bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2223 Glycosylated hemoglobin levels and bone phenotype in patients with end-stage kidney disease
Authors: Hauge Sabina Chaudhary , Jørgensen Hanne Skou , Claes Kathleen , D'haese Patrick , Verhulst Anja , Cavalier Etienne , Hansen Ditte , Evenepoel Pieter 
Published: May 2024

Abstract

Background and Aims
Diabetes mellitus is common as both cause and comorbidity of patients with chronic kidney disease (CKD). Both diabetes and CKD are states of increased fracture risk compared to healthy controls, with multiple potential contributing mechanisms. In type 2 diabetes, hyperglycemia contributes to the accumulation of advanced glycation end-products and osteocyte dysfunction, and it may play a pathogenic role in bone fragility. In this study, we wanted to examine the association between glycemic status and bone phenotype in patients with end-stage kidney disease (ESKD).

Method
This is a cross-sectional cohort study of 626 patients with CKD G5-5D referred for kidney transplantation between April 2006 and December 2013. Patients with type 1 diabetes were excluded. Patients were divided into quartiles based on HbA1c. Laboratory parameters of bone mineral metabolism (including biointact parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23), and sclerostin), and bone turnover markers (bone alkaline phosphatase (BALP), trimeric pro-collagen type 1 N-terminal pro-peptide (intact P1NP), and tartrate-resistant acid phosphatase 5b (TRAP5b)) were measured. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DEXA) (n = 537), bone histomorphometry (n = 180), and bone trabecular score (TBS) (n = 192) were available for subsets of patients.

Results
The median HbA1c were 4.8% in Q1, 5.1% in Q2, 5.4% in Q3, and 5.9% in Q4. Age and BMI differed across quartiles, with the highest age and BMI in Q4. Differences in bone turnover markers were found, with decreasing bone formation (BALP and intact P1NP) and decreasing bone resorption (TRAP5b) with ascending quartiles (Fig. 1). No differences across quartiles were found for FGF23, or circulating levels of sclerostin; however a weak, positive correlation between HbA1c and sclerostin was noted (rho = 0.08, p = 0.047). Overall, BMD at lumbar spine, femoral neck, and total hip increased across quartiles, the highest values in Q4 (Table 1). There were no differen in bone histomorphometry or TBS based on glycemic status.

Conclusion
Chronic hyperglycemia associates with suppressed bone turnover and higher BMD in patients with ESKD, even in non-diabetics. Potential mechanisms linking glucose metabolism to bone quantity and quality requires further investigation.
#1564 Clinical implication of hyperfiltration and metabolic syndrome on the cardiovascular events, kidney failure, and all-cause mortality
Authors: Kim Dae Kyu , Kim Hyun Kyu , Lee Jeong-Yeun , Yoon Soo-Young , Kim Jin Sug , Jeong Kyung Hwan , Hwang Hyeon Seok 
Published: May 2024

Abstract

Background and Aims
Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality.

Method
We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) &gt; 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF.

Results
In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005).

Conclusion
The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.
#1910 Echocardiographic findings in patients with advanced diabetic kidney disease and obstructive sleep apnea
Authors: Nielsen Sebastian , Nyvad Jakob Tobias , Grove Erik Lerkevang , Poulsen Per Løgstrup , Laugesen Esben , Christensen Kent Lodberg , Buus Niels Henrik 
Published: May 2024

Abstract

Background and Aims
Obstructive sleep apnea (OSA) is associated with accelerated development of cardiovascular disease. The prevalence of OSA is increased in both type 2 diabetes (DM2) and in chronic kidney disease, and is very high in patients with diabetic kidney disease. However, the contribution of OSA to alterations in cardiac structure and function in diabetic kidney disease remains unknown. We therefore compared cardiac structure and function in diabetic kidney disease patients with or without OSA.

