bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO396: Development, Establishment and Validation of in Vitro and EX Vivo Assays of Vascular Calcification
Authors: Orth-Alampour Setareh , Holmar Jana , Jankowski Joachim 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Vascular calcification is one major complication in patients with chronic kidney disease (CKD), with a misbalance in calcium and phosphate metabolism playing a crucial role. The mechanisms underlying vascular calcification have not been entirely revealed to date. As studies aiming at the identification and characterization of the involved mediators are highly relevant, standardized operating protocols (SOP) for reliable assays to make different studies comparable, are needed.

METHOD
We are dealing with the following in vitro and ex vivo experimental conditions to study vascular calcifications: induction of calcification by phosphate and CaCl2, incubation time, as well as foetal calve serum concentration and ageing. Furthermore, the location and inhibition of vascular calcifications are studied. Human aortic smooth muscle cells are used for in vitro experiments and rat aorta for ex vivo experiments. The degree of calcification is estimated by quantification of calcium concentrations and by von Kossa staining.

RESULTS
As a result, a step-by-step protocol for performing experiments on vascular calcification was created.

CONCLUSION
Through the established protocol and examination of decent modifications nuances, we aim to promote standardized research on vascular calcification.
MO401: Low Glomerular Density, a Risk Factor for Progression of Extra-Membranous Nephropathy
Authors: Ajimi Khawla , Ben Salem Meriem , Hammouda Mouna , Ben Salah Manel , Ben Mahmoud Nouha , Jafar Ines , Letaief Ahmed , Sabra Aloui , Skhiri Habib 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Before the onset of renal failure in idiopathic membranous nephropathy (MN), the role of certain histological factors in the progressive loss of renal function are still poorly understood. The present study examined the relationship between glomerular density (GD: non-sclera glomerular number/renal cortical biopsy area) and renal prognosis in patients with idiopathic MN, particularly in those without apparent renal dysfunction at diagnosis.

METHOD
The predictive value of GD on renal outcome was analyzed retrospectively in 40 patients with idiopathic MN with estimated glomerular filtration rate (eGFR) ˃60 mL/min/1.73 m2 (mean, 80 mL/min/1.73 m2) at the time of the biopsy.

RESULTS
Individual GD values ​​ranged from 1.3 to 5.5/mm2 with a 3-fold variation. Lower GD was associated with progression based on ≥ 50% reduction in GFR or onset of end-stage renal disease (ESRD). An association between decreased GD and progression of renal failure was observed, particularly in patients with persistent proteinuria ≥ 1 g/day at follow-up. In contrast, no patient who achieved proteinuria &lt; 1 g/day at follow-up showed progression regardless of their GD level. In addition, among the various clinicopathologic factors studied, we found that GD was the only histologic factor that independently predicted the deterioration of renal function during the observation periods.

CONCLUSION
These results suggest that low GD is a plausible risk factor for progression to ESRD in patients with idiopathic MN, particularly in those who did not achieve remission during the follow-up.
MO402: Symmetric Dimethylarginine Inhibits Renal Fibrosis in Obstructive Kidneys
Authors: Wang Yanzhe , Wu Ming , Ye Chaoyang 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Symmetric dimethylarginine (SDMA) is regarded as an independent cardiovascular risk factor in patients with chronic kidney diseases. Renal interstitial fibrosis is a common pathway of all kinds of chronic kidney diseases progressing to the end-stage of renal diseases. In this study, we investigated the role of SDMA in renal fibrosis and its underlining mechanisms.

METHOD
Normal saline (NS) and SDMA (2.50 µmol/kg) were administered to the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested on day 7. Western blotting and Masson's trichrome staining were performed to evaluate renal fibrosis. Moreover, human kidney 2 (HK2) cells were treated with various concentrations of SDMA (0.01 µM–10 µM) in the presence of 2.5 ng/mL TGF-β. Protein samples were collected from cells to measure the expression of fibrotic markers.

RESULTS
We observed that intrarenal administration of SDMA attenuated renal fibrosis as shown by Masson staining and Western blotting analysis of the expression of fibronectin, collagen-I and α smooth muscle actin (αSMA). In parallel, SDMA dose-dependently reduced the expression of pro-fibrotic proteins in TGF-β stimulated HK2 cells. Phosphorylation of Smad3 protein was analyzed in vivo and in vitro, which showed that SDMA inhibited phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells.

