bluuebunny/crossref_metadata_2025_split huggingface dataset:
#755 Endotrophin as an early marker of kidney outcomes in persons with type 2 diabetes: findings from the PROVALID study
Authors: Møller Alexandra Louise , Thöni Stefanie , Keller Felix , Sharifli Samir , Genovese Federica , Karsdal Morten Asser , Mayer Gert 
Published: May 2024

Abstract

Background and Aims
Diabetic kidney disease (DKD) is driven by a set of pathophysiological processes, including fibrosis. Endotrophin (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has previously been shown to be a biomarker of DKD progression. The aim of this study was to investigate, for the first time, circulating ETP as a risk marker for kidney outcomes in persons with type 2 diabetes (T2D) being taken care of at the primary level of healthcare.

Method
Levels of ETP were measured using the nordicPRO-C6TM ELISA in plasma at baseline from 3226 persons with T2D enrolled in the Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID). Outcomes included a composite kidney endpoint defined as a sustained 40% decline in estimated glomerular filtration rate (eGFR) &lt; an eGFR of 60 ml/min/173 m2, sustained 30% increase in albuminuria including a transition in albuminuria stage, or kidney failure with replacement therapy or kidney death. A decline in eGFR and an increase in albuminuria were considered sustained if they persisted over at least two consecutive measurements. Crude and adjusted Cox proportional hazards regression models were applied to investigate the potential of ETP as a risk marker of the kidney endpoint. Levels of ETP were log-transformed before analysis. The Kaplan–Meier estimator was used to compare the risks of experiencing the kidney endpoint according to ETP levels split by the median in persons with baseline eGFR &gt; 90 ml/min/1.73 m2 (n = 976).

Results
The cohort consisted of 57% males; median age was 64 (58-70) years, and mean eGFR was 79 ± 24 ml/min/1.73 m2. Median follow-up was 3.9 years. Higher levels of ETP were associated with a higher risk of developing the kidney endpoint, with a hazard ratio (HR) of 1.63 (p = 0.0012; n = 293/3226). After adjustment for the refined variables: age, diabetes duration, HbA1c, atherosclerotic cardiovascular disease, blood pressure, duration of hypertension, BMI, LDL-cholesterol, HDL-cholesterol, and eGFR, the HR was 1.55 (p = 0.012). In persons with an eGFR &gt; 90 ml/min/1.73 m2, higher ETP was also associated with an increased risk of developing the kidney endpoint (p = 0.03; n = 69/976).

Conclusion
Plasma ETP was an independent risk marker for kidney outcomes in persons with T2D with early kidney disease. Higher levels of plasma ETP were associated with a significantly increased risk of developing the kidney endpoint in persons with eGFR &gt; 90 ml/min/1.73 m2. These findings demonstrate that biomarkers of fibrosis, such as ETP, may serve as early markers for kidney disease progression or kidney failure in persons with T2D and apparently normal kidney function.
#1320 Differential microRNA expression profile in obesity-induced kidney disease driven by high-fat diet in mice
Authors: Sanjuan Auria Eritja , Caus Maite , Belmonte Thalia , de Gonzalo Calvo David , García-Carrasco Alicia , Bardaji Ana Martinez , Bozic Milica 
Published: May 2024

Abstract

Background and Aims
Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney dysfunction in obesity-induced kidney disease (OIKD) remain unclear. MicroRNAs (miRNAs) have been implicated in the development and progression of obesity, and several candidates have been identified as critical regulators of adipogenesis and lipid metabolism, while their dysregulation contribute to obesity-related metabolic abnormalities. The aim of the present study was to decipher the kidney microRNA (miRNA) expression profile in a mouse model of obesity-induced kidney disease characterized by systemic metabolic disturbances and kidney injury that closely resemble those observed in human disease.

Method
Male C57BL/6J mice were randomly divided and placed either a standard diet (STD) or a high fat diet (HFD) for 10 weeks. Serum triglycerides and total, HDL and LDL cholesterol were determined by standard clinical methods. In the kidney sections, histopathological assessments were done by using PAS and Oil-Red-O staining's. Expression of renal MCP1, TNFα, α-SMA, Fibronectin, miR-146a, miR-551b and miR-5099 was assessed by real time PCR. In order to elucidate the role of differentially expressed miRNAs, a search for target genes was done using an online computational resource DIANA-miRPath v4.0.

