bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1895 Elucidating Asprosin's role as an intracellular metabolism regulator in diabetes and obesity-induced renal damage
Authors: Park Cheol Whee , Lim Ji Hee , Kim Yaeni , Kim Tae Woo , Kim Eun Nim 
Published: May 2024

Abstract

Background and Aims
Asprosin, an adipokine with a multifaceted function that encompasses inducing insulin resistance, promoting inflammation, and stimulating appetite, is the focus of our investigation. We seek to establish its pivotal role as a mediator in regulating cellular energy metabolism, particularly in the context of renal damage induced by diabetes and obesity.

Method
We conducted experiments using type 2 diabetic db/db mice and obesity-induced high-fat diet mice. These animal models were categorized into two groups: one received Asprosin neutralizing antibodies (250 μg/mouse/21 days), targeting the 28-amino acid peptide located proximal to Asprosin's C-terminus (KKKELNQLEDRYDKDYLSGELGDNLKMK), while the other received an AMPK activator (Metformin) associated with the regulation of Asprosin receptors (OLFR734/G proteins-cAMP-PKA). Additionally, we cultured renal constituent cells (mesangial cells, glomerular endothelial cells) in high glucose and palmitic acid conditions and silencing Asprosin expression using siRNA. We assessed the levels of Asprosin, AMPK, and their respective downstream signaling pathways.

Results
Asprosin was found to be overexpressed in the serum and kidney tissues of both db/db mice and high-fat diet mice, as well as in renal constituent cells cultured under high glucose and palmitic acid conditions. Interfering with Asprosin led to reduced body and liver weight in mice, improved glucose tolerance, and mitigated renal injury in vivo. Asprosin knockdown ameliorated lipid accumulation and inflammatory infiltration, both in vitro and in vivo. Moreover, Asprosin absence activated the AMPK/Sirts/mTOR signaling pathway, while the AMPK activator Metformin reversed the effects of Asprosin on lipid accumulation and inflammatory response, confirming Asprosin's direct role in intracellular lipid metabolism.

Conclusion
The mechanism of intracellular energy metabolism regulation mediated by Asprosin presents promising potential for targeted organ therapy in the development and prevention of diabetic kidney disease. Inhibiting Asprosin suppressed lipid accumulation and inflammation in diabetic kidney disease through the activation of AMPK-associated signaling pathway.
#539 The active ingredient in the Nuphar lutea plant DTBN, ameliorates kidney damage and inflammation in a mouse model of chronic kidney disease (CKD)
Authors: Landau Daniel , Khalilia Jannat , Arazi Eden , Tobar Ana , Gopas Jacob , Segev Yael 
Published: May 2024

Abstract

Background and Aims
Complications associated with Chronic Kidney Disease (CKD), such as disease progression and anemia, are closely linked to heightened inflammation mediated by the innate immune response. This inflammation can be mitigated through the use of anti-inflammatory agents. 6,6′-dihydroxythiobinupharidine (DTBN), an active compound derived from the aquatic plant Nuphar lutea, demonstrates notable anti-inflammatory properties, primarily by inhibiting NF-κB and LPS-induced cytokine activation. DTBN has shown efficacy in priming neutrophils, enhancing phagocytosis, regulating reactive oxygen species (ROS) production, and modulating NET formation. This study aimed to assess the impact of DTBN on CKD in mice.

Method
Male C57BL/6J mice, aged 8 weeks, were subjected to an adenine diet known to induce CKD through crystal deposition and tubulointerstitial inflammation. Both control and CKD-induced mice received intraperitoneal injections of DTBN (25 μg QOD) or saline and were euthanized after 8 weeks for evaluation.

Results
CKD mice treated with DTBN exhibited a significant decrease in serum urea and creatinine levels compared to untreated CKD mice (reduction by 1.4-fold and 1.3-fold, respectively). Histological analysis of kidney tissues revealed a notable reduction in F4/80 positive macrophage infiltration (3.4-fold decrease) and damaged renal areas (three-fold decrease), along with diminished kidney TGF-β levels in DTBN-treated CKD mice. Moreover, the p65 subunit of NF-κB showed a three-fold reduction in CKD mice treated with DTBN compared to untreated CKD mice. Indices of kidney inflammation (IL-1β, IL-6, and P-STAT3) were notably decreased in CKD mice treated with DTBN (reduction by 1.4-fold, 1.6-fold, and 2.9-fold, respectively) compared to untreated CKD mice. Notably, DTBN treatment in control mice did not induce apparent tissue damage; however, it led to reduced weight gain and mild hypoalbuminemia without proteinuria.

