bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1841 Trimethylamine N-oxide (TMAO) induces the formation of endothelial extracellular vesicles
Authors: Azevedo Carolina Amaral Bueno , Da Cunha Regiane Stafim , de Almeida Guilherme Miniskiskosky , de Souza Ingrid Larissa Melo , Stinghen Andréa E M 
Published: May 2024

Abstract

Background and Aims
Endothelial dysfunction caused by the accumulation of uremic toxins is an important contributor to the development of cardiovascular disease in patients with chronic kidney disease (CKD). The uremic toxin trimethylamine n-oxide (TMAO) is associated with oxidative stress, vascular calcification, and inflammation, triggering the release of several proinflammatory molecules and Extracellular Vesicles (EVs). Clinical studies have shown that patients with CKD have high levels of circulating EVs, however, their role is still poorly understood. In this dysfunctional scenario, EVs can be used as damage biomarkers for CKD, as they carry information from their cells of origin. Here, we aim to elucidate the formation of EVs in endothelial cells exposed to TMAO.

Method
Human endothelial cells (EA.hy926, ATCC CRL-2922) were exposed for 24 h with TMAO at uremic concentrations (7.49 mg/L). EVs were isolated by differential ultracentrifugation. Protein concentration was analyzed by Pierce™ BCA Protein Assay Kit, and particle size and particle concentration were analyzed by NanoParticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), and Scanning Electron Microscopy (SEM). EVs were stained with calcein and their internalization in endothelial cells was analyzed with Fluorescence Confocal Microscopy.

Results
TMAO treatment at uremic concentration induced the formation of EVs with a size of 202.8 ± 3.1 nm (image 1B) and 1.09 × 109 ± 2.68 × 107 particles/mL and a total protein concentration of 88.57 µg/mL. The morphological features of EVs are shown in images 1C-1F. TMAO-induced EVs were incorporated by endothelial cells, being dispersed in the cytoplasm or perinuclear regions (images 1G and end 1H).

Conclusion
TMAO was able to induce the formation of EVs in endothelial cells, with characteristics morphological features. When compared to control EVs (image 1A), TMAO-EVs have a more heterogeneous size, which indicate a change in the size pattern, and thus the nature of the EVs induced by TMAO. TMAO-EVs were able to be internalized by human endothelial cells. This uptake can be closely related to the effects of EVs in endothelial cells, but more experiments need to be performed. Taken together, these data could contribute to understanding how the formation and uptake of TMAO-EVs by the endothelium occurs, relating their effects to the cardiovascular complications of CKD.
#991 Estimated small dense low-density lipoprotein-cholesterol and the risk of renal and cardiovascular outcomes in diabetic kidney disease
Authors: Yang Qing , Liu Fang 
Published: May 2024

Abstract

Background and Aims
This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage renal disease (ESRD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD).

Method
We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and the participants with DM and CKD in the NHANES 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was used to estimate associations between esd-LDL-c and the incidence of ESRD, cardiovascular mortality, and all-cause mortality.

Results
There were 175 ESRD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1&lt;33.7 mg/dL, T2≥33.7 mg/dL to &lt;45.9 mg/dL, T3≥45.9 mg/dL). The highest tertile of esd-LDL-c was independently associated with ESRD (adjusted HR 2.016, 95% CI 1.144–3.554, P = 0.015). There were 99 death (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was independently associated with cardiovascular mortality (adjusted HR 2.84, 95% CI 1.02–7.97, P = 0.047) and all-cause mortality (adjusted HR 2.18, 95% CI 1.08–4.4, P = 0.029).

Conclusion
Higher esd-LDL-c increased the risk of ESRD in people with DKD and the risk of cardiovascular and all-cause mortality among those with DM-CKD.
#1427 Comparison of METS-IR and HOMA-IR for predicting new-onset CKD in middle-aged and older adults
Authors: Lee Jung Eun , Kwon Yu-Jin , Park Hyeong Cheon 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) has emerged as a mounting public health issue worldwide; therefore, prompt identification and prevention are imperative in mitigating CKD-associated complications and mortality rate. We aimed to compare the predictive powers of the homeostatic model assessment for insulin resistance (HOMA-IR) and the metabolic score for insulin resistance (METS-IR) for CKD incidence in middle-aged and older adults.

