bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1848 Body composition and multimorbidity in patients with chronic kidney disease
Authors: Randhay Ashveer , Kokab Khushbakht , Khan Farrah , Selby Nicholas , Taal Maarten W , Eldehni Tarek 
Published: May 2024

Abstract

Background and Aims
Frailty and multimorbidity are increasingly prevalent, particularly in the chronic kidney disease (CKD) population, and they seem to be more pronounced and accelerated in people receiving haemodialysis. We aimed to study the relationship between body composition, frailty and multimorbidity in people with CKD and end stage renal disease (ESRD) on haemodialysis (HD).

Method
This was a single centre study, involving 42 patients with CKD stage 3 to 5 (pre-dialysis) and 29 patients receiving in-centre haemodialysis. InBody 770 was used to measure body composition using bioelectrical impedance analysis. Multimorbidity of participants were assessed using the simplified Cambridge multimorbidity score. Frailty assessment was performed using the Clinical Frailty Scale.

Results
Phase angle was lower in later stages of CKD—mean phase angle in CKD stage 3 was 5.28°, stage 4 was 4.44 and stage 5 was 4.13 (p = 0.008). Visceral adiposity correlated with multimorbidity scores but in a multivariate regression analysis (including albumin and visceral fat area) only whole body phase angle independently predicted multimorbidity in CKD stage 4-5 (adjusted R2 for the whole model = 0.47, p = 0.007). In haemodialysis patients, there was no correlation between multimorbidity and phase angle (r = −0.149, p = 0.441). However, there was a significant correlation between frailty score and whole body phase angle in this group (r = −0.559, p = 0.002). In a univariate analysis, age (R2 = 0.2, Beta = 0.045, p = 0.015), albumin (R2 = 0.217, Beta = −0.214, p = 0.009) and skeletal muscle mass (R2 = 0.282, Beta = −0.101, p = 0.003) predicted frailty score in haemodialysis patients. In multivariate regression analysis age, albumin level and skeletal muscle mass continued to independently predict frailty scores in HD patients (adjusted R2 for the whole model = 0.503).

Conclusion
Phase angle measurement refers to cell membrane integrity and fat-free mass, with higher values suggesting improved cell health. Using body composition measures, in particular phase angle, is a useful measure to predict multimorbidity and frailty in CKD patients. They are quick, accessible and easy to use tools that can be incorporated in clinical practice routinely. The relationship between visceral adiposity and multimorbidity merits further investigation. Preservation of skeletal muscle mass through nutritional and exercise interventions could be a clinical target to reduce frailty in this population.
#206 The effect of dapagliflozin on anemia in patients with CKD
Authors: Abdullaev Sherzod , Igamberdieva Ranokhon 
Published: May 2024

Abstract

Background and Aims
SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients.

Method
We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy.

Results
Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p &lt; 0.01) before and after initiating SGLT2i therapy.

Conclusion
The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.
#749 Components in blood collection tubes interfere with the spectral signatures of patients with kidney disease: analysis by infrared microspectroscopy
Authors: Da Silva Jéssica Verônica , Nepomuceno Gabrielle Teodoro , Batista Andre Mourão , Veiga Glaucia , Fonseca Fernando , Martinho Herculano Da Silva , Carneiro-Ramos Marcela 
Published: May 2024

Abstract

Background and Aims
Kidney disease is a worldwide public health problem, affecting between 8%-16% of the global population. Chronic Kidney Disease (CKD) is a silent disease and its detection is often late, making the treatment difficult. Considering the emerging Fourier-Transform Infrared spectroscopy (FTIR) as a biophotonic resource for the biomedical sciences, we aimed to identify spectral signatures related to biomarkers of CKD in human blood serum using the microscopy FTIR option.

Method
Blood serum samples from 17 healthy in comparison to 33 CKD patients were analyzed by micro-reflectance FTIR spectroscopy. The first aspect to be addressed refers to the possible influence of components present in the container tube. Here we showed that separator gel in VACUETTE® tubes is a relevant source of spectral interference which could decrease the accuracy of discrimination from 85% to 65%. Acquiring a diluted gel signal as a background would improve the discrimination performance in spite of some gel bands still present in sample data.

Results
In this case, our results indicated that vibrations associated with galactose-4-sulfate, CH2 bending of the methylene chains, C=C in lipids and fatty acids, C=N stretching, CH bending vibration from the phenyl rings, N-H bending vibration coupled to C-N stretching and β-sheet of Amide II and ring base are modulated in blood serum samples of chronic kidney disease patients compared to healthy patients. Urinary trypsin inhibitors, fatty acids, phenolic derivatives, tryptophan, and plasminogen were the biomolecules related to these assignments were the biomolecules related to these assignments.