Method
In a cross-sectional study, 120 patients with DM2, a urine albumin-creatinine ratio (UACR) &gt; 30 mg/g and an estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/1.73 m2 were tested for OSA. OSA severity was quantified by the apnea-hypopnea-index (AHI). Patients without OSA (AHI &lt; 5 events/hour) were compared to patients with moderate (AHI 15-29 events/hour) or severe OSA (AHI ≥30 events/hour). Transthoracic echocardiography was conducted in all patients to evaluate cardiac structure and function. Linear regression analyses were used to assess the associations between OSA and echocardiographic parameters.

Results
AHI-data were available for 114 patients; 43 had no OSA, 33 had mild OSA and 38 had moderate-severe OSA. A total of 74 patients (73% men), 39 with no OSA and 35 with moderate-severe OSA, had complete data for both echocardiography and OSA. Their mean age was 71.5 ± 9.4 years, mean eGFR was 32.2 ± 12.3 mL/min/1.73 m2 and the median UACR of 533 (192–1707) mg/g. Age, smoking status, diabetes duration, eGFR, blood pressure, antihypertensive medicine, chronic obstructive pulmonary disease and atrial fibrillation were not significantly different between patients with and without OSA. Patients with moderate-severe OSA had significantly larger left atrial volume index (LAVI) (39.0 ± 19.6 vs. 28.1 ± 10.5 mL/m2, P = 0.0035), left ventricular mass index (LVMI) (49.2 ± 12.0 vs. 41.8 ± 9.7, g/m2, P = 0.0043), and right ventricular diameter (34.3 ± 5.8 vs. 28.4 ± 4.4 mm, P &lt; 0.0001) compared to those without OSA (Fig. 1). Global longitudinal strain (GLS) was significantly reduced in OSA patients (−14.9 ± 3.1 vs. −16.6 ± 2.8, P = 0.0196), while no difference was observed in LV ejection fraction (54.4 ± 8.1 vs. 56.5 ± 6.2, p = 0.21). The association between OSA and LAVI, LVMI, right ventricular diameter and GLS remained significant after adjustment for age, sex, eGFR and mean arterial pressure.

Conclusion
Moderate-severe OSA is independently associated with alterations in cardiac structure and function in patients with diabetic kidney disease and reduced renal function. OSA could be an independent contributor to the development of heart failure in patients with diabetic kidney disease.
#1311 Cardiac damage in a multifactorial DKD/CKD mouse model resembles HFpEF and can be reduced by standard-of-care treatment
Authors: van Koppen Arianne , Pieterman Elsbet , Hinke Simon , Nguyen Tri , Dendooven Amélie , Bajema Ingeborg , van Goor Harry , Smits Anke , Stoop Reinout 
Published: May 2024

Abstract

Background and Aims
We developed a diet-induced hypertension-accelerated mouse model of diabetic kidney disease characterized by progressive loss of GFR resulting in chronic kidney disease. Since cardiovascular disease is the major cause of death in CKD, we characterized the functional and structural cardiac damage in this model. Additionally, we studied the efficacy of combination therapy with an ACE-inhibitor (Lisinopril) and SGLT2-inhibitor (Dapagliflozin) on cardiac histopathology.

Method
Male KKAy mice underwent uninephrectomy. After recovery mice received high fat diet (45% LARD) and drinking water with or without 50 mg/L LNNA (wk0). At 12 weeks, imaging was performed to study cardiac function and mice were terminated at week 13. In the intervention study, at week 4, lisinopril (2.5 mg/kg/day; drinking water) and at week 8 dapagliflozin (5 and 20 mg/kg/day; foodadmix) treatment were started. At week 16 mice were terminated and lung and heart weight and cardiac histology were determined.