CONCLUSION
Thus, our data suggest that renal SDMA exerts direct anti-fibrotic effects in fibrotic kidneys probably through inhibition of the Smad3 signalling pathway.
MO417: Obesity Associated With Vitamin D Deficiency Impairs Renal Function, Haemodynamics, Metabolic Parameters And Aggravates the Renal Morphological Damage in Rats Submitted To Ischaemia-Reperfusion Injury
Authors: Bernardo Desiree , Carolina de Braganca Ana , Heloisa Massola Shimizu Maria , Carlos Seguro Antonio , Moura Nascimento Mariana , Canale Daniele , Aparecido Volpini Rildo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Acute kidney injury (AKI) alters renal haemodynamics, leads to tubular injury, activates pathways of inflammation, proliferation and cell death. The initial damage caused by ischaemia/reperfusion injury (IRI) plays an important role in the pathogenesis of the AKI and predisposition to chronic kidney disease (CKD). Vitamin D deficiency has been considered a risk factor for kidney disease and is associated with haemodynamic changes and tubulointerstitial damage. Obesity is directly related to diabetes mellitus (DM) and hypertension, the main metabolic disorders responsible for the progression to end-stage kidney disease. In addition, studies have been showing that adipose tissue expansion can increase the secretion of pro-inflammatory cytokines and its possible influence on the course of CKD. Thus, we evaluated the influence of both obesity and vitamin D deficiency risk factors on renal disease progression in a murine model of renal IRI.

METHOD
We followed Male wistar rats during a 90-day protocol. On day 45, we submitted all rats to bilateral 45 min IRI surgery. We shared the animals into four groups: i) Standard (S)—fed a standard diet for 90 days; ii) Vitamin D Deficient (VDD)—fed a vitamin D-free diet for 90 days; iii) High-fat (H)—fed a high-fat diet for 90 days; and iv) High-fat vitamin D deficient (H + VDD)—fed a high-fat vitamin D-free diet for 90 days. We evaluated insulin clearance (Cin); mean arterial pressure (MAP); anthropometrical parameters such as body mass index (BMI) and abdominal circumference (AC); plasma levels of 25(OH)D, aldosterone, leptin, glucose, triglycerides and cholesterol as well as renal tissue levels of collagen type 3 (COL-3) and MCP-1 by ELISA. Moreover, we performed qPCR and immunoblotting for vitamin D receptor (VDR) in adipose and renal tissues, respectively. We also analysed α-actin expression by immunohistochemistry and evaluated the fractional interstitial area (FIA). All the results are described in Table 1.

RESULTS
H + VDD animals presented a lower glomerular filtration rate, higher MAP and increased anthropometrical and metabolic parameters compared to the other groups. In addition, we observed severe morphological damage, characterized by an increase in the fractional interstitial area and renal expression of α-actin, MCP-1 and COL-3.

CONCLUSION
Our study suggests that the association between vitamin D deficiency and obesity impairs the haemodynamics, renal function and metabolic parameters in the H + VDD rats. In addition, obesity-associated to vitamin D deficiency aggravated the renal inflammation and morphological alterations associated to renal disease progression.
FUNDING: CAPES and FAPESP (2019/20840–0, 2018/12297–1, 2018/04930–6).
MO430: Octogenarians Referred to the Nephrologist: Evolution and Progression Risk Factors
Authors: Frías González Aida , Vargas Francisco , Berzal Rico Raquel , Rivero Martínez Marta , Cordero García-Galán Lucía , Hernández Paúl , González García Celia , Pascual Julio , Morales Enrique 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The actual definition of chronic kidney disease (CKD) applied to patients ˃80 years has generated an increase in the number of referrals to Nephrology for consultation. Nowadays there is a debate about the evolution of kidney function in elderly patients, from physiological evolution of kidney function to identifying which factors are associated with a real progression of CKD.
The aim of this study is to analyse the evolution of kidney function in patients ˃80 years referred to Nephrology for consultation for the first time.

METHOD
A single-centre retrospective study in which we included patients ˃80 years with an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1,73m2 who were referred to Nephrology consultation from 2015 to 2018.
We collected clinical and analytical parameters at the following points in time: 12 months before the visit, baseline and 12 months after the initial visit. We divided patients into two groups based on annual eGFR loss: Group 1 progressors (&gt;5 mL/min/1.73m2) and group 2 non-progressors (≤5 mL/min/1.73m2).