Conclusion
In conclusion, FTIR is a viable option for fast diagnosis of chronic kidney disease being also a powerful tool for monitoring the disease. Due to its capability of large batch analysis, the micro-FTIR would be an eligible technology for clinical laboratories in healthcare facilities. However, for direct clinical applications, ATR-FTIR would be the option of choice.
#2347 Multi-omics analysis identifies traditional Chinese medicine targets for chronic kidney disease
Authors: Tang Lei , Zeng Xiaoxi 
Published: May 2024

Abstract

Background and Aims
As a major public health problem, chronic kidney disease (CKD) has substantial comorbidities and disease burden. It is necessary to discover new therapeutic targets considering its irreversibly. Traditional Chinese medicine (TCM) has become indispensable for the integrated treatment of CKD. The current study aims to explore potential new TCM targets in high-throughput experiment- and reference-guided database (HERB) that are related to renal phenotypes utilizing multi-omics.

Method
We conducted comprehensive Mendelian Randomization and Bayesian colocalization on more than 2,000 HERB target integrating genomes and transcriptomes, using summary statistics of genome-wide association study and cis gene expression quantitative trait loci. The results were validated through differential gene expression in public database, previous literature reports and clinical kidney biopsy specimens.

Results
In all, we discovered 34 targets associated with renal phenotypes among the 2,421 HERB TCM targets in the data mining part. Among them, most of the targets can be validated by differential gene expression analysis in GEO and Nephroseq, and have been reported by basic research, thus confirming the reliability of this method. In addition, PRKCI, KNG1, PKN3, GGT7, GBA, APEH and GSTA2 are expected to be potential new therapeutic targets for CKD. Immunohistochemical staining using clinical kidney biopsy specimens of PKN3 and KNG1, two targets with the highest evidence level, further confirm the results.

Conclusion
Integration of multi-omics can extensively and efficiently screen potential drug targets related to CKD. The new targets discovered in the current study, especially PKN3 and KNG1, need to be further validated in basic research.
#1927 Efficacy and safety of ripertamab in paediatic glomerular disease
Authors: Yue Yuqi , Chen Qiuxia , Li Sijia , Zhu Chunhua , Feng Quancheng , Zhao Sanlong , Ding Guixia , Han Yuan , Cheng Xueqin , Zhao Fei 
Published: May 2024

Abstract

Background and Aims
Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases.

Method
We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center

Results
A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events.

Conclusion
This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.
#2925 PI3K/AKT/mTOR pathway regulates renal expression of Klotho
Authors: Pérez-Gómez Aurora , Tocados Juan Miguel Díaz , Coral Juan Diego Domínguez , García-Carrasco Alicia , Caus Maite , Schanstra Joost , Del Bello Arnaud , Klein Julie , Valdivielso José Manuel 
Published: May 2024

Abstract

Background and Aims
Renal Klotho expression decreases early in chronic kidney disease (CKD), increasing circulating FGF23 and phosphate levels. This negatively affects renal disease progression and cardiovascular complications. Preserving renal Klotho expression is of interest, but the underlying mechanisms are unclear. During early stages of CKD, kidneys activate mechanisms of hypertrophy, in which the PI3K/Akt/mTOR pathway plays a role. The main negative regulator of this pathway is PTEN, which reduces the activation of canonical insulin signaling. Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, complications may appear after transplantation, such as allograft reaction, compromising the function and the integrity of the transplanted kidney. Different immunosuppressants are currently administered to prevent this response, such as mTOR inhibitors or calcineurin antagonists. We aimed to investigate the role of PTEN and the PI3K/AKT/mTOR pathway in kidney Klotho levels and their possible implication in CKD.

Method
We measured renal Klotho levels, circulating FGF23, and phosphate in mice lacking PTEN in renal proximal tubular cells (PTEC) and in HK2 cells in vitro. We also examined normal mice with models of decreased renal mass caused by uninephrectomy (UNX) and 5/6 nephrectomy (SNX). Additionally, we tested the effect of mTOR inhibition. We analyzed PTEN and Klotho expression in kidney samples from CKD patients. Furthermore, we stablished whether there are improvements in Klotho expression in patients treated with an mTOR inhibitor versus other treatments.

