bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B09-6: BIGLYCAN, A NEWLY IDENTIFIED MEDIATOR OF MINERALOCORTICOID RECEPTOR ACTIVATION-INDUCED NEPHROPATHY
Authors: Nakamura Toshifumi , Bonnard Benjamin , Ramirez Roberto Palacios , Celis Amaya Fernandez , Jaisser Frederic , Andres Natalia Lopez 
Published: January 2023

Background:
The activation of mineralocorticoid receptor (MR) is known to be involved in kidney disease progression. MR antagonists (MRAs) have been reported to have beneficial effects on various kidney diseases. However, it is still unclear which mechanism underlies kidney and glomeruli injury related to MR activation. Recently, we demonstrated that aldosterone promotes proteoglycan synthesis in mitral valve interstitial cells and its association with the development of cardiac valvular disorder. Proteoglycans are glycosylated molecules sequestered in the extracellular matrix (ECM), interacting with other components of ECM. In addition, some proteoglycans are known to interact with several bioactive partners to activate cell signaling. Since increased expression of certain proteoglycans has been reported in several kidney diseases, we investigated the association between the proteoglycans expression and kidney injury upon aldosterone/MR pathway activation.

Methods:
We analyzed the alteration and localization of proteoglycan expression in the kidney of uninephrectomy/aldosterone/salt (NAS)-treated mice. The MRA eplerenone was administered to these mice to evaluate the contribution of the MR pathway in NAS-induced kidney injury. Glomeruli samples were isolated from the kidneys to assess the localized expression of proteoglycans and the glomerular injury. Additionally, we performed cellular experiments using isolated peritoneal macrophages to assess the direct effect of a proteoglycan biglycan on macrophages.

Results:
NAS treatment enhanced renal fibrosis and urinary albumin levels. Renal expression of proteoglycans was increased. Among various proteoglycans, biglycan showed increased expression, especially in the glomeruli. Isolated glomeruli samples revealed glomerular macrophage infiltration, accompanying enhanced expression of TNF-α (tumor necrosis factor-alpha), iNOS (inducible nitric oxide synthase), Nox2 (NADPH oxidase 2), CCL3 (C-C motif chemokine ligand 3), and phosphorylated NF-κB (nuclear factor-kappa B). The expression of CD86, a surface marker for M1 macrophage, also increased by 11.5-fold in the glomeruli of NAS-treated mice. These changes were blunted by eplerenone. Treatment with purified biglycan induced expression of TNF-α, iNOS, Nox2, and CCL3 in the isolated macrophages. An inhibitor of toll-like receptor 4 (TLR4) or NF-κB prevented this increase, indicating that the effect of biglycan stimulation is dependent on the TLR4/NF-κB pathway.

Conclusion:
This study identified the proteoglycan biglycan and its downstream TLR4/NF-κB/CCL3 cascade as a novel mediator of MR activation-induced glomerular injury.
PS-C17-3: ONE-YEAR TIME-SERIES OBSERVATIONS OF VARIABLE COMPONENTS OF URINE PROTEIN AND EGFR PREDICT WORSENING RENAL FUNCTION IN TYPE 2 DIABETES
Authors: Watanabe Mari , Meguro Shu , Kimura Kaiken , Furukoshi Michiaki , Masuda Tsuyoshi , Enomoto Makoto , Itoh Hiroshi 
Published: January 2023

Objective:
Type 2 diabetes, along with hypertension, is a major cause of worsening renal function. It would be very meaningful if we could detect future deterioration of renal function.

Design and method:
Predictive models were created using machine learning techniques. We used the medical information database of 2533 patients who attended the outpatient clinic of our hospital between January 2003 and March 2015. The point at which the estimated glomerular filtration rate(eGFR) first falls below 60 mL/min/1.73 m2 is used as the reference point. The input period was defined as the period from the reference point to one year before the reference point. Time series during the input period for eGFR, hematocrit, and urinary protein were extracted from blood and urine tests as features for predicting worsening renal function. The primary endpoint was a 50% reduction in eGFR during the evaluation period of three years since reference point from the mean value during the input period. The optimal combination was selected to maximize prediction performance using up to 4 features considering the number of endpoints reached. The prediction results were evaluated on AUC with 10 repeated 2-fold cross validation.