RESULTS
A total of 348 patients were included in the study, 55.2% were women and the mean age was 84 years (80–97). At the time of first medical visit, the mean creatinine value was 1.6 ± 0.6 mg/dL, median eGRF was 38 mL/min/1.73m2 (29–44) and median albumin/creatinine ratio was 55 mg/g (6–419), with 12% of the patients, presenting albuminuria over 1000 mg/g. The most frequent referral criteria were worsening of renal function (85.6%). Comorbidities were very common, and hypertension, dyslipidaemia and diabetes mellitus were present in 89.4%, 42.8% and 42.2% respectively. A total of 51% of the patients met the definition of progressor at baseline (initial-progressors) and 29.4% were progressors after a 12-month follow-up. Interestingly, only 21.6% of initial-progressors kept meeting this definition 12 months after (Figure 1). The main risk factors for progression were a higher baseline eGFR (P &lt; 0.001) and albuminuria (P &lt; 0.002). No association with comorbidities was found in the multivariate analysis.

CONCLUSION
The majority of patients ˃80 years evaluated by a Nephrologist were non-progressors at 12 months according to our definition (70.6%). It is more important to estimate the progression of CKD patients and request albuminuria and/or proteinuria than an isolated GFR value. It is likely that non-progressors do not need to be followed by a Nephrologist and may remain under primary care control.
MO431: Estimation of the Risk of Progression and Renal Substitution Treatment in Patients With Chronic Kidney Disease Using an Artificial Intelligence Model
Authors: Isaza Ruget Mario A , Yomayusa Nancy , Gonzalez Camilo , Alvarado H Catherine , De Oro V Fabio A , Gonzalez-Velez Abel , Colmenares-Mejía Claudia C 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The use of tools that allow to estimate the probability of progression of chronic kidney disease (CKD) to advanced stages, has not yet gained a notable space in our clinical practice. The aim of this study was to develop and validate a model to predict disease progression, and the need for renal replacement therapy, based on machine learning, for patients with CKD grades 3 to 5. This is the first model of its kind to be implemented in Colombia.

METHOD
This is an observational retrospective closed cohort study. We included patients with CKD from a primary care program and followed them for 5 years. Demographic, clinical and laboratory predictors were included. The outcomes were CKD stage progression, &gt;25% reduction in baseline glomerular filtration rate (eGFR) and the need for renal replacement therapy (RRT), dialysis, or kidney transplantation. We designed two prediction models, one time-independent, based on logistic regression, neural networks and random forest; and a second model, a survival analysis (time to event), by Cox regression, random forest and gradient boosting. Finally, we conducted an internal validation with bootstrapping for the first model, and external validation for the second model in a second real cohort. As a result, we designed a risk calculator.

RESULTS
Time-independent model included 2619 patients, 62.7% female, 92.6% with hypertension, 23.5% diabetics, with a baseline eGFR 51.06 mL/min/1.73m2 (40–61.9). An estimated performance for predicting RRT risk of F1: 0.61 and Kappa: 0.60 (113 events) was detected; stage progression of F1: 0.4 and Kappa: 0.25; reduction in eGFR F1: 0.29 and Kappa: 0.21. For this first model, the most relevant predictors were: initial eGFR, hemoglobin, sex, central region, total cholesterol and socioeconomic status.
The second, a 5-year Time-to-Event prediction model, included data from 1803 patients, had good accuracy with a C-Index assessed performance for RRT risk of 0.96, grade progression of 0.71 and eGFR reduction of 0.69 respectively. The most relevant predictors were initial eGFR, mean heart rate, hemoglobin, hospitalizations, sex, hypertension, diabetes, total cholesterol and central region. The validation cohort, with 658 patients with CKD, 63.9% male, 39% diabetics, with a mean eGFR of 34.9 mL/min/1.73m2, showed good accuracy with a C-Index for RRT risk of 0.935, grade progression of 0.69 and eGFR reduction of 0.0.62 respectively.