Results
Upon termination, macroscopic evaluation of the hearts showed extensive scar tissue formation on the outside of the left ventricle. Histological evaluation showed the presence left ventricular hypertrophy, coronary calcification and myocardial fibrosis in male KKAy mice with UNX, HFD and LNNA. KKAy mice with UNX and HFD but without LNNA also showed myocardial fibrosis, monocyte infiltration and focal mineralization. Imaging showed preserved ejection fraction, a significant reduction, increased left ventricle posterior wall thickness and decrease left ventricle inner diameter. Treatment with combination therapy reduced lung wet weight, significantly reduced heart weight and significantly decreased cardiac fibrosis. Macroscopically, less scar tissue was observed after treatment.

Conclusion
This multifactorial mouse model shows cardiac damage on a background of hypertension, diabetes, renal dysfunction and obesity. Functional measurement including preserved ejection fraction, left ventricle hypertrophy, diastolic dysfunction and increased fibrosis resembling the clinical HFpEF phenotype.
Combination therapy with Lisinopril and Dapagliflozin reduced cardiac weight and cardiac fibrosis. This indicates cardiac involvement in the DKD mouse model which confirms that this multifactorial model is clinically relevant.
#1088 Interaction of general obesity and abdominal obesity with frailty in patients with chronic kidney disease: a nationally representative analysis
Authors: Yang Changyuan , Qin Xindong , Duan Ruolan , Avesani Carla Maria , Cai Qingqing , Xia Ai , Shen Lingshan , Zhong Jingyi , Liu Xusheng , Lindholm Bengt , Lu Fuhua , Su Guobin 
Published: May 2024

Abstract

Background and Aims
General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. We explored the relationship between general and abdominal obesity and frailty in CKD patients.

Method
This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as body mass index (BMI) above 30 kg/m2, and abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The association of general and abdominal obesity with frailty were analyzed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined.

Results
5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 mL/min/1.73 m2. The prevalence of frailty was 40.7%. The prevalence of general obesity and abdominal obesity was 43.3% and 71.5%, respectively. Neither general nor abdominal obesity alone was associated with frailty. There was interaction between general and abdominal obesity with frailty (Table 1). Compared to individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty [odds ratio (OR): 1.53, 95% confidence interval (CI): 1.20-1.95]. General obesity was associated with being frail when CKD patients had abdominal obesity (OR: 1.59, 95% CI: 1.08-2.36) (Fig. 1).

Conclusion
There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects.
#1981 Experience with the use of semaglutide in cardiorenal syndrome patients followed in a cardiorenal unit (CRU)
Authors: Vidas Maria De San Miguel Marques , Crespo Silvia , Cobo Marta , Montero Esther , Lopez-Azor Juan Carlos , González Julia , Portolés Jose Maria 
Published: May 2024

Abstract

Background and Aims
GLP-1 receptor agonists are antihyperglycemic drugs that have shown an interesting cardio and nephroprotective effect beyond glycemic control and also induce weight loss, which is likely a facilitating element in the renal and cardioprotection of patients with elevated BMI. Patients with cardiorenal syndrome are often approached as particularly complex cases, which can lead to the underutilization of certain therapeutic groups. We have analyzed the use of semaglutide in patients followed in the CRU of Puerta de Hierro University Hospital to evaluate the drug's efficacy in glycemic and weight control and its safety profile.

Method
Retrospective real-life analysis performed in patients who received semaglutide while being under follow-up in the CRU, from January 21-December 22. Follow-up time was 6 months. Patients who had previously been on GLP1-AR treatment, on renal replacement therapy, or while waiting for any percutaneous or surgical cardiovascular procedure were excluded from the study.