Results:
Among 2533 patients, 1409 patients had the reference point. Of those, 377 patients for whom a record existed for the input and evaluation periods but did not reach the primary endpoint, and 36 patients reached the primary endpoint. The mean eGFR during the input period was 67.9 ± 8.8 mL/min/1.73 m2, the mean age was 64.9 ± 10.2, 41.6% was women. The mean AUC was 0.82 ± 0.033 when the maximum and minimum values of urinary protein, minimum of eGFR and the difference between maximum and minimum values of eGFR during the input period were used as features.

Conclusions:
In this study, we developed a prediction model for worsening renal function using time series measurements in patients with relatively preserved renal function(eGFR> 60 mL/min/1.73 m2), and the results showed that it is very important to consider the variable components of urine protein and eGFR, which are laboratory values reflecting renal impairment. Recently, SGLT2 inhibitors have been used to treat kidney disease, but this study analyzed data before the release of SGLT2 inhibitors. We would like to examine whether our model can be applied to patients taking SGLT2 inhibitors.
PS-C17-5: HYPOBILIRUBINEMIA AND HYPERTENSION AS RISK FACTORS FOR DIABETIC RETINOPATHY OF TYPE 1 AND TYPE 2 DIABETES MELLITUS
Authors: Tanaka Masami , Nishimura Takeshi , Itoh Hiroshi 
Published: January 2023

Objective:
Previously, we reported that hypobilirubinemia is an important risk factor for diabetic retinopathy. On the other hand, high systolic blood pressure (SBP) is reported to be a risk factor for this condition. Therefore, we conducted this retrospective study to evaluate a significance of hypobilirubinemia and hypertension as risk factors for diabetic retinopathy of type 1 and type 2 diabetes mellitus (DM).

Design and Methods:
One hundred and thirty-one patients (59 men) with type 1 and 293 patients (159 men) with type 2 DM were included in this cross-sectional study. We compared serum total bilirubin concentration (TBC) between the patients with and without diabetic retinopathy, and compared it according to the severity of retinopathy. Logistic regression analysis was used to examine the effects of various factors on retinopathy, and the following factors were considered as independent variables: SBP, TBC, gender, age, diabetes duration, HbA1c, eGFR, and BMI.

Results:
The age, diabetes duration, BMI, HbA1c and TBC of the subjects with type 1 and type 2 DM were 54.9 + 15.0 years, 17.4 + 12.2 years, 21.9 + 3.6 kg/m2, 7.9 + 1.5%, 0.70 + 0.24 mg/dL and 64.1 + 12.8 years, 14.4 + 9.5 years, 25.4 + 5.4 kg/m2, 9.2 + 1.8%, 0.75 + 0.29 mg/dL, respectively. Forty-three (33%) patients with type 1 and 124 (42%) patients with type 2 DM patients were complicated by diabetic retinopathy, respectively. Sixty (46%) patients with type 1 and 211 (72%) patients with type 2 DM were complicate by hypertension. Among type 1 and type 2 DM patients, SBP was higher and TBC was lower significantly in patients with retinopathy than in those without retinopathy. It was shown that serum TBC was negatively associated with increasing severity of retinopathy in patients with both type 1 and type 2 DM. The results of logistic regression analysis showed that TBC was an independent explanatory factor for retinopathy of both type 1 (p = 0.001) and type 2 (p < 0.001) DM. Among type 1 diabetics, systolic blood pressure was an independent risk factor (p = 0.001), but SBP was not (p = 0.067).

Conclusions:
Low TBC might have pathophysiological significance in the onset of retinopathy for both type 1 and type 2 DM patients. On the other hand, the significance of hypertension might be higher for type 2 than type 1 DM.
PS-C17-9: RELEVANT BLOOD PRESSURE REDUCTION WITH ORAL SEMAGLUTIDE IN PATIENTS WITH TYPE 2 DIABETES AND OBESITY, INDEPENDENT OF PREVIOUS ANTIHYPERTENSIVE TREATMENT
Authors: Martinez-Martin Francisco Javier , Kuzior Agnieszka , Hernandez-Lazaro Alba , de Leon-Durango Ricardo , Rios-Gomez Carlos , Santana-Ojeda Borja , Perez-Rivero Jennifer Maria , Fernandez-Trujillo-Comenge Paula Maria , Santana-Suarez Ana Delia , Gonzalez-Diaz Paula , Arnas-Leon Claudia , Acosta-Calero Carmen 
Published: January 2023

Objective:
The antihypertensive effect of oral semaglutide is apparently modest in published trials but it has not been explored in uncontrolled hypertensive patients. We sought to assess whether oral semaglutide may elicit a clinically relevant reduction of systolic blood pressure (SBP) in patients with type 2 diabetes (T2D), obesity and uncontrolled hypertension, and whether the attained SBP reduction is diluted by the previous antihypertensive treatment.