CONCLUSION
Our study demonstrated the utility of novel tools to predict renal outcomes in a CKD population in Colombia. This is the first study conducted with our local population. The resulted risk calculator is intended to be part of the electronic medical history in our hospitals.
MO437: Decreased Urinary Citrate Levels as a Marker of Progressive Deterioration of Glomerular Filtration in Patients With Autosomic Dominant Polycystic Kidney Disease (ADPKD)
Authors: Borrego-Utiel Francisco-Jose , Merino Garcia Enoc , Herrera Isidoro , Camacho Reina Victoria , Luisa Garnica Alvarez Maria , Ocaña Perez Esther 
Published: May 2022

Abstract

BACKGROUND AND AIMS
In a previous work we have found that there is a reduction in urinary citrate levels in autosomic dominant polycystic kidney disease (ADPKD) patients. Their levels are related to GFR but not serum bicarbonate levels. Our aim was to analyse whether there is any relationship between rate of GFR deterioration and citraturia in ADPKD patients.

METHOD
We collected routinary determinations of urine citrate in 24-h urine samples and analysed its predictive role for GFR deterioration with general linear modelling.

RESULTS
We included 94 patients, 42 ± 14 years old, 59.6% men and 40.4% women. Follow-up from citrate determination 55 ± 28 months (range 16–119).
Baseline data: urea 40.2 ± 12.3, Cr 1.15 ± 0.38 mg/dL, GFR 78 ± 26 mL/min/1.73 m2. Bicarbonate 25.1 ± 2.5 (18.2–29.2) mEq/L.
Final GFR: 69 ± 32 mL/min/1.73 m2. GFR variation: −2.23 ± 4.14 mL/min/year (range −13.7 to 10).
We classified patients according to urinary citrate tertiles (≤117, 117 to ≤ 303, &gt;303 mg/gCr). GFR was different at baseline (67.5 ± 27.9, 74.3 ± 24.3, 92.4 ± 19.7, respectively, P &lt; 0.001) and at final observation (51.1 ± 31.8; 71.4 ± 30.1; 85.3 ± 24.9, respectively P &lt; 0.001). There were no differences in albuminuria or proteinuria at baseline, but there were differences in uric acid serum levels and urine output. There were no differences in follow-up time.
We observed that GFR rate was different according to tertiles: −4.62 ± 3.66, −0.58 ± 2.78 and −1.53 ​​± 4.74 mL/min/year, respectively (P &lt; 0.001).
When comparing CKD by stages, we found that patients with citrate ≤ 117 mg/gCr showed higher GFR rates than when they had higher levels: CKD1 −7.74 ± 3.37, CKD2 −4.5 ± 4.4, CKD3 −3.04 ± 1.79 versus citrate patients &gt; 117 mg/gCr with deterioration &lt; 2 mL/min/year (P &lt; 0.05).
With multivariate analysis, we found that final GFR was positively associated with baseline GFR and negatively with age, follow-up time and citrate levels ˂ 117 mg/gCr.

CONCLUSION
Urinary citrate levels decrease as GFR reduction is observed in ADPKD. The reduction of urinary citrate to values ≤ 117 mg/gCr is associated with faster deterioration of renal function in patients with ADPKD.
MO438: Excessive Mitochondrial Copper Load Driven by Upregulated Copper Transporter 1 Contributes to Mitochondrial Dysfunction and Renal Fibrosis
Authors: Zhu Saiya , Yu Chen 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Copper is an essential trace element for eukaryotes and a vital cofactor for various enzymes for a multiplicity of functions. Our previous study indicated that intracellular copper overload plays an important role in renal fibrosis. However, the underlying mechanism invoked by copper overload in renal fibrosis remains largely unknown. In this study, we found copper ions in cells were mainly accumulated in mitochondria, which damage the structure and function of mitochondria. Furthermore, copper transporter 1 (CTR1), the major transporter for the copper influx, was significantly increased in fibrotic kidneys. The activity of cytochrome C oxidase (COX), a copper coenzyme mediating the final step in the electron transport chain, was decreased. Therefore, we proposed that CTR1 might be involved in mitochondrial copper overload and renal fibrosis.

METHOD
The expression of CTR1 was examined in ischemia-reperfusion injury (IRI 28d) mice model. The regulatory mechanisms of CTR1 in vitro were investigated by treating renal tubule epithelium cell line (NRK-52E) with TGF-β1 or copper ions with or without copper chelator tetrathiomolybdate (TM) and in vivo, we use CTR1 transgenic mice subjected to IRI operation.
ICP-MS, mitoSOX Red, electron microscopy, realtime-PCR and western blot analysis were applied in the current study.