Results
High fat diet (HFD)-induced obesity led to evident structural alterations in tubular and glomerular regions of the kidney, increased renal expression of adiposity-related proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism. The miRNA sequencing analysis identified a set of 9 miRNAs differentially expressed in the kidney upon HFD feeding, with miR-5099, miR-551b-3p, miR-223-3p, miR-146a-3p and miR-21a-3p showing most significant differential expression between standard diet (STD) and HFD mice. Consistently, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that 3 validated miRNAs (miR-5099, miR-551b-3p and miR-146a-3p) modulated target genes involved in metabolic and adipocytokine pathways, fatty acid and lipid metabolism, inflammatory, senescence and profibrotic pathways.

Conclusion
Our results propose that differentially expressed miRNAs play pivotal roles in the intricated pathophysiology of obesity-associated kidney disease and could potentially create novel treatment strategies to counteract the deleterious effects of obesity on kidney function.
#2484 Diffusion magnetic resonance imaging, a noninvasive tool to assess fibrosis level in both native and allograft kidneys
Authors: Huber Aurélie , Aslam Ibtisam , de Seigneux Sophie , De Perrot Thomas , Vallée Jean-Paul , Pruijm Menno , Berchtold Lena 
Published: May 2024

Abstract

Background and Aims
Renal cortical interstitial fibrosis is a well-established prognostic indicator for renal health, conventionally estimated by biopsy. Our prior research has enhanced DW-MRI sequencing, facilitating precise distinction between the renal cortex and medulla. This has enabled the measurement of the cortico-medullary apparent diffusion coefficient difference (ΔADC), which inversely correlates with the extent of histologically assessed interstitial fibrosis. The present study is designed to validate these findings, assess their reproducibility in a separate institution, and ascertain their significance in delineated subgroups, particularly between allograft recipients and native kidney patients.

Method
From 2014 to 2023, we orchestrated a prospective cohort study encompassing 309 patients diagnosed with chronic kidney disease (n = 106) or those with a renal allograft (n = 203). Each patient had undergone a biopsy, subsequent to which a multimodal magnetic resonance imaging (MRI) was systematically conducted in the following weeks. Initially, participants were recruited from Geneva hospitals, with subsequent inclusion of patients from Lausanne in Switzerland.
The study's objective was to evaluate the correlation between ΔADC and the degree of renal fibrosis at biopsy. We performed subgroup analyses (per center, native/allograft kidneys) and applied linear regression models to investigate these associations rigorously.

Results
We included 270 participants in Geneva and 39 patients in Lausanne. A significant negative correlation was observed between ΔADC and the degree of fibrosis across the entire cohort (R = −0.41, p &lt; 0.001). Subgroup analyses yielded consistent findings in both Geneva (R = −0.43, p &lt; 0.001) and Lausanne University Hospitals (R = −0.35, p &lt; 0.001). Furthermore, this association remained significant within subgroups of both native and allograft kidneys (respectively: R = −0.48, p &lt; 0.001 and R = −0.38, p &lt; 0.001).

Conclusion
Our findings reinforce the link between ΔADC and renal fibrosis, indicating that this association is consistent regardless of the center or kidney type (native or allograft). This supports the potential utility of diffusion MRI as a non-invasive tool for the assessment of renal fibrosis.
#995 Effectiveness of Semaglutide once weekly as add-on to SGLT-2Is in T2DM and CKD: a single-center observational study with body composition assessment
Authors: Yang Qing , Liu Fang 
Published: May 2024

Abstract

Background and Aims
To explore body composition and metabolic profile changes in type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD) using Semaglutide added to sodium-glucose transporter 2 inhibitors (SGLT-2Is).

Method
The study was performed on patients with T2DM-CKD in West China Hospital of Sichuan University. The outcomes were changes in body composition and metabolic profile after 6 months among patients administrated Semaglutide based on SGLT-2Is (Semaglutide plus SGLT-2Is group) and the comparison with patients only administrated SGLT-2Is (SGLT-2Is group).