Design and Methods:
Retrospective analysis of the SBP and antihypertensive medication data were performed in consecutive patients with T2D and obesity who started therapy with oral semaglutide. Data were obtained from a baseline visit in which oral semaglutide was initiated, and a second visit after 3–4 months. Patients who initiated or changed antihypertensive medication simultaneously with oral semaglutide were excluded. Consent for anonymous analysis and reporting of data were obtained from all included subjects.

Results:
50 patients with T2D (by usual clinical criteria) and obesity (BMI < 30 kg/m2) were included; their age was 56 ± 11 years. 32 (64%) were female, and their diabetes duration was 6.9 ± 2.9 years. 41 (82%) of them were diagnosed with hypertension (sitting office SBP > 140 and/or taking antihypertensive drugs). Globally there was a significant but modest reduction in SBP (149.8 ± 11.7 to 146.7 ± 12.4 mmHg, p = 0.041, paired t-test), but this reduction was strongly correlated with the baseline SBP (Pearson's r 0.39, p < 0.001). In the Figure (A) the reductions in SBP for patients with controlled SBP (< 140 mmHg), stage 1 (SBP 140–159 mmHg), stage 2 (160–179 mmHg) and stage 3 hypertension (> 180 mmHg) are shown (p = 0.0056 for differences among SBP categories, one-way ANOVA). The Figure (B) also shows the reductions in SBP for patients taking 0, 1, 2 or > 3 different antihypertensive drugs, but there are no significant differences (p = 0.2312, one-way ANOVA). In the second visit the number of patients with SBP < 140 mmHg had increased from 19 (38%) to 25 (50%).

Conclusions:
Treatment with oral semaglutide in patients with T2D, obesity and uncontrolled hypertension elicits a clinically significant decrease in SBP, enough to bring about acceptable SBP control in a relevant fraction. As expected, the reduction in SBP was strongly dependent on the baseline SBP. Interestingly, this reduction does not seem to be diluted by the use of multiple antihypertensive drugs, suggesting that oral semaglutide could be considered as an add-on in patients with apparent resistant hypertension.
PS-C17-10: ORAL SEMAGLUTIDE REDUCES ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES, OBESITY AND HYPERTENSION, WITH PARTIAL DEPENDENCE ON BLOOD PRESSURE CONTROL
Authors: Martinez-Martin Francisco Javier , Kuzior Agnieszka , Hernandez-Lazaro Alba , de Leon-Durango Ricardo , Rios-Gomez Carlos , Santana-Ojeda Borja , Perez-Rivero Jennifer Maria , Fernandez-Trujillo-Comenge Paula Maria , Santana-Suarez Ana Delia , Gonzalez-Diaz Paula , Arnas-Leon Claudia , Acosta-Calero Carmen 
Published: January 2023

Objective:
GLP-1 receptor agonists reduce blood pressure (BP) and proteinuria in people living with type 2 diabetes (T2D) and obesity, but data on patients with uncontrolled hypertension are very scarce. Oral semaglutide showed interesting results in patients with moderate renal impairment in PIONEER 5, but their BP was well controlled, with SBP < 140 mmHg. We sought to assess the antiproteinuric effect of oral semaglutide in a group of patients with T2D, obesity and uncontrolled hypertension, and whether this effect is dependent on BP reduction.

Design and Methods:
Retrospective analysis of the data on SBP and albuminuria were performed in consecutive patients with T2D, obesity and uncontrolled hypertension (office sitting SBP < 140 mmHg) who started therapy with oral semaglutide. Data were obtained from a baseline visit in which oral semaglutide was initiated, and a second visit after 3–4 months. Mediation analyses with SBP reduction as mediator were performed post-hoc to quantify its relative contribution to albuminuria reduction. Patients who initiated or changed antihypertensive medication simultaneously with oral semaglutide were excluded. Consent was obtained from all included subjects.