RESULTS
We found that stimulated by TGF-β1, COX activity was declined. Mitochondria and cytosol, especially mitochondria, accumulated a large amount of copper in fibrotic kidney tissues. Furthermore, we found Copper transporter 1 (CTR1) expression was increased in fibrotic kidneys from chronic kidney disease patients, experimental fibrosis model mice and in vitro. More importantly, compared with WT mice, CTR1+/- mice subjected to an ischemia-reperfusion injury (IRI) had reduced mitochondrial copper level and ameliorated mitochondrial function and renal fibrosis, as evidenced by improving mitochondrial structure, inhibiting mtROS production and reducing expression of α-smooth muscle actin (α-SMA), collagen I and fibronectin. In addition, after treatment with the copper chelator tetrathiomolybdate (TM), mitochondrial function and kidney fibrosis were improved.

CONCLUSION
Collectively, our study showed that copper overload in mitochondria could damage the mitochondrial function and lead to renal fibrosis and CTR1 is involved in the mitochondrial copper overload. Copper overload inhibits the activity of COX and impairs mitochondria, subsequently leading to renal fibrosis.
MO445: Implications of Cardiac Biomarkers in Patients With Renal Insufficiency on Probability of Coronary Angiography and Subsequent Cardiovascular Outcomes
Authors: Illum Emilie , Baumbach Zille , Linnea Freese Ballegaard Ellen , Haagensen Kofod Dea , Nelveg-Kristensen Karl-Emil , Hornum Mads , Schou Morten , Torp Christian , Gislason Gunnar , Flensted Lassen Jens , Carlson Nicholas 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Renal insufficiency is associated with an increased risk of cardiovascular morbidity and mortality. Although cardiac troponin remains essential marker for the diagnosis of myocardial injury in the general population, the diagnostic utility remains uncertain in patients with renal insufficiency. We examined the likelihood of coronary angiography and the risk of myocardial infarction after hospitalization with elevated troponin levels in patients with renal insufficiency.

METHOD
Based on data from multiple Danish nationwide healthcare registries, all hospitalized patients with elevated troponin I or T were identified between 2000 and 2021. Patients with age &lt; 18 years, estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 and patients hospitalized with myocardial infarction &lt; 30 days prior to the index were excluded. Renal function was calculated based on preceding plasma creatinine using the CKD-EPI equation. The probability of being referred for coronary angiography was computed across strata of renal insufficiency [eGFR (mL/min/1.73m2) 59–45, 44–30, 29–15 and &lt; 15, respectively] based on multiple Cox regression calculating hazard ratios for 30-day likelihood of coronary angiography, with subsequent comparison of cumulative risk and hazard ratios for myocardial infarction using the Aalen-Johansen estimator and multiple Cox regression, respectively.

RESULTS
In total 57 044 patients were included in the study. Patients were predominantly male (53%, n = 30 222), with a median age of 81 years (IQR 74–87 years). eGFR strata (%): 59–45: 46.8%; 44–30: 30.6%; 29–15; 15.6%; &lt;15: 7.%. Cardiovascular comorbidity was substantial; 47.1% of patients had a history of hypertension, 20.5%% of patients had a history of heart failure, 26.6% of patients had a history of diabetes and 25.3% of patients had a history of ischemic heart disease. Hazard ratios for 30-day likelihood of coronary angiography were 1.26 [95% confidence interval (CI) 1.10–1.44] for eGFR 15–29 mL/min/1.73m2, 2.00 (95% CI 1.77–2.25) for eGFR 30–44 mL/min/1.73m2 and 2.95 (95% CI 2.63–3.31) for eGFR 45–59 mL/min/1.73m2, using eGFR &lt; 15 as reference. Subsequent cumulative risk of myocardial infarction is shown in Figure 1. Hazard ratios for risk of myocardial infarction were 0.86 (95% CI 0.71–1.03) for eGFR 15–29 mL/min/1.73m2, 0.58 (95% CI 0.49–0.69) for eGFR 30–44 mL/min/1.73m2 and 0.49 (95% CI 0.42–0.58) for eGFR 45–59 mL/min/1.73m2, using eGFR &lt; 15 as reference.

CONCLUSION
In patients with elevated troponin levels, renal insufficiency is associated with an incrementally decreased probability of coronary angiography despite a graded proportional increase in the risk of subsequent myocardial infarction.