Method
This study used longitudinal prospective cohort data from the Korean Genome and Epidemiology Study. A total of 10,030 participants, aged 40–69 years, residing in the Ansung or Ansan regions of the Republic of Korea, were recruited between 2001 and 2002 through a two-stage cluster sampling method. We compared the predictive powers of METS-IR and HOMA-IR for CKD prevalence and incidence, respectively. CKD prevalence was measured by the area under the receiver operating characteristic (ROC) curve (AUC), and the indices’ predictive performance for CKD incidence were assessed using Harrell's concordance index and time-dependent ROC curve analysis.

Results
A total of 9261 adults aged 40–69 years at baseline and 8243 adults without CKD were included in this study. The AUCs and 95% confidence intervals (CIs) of HOMA-IR and METS-IR for CKD prevalence at baseline were 0.577 (0.537–0.618) and 0.599 (0.560–0.637), respectively, with no significant difference (p = 0.337). The Heagerty's integrated AUC for METS-IR in predicting CKD incidence was 0.772 (95% CI 0.750–0.799), which was significantly higher than that of HOMA-IR (0.767 [95% CI 0.742–0.791], p = 0.015).

Conclusion
METS-IR surpassed HOMA-IR in predicting CKD incidence and was as effective as HOMA-IR in predicting CKD prevalence. This implies that METS-IR could be a valuable indicator for early detection and prevention of CKD among Korean adults.
#913 Impact of retinal photography-based deep learning system on risk stratification for chronic kidney disease progression
Authors: Park Jung Tak , Joo Young Su , Rim Tyler Hyungtaek , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook 
Published: May 2024

Abstract

Background and Aims
We had previously developed a deep-learning-based risk evaluation system from retinal photographs, Reti-CKD, for stratifying chronic kidney (CKD) development risk in kidney function preserved people. This study aims to evaluate whether Reti-CKD can improve risk assessment of kidney disease progression in diabetic patients with prevalent CKD.

Method
Total of 5348 diabetic patients from two tertiary hospitals in Korea were evaluated. Patients with estimated glomerular filtration rate (eGFR) &lt;90 ml/min/1.73 m2 or albuminuria were included. Those with missing data for retinal photograph, serum creatinine, or albuminuria were excluded. Patients were categorized into low-risk, moderate-risk, and high-risk groups according to the KDIGO criteria for prognosis of CKD. The KDIGO groups were additionally dichotomized based on Reti-CKD score (Reti-CKD &lt;20 and ≥20). CKD progression was compared between the categories using Cox regression models. Primary outcome was CKD progression, defined as incremental progression to a higher NKF-KDOQI CKD stage.

Results
The mean age of the patients was 62.4 ± 11.4 years and 60.6% were male. Mean eGFR was 86.6 ± 15.3 mL/min per 1.73 m2 and albuminuria was present in 46.9%. During a median follow-up of 5.0 (interquartile range, 2.5-7.8) years, primary outcome developed in 1379 (25.8%) patients. The primary outcome incidence rate gradually increased with higher KDIGO and Reti-CKD combined risk categories. The risk for CKD progression progressively increased in KDIG moderate-risk and high-risk groups compared to low-risk. When Reti-CKD was incorporated to the KDIGO category, significant stratification of CKD progression risk was noted in the KDIGO low-risk and moderate-risk groups (Table and Figure). Additionally, the combination of KDIGO and Reti-CKD classification showed better discrimination power compared to the KDIGO only classification (delta c-statistics, 0.03; 95% CI 0.02 to 0.040).