Results
41 patients, 14 on oral semaglutide and 24 on subcutaneous semaglutide were analyzed. Demographic data and main comorbidities are shown in the table and were similar in both formulations. 53% of the patients were on maximum semaglutide dose at the end of follow-up (59.3% sbc and 42.9% oral, p 0.3). Weight loss and decrease in HbA1C% were significant without differences between formulations. We observed a significant decrease in systolic blood pressure of 11.1 (18) p 0.007 also similar in both drug formulations. No significant modifications in renal parameters were observed during follow-up. Adverse events were observed in 9 patients (22%), mainly gastrointestinal intolerance, and were more frequent with oral formulation (50% vs. 7.4%, p 0.004). 6 patients (14%) stopped semaglutide treatment without differences between formulation groups. 3 patients experienced at least one episode of HF decompensation, but no other events, hospitalizations, or deaths were observed. 3 (7.9%) patients experienced an eGFR decrease of&gt; 30% without differences among the formulation groups.

Conclusion
We conclude that semaglutide in both formulations is an excellent option for glycemic and weight control in CRS patients’ blood pressure, with an additional significant improvement in blood pressure control and a good safety profile in this special population.
#1763 Risk factors and clinical prediction models for osteoporosis in predialysis chronic kidney disease patients
Authors: Chen Liangmei , Liu Fanna , Kuang Chaoying 
Published: May 2024

Abstract

Background and Aims
The research concerning osteoporosis among individuals with predialysis chronic kidney disease (CKD) has been relatively neglected in existing literature. Furthermore, the risk factors for osteoporosis in this demographic have not been adequately investigated. The objective of this study was to explore the risk factors associated with osteoporosis in predialysis CKD patients and to construct a predictive model capable of estimating the likelihood of osteoporosis in these individuals.

Method
A retrospective study was conducted on 326 predialysis CKD patients. Relevant clinical examination results and measurements of bone mineral density (BMD) using dual-energy X-ray absorptiometry were collected. Binary logistic regression was utilized to explore the risk factors associated with osteoporosis and to develop predictive models.

Results
In male predialysis CKD patients, age represents a risk factor, while 25-(OH)-Vitamin D acts as a protective factor against osteoporosis. Among female patients, age, underweight status, NBAP, and advanced CKD (G5) are significant risk factors for osteoporosis, whereas PTH serves as a protective factor. In pre-dialysis CKD patients in stages CKD1-4, age, underweight status, and NBAP are identified as risk factors for osteoporosis. For G5 predialysis patients, advanced age and NBAP pose a high risk of osteoporosis, while 25-(OH)-Vitamin D and PTH exhibit protective effects. Additionally, nomogram models illustrating the risk of osteoporosis in pre-dialysis patients of different genders and renal function stages were created.

Conclusion
Age, underweight, severity of renal dysfunction, NBAP, PTH, and 25-(OH)-vitamin D are strongly associated with osteoporosis in predialysis CKD patients.
#2505 PTEN ablation in osteocytes exacerbates anemia in mice with subtotal nephrectomy
Authors: Tocados Juan Miguel Díaz , Pérez-Gómez Aurora , Coral Juan Diego Domínguez , García-Carrasco Alicia , Bardaji Ana Martinez , Caus Maite , Sanjuan Auria Eritja , Bozic Milica , Valdivielso José Manuel 
Published: May 2024

Abstract

Background and Aims
The identification of novel roles for bone as a principal endocrine organ has grown in recent decades, being now recognized for its contribution to the regulation of numerous systemic functions. In previous studies, we observed that 5/6Nx mice with osteocytic deletion of phosphatase and tensin homolog (PTEN), exhibited higher bone volume in 5/6Nx mice, consistent with studies under normal renal conditions. However, we also noted a decrease in blood hemoglobin levels, prompting further exploration.
This study aims to elucidate the causative actions by which specific PTEN deletion in osteocytes influences red blood cell (RBC) homeostasis and to identify its possible involvement in anemia development.

Method
To achieve this goal, we used mice with targeted PTEN deletion in osteocytes (PTEN Ocy-cKO) by crossing DMP1-Cre ± and PTENflox/flox mice, subjected to subtotal nephrectomy (5/6Nx) at 2 months of age. Two weeks post-surgery, bone and blood samples were collected for plasma biochemistry, blood count, RBC membrane integrity, and preliminary bone+bone marrow proteomic analysis. Cre-negative mice and animals with normal renal function were included as controls.