Results:
Data were obtained from 33 patients, 21 (64%) were female, age 54.2 ± 11.9 years, diabetes duration 6.8 ± 2.7 years, baseline BMI 36.7 ± 5.2 kg/m2, baseline SBP 166 ± 12.2 mmHg, baseline eFGR (CKD-EPI) 58 ± 11.6 ml/min/1.73m2 and baseline albuminuria (geometric mean) 134 ± 125 mg/g Cr, with 16 patients (48.5%) having < 30 mg/g, 12 (36.4%) 30–300 mg/g and 5 (15.1%) > 300 mg/g. SBP reduction was 4.8 ± 2.1 mmHg (p = 0.012, paired t-test), albuminuria reduction was 36 ± 27 mg/g (-27%; p = 0.026, paired t-test), and eGFR change + 1.3 ± 1.6 mL/min/1.73m2 (not significant). There was a significant correlation between SBP and albuminuria reductions (Pearson's r: 0.26, p = 0.002). The mediation analyses showed that albuminuria reduction of 11 ± 10 mg/g (8.3%) was mediated by SBP reduction while 25 ± 14 mg/g (18.7%) was SBP-independent. 4 patients (12.1%) reduced their albuminuria to < 30 mg/g (Figure).

Conclusions:
In patients with T2D, obesity and uncontrolled hypertension, oral semaglutide significantly reduced SBP and albuminuria, without change in eGFR, and a relevant fraction of them (about 1/8) reduced albuminuria below the conventional normality threshold (< 30 mg/g). The decrease in albuminuria was only partially mediated by SBP reduction, suggesting additional mechanisms, possibly direct glomerular and/or tubular effects.
PS-C18-3: RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE ASSOCIATED WITH A LOWER RISK OF UNPLANNED DIALYSIS INITIATION
Authors: Nakayama Takashin , Morimoto Kohkichi , Uchiyama Kiyotaka , Kusahana Ei , Washida Naoki , Azegami Tatsuhiko , Kanda Takeshi , Yoshida Tadashi , Itoh Hiroshi 
Published: January 2023

Objective:
Unplanned dialysis initiation is associated with poor outcomes. Whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitors remains controversial. This study aimed to evaluate the effect of RAS inhibitors in patients with advanced CKD on the incidence of unplanned dialysis initiation. Furthermore, the association between RAS inhibitor therapy and the estimated glomerular filtration rate (eGFR) decline rate for 6 months before dialysis initiation was also investigated.

Design and method:
This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within six months of nephrology referral or after kidney transplant were excluded. Unplanned dialysis initiation was defined as urgent hospitalization for starting dialysis or unexpectedly starting dialysis in the hospital for any purpose other than dialysis initiation. Missing values were handled with multiple imputations.

Results:
Among 334 patients (median age 70.0 [interquartile range 59.0–79.0] years; 28.4% females), 186 (55.7%) and 148 (44.3%) had a planned and unplanned dialysis initiation, respectively. Overall, 144 patients (43.1%) did not use, 51 (15.3%) stopped, 136 (40.7%) continued, and 3 (0.9%) started RAS inhibitors for 6 months before dialysis initiation. Multivariate logistic regression revealed that use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.35; P < 0.01). Female sex (OR, 0.51; P < 0.05), use of potassium binders (OR, 0.25; P < 0.01), earlier referral to nephrology (OR, 0.45; P < 0.01), and earlier discussion of renal replacement therapy (OR, 0.35; P < 0.01) were also significantly associated with a lower incidence, whereas older age (OR, 1.25; P < 0.05), higher Charlson comorbidity index (OR, 1.34; P < 0.01) and faster decline in eGFR (OR, 1.29; P < 0.01) were associated with a higher risk of unplanned dialysis initiation. In multivariate linear regression to assess the rate of eGFR decline for 6 months before dialysis initiation, use of RAS inhibitors (β;, -4.2; P < 0.05) as well as older age (β;, -2.5; P < 0.01), higher geriatric nutritional risk index (β;, -2.9; P < 0.01) and use of bicarbonate (β;, -6.3; P < 0.01) was significantly associated with preserved kidney function.

Conclusions:
RAS inhibitor therapy in patients with advanced CKD was associated with a lower risk of unplanned dialysis initiation and preserved kidney function.
PS-C18-9: THE ASSOCIATION BETWEEN FRAILTY OR SARCOPENIA AND INTRADIALYTIC HYPOTENSION
Authors: Ozawa Moe , Hirawa Nobuhito , Haruna Aiko , Haze Tatsuya , Kawano Rina , Komiya Shiro , Ohki Yuki , Kobayashi Yusuke , Fujiwara Akira , Saka Sanae , Hanaoka Masaaki , Mitsuhashi Hiroshi , Yamaguchi Satoshi , Ohnishi Toshimasa , Tamura Kouichi 
Published: January 2023