Results
We found that PTEC with downregulated PTEN exhibited decreased Klotho expression both in vitro and in vivo, accompanied by increased mTOR activity. Animals with PTEN elimination in PTEC also showed increased circulating phosphate and FGF23 levels, as well as a decrease in the fractional excretion of phosphate. These alterations were normalized by treatment with rapamycin. Normal mice with UNX or SNX exhibited increased renal IGF-1 expression and activation of the PI3K/AKT/mTOR pathway. Furthermore, these mice showed a reduction in renal Klotho expression and an increase in circulating FGF23 and phosphate. Both of these alterations were restored with rapamycin administration.
In renal samples from CKD patients, we observed a positive correlation between the expression of PTEN and KLOTHO. Finally, kidney transplanted patients treated during 9 months with mTOR have an increase of 22.8% Klotho levels and patients with other treatments a 14%.

Conclusion
The overactivation of the PI3K/AKT/mTOR pathway in PTEC modulates Klotho levels in the kidney. Our findings represent a significant advancement in the search for new therapeutic targets to maintain and prevent reductions in renal Klotho levels, potentially benefiting kidney disease patients.
#624 The impact of hemoadsorption in patients with borderline chronic kidney disease undergoing coronary artery bypass grafting
Authors: Gunaydin Serdar , Karaca Okay Guven , Simsek Erdal 
Published: May 2024

Abstract

Background and Aims
With an annual incidence of up to 30%, cardiac surgery–associated acute kidney injury (CSA-AKI) may be one of the most underappreciated yet frequent complications and renal protective adjustments are crucial. We evaluated the impact of hemoadsorption as adjunctive therapy on clinical outcome in Kidney Disease Improving Global Outcomes (KDIGO) G2/A2) patients undergoing coronary artery bypass grafting (CABG).

Method
During a three-year period, 40 patients undergoing CABG with borderline chronic kidney disease (KDIGO-G2/A2) were treated with adjunctive hemoadsorption therapy and were compared by propensity score-matched 40 patients (KDIGO G2/A2) (Control). Primary endpoints were the need for renal replacement therapy (RRT)/dialysis and/or worsening of KDIGO stage in the perioperative period. Secondary endpoints were the change in inflammatory biomarkers, vasopressor requirement and ICU/hospital stay. In the study group, a 300 mL hemoadsorber (Cytosorbents Inc, NJ) was used for the entire duration of cardiopulmonary bypass (CPB). All patients were prepared via enhanced recovery after surgery (ERAS) protocol and surgical procedures were performed under moderate hypothermia with pulsatile flow and ultrafiltration. Patients with septic shock, limited life expectancy and refused to give consent were excluded.

Results
After institutional ethics committee approval was obtained, written informed consent was received from each patient. No significant difference was noted between groups in demographic, operative data and preoperative baseline laboratory. At the end of CPB; s-Creatinine (mg/dL) (1.85 ± 0.6 vs 2.751 ± 0.6; p = 0.035), NT-proBNP (pg/L) (130 ± 30 vs 180 ± 40; p = 0.04), IL-6 (pg/mL) (8.2 ± 4 vs 22.2 ± 4; p = 0.012) and myoglobulin (pg/L) (210 ± 75 vs 310 ± 80; p = 0.04) levels were significantly lower in the study group versus control. Clinical outcome is summarized in Figure.

Conclusion
This pioneering study demonstrated the additional protective effects of hemoadsorption in patients with borderline chronic kidney disease (KDIGO-G2/A2) undergoing CABG. Elimination of inflammatory parameters might be a complementary mechanism resulting in lesser worsening of kidney function/need of RRT and ICU stay. These findings require validation in large, multicenter trials.
#2188 Challenges in lipid control in the advanced chronic kidney disease clinic: findings from a cross-sectional study
Authors: Monzo Jose Jesus Broseta , Legarra María Iraola , Moncada Marina , Rodríguez Diana , Rodas Lida , Baldellou Néstor Fontsere , Vera Manel , Guillen Marta Arias , Cases Aleix , Maduell Francisco 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is associated with lipid metabolism disruptions and heightens cardiovascular (CV) risk. International guidelines categorize CKD patients into high CV risk (LDL target &lt; 70 mg/dL and a reduction &gt;50% from baseline) for CKD G3b A1, CKD G3a A2, and CKD G2 A3; and very high CV risk (LDL target &lt; 55 mg/dL and a reduction &gt;50% from baseline) for CKD G4 and G5, CKD G3b A2-3, and those with type 2 diabetes and G3a A2-3, G3b regardless of UACR, or UACR &gt; 300 mg/g regardless of eGFR. This cross-sectional study aims to evaluate the challenges of achieving LDL targets in advanced CKD patients, focusing on statin use.

