construct of an elastin-like polypeptide fused to VEGF (ELP-VEGF) and showed its efficacy to target and protect the kidney after single systemic administration in a swine model of unilateral renovascular disease (RVD) via therapeutic angiogenesis. Despite a demonstrated renal efficacy, the possibility of off-target binding of VEGF to other organs and undesired effects exists. Thus, we augmented renal specificity by adding a kidney-targeting peptide (KTP) and showed that KTP-ELP accumulates in the kidney to a greater extent than ELP (rodents and swine). Furthermore, addition of KTP redirected ELP-VEGF, which was found at high levels in the liver, to the kidney (rodents). The current proof-of-concept study aims to define the renal therapeutic efficacy of the KTP-ELP-VEGF construct after systemic administration in RVD.

METHOD

RVD was induced in 12 pigs by unilateral renal artery stenosis and observed for 10 weeks. After 6 weeks, pigs were treated with a single IV dose of untargeted ELP-VEGF, KTP-ELP-VEGF (1 mg/kg, through ear vein) or placebo (n = 4 each). RBF, GFR and cortical perfusion were quantified in vivo using multi-detector CT before and 4 weeks after treatment/placebo. An additional four animals were used as normal controls.

RESULTS

Stenotic-kidney hemodynamics were similarly reduced in all RVD pigs 6 weeks after induction of renal artery stenosis. Administration of ELP-VEGF or KTP-ELP-VEGF led to significant improvements in RBF, GFR and cortical perfusion compared with pretreatment values, suggesting no interference with VEGF's biological activity. Notably, KTP-ELP-VEGF showed a slightly greater improvement in stenotic kidney hemodynamics than untargeted ELP-VEGF.

CONCLUSION

This study builds on our recent work and shows for the first time the biological activity and therapeutic efficacy of KTP-ELP-VEGF, expanding the potential of strategies using targeted renal treatments and offering the possibility of intra-renal and systemic routes of administration. The traits of KTP-ELP carriers strengthened drug-delivery strategies by minimizing off-target effects of VEGF or any other therapeutic cargo, which may help to extend applications to other forms of renal disease.
MO103: ANCA Vasculitis with Renal Impairment in the Elderly
Authors: Chemli Imen , Hammouda Mouna , Ben Salem Meriem , Ben Salah Manel , Handous Insaf , Letaief Ahmed , Aloui Sabra , Skhiri Habib
Published: May 2022

BACKGROUND AND AIMS

ANCA vasculitis is a serious pathology and life threatening. Kidney damage is common. Few studies have focused on ANCA vasculitis in the elderly. The geriatric population is particular by its polypathology and its polypharmacy. Our objective was to detail the clinical-biological, immunological and histological characteristics of patients aged 65 years or over with ANCA vasculitis with renal impairment as well as the therapeutic and evolutionary modalities.

METHOD

This is a retrospective, monocentric and descriptive study, carried out in the nephrology department of the CHU Fattouma Bourguiba in Monastir during a period of 12 years extending between January 2008 and January 2021. We collected 21 elderly patients aged 65 years and over with ANCA vasculitis with renal impairment diagnosed in the nephrology department, according to the criteria of ACR 1990 and Chapel Hill 1994.

RESULTS

The mean age of our patients was 69.52 ± 5.53 years with a predominance of women (sex ratio: 1.1). Essential hypertension was the most common medical history, observed in 19% of cases followed by diabetes and a history of asthma. The circumstance of discovery was renal signs in 80.9% of cases and haemoptysis in 9.5%. The median time between the onset of symptoms and the diagnosis was 15 days. General signs dominated the clinical picture: a deterioration in general condition was observed in 61.9% of cases, fever in 33.3% of cases and headache in 19% of cases. Proteinuria and haematuria were found in all cases, oliguria in 68.42% of cases, oedema in 36.68% and arterial hypertension in 26.31%. Extrarenal signs were dominated by respiratory involvement observed in 71.42% of cases. Microscopic polyangiitis was the most common type observed in 81% of cases, followed by granulomatosis with polyangiitis in 9.5% and eosinophilic granulomatosis with polyangiitis in 9.5%. All patients had received corticosteroid therapy with a median duration of 6 months. Intravenous cyclophosphamide was prescribed for 57% of patients. Seven patients had received corticosteroid therapy alone. In 57% of cases, maintenance treatment with azathioprine (Imurel) was administered during 17.25 ± 10.10 months. Plasmapheresis was performed only in a patient who presented with intra-alveolar haemorrhage. Complete remission was noted in four cases (19%) and partial remission in six cases (28.57%). At the third month of follow-up, 81% of patients were alive, 76.2% of cases at 1 year and 62% of cases at 5 years. Mortality was 19%. Infectious complications secondary to treatment were noted in 38.1% of cases.

CONCLUSION

ANCA vasculitis in the elderly was characterized by a high clinical polymorphism. Despite the low mortality, disease-related and treatment-related morbidity was significant. Thus, an initial standardized geriatric assessment appears useful in order to better anticipate the occurrence of complications and their management.