Results
12 individuals with T2DM-CKD and BMI ≥28 kg/m2 were included in two groups, respectively. After 6 months, total fat mass was reduced by 0.9 kg (IQR −3.73, 0.4) vs. 0.7 kg (IQR −1.9, −0.37) with Semaglutide plus SGLT-2Is group and SGLT-2Is group (P = 0.908). Skeletal muscle mass was reduced by 0.97 kg (SD 0.86) vs. 0.5 kg (SD 0.93), respectively (P = 0.215). ACR (229.55 mg/g (IQR −389.7, −119.92) vs. 0.5 mg/g (IQR −104.6, 84.9), P = 0.032), HbA1c (−0.35% (IQR −0.85, 0) vs. 0.3% (IQR 0.15, 1.1), P = 0.024) and total cholesterol (−0.51 mmol/L (SD 1.1) vs. 0.75 mmol/L (SD 0.93), P = 0.015) significantly declined in Semaglutide plus SGLT-2Is group compared to SGLT-2Is group.

Conclusion
Semaglutide plus SGLT-2Is did not exacerbate muscle loss compared with SGLT-2Is alone in obese patients with T2DM-CKD, and improved glucolipid metabolism and albuminuria.
#217 Renin-angiotensin-aldosterone system blockers effect in CKD progression in hypertensive elderly patients without proteinuria: PROERCAN trial
Authors: Garcia-Prieto Ana , Guzmán Ursula Verdalles , de José Ana Pérez , Arroyo David , Aragoncillo Ines , Barbieri Diego , Juarez Rosa Camacho , Villa-Valdés Miguel , Pervan Emina , Goicoechea Marian 
Published: May 2024

Abstract

Background and Aims
Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria.

Method
Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years (Figure). Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality.

Results
88 patients were included with a mean age of 77.9 ± 6.1 years and a follow up period of 3 years: 40 were randomised to RAAS group and 48 to standard treatment. Etiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown etiology. In the RAAS group eGFR slope during follow up was −4.3 ± 1.1 ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6 ± 0.4 ml/min), p = 0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period.

Conclusion
In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression.
#1982 Transcriptomic approach to predict drug targets in late-stage hypertensive nephropathy
Authors: Chen Tony , Furriol Jessica , Landolt Lea Zoe , Knoop Thomas , Hallan Stein I , Øvrehus Marius , Scherer Andreas , Eikrem Øystein , Marti Hans-Peter 
Published: May 2024

Abstract

Background and Aims
Hypertensive nephropathy (HN) is a significant contributor to chronic kidney disease, yet the factors influencing the disease progression remains elusive. Notably, late-stage chronic kidney disease significantly impacts patient outcome. This project aims to unveil novel therapeutic targets for late-stage of HN using transcriptomic approach.

Method
A cohort of adult patients (n = 21; n = 9 females, mean age 57 years) with biopsy-confirmed HN were selected from the Norwegian Kidney Biopsy Registry (NKBR). Patients were classified as late-stage if eGFR≤45 ml/min/1.73 m2 at the time of biopsy. Patients were thereafter divided into “stable” (eGFR decline &lt;3 ml/min/year) or “progressive” (eGFR decline ≥3 ml/min/year or start of renal replacement therapy) after a median follow-up of 9 years (5-15). TruSeq Exome sequencing was performed post-RNA extraction (miRNeasy FFPE kit, Qiagen) at Novogene, Cambridge, UK. R Studio (v4.2.0) and drug CTD repository in ShinyGO 0.80 facilitated data and drug interaction analysis.

Results
We focused on two distinct subgroups of HN patients: late stable (LS, n = 9) and late progressive (LP, n = 12). A total of n = 674 of differentially expressed genes (DEG, p-value &lt; 0.05 and fold change (FC) ≥1.5) was identified in LS vs. LP.
The subsequent drug interactive analysis of these DEGs unveiled 336 pathways with false discovery rate (FDR) &lt; 0.05. Notably, the probenecid-related pathway demonstrated significant fold enrichment (FE=9, FDR = 1.5E-04), as depicted in Fig. 1. Particularly, key members of the SLC22 family, including SLC22A6 (FC=2.49, p-value = 0.002), SLC22A8 (FC=2.65, p-value = 0.004), SLC22A11 (FC=1.65, p-value = 0.036) and SLC22A12 (FC=1.97, p-value = 0.009) were prominently featured in this pathway. Besides their role as sole transporters, it is postulated that these proteins have central role in modulating local and systemic physiology, such as blood pressure, suggesting a potential significance of probenecid in the context of hypertensive nephropathy.