Method
A cross-sectional study enrolled 312 patients with advanced CKD. Collected data included demographics, renal function stage, albuminuria/proteinuria, diabetes, and cardiovascular history. Documented statin use specified type and potency. Statistical analysis employed descriptive measures.

Results
Of the 312 patients, 207 were males, with a mean age of 69.18 ± 10.26 years, mean eGFR of 27.54 ± 12.22, and LDL of 86.64 ± 32.9. The majority had a history of diabetes (158) and previous cardiovascular disease (100). 69.6% used statins, with atorvastatin being the most common (165), followed by simvastatin (26), pravastatin (11), rosuvastatin (10), and pitavastatin (5). Statin potency varied, with high potency in 49.4%, moderate in 49.2%, and low in 1.4%. Only 19.6% of patients achieved adequate lipid control per guidelines.

Conclusion
This study underscores the high prevalence of dyslipidemia and the challenges in achieving LDL targets in advanced CKD patients. Despite the presence of cardiovascular risk factors, including a history of cardiovascular events, the majority did not attain adequate lipid control, highlighting the imperative to address therapeutic inertia to prevent LDL detrimental consequences. Specific strategies are warranted, focusing on mitigating statins’ underutilization and low potency. Additionally, consideration of adjunct therapies such as ezetimibe and bempedoic acid is crucial. Exploring novel agents like iPCSK9 or inclisiran emerges as promising avenues for safer and more effective alternatives in this population at high cardiovascular risk.
#2703 Venous chambers vary in the reduction capacity of air microbubbles: a randomized study of chronic haemodialysis patients
Authors: Forsberg Ulf , Jonsson Per , Stegmayr Bernd 
Published: May 2024

Abstract

Background and Aims
The extracorporeal circuit (ECC) enables haemodialysis (HD) of patients. When the blood passes the ECC air contamination occurs, and consequently microbubbles (MBs) enter into the patient. MBs are verified at autopsy of HD patients and are covered by clots manifested as microemboli that are deposited within the lung, heart and brain tissue. A venous chamber is inserted in the ECC to reduce air contamination. However, venous chambers in clinical use have limited capacity in eliminating MBs from entering the return bloodline. In an in vitro study, the Emboless® chamber showed better results in comparison to models commonly used clinically (the best of the clinical models was the Fresenius 5008). Our aim was to determine if the Emboless® venous chamber differed in its capacity to limit MB exposure compared to the Fresenius 5008 (F5008) during HD and hemodiafiltration (HDF).

Method
Twenty chronic HD patients were included in a cross-over randomized study to compare the Emboless® to the F5008 venous chamber during HD. Each patient underwent a total of four dialyses divided into two paired series. This resulted in 80 studied dialyses, of which 32 included HDF. Dialyzers, blood-pump speed, HD or HDF, and ultrafiltration was the same between the pairs. MBs (20-500 µm, merged in intervals of 5 µm) were measured with an ultrasound device adjusted for HD (BCC200, GAMPT) at the ‘inlet’ and ‘outlet’ of the venous chamber. Measurements of MBs were done in the HD mode during the first 30 minutes, and if HDF was prescribed the measurement proceeded for another 30 minutes after the switch to the HDF mode (time was extended if fewer than 1000 MBs were detected at the inlet). The percentage of change in the ‘outlet’ versus ‘inlet’ counts was compared (paired Wilcoxon test). A total reduction was equal to −100%, while an increase (+) of MBs (worsening) was expressed as an unlimited percentage. If a diameter of an MB was without counts, it was not included in the analysis.

Results
For patients during HD, the median change of MBs in the outlet versus the inlet bloodline was −39% with the F5008 (n = 3807) and −76% with the Emboless® (n = 3805) venous chambers (p &lt; 0.001, Fig. 1). For patients during HDF, the median change of MBs in the outlet versus the inlet bloodline was −28% with the F5008 (n = 1549) and −70% with the Emboless® (n = 1517) venous chambers (p &lt; 0.001, Fig. 2).

Conclusion
Fewer MBs and subsequently fewer microemboli entered the patient using the Emboless® compared to the Fresenius 5008 venous chamber during HD, as well as during HDF. In considering previous autopsy studies, our results support less patient tissue damage when using the Emboless® venous chamber.