Conclusion
Retinal photography-based deep learning system (Reti-CKD) further stratifies the risk of CKD progression and improves predictability in diabetic patients with reduced renal function.
#1037 Urinary marinobufagenin reflects the severity of renal disease in non-advanced CKD: a pilot study
Authors: Zicarelli Mariateresa , D'agostino Mario , Tripodi Loredana , Musolino Michela , Cianfrone Paola , Andreucci Michele , Coppolino Giuseppe , Bolignano Davide 
Published: May 2024

Abstract

Background and Aims
The identification of new biomolecules involved in the pathogenesis of chronic kidney disease (CKD) which may improve clinical understanding remains a research priority. Marinobufagenin (MBG) is an endogenous cardiotonic steroid endowed with natriuretic and vasoactive properties, which altered levels trigger fibrosis of various organs, including the kidney. The kidney plays a central role in regulating the systemic MBG balance through its urinary excretion (uMBG) but the impact of a reduced clearance due to CKD remains unknown. In this pilot study, we analyzed the clinical and diagnostic significance of uMBG in a cohort of CKD patients with mild-to-moderate CKD (stage 2-4)

Method
uMBG was measured in 108 CKD patients (mean age 71.6 ± 10 yrs, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) together with a series of clinical, anthropometric, laboratory and instrumental parameters to identify clinical predictors in this cohort. Additionally, uMBG was measured in 25 healthy matched subjects.

Results
CKD patients displayed lower uMBG values as compared with controls (0.37 [IQR 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L; p = 0.004). Clinical, independent predictors of uMBG in our study cohort were eGFR (β = 0.248; p = 0.01), the use of statins (β=-0.326; p = 0.001), diabetes (β = 0.243; p = 0.009) and urinary sodium (β = 0.204; p = 0.01). At logistic regression analysis, higher uMBG levels were associated with a lower probability of having an eGFR ≤30 mL/min (OR 0.868; 95% CI 0.798-0.986; p = 0.03). At ROC analyses, uMBG displayed a good diagnostic capacity in identifying patients with more advanced CKD (AUC 0.675; 95% CI 0.578 to 0.762; p = 0.002; Fig. 1).

Conclusion
Conclusions: Overall, CKD patients display a reduced uMBG excretion which parallels the severity of renal clearance impairment. Sodium intake, diabetes and the assumption of statins may modulate such relationship. Additional studies are needed to confirm the diagnostic usefulness and biological meaning of measuring uMBG as a way to assess CKD severity.
#1694 The Cl-/HCO3-ratio as a predictor of decompensated metabolic acidosis in CKD stages G4 and G5
Authors: Gołębiowski Tomasz , Korus Justyna , Banasik Miroslaw , Szymczak Maciej 
Published: May 2024

Abstract

Background and Aims
Metabolic acidosis (MA) is a common disorder in patients with chronic kidney disease (CKD) and is associated with both a normal anion gap (AGMA) and a high anion gap (HAGMA). AGMA is typically detected early in the course of CKD, whereas HAGMA appears later in the course of CKD due to the accumulation of non-chloride anions such as phosphate, sulphate, and an array of organic acids. The anion gap (AG) is usually calculated as the difference between serum concentration of cations and anions using the formula AG=Na+-(Cl−+HCO3−). The most important anions in serum are chlorides (Cl−) and bicarbonates (HCO3−). The more advanced the CKD, the higher the AG. As eGFR decreases, a reciprocal decrease in HCO3− and an increase in chloride concentration is observed to correct the AG. The aim of this study is to determine whether the Cl−/HCO3− ratio can be used to predict decompensated metabolic acidosis with pH decline in CKD stages G4 and G5.

Method
A total of 115 patients (median age 63 ± 17 years), with CKD stage G4 or G5 were enrolled in this cross-sectional study. Demographic and comorbidity data was obtained from medical records, and the Charlson Comorbid Index (CCI) was calculated. A two-year clinical follow-up was conducted to assess the clinical status of each patient. The number of patients, the time dialysis was started, and deaths were all recorded. All patients were qualified for arteriovenous fistula creation in predialysis period. The arterial (A) and venous (V) blood samples were taken during surgery, directly after vessel dissection, and evaluated in a point of care testing analyzer (POCT). The ratio of arterial Cl− and HCO3− concentration were calculated. According to mean arterial pH (pH-A) the group was divided into Group A pH-A&lt;7.33 and Group B pH-A≥7.33 (Table 1).