Conclusion
Transcriptomic profiling of kidney biopsies has strong potential to discover novel therapeutic targets, such as the probenecid-related pathway, in hypertensive nephropathy patients.
#607 Pre- and post-hemodialysis differences in heart failure diagnosis by current heart failure guidelines in patients with end-stage renal disease
Authors: Shin Ho Sik , Kim Ye Na , Kil Song Yi , Park Byung Hwa , Lim Sungil , Jung Yeonsoon , Rim Hark 
Published: May 2024

Abstract

Background and Aims
Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). Dialysis patients experience a volume change of ∼3–4 kg before and after HD, which can affect hemodynamic indicators, some of which are highly influenced by a patient's volume status. Therefore, depending on when echocardiography is performed, there may be differences in hemodynamic parameters. However, it is not easy to perform echocardiography in the euvolemic state in the clinical setting. This study estimated pre- and post-HD in ESRD HF diagnosis prevalence using the current guidelines.

Method
We prospectively investigated ESRD patients on HD using echocardiography between pre and post HD. We used structural or functional abnormality criteria of 2021 ESC guideline.

Results
A total of 54 patients were enrolled. The mean age was 62.6 years and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, 20 (37.0%) had ischemic heart disease. Mean NT-pro BNP level was 11959.9pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 minutes, and mean real filtration was 2.8 kg. The mean LVEF was 62.4% and mean LVEDD was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower LAVI (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), TR jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p &lt; 0.001), and RVSP (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There was no difference in LVEF, E/E’ ratio, or LV GLS. A total of 88.9% for pre-HD and 66.7% for post-HD had at least structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines, p = 0.007).

Conclusion
Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines, and the difference of prevalence of HF was 22.2% between pre- and post- HD.
#935 Exploring the impact of sensory-feedback in foot on physical activity in frail hemodialysis patients: a randomized controlled trial
Authors: Hamad Abdullah , Lee Myeounggon , Ibrahim Rania , Ateya Heba , Mathew Mincy , Talal Talal , Rodriguez Naima , Najafi Bijan , Al-Ali Fadwa 
Published: May 2024

Abstract

Background and Aims
Patients undergoing hemodialysis (HD) often face fatigue, time constraints, and impaired mobility, contributing to reduced physical activity and frailty. Intradialytic electrical stimulation (E-stim), particularly targeting the plantar region of the feet, is suggested as an alternative to traditional exercise programs. This study aims to investigate the association between sensory feedback in the foot and physical activity characteristics to demonstrate the efficacy of plantar electrical nerve stimulation (PENS) during HD in patients with frailty.

Method
43 participants with pre-frail to frail levels based on the Fried frail criteria were enrolled. They were randomized to either an intervention group (IG: n = 21, age=55.5 ± 14.3 years, BMI = 28.5 ± 6.0 kg/m2, female = 28.6%, pre-frail=38.1%, frail=61.9%) receiving PENS or a control group (CG: n = 22, age = 61.0 ± 7.8 years, BMI = 30.7 ± 6.2 kg/m2, female = 45.5%, pre-frail = 36.4%, frail = 63.6%). The IG received 1-hour PENS during HD session (3 sessions/week), while CG received an identical but non-functional device for 12 weeks. The maximum Vibratory Perceptual Threshold (VPT) value was measured to assess sensory-feedback in foot, and daily life physical activity was assessed using the wearable pendant at the baseline and 12-weeks. The delta values (Δ) between 12-weeks and baseline were calculated to explore the association between VPT and physical activity.
This study was supported by the Qatar National Research Foundation (QNRF, Award #NPRP10-0208-170400I).

Results
Age, gender, demographics, and other baseline characteristics were similar among IG and CG. 95% of participants completed 12 weeks regimen. In the IG, Δ walking duration (rho = −0.458, p = 0.037) and total step numbers (rho = 0.484, p = 0.026) were negatively correlated with Δ maximum VPT value, whereas there was no correlation in the CG.

Conclusion
Our study suggests that 12 weeks of E-stim therapy may enhance foot sensory feedback in the IG, potentially boosting walking-related activities in HD patients. Thus, we advocate for this practical therapy, especially for HD patients with frail symptoms, to promote increased physical activity.
#1744 Characteristics of patients on long-term dialysis for more than 30 years in our hospital
Authors: Sakamoto Emi , Suda Akio , Kobayashi Hideo 
Published: May 2024

Abstract

Background and Aims
In Japan, the prognosis of dialysis patients has improved over the years. The number of patients on dialysis for more than 20 years dramatically increased from less than 1% in 1992 to 8.6% in 2021. We analyzed the factors that contribute to the prolonged prognosis of dialysis patients.