Results
Our findings revealed that PTEN Ocy-cKO mice, under both normal and reduced renal function conditions, showed higher bone volume than corresponding controls. In terms of blood homeostasis, PTEN Ocy-cKO mice with normal renal function showed splenomegaly and a lower number of circulating RBCs. Notably, PTEN Ocy-cKO mice undergoing 5/6Nx experienced a profound decrease in RBC number in only two weeks, independent of renal erythropoietin expression. Further exploration ruled out bone marrow failure as a cause, as the erythroid progenitor (CD45-CD71+Ter119+) population remained similar in both groups. Extramedullary hematopoiesis was observed in the spleen, in addition to increased circulating reticulocyte number in the PTEN Ocy-cKO mice. Finally, altered RBC membrane protein patterns in PTEN Ocy-cKO mice suggested reduced mechanical/osmotic resistance. Preliminary proteomic analysis identified downregulation of Slc4a1 (Band3) and Phosphofructokinase (Pfkm), whose deficiencies have been previously linked to anemia.

Conclusion
In conclusion, our results propose that osteocytes contribute to RBC homeostasis through a pathway downstream of PTEN, and open a new avenue for understanding anemia in chronic kidney disease and a potential target for future treatments.
#2987 Describing inflammatory markers in end-stage renal disease and hemodialysis
Authors: Martínez Jordi Calabia , Saltos Jehimy Jean Alvarez , Carcasi Mara Lisbet Cabana , Ribas Ana Merino , Alemany Nadia Martín , Suárez Gabriel Manuel González , Cantalejo Leyre Garcia , Devia Claudia Marcela Castillo , Paez Cristina Noboa , Soler Laura Boix , Baptista Yanel Adriana Acosta , Escuder Pere Torguet 
Published: May 2024

Abstract

Background and Aims
There is an increased inflammatory state in patients with End-Stage Renal Disease (ESRD). It is crucial to investigate if the decline in renal function influences on the levels of infectious and inflammatory parameters, particularly procalcitonin (PCT) which exhibits the highest specificity for bacterial infections. Additionally, it would be useful establish a PCT cut-off-value for patients on renal replacement therapy and ESRD in the absence of infection, facilitating the differentiation between those with and without bacterial infection.
The aim of this study is to analyze infectious and inflammatory parameters, including PCT, in ESRD and HD patients. A secondary objective is to explore the link among inflammatory markers between themselves and with some specific clinical conditions.

Method
A cross-sectional observational comparative study was conducted involving HD patients (Group 1) and ESRD (Group 2). We assessed PCT, C-Reactive Protein (CRP), Sedimentation Velocity (SV), and Ferritin, among others. Patients with active infection were excluded. For HD patients, analytical extraction was conducted before the midweek session.
Results are presented as mean ± standard deviation for variables exhibiting a normal distribution, and as the median for variables displaying a non-normal distribution. Normality was assessed using the Shapiro-Wilk test. Group comparisons were conducted using Mann Whitney test for variables with a non-normal distribution. Relationships between parameters were examined using the Spearman correlation test and linear regression analysis. Significance was established at p &lt; 0.05. The statistical software utilized was Jamovi (Version 2.3).

Results
We found in HD patients (Group 1) when compared to ESRD patients (Group 2) higher PCT levels, higher ferritin levels, and lower albumin levels, with statistical significance (Table 1).

Conclusion
There is a decrease in albumin levels and an increase in PCT, and ferritin levels in HD patients compared to ESRD patients. We observed that RCP, and ferritin were independent predictive factors of PCT levels, but, unexpected, diabetes was not. Given the fact that ESRD, and HD patients are in a chronic inflammatory status, it is difficult to assess the acute infectious severity in these patients. For that reason, the cut-off-values of inflammatory parameters in these patients in a non-infectious time-point needs to be clarified.