Results
In Group A was significantly lower pH-A, pH-V, HCO3−-A, HCO3−-V, pCO2-A, pCO2-V, and significantly higher both arterial and venous Cl− and the Cl−/HCO3− ratios compared to Group B. No such differences were observed in the case of AG. Cl−/HCO3−-A ratio negatively correlated with pH (r = −0.77, p &lt; 0.01) (Fig. 1A). The discriminative power of Cl−/HCO3−-A ratio for predicting pH-A≤7.33 was 0.917 (95% confidence interval [CI] = 0.87–0.97; p &lt; 0.01) which provided 87% sensitivity and 84% specificity (Fig. 1B). The best cut-off was 6.22 (mmol/l)/(mmol/l).

Conclusion
The Cl−/HCO3− ratio lower than 6.22 (mmol/l)/(mmol/l) may be used as predictor of decompensated metabolic acidosis.
#3029 Vitamin D-binding protein: a candidate biomarker for CKD progression
Authors: Gaipov Abduzhappar , Makhammajanov Zhalaliddin , Kabayeva Assem , Tarlykov Pavel , Turebekov Duman 
Published: May 2024

Abstract

Background and Aims
The toxic effects of filtered proteins on the tubules cause a more rapid progression of disease in individuals with higher levels of proteinuria, suggesting the presence of “high-risk candidate” proteins that could contribute to CKD progression. In our previous cross-sectional proteomic study, vitamin D-binding protein (VTDB) showed a significant association with kidney function. However, its persistent expression as a urinary protein in CKD patients remains unknown. Therefore, our aim was to investigate the persistent expression of VTDB in CKD patients and healthy controls during the follow-up period.

Method
The urinary proteomics was investigated using liquid chromatography-mass spectrometry in 18 follow-up CKD patients with stages 1-3 and 15 follow-up healthy individuals. Data analysis was performed by Mascot-SwissProt and STATA software. Parametric and nonparametric statistics were used to analyze results and the relationship between baseline characteristics and proteomic profile. Exponentially Modified Protein Abundance Index (emPAI) was used to estimate peptide count of proteins.

Results
The participant's baseline characteristics are presented in Table 1. The median (IQR) follow-up time for all participants was 368 (250-472) days. A statistically significant difference was found in the initial emPAI of VTDB between the HC and CKD groups. However, there was no statistically significant difference in the follow-up emPAI of VTDB between the two groups. Notably, emPAI values of VTDP decreased over the follow-up period compared to the initial values.
Correlation analysis (Table 2) showed that the elevated levels of urinary VTDB emPAI are associated with decreased levels of initial and follow-up eGFR. A higher negative percentage change (a decline in eGFR over time) was also associated with elevated levels of VTDB protein over the follow-up period. Also, urinary VTDP protein has demonstrated a significant positive correlation with 24 h proteinuria.

Conclusion
In this proteomics study cohort, we observed persistent expression of urinary VTDB protein during the follow-up period in CKD patients compared to healthy controls. Additionally, a statistically significant negative correlation between VTDB protein and eGFR was observed. These findings need further validation using different measurement tools for urinary VTDB assessments and in a larger cohort of CKD patients.

Declaration
We have no conflict of interest to disclose.
#2934 The risk of APOL1 variants in the development of ESKD—a case-control study among cohorts of ESKD with HIV and non-ESKD with and without HIV
Authors: Mooko Teboho , Bisiwe Busiswa , Marx Gerda , Chikobvu Perpetual , Morobadi Daniel , Kemp Gabre , Goedhals Dominique , Nyaga Martin , Mofokeng Thabiso , Ndlovu Kwazi 
Published: May 2024

Abstract

Background and Aims
Apolipoprotein 1 (APOL1) renal allelic risk variants are common in kidney disease patients of African ancestry. This study evaluated the prevalence of APOL1 variants and their influence on end-stage kidney failure (ESKD) and non-ESKD HIV-positive and HIV-negative study cohorts.