Conclusion
DTBN demonstrated significant improvements in renal function and inflammation indices in CKD mice. Hence, DTBN and substances similar to DTBN could be considered as supplementary treatments for CKD patients.
#181 Dysbiosis of gut microbiota in patients with chronic kidney disease
Authors: Yasuno Tetsuhiko , Ito Kenji 
Published: May 2024

Abstract

Background and Aims
The human intestinal tract contains 100 trillion microorganisms, and 500–1000 microbial strains exist in each individual, classified into two main phyla: Firmicutes and Bacteroidetes.
The gut bacterial microbiota is altered in patients with chronic kidney disease (CKD). However, the bacterial composition at each stage of CKD is unclear in these patients, including those receiving renal replacement therapy. In this report, we present the changes in the gut microbiota among patients with CKD.

Method
A total of 93 individuals were recruited for the study. Seventy-three patients had stage 3–5 CKD, including those receiving renal replacement therapy (CKD group), and 20 were age- and sex-matched controls (CKD stage 1–2). Gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.

Results
The beta diversity of the samples was evaluated via principal coordinates analysis (PCoA).
The unweighted and weighted UniFrac distances revealed a tendency toward separation of microbiota in the samples according to the CKD stage 1–2 and CKD stage 3–5, 5D groups. At the genus level, the butyrate-producing bacteria Lachnospira, Blautia, Coprococcus, Anaerostipes, and Roseburia were more abundant in the control group (Linear Discriminant Analysis score of &gt;3) than in the CKD group. Lachnospira was more abundant in the control group than in patients with CKD stage 3a. Compared to the control group, multiplex butyrate-producing bacteria were deficient in patients with CKD stage 3b–5D, including in patients receiving renal replacement therapy.

Conclusion
Our findings highlight that the gut bacterial composition, including butyrate-producing bacteria, deteriorates from CKD stage 3b. Even after renal replacement therapy, the bacterial composition did not change.
#2494 Pharmacological enhancement of circadian clock ameliorated fibrosis in adenine induced chronic kidney disease
Authors: Park Sang Hoon , Jo Sang Kyung , Kim Myung-Gyu 
Published: May 2024

Abstract

Background and Aims
Circadian clock regulates diverse biological processes. Recent studies demonstrating the important role of dysregulated molecular clock system in several metabolic diseases as well as in chronic kidney disease (CKD) suggest that modulation of clock machinery might be an attractive therapeutic target.

Method
We optimized a substance (compound X) that enhances the circadian molecular rhythm and validated its effect in HK-2 cells as well as in mouse model of adenine induced CKD.

Results
By using transcriptome analysis of whole kidneys, we identified that 19% of CKD associated genes showed rhythmic expressions in circadian manner. Gene enrichment analysis revealed that the rhythmic genes involved in extracellular matrix/collagen/myofibroblasts showed upregulation while those involved in transport/brush border/proximal tubule showed downregulation in CKD. Treatment with compound X in HK-2 cells resulted in marked attenuation of epithelial mesenchymal transition upon transforming growth factor-b (TGF- b) stimulation. Along with these in vitro data, we also observed the preserved kidney function and less interstitial fibrosis in compound X treated CKD mice. The protective effect was associated with suppression of inflammation, cell cycle arrest/cellular senescence as well as restoration of several transporters in proximal tubular cells.

Conclusion
This is the first study that showed that circadian rhythm might be a novel target for CKD progression by suppressing inflammation/fibrosis and enhancing tubular functions. Unlike other strategies targeting single pathway, targeting circadian rhythm seems to be more promising due to its multi-target effects. A better understanding of the complex role of circadian clock in kidney diseases may provide new perspectives for the prevention and treatment of CKD.
#177 Assessment and comparison of physician gaps related to clinical knowledge of IgA nephropathy
Authors: Larkin Amy 
Published: May 2024

Abstract

Background and Aims
Understanding physician gaps related to IgA nephropathy (IgAN) can inform development of tools to improve physician knowledge and competence related to both diagnosis and treatment. Additionally, comparisons among specialists (nephrologists) and generalists (primary care physicians, PCPs) can segment educational needs for combined or customized education to close identified gaps.

