bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5216 DIALYSIS MODALITIES, URAEMIC TOXINS AND MICROINFLAMMATION: CAN WE DO MORE?
Authors: López Raquel Ojeda , Pavón Fátima Guerrero , López-López Isabel , Peregrín Cayetana Moyano , Carmona Andres , Martin-Malo Alejandro , Soriano Sagrario 
Published: June 2023

Abstract

Background
Patients on hemodialysis (HD) have a high morbidity and mortality from cardiovascular disease (CVD). Despite advances in HD -new membranes, such as medium cut-off (MCO) or techniques that combine diffusion+convection+adsorption such as hemofiltration with ultrafiltrate regeneration- (HFR)-, only online hemodiafiltration (OL-HDF) has been shown to improve survival in these patients. It is important to investigate whether the new HD filters/techniques help to improve the clearance of uremic toxins that are difficult to eliminate (those bound to proteins) and molecules associated with microinflammation in uremic patients, due to the important role they play in the development of CVD.

Aim
To study whether different HD membrane-techniques improve the clearance of uremic toxins and/or parameters associated with the microinflammation present in these patients.

Method
12 stable patients on HD were included, with a minimum time on HD of 3 months. Each patient underwent 4 random HD sessions in which only the dialysis membrane and/or the modality were changed. They underwent an HD session with a high-flux polyphenylene membrane, another session with this same filter in OL-HDF, another with MCO membrane, and another with HFR-H. All sessions were held in a short period. In all of them, pre- and post-dialysis blood samples were taken to assess the clearance of both conventional uremic toxins and protein-bound toxins (indoxyl-sultate and p-cresol), as well as molecules associated with the microinflammation process (proinflammatory monocytes: CD14+/CD16++ and proinflammatory cytokines).

Results
When evaluating the effect of the different HD techniques on the percentage of proinflammatory monocytes, a relevant, although not significant, decrease was observed in the OL-HDF and HFR-H techniques. Likewise, when evaluating the profile of markers of inflammatory activity, such as IL-12B, IL-17C, CD8A or TNFRSF9, a significant decrease was observed after the dialysis session in HFR-H compared to the rest of the techniques analyzed.

Conclusion
After analyzing the results of our study, the HD technique that combines convection+adsorption+diffusion (with a novelty high permeability filter), HFR-H, is the only one that has shown significantly greater clearance of proinflammatory cytokines, as well as a greater elimination of activated monocytes and protein-bound toxins, although without reaching statistical significance. These results, although preliminary, are promising and open up a new line of research to improve CVD in HD patients.
#5217 PROTOCOL AND PRELIMINARY RESULTS OF DAPAGLIFLOZIN IN INACTIVE LUPUS NEPHRITIS CROSS-OVER RANDOMIZED TRIAL
Authors: Vajgel Gisele , Filho Carlos Miranda , Oliveira Camila , Costa Denise Maria , Cavalcante Maria Alina , Junior Braziliano Silva , Lima Camilla , Sandrin-Garcia Paula , Valente Lucila 
Published: June 2023

Abstract

Background and Aims
Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) with and without type 2 diabetes. Lupus nephritis (LN) patients under immunosuppression were excluded from the most important trials with SGLT2 inhibitors. Thus, efficacy and tolerance of these drugs are unknown in such patients. The present trial will assess the effect of Dapagliflozin in patients with inactive Lupus Nephritis with residual proteinuria.

Method
For this cross-over randomized trial, we will include adult patients with LN class III, IV (+/-V) without active nephritis but with proteinuria &gt; 500mg/24h or UPC &gt; 200mg/g and eGFR ≥ 20ml/min, in the maintenance treatment. RAAS inhibition should be stable for at least four weeks before the randomization. We will exclude patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI&gt;2), use of induction therapy in the last 12 months (Cyclophosphamide, Mycophenolate Mofetil &gt;2 g/day and Calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we will exclude patients with recurrent urinary infections (&gt;3 times/year). They will be randomized to receive Dapagliflozin 10mg on top of standard of care therapy or not. After 24 weeks the groups will be switched and those without Dapagliflozin will receive it for the next 24 weeks. Primary endpoint will be reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints will include sustained reduction of eGFR &gt; 30%; changes in weight and blood pressure compared to baseline; and number of infections on Dapagliflozin treatment versus exclusive standard of care therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05).