Method
This case‒control study enrolled 60 HIV-positive ESKD cases and 160 non-ESKD (80 HIV-positive and 80 HIV-negative) as controls. Participants’ demographic and clinical information and laboratory data as well as blood samples were collected. Genomic DNA was extracted, and purified, and APOL1 risk variants genotyped using TaqMan® predesigned commercial assays.

Results
Study participants in the case and two control cohorts were enrolled with a median age of 42.8 (IQR,38.47-48.57), 41 (IQR,37-46.5), and 41 (IQR,37–47) years, respectively; the frequencies of APOL1 risk variants (G1: rs73885319 and rs60910145 and G2: rs71785313) were 21.8% (48/220), 10.9% (24/220), and 26.4% (58/220), respectively, in the entire study population. The frequency of G1 variants was significantly increased among those with ESKD at 55.0% (33/60) compared to non-ESKD HIV-positive and HIV-negative cohorts at 13.8% (11/80) and 17.5% (14/80), respectively (p &lt; 0.001). The presence of both G1 risk genotypes (rs73885319 and rs60910145) was higher among those with ESKD at 20% (12/60) compared to the two control cohorts without ESKD at rates of 3.8% (3/80) and 1.3% (1/80), respectively (p &lt; 0.001). In logistic regression, the presence of both G1 (OR,14.6; p ≤ 0.001) and G1/G2 (OR,11.9; p ≤ 0.001) risk genotypes were strong predictors of ESKD development.

Conclusion
The presence of G1:rs73885319 and rs60910145 polymorphisms of the APOL1 gene is suggested to be a significant factor in the development of ESKD.
#934 Mortality predictors in advanced chronic kidney disease patients on conservative kidney management: insights from a retrospective multicenter study
Authors: Trigo Filipa , Figueiredo Cátia , Farinha Ana , Cunha Teresa , Azevedo Ana , Santos Paulo 
Published: May 2024

Abstract

Background and Aims
In general, patients with advanced chronic kidney disease (ACKD) on dialysis have a better survival than patients on conservative kidney management (CKM). However, in elderly and frail individuals, with multiple comorbidities, the survival benefits of dialysis seem to be lost. Although the focus of CKM is not quantity but quality of life (QoL), it is important to identify survival modifiers and mortality predictors that may eventually influence QoL and the development of symptoms.

Method
An observational retrospective and multicenter study of ACKD patients on CKM was conducted from July/2015 to December/2023. Data was retrieved from electronic records, encompassing kidney function, analytical parameters, functional and fragility state, and symptoms evaluation (using Palliative Outcome Scale—Renal). The Kaplan-Meier curves and Cox proportional hazards multivariable regression were used for survival analysis and to evaluate 180-day mortality predictors.

Results
A total of 212 patients (56.6% females), with a mean age of 83 years old and a mean follow up time of 220 ± 239 days, were included. The follow-up time was determined by the end of the observational period or the patient's death. 56.1% died before a 180-day follow-up period. The main causes for the ACKD were multifactorial (29.7%) and indeterminate (25.9%). The majority (80.7%) had nephrologist oversight before a CKM team initiated its follow-up, and 63.6% opted for CKM as their first treatment choice.
Survival at 180 days (Fig. 1) differed significantly depending on sex (51.3 vs 65.6, p = 0.021), age under 80 years-old (51.3 vs 73.9, p = 0.000), provenance (0 vs 39.4 vs 83 vs 93.8, p = 0.000), albumin value (32.7 vs 65.5, p = 0.032), and symptoms such as anorexia and pain (53 vs 95.5, p = 0.000; and 54.5 vs 88.9, p = 0.000).
Regarding to mortality predictors (Table 1), albumin under 3g/dL, anorexia and pain were independent predictors of mortality.

Conclusion
Understanding factors associated with increased mortality and higher rates of survival in CKM patients is crucial to better manage this population. Pain, albumin &lt;3g/dL and anorexia, which may reflect patients with worse nutritional status, were shown to be independent predictors of mortality. Therefore, controlling these symptoms, which often impair QoL, and improving nutritional status appears to have an impact not only on QoL but also on survival of ACKD patients on CKM.