Method
A survey instrument of 25 multiple choice, knowledge- and case-based questions allowed participants to assess their clinical knowledge related to IgAN. The survey was available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. Initial data collection occurred from March 16, 2023 to May 19, 2023.

Results
In total, 98 nephrologists and 57 PCPs completed the full assessment within the data collection period.

Conclusion
This assessment of physicians’ clinical knowledge yielded important insights into gaps related to IgAN. Both nephrologists and PCPs need education on pathophysiology of IgAN and emerging treatment pathways, role of proteinuria and risk correlations to ESRD with IgAN, clinical use of the International IgAN Prediction Tool, and KDIGO recommendations for managing IgAN. PCPs need additional education on basic IgAN prevalence as well as clinical strategies for diagnosis. Further studies are planned to assess the effect of medical education on decreasing these clinical practice gaps.
#2836 Prevalence and risk factors associated with chronic kidney disease among type-2 diabetes mellitus patients – a single centre experience
Authors: Suvvari Tarun Kumar 
Published: May 2024

Abstract

Background and Aims
Globally, diabetes mellitus is one of the major causes of increased morbidity. One of the key complications of T2D is chronic kidney disease (CKD). Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. So, we aimed to find out the prevalence of CKD among T2DM patients and to evaluate the correlation between age, duration of diabetes, HbA1c, and UACR with eGFR among T2DM patients.

Method
An observational cross-sectional study was conducted at department of medicine, tertiary care hospital for 2 months. Along with demographic and anthropometric data The following clinical data were collected: estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Spearman rank correlation was used to determine the correlation between eGFR and various parameters.

Results
A total of 96 patients were included in the study. 65% of the study participants were sedentary and 35% were physically active. 41 (42.7%) were obese and 21 (21.9%) were overweight. The mean Duration of diabetes is 5.62 ± 4.68 years. The mean estimated glomerular filtration rate (eGFR) is 74.33 ± 31.01 mL/min/1.73 m2. The Prevalence of CKD is 35.4%. 21.8% belongs to G3a category and 8.3% belongs to G3b category. Spearman's correlation coefficient test revealed negative correlation between eGFR and duration of diabetes, HbA1c and UACR (Spearman's correlation coefficient values are −0.577, −0.595 and −0.709 respectively).

Conclusion
In conclusion, nearly 1/3rd of study participants reported CKD. Our study provides consistent and recent clinical data showing an inverse association of eGFR with age and duration of diabetes. This study highlights that age and duration of diabetes are key parameters associated with declining renal functions in people with T2DM.
#1082 Early-stage chronic kidney disease as a risk factor for suicide: a nationwide observational cohort study
Authors: Joo Kwon Wook , Park Sehoon , Kim Jung-Hyun 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is associated with poor psychological well-being. Whether early-stage CKD is a risk factor for suicide warrants further research.

Method
This nationwide, retrospective, cohort study aimed to evaluate the risk of suicide in patients with early-stage CKD and identify the associated risk factors. A total of 3 945 198 individuals aged ≥19 years who underwent the 2009 national health screening were enrolled. Among them, 202 291 patients had early-stage CKD (estimated glomerular filtration rate (eGFR) ≥30 and &lt;60 mL/min per 1.73 m2 and/or dipstick albuminuria ≥1+). The study outcome was suicide as confirmed by the nationwide death register based on death certificates.

Results
The study population had a mean age of 59 ± 15 years, and 47% were male. We identified 930 suicides (incidence rate, 0.45 per 1 000 person-years) in the CKD group and 11 332 suicides (incidence rate, 0.27 per 1 000 person-years) in the non-CKD group. Early-stage CKD was significantly associated with an increased risk of suicide in multivariable analysis adjusted for demographic characteristics; lifestyle habits; comorbidities, including diabetes and hypertension; economic status; and depression (hazard ratio, 1.16; 95% confidence interval, 1.09‒1.25). Suicide risk was higher in individuals with proteinuria but preserved kidney function (eGFR &gt;60 mL/min per 1.73 m2 and dipstick albuminuria &gt;1+) than in those without CKD. In the CKD group, older males and current smokers had a higher risk of suicide.