Results
From 85 screened class III, IV (+/- V) LN patients under maintenance therapy, we excluded 65 due to active nephritis, low proteinuria or low eGFR. Until now we included 17 patients that were randomized 1:1 to start the treatment with Dapagliflozin on top of standard care or remain with the usual therapy for 24 weeks. Patients’ baseline characteristics are described in Table 1. All patients randomized were using Mycophenolate Mofetil ≤2 g/day and RAAS inhibition and 14 of them were receiving Hydroxychloroquine.

Conclusion
We expect that the present trial will determine whether the SGLT2 inhibitor Dapagliflozin, added to LN maintenance therapy, could safely reduce the residual proteinuria of inactive LN patients.
#5267 INITIAL EMERGENCY ROOM 6-HOUR URINE VOLUME IS AN IMPORTANT FACTOR FOR THE SURVIVAL OF CRITICALLY ILL PATIENTS UNDERGOING CRRT
Authors: Choi Dae Eun , Park Heyrim , Lee Eu Jin , Ham Young Rok , Kim Hae Ri , Na Ki Ryang , Hwang Yunkyeong , Park Heewon , Lee Kang Wook , Jeon Jae Wan , Shin Jin Ah , Jeong Jin Young 
Published: June 2023

Abstract

Background and Aims
It has been little known whether initial emergency room factors affect survival or renal function in critically ill patients undergoing continuous renal replacement therapy. We examined whether initial factors in ER impact survival and renal recovery in critically ill patients undergoing continuous renal replacement therapy.

Method
The study was a single-center, retrospective study of 332 patients for critically ill patients admitted to ICUs for continuous renal replacement therapy via emergency room from March 1, 2018 to May 31, 2021. Clinical parameters including urine output, eGFR, and serum NGAL were identified. The primary outcomes were the 30-day and 90-day mortality. Secondary outcomes were the 30-, and 90-day dialysis-free duration.

Results
Low urine output (LUO, defined as &lt; 0.5 mL/kg/hr x 6 hours) group was significantly associated with 30-day mortality and 90-day mortality. Multivariable Cox regression analysis showed that LUO group was significantly more associated with the increased risk of 30-day mortality and 90-day mortality (hazard ratio, 1.935 and 2.141, respectively) compared to high urine output (HUO, defined as ≥ 0.5 mL/kg/hr x 6 hours) group. There was no significant association between 30-day or 90-day mortality and initial estimated glomerular filtration rate (eGFR) plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. In critically ill patients undergoing continuous renal replacement therapy, HUO group and initial eGFR ≥ 30 ml/min/1.73m2 groups was associated with decreased 30-, and 90-day dialysis-free duration. However, serum NGAL had no significant relation with 30-, and 90-days RRT free durations.

Conclusion
During admission to emergency room, the initial low urine output is an important factor for 30-day and 90-day mortality in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.
#5277 THE EVALUATION OF FLUID VOLUME AND PROGNOSIS IN HEMODIALYSIS PATIENTS UTILIZING PLASMA HUMAN ATRIAL NATRIURETIC PEPTIDE
Authors: Suzuki Yuya , Otsuka Tadashi , Yoshioka Yuki , Iida Tomomichi , Watanabe Hirofumi , Kaseda Ryohei , Yamamoto Suguru , Kaneko Yoshikatsu , Goto Shin , Aoyagi Ryuzi , Narita Ichiei 
Published: June 2023

Abstract

Background and Aims
Volume overload leads to the development of heart failure, which contributes to the high mortality in patients on hemodialysis. The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied.