Objective:
Recently, osteoporosis, sarcopenia, and frailty have become prognostic issues due to the increasing number and aging population of dialysis patients. Dialysis patients have high bone and muscle fragility due to their unique pathology, and we previously investigated the association between osteoporosis and muscle mass or strength in the cross-sectional study. We found that shorter calf circumference and weaker grip strength were associated with lower bone mineral density and the risk for osteoporosis among hemodialysis patients, independently of the management of chronic kidney disease-mineral and bone disorder, nutritional status, and dialysis adequacy. On the other hand, intradialytic hypotension is also one of the most common intradialytic complications, which can affect dialysis adequacy and prognosis. Although sarcopenia and frailty have been reported to cause orthostatic hypotension, the association between sarcopenia or frailty and intradialytic hypotension is not clear. Therefore, in this study, we examined the association between sarcopenia or frailty and intradialytic hypotension using our previous osteoporosis study.

Design and method:
This was a single-center cross-sectional study. We screened patients aged 20 years or older who underwent hemodialysis three times a week and selected 200 patients with a history of hemodialysis for at least 6 months for the study. Calf circumference, grip strength, and normal walking speed were measured to assess sarcopenia, and frailty was diagnosed based on the Japanese version of the Cardiovascular Health Study criteria. The behavioral characteristics and clinical history were obtained using a questionnaire and medical records. We analyzed the association between the frequency of intradialytic hypotension and frailty, or physical functions related to sarcopenia.

Results:
The final analysis included 121 subjects, mean age 66.1 ± 12.6 years, 28 women (23.1%). Mean calf circumference was 35.6 cm ± 3.8 cm, grip strength was 27.8 kg ± 9.6 kg, 26 (21.5%) were frail, 64 (52.9%) were prefrail, and 31 (25.6%) were robust. We are currently collecting and analyzing the data and will present our findings at the conference.

Conclusions:
We plan to present the relationship between intradialytic hypotension and frailty or physical function at the conference.
PS-C18-10: COVID 19 IMPAIRS ENDOTHELIAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE ON HEMODIALYSIS
Authors: Santos Juan Carlos , Lepera Rosa Mabel , Serra Rocio Fernandez , Lossi Susana , Alanoca Saul , Turoni Claudio Joo , de Bruno Maria Peral , Maranon Rodrigo Oscar 
Published: January 2023

Introduction:
Cardiovascular events are the leading cause of mortality in patients with chronic kidney disease on hemodialysis (CKD-HD). Recent evidence suggests that coronavirus-19 disease (COVID-19) would induce vascular endothelial function alterations to increase cardiovascular risk. However, whether COVID-19 contributes to endothelial dysfunction in patients with CKD-HD is unclear.

Objective:
To assess whether COVID-19 worsens endothelial function in a cohort of patients with chronic kidney disease on hemodialysis.

Materials and Methods:
Patients with chronic kidney disease on hemodialysis were divided into those without COVID-19 (CKD; n = 68) and mild COVID-19 (CKD-C19; n = 11, WHO criteria and PCR+). Informed consent was obtained. Systolic (SBP), diastolic (DBP) and mean (MAP) blood pressures, heart rate (HR), and endothelial function (EF) were evaluated for reactive hyperemia. It was determined dry weight, height, fat mass index (FMI), muscle mass index (MMI), and body mass index (BMI). Results were compared with normal people without CKD (Control = C, n = 10).

Results:
CKD and CKD-C19 presented a high SBP compared to the controls and without differences between them (C: 119 ± 3, n = 10 vs. CKD: 145 ± 2, n = 68 vs. CKD-C19: 143 ± 3 mmHg, n = 11; p < 0.05 vs. C). Patients CKD-C 19 presented greater endothelial dysfunction compared to CKD and the control group (EF: CKD-C19:2 ± 1, n = 11 vs CKD:4.5 ± 1, n = 28 vs. C:12.1 ± 1, n = 10; p < 0.05). In CKD and C-C19 an increase in BMI was observed in conjunction with an increase in fat mass, without differences in the muscle mass index between both groups (X2:p: NS). No association was observed between EF and BMI or IMG.

Conclusions:
The present study indicates that COVID-19 would aggravate endothelial dysfunction in patients with chronic kidney disease on hemodialysis. This would not be related to increased BMI or elevated blood pressure. However, more studies are needed to determine the role of COVID-19 on vascular function in this population.