Conclusion
CKD even in the early stages is associated with significantly higher risk of death from suicide. Hence, healthcare providers may need to examine the mental health of patients with early-stage CKD and other risk factors to prevent suicide.
#501 Evaluation of the accuracy of serum creatinine-based GFR calculations across the different levels of renal function among Filipinos
Authors: Pangan Ghiyll Evannie , Villanueva Anthony Russell 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is a worldwide health concern which continues to increase in prevalence. Early studies have evaluated kidney function by measuring serum creatinine (sCr) and/or the estimated glomerular filtration rate (eGFR). To date, there are limited studies that correlate nuclear GFR scans and eGFR by equations that include the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 in Asians, specifically in a Filipino population. This study aims to compare the accuracy of GFR scan results and GFR estimated from the formulas across different levels of kidney functions, age groups, gender, and co-morbidities among a Filipino subset.

Method
A cross-sectional study was done among 2986 patients who underwent Nuclear GFR scan in a single kidney center. Results obtained were compared to estimated GFR results. Weighted Kappa and Bland-Altman Analyses were used to test for agreement between the measured and estimated GFR results.

Results
Absolute GFR values derived from the three equations demonstrated moderate reliability with results from nuclear scan when intraclass correlation coefficients were calculated with CKD-EPI 2021 being the highest. When further categorized into GFR levels, there was substantial level of agreement between each equation and GFR scan, with all weighted kappa coefficients being at least 0.700 with CG having the highest result (Table 1). Furthermore, when subgroup analysis was done according to age group, gender, and comorbidities, CG was found to be the most accurate per category (Table 2).

Conclusion
CKD-EPI 2021 was the most accurate in the actual GFR values however we cannot fully eliminate the utility of CG due to its categorical accuracy and in monitoring the deterioration of renal function.
#1575 Cardio-renal syndrome in patients with Fabry disease on enzyme replacement therapy
Authors: Parshina Ekaterina , Prokopenko Elena , Zulkarnaev Aleksei , Popov Mikhail , Kotalevskaya Yulia , Shumakov Dmitry , Gubina Daria 
Published: May 2024

Abstract

Background and Aims
Fabry disease (FD) is a rare X-linked lysosomal storage disorder in which mutations of the GLA gene cause a decreased or absent activity of the alpha-galactosidase A (α-Gal A) and intracellular accumulation of globotriaosylceramide and other sphingolipids [1]. FD causes a variety of symptoms, including heart and kidneys damage - cardiorenal syndrome (CRS) type 5. In patients with FD, CRS is known to increase the risk of cardiovascular events and death [2].
The aim of our study was to assess renal function and outcomes in patients with FD and CRS receiving enzyme replacement therapy (ERT).

Method
We performed a retrospective analysis of the medical records of 10 patients (pts) from 7 unrelated families with established diagnosis of FD and cardiac and renal involvement. Pts #1 and #3 are siblings, pt # 10 is their mother; pt #9 is mother of pt #8 (Table 1). The diagnosis was confirmed by DNA diagnostics in all plus levels of α-Gal A enzymatic activity, globotriaosylsphingosine concentrations in some patients. All the patients underwent ERT. Seven out of 10 patients received blockers of the renin-angiotensin-aldosterone system, 3 - did not receive due to contraindications.

Results
All 10 patients, including 3 women, had left ventricular hypertrophy - left ventricular wall thickness (LVWT) ≥ 1.2 cm. (Table 1). Average LVWT was 1.850 ± 0.097 cm. Two patients had atrial fibrillation. None of the patients had proteinuria 1 g/24 h or higher. In all еGFR was below 60 ml/min/1,73 m2: 4 patients had CKD-G3a, 4 – G3b, 1 – G4 and 1 – G5. Average еGFR was 41,111 ± 8.069 ml/min/1,73 m2 excluding hemodialysis (HD) patient.
There were 4 unfavorable outcomes in our group: death occurred in 3 patients from cardiac pathology (congestive heart failure), one patient reached CKD-G5 at 25 years of age and started HD treatment. Patient on HD, brother of deceased pt #1, began receiving ERT after the start of renal replacement therapy. The death of pt #1, who had a very high Lyso-Gb3 level - 118.36 ng/ml (normal 0.05-3.0 ng/ml), appears to be related to the late diagnosis and delayed start of ERT.