Method
We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP.

Results
Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06–11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P &lt; 0.001, respectively). Analysis of echocardiography data showed that the presence of reduced left ventricular ejection fraction and left ventricular diastolic disfunction were significantly associated with high plasma hANP levels. However, the threshold hANP level (100 pg/mL) remained independently associated with hospitalization due to AHF after adjusting for cardiac disfunctions in the multivariable model.

Conclusion
The hANP level is indicative of both fluid volume and cardiac dysfunction. In clinical practice, we suggest utilizing hANP as an easily accessible measure to identify high-risk patients for developing AHF initially. If the hANP level exceeds 100 mg/dL, we propose to perform echocardiography and consider reducing the DW. In clinical practice, the plasma hANP level could serve as a valuable indicator for assessing the risk of developing AHF and managing fluid volume.
#5289 INTRARENAL RENIN-ANGIOTENSIN SYSTEM ACTIVATION ALTERS RELATIONSHIP BETWEEN SYSTOLIC BLOOD PRESSURE AND PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Kang Dong Hoon , Park Cheol Ho , Kim Hyung Woo , Park Jung Tak , Chang Tae-Ik , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok 
Published: June 2023

Abstract

Background and Aims
Elevated blood pressure (BP) and intrarenal renin-angiotensin system (RAS) activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between BP and intrarenal RAS activity on the risk of CKD progression is unknown.

Method
We analyzed 2,076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic BP (SBP). The urinary angiotensinogen-to-creatinine (u-AGT/Cr) ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy.

Results
During 10,550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and u-AGT/Cr ratio on the risk of the primary outcome (P-for-interaction = 0.019). In patients with u-AGT/Cr &lt;3.65 μg/gCr, the hazard ratios (HRs) (95% confidence intervals [CIs]) for SBP 120–129, 130–139, and ≥140 mmHg were 1.47 (1.08-2.01), 1.74 (1.26-2.39), and 2.43 (1.76-3.37), respectively, compared with SBP &lt;120 mmHg. In addition, each 10 mmHg increase in SBP was associated with an 18% higher risk of CKD progression. Moreover, there was a greater decline in the estimated glomerular filtration rate among the higher SBP categories. However, these associations were not observed in patients with u-AGT/Cr ≥3.65 μg/gCr.

Conclusion
Urinary angiotensinogen levels may modify the association between SBP and adverse kidney outcomes.
#5322 RENAL AEROBIC GLYCOLYSIS AND LOCAL LACTATE PRODUCTION IN AKI
Authors: LI Jiaying , Shi Xiaoxiao , Chen Zhixin , Xu Jiatong , Chen Limeng 
Published: June 2023

Abstract

Background and Aims
Kidney is a high energy-consuming organ depending on fatty acid β-oxidation (FAO) to fulfil energy supply. During various biological stresses in AKI, FAO shuts down, and the aerobic glycolysis is enhanced. In this study, we aimed to investigate the effect of aerobic glycolysis and local lactate production in AKI.

Methods & Results
A maleic acid (MA) induced AKI model (MA-AKI) was established by MA intraperitoneally (i.p.) in C57BL/6J mice and sacrificed after 24h. The renal function in MA-AKI mice was damaged, accompanied by proximal tubular injury and mitochondrial dysfunction. RNA sequencing revealed a relative increase in glycolytic enzymes (HK1, PKM and PFKP) mRNA levels in the AKI phase. The protein level of glycolysis-related enzymes was also elevated with increased urinary lactate significantly (0.25±0.10 versus 8.60±0.74 mmol/L, P&lt;0.0001) in MA-AKI. Furthermore, glycolysis inhibitor 2-DG was administrated after 2h of MA injection, which improved the renal function (indicated by decreased serum creatinine (Scr), 33.52±2.78 versus 57.15±4.81 μmol/L, P&lt;0.001), proximal tubular histopathological injuries and mitochondrial dysfunction in MA-AKI. Mechanistically, we observed a significant positive correlation between the Scr and urinary lactate levels (R2 = 0.78, P &lt; 0.0001). In order to examine the role of lactate in AKI, the mice were pretreated with oxamate, an inhibitor of lactate dehydrogenase A (LDHA), and the level of Scr (59.18±5.83 versus 28.82±3.41 μmol/L, P&lt;0.0001) was mitigated, with the reduction of urinary lactate (8.60±0.74 versus 4.90±0.98 mmol/L, P&lt;0.01).