Method
Of our 117 maintenance dialysis patients, we examine the dialysis profile of 26 (22.2%) long-term dialysis patients who have been on dialysis for more than 30 years.

Results
The mean age of dialysis induction is 32 years (13-55, ±10), the mean age is 71 years (46-87, ±9), and the longest duration of dialysis is 42 years. 12 patients are male. The majority cause of hemodialysis in them is chronic glomerulonephritis (22 patients). In addition, there are no patients with diabetes complications, 4 patients with hypertension, and 2 patients with coronary artery disease. 12 patients have carpal tunnel syndrome or destructive spondyloarthropathy. On-line HDF is generally used in 19 patients, mean blood flow is 215 ml/min (180-260, ±24), and mean dialysis time is 4.2 hours (3.5-5.0, ±0.4). Mean Kt/V is 1.76 (0.97-2.23, ±0.30), urea removal rate is 75.1% (57.8-84.2, ±6.6), β2-microglobulin is 23.8 μg/L (12.9-31.0, ±5.0). Mean DW is 51.0 kg (36.8-67.0, ±9.2), body mass index is 20.3 kg/m2 (16.1-24.4, ±2.5). Mean inter-dialysis weight gain is DW × 3.5% (2.9-4.9, ±0.9), nPCR is 0.9 g/kg/day (0.6-1.3, ±0.2), mean Albumin is 3.7 g/dl (3.2-4.4, ±0.3), whole-PTH is 160.4 pg/mL (0.0-902.7, ±178.8), Hemoglobin is 10.2 g/dL (7.8-13.9, ±1.4), 4 patients don't use ESA products.

Conclusion
According to the Japanese statistical survey of dialysis patients in 2020, 2.3% of the patients have been on dialysis for more than 30 years, which means that our hospital has a larger rate of long-term dialysis patients. These patients exceed the Japanese average in terms of both nutritional status and dialysis efficiency. The reasons for this may include the fact that our patients were on dialysis for at least 4 hours, and we intended to adhere to very mild dietary restrictions, specifically, the same diet as the family and that we did not recommend a low-protein diet.
#766 A prognostic model (BLEND35) with internal validation for treatment failure in patients with peritoneal dialysis-associated peritonitis
Authors: Liang Qichen , Zhao Huiping , Wu Bei , Niu Qingyu , Lu Lixia , Qiao Jie , Men Chuncui , He Yuting , Chu Xinxin , Zuo Li , Wang Mei 
Published: May 2024

Abstract

Background and Aims
Globally, peritoneal dialysis (PD)-associated peritonitis (PDAP) is a common and severe complication in PD. Early identification of high risk PDAP helps to prevent adverse outcomes. Currently, there is no recognized predictive tool for treatment failure of PDAP. Therefore, this study aimed to develop and validate a prediction model for treatment failure in patients with PDAP.

Method
We retrospectively collected 313 PDAP episodes occurred between January 2007 and August 2023, from real-world clinical practice in a tertiary center in Beijing, North China. The candidate predictors including patient characteristics, latest laboratory tests before PDAP, laboratory tests at PDAP onset and the causative organisms in peritoneal effluent. The prognostic model was developed from a multivariable logistic regression model with predictors selected using the stepwise backward regression. The C-statistic and the calibration curve plot were used to assess the discrimination and calibration of the prediction model. A bootstrap with 100 resampling was also performed as internal validation to further determine the robustness of the model.

Results
Among 313 PDAP episodes, 63 was reported treatment failure. The final model included 7 variables and was termed BLEND35 (sex, PD duration, platelet-to-lymphocyte ratio before PDAP, Gram-negative peritonitis, blood white cell counts at PDAP onset, dialysate white blood cell counts on day 3 and day 5). The C-statistic of the model was 0.936 (95% CI 0.897–0.974), revealing great discrimination. Calibration plot indicated that the model-predicted probabilities correlated well with the actual observed frequencies (Hosmer-Lemeshow test, P = 0.1223; Brier score = 0.064). Decision-curve analysis also revealed a positive net benefit.

Conclusion
The BLEND35 model will help to identify those with most high risk of treatment failure of PDAP and contribute to personalize and precise treatment. However, external validation is required before future application.