Conclusion
Patients with FD and CRS are likely to have a high risk of cardiovascular complications, loss of kidney function and death, especially with a late start of enzyme replacement and cardio-renoprotective therapy. Early diagnosis of FD and timely initiation of treatment are important in preventing the serious complications and death.
#742 High TSH and low FT3 levels are associated with chronic kidney disease in three population-based studies from Germany
Authors: Stracke Sylvia , von Rheinbaben Sabrina Freiin , Voelzke Henry , Gollasch Maik , Koenig Maximilian , Steinhagen-Thiessen Elisabeth , Ittermann Till 
Published: May 2024

Abstract

Background and Aims
High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. The aim of our study was to investigate associations of serum levels of TSH, fT3 and fT4 with eGFR and albuminuria in population-based cohorts.

Method
We used cross-sectional data from 7,933 individuals aged 20 to 93 years of the Berlin Aging Study II (BASE II) and the Study of Health in Pomerania (SHIP-START; SHIP-TREND) to associate serum TSH, fT3, and fT4 levels with eGFR and albuminuria. To calculate eGFR, CKD-EPI and FAS equations were used. Albuminuria was defined as an urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.

Results
In multivariable analyses adjusted for confounding, we found inverse non-linear associations of serum TSH levels with eGFR, while serum fT3 levels showed a positive association with eGFR. High as well as low serum fT4 levels were associated with a lower eGFR. Age but not sex modified the association between thyroid hormone levels and eGFR. The inverse associations between serum TSH levels with eGFR were strongest in the youngest age groups, while the positive associations between serum fT3 levels and eGFR were strongest in older individuals. No significant associations between thyroid hormone levels and albuminuria were found.

Conclusion
In conclusion, we showed that high TSH, low fT3 as well as low and high fT4 levels were independently associated with a reduced kidney function in a non-linear fashion. Our results indicate that high TSH / hypothyroidism might be associated with a reduced kidney function. Thyroid function might be more tightly related to the eGFR than to albuminuria in the general population.
#1668 The 60:40 conundrum: are women with CKD discriminated against after referral to a nephrology clinic?
Authors: Vautcranne Adèle , Bianco Lavinia , Mazé Béatrice , Fois Antioco , Chatrenet Antoine , Moio Maria Rita , Torreggiani Massimo , Piccoli Giorgina 
Published: May 2024

Abstract

Background and Aims
The representation of women in kidney medicine clinical trials has diffused the belief that women are discriminated although epidemiological data suggest that chronic kidney disease (CKD) is more prevalent among females than males. We aimed to test whether sex distribution varies at nephrology referral, inclusion in a clinical study or at the starting of dialysis.

Method
This was a retrospective, monocentric study conducted in a large non-university hospital in central France. We exploited data from patients included in the PRO-RE-RE-PRO study on the effect of diet on the progression of CKD. We evaluated patients’ characteristics and gender at the time of the first consultation in the Unit for the Care of Advanced CKD (UIRAV), at the inclusion in the PRO-RE-RE-PRO study and at the beginning of the kidney replacement therapy.

Results
866 patients were included in this study as they were referred to the UIRAV, 59% males and 41% females. Female patients were older but less comorbid and were referred at the same eGFR than males. The same proportion of males/females was observed in patients included in the PRO-RE-RE-PRO study. No sex differences were observed at dialysis start. Survival was significantly higher in females. Overall, distribution across sex remained stable over time.

Conclusion
The main result of this study is the stability of the approximately 35-40% female to 60-65% male ratio from start of follow-up in all subsets of cases: patients referred to the unit dedicated to advanced CKD, patients recruited in the observational study, patients not included, or who refused to participate, patients on follow-up at the completion of the database. Furthermore, the same distribution is observed in dialysis patients, from dialysis start to the most recent update. Our data suggest that if a gender-selection bias exists in nephrology, it should be sought before the first nephrology referral. However, further studies are needed to ensure health equity.