Conclusion
Our study demonstrated that inhibition of aerobic glycolysis to protect kidney function in MA-AKI might be via reducing lactate accumulation.
#5333 IMPROVING AUTOPHAGY FLUX BY TFEB ACTIVATION WITH CERIA NANOPARTICLES ATTENUATED CHRONIC KIDNEY INJURY IN CELLULAR AND ANIMAL MODELS OF FABRY DISEASE
Authors: Yun Sung-Ro , Hwang Won-Min , Yoon Kuk Ro , Park Yohan , Lee Ji-Won , Kim Eun Kyung , Yoon Se-Hee 
Published: June 2023

Abstract

Background and Aims
Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid–polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We accessed the action mechanisms of PEG-CZNPs in autophagy regulation and checked the effect on chronic kidney injury in cellular and animal models of FD.

Method
PEG-CZNPs were synthesized using a non-hydrolytic sol-gel reaction method. HK-2 cells were transfected with α-galactosidase A (α-GLA) shRNA for permanent cellular model of FD. For in-vivo study 4-week-old male B6;129-Glatm1Kul/J mice were treated for 48 weeks with 10mg/kg of PEG-CZNPs twice per week via intraperitoneal injection. PCR, immunoblotting, immunoflouresce assay, electron microscopy analysis, ICP-MS, biochemical and histological analysis were done

Results
TFEB tanslocated to the nucleus by treatment with PEG-CZNPs. Autophagy flux was evaluated with chloroquine. Autophagy flux was enhanced by PEG-CZNPs treatment. To show whether TFEB plays the important role in autophagy flux, we transfected HK-2 cells with siTFEB. Autophagy flux significantly decreased after knockdown of TFEB with PEG-CZNPs treatment. We next assessed upper signaling pathway of TFEB by PEG-CZNPs. TFEB dephosphorylation was independent of both mTOR and ERK but GSK3ß signaling pathway showed massive impact on TFEB dephosphoryation by PEG-CZNPs. PEG-CZNPs decrease intracellular globotriaosyceramide (Gb3) accumulation and decreased the levels of Collagen type IV, αSMA and MMP9 expression in cellular model of FD. Gb3 levels were significantly reduced in the kidney tissues and the levels of Fibronectin, Collagen type 4 and αSMA was decreased by PEG-CZNPs in animal model of FD.

Conclusion
These results suggested PEG-CZNPs promote autophagy flux through GSK3ß -TFEB signaling pathways, showed the beneficial effect on renal fibrosis in cellular and animal models of FD. It thus provided a new insights of the potential therapeutics on FD.
#5341 EFFECTS OF URIC ACID-LOWERING THERAPY ON RENAL OUTCOMES IN CKD PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Luo Yuxin , Song Qirong , Fu Sha , Wang Honglei , Shao Xiaofei , Chen Junzhe , Tang Ying 
Published: June 2023

Abstract

Background and Aims
It is well known that hyperuricemia and gout play an important role in the adverse cardiovascular and renal events both in patients with and without renal disease. However, the effect of uric acid-lowering therapy (ULT) on renal outcomes of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, our study summarized reliable results draw from published randomized controlled trials (RCTs) to evaluate the effects of ULT on renal and cardiovascular outcomes in CKD patients with asymptomatic hyperuricemia.

Method
Pubmed, EMBASE, China National Knowledge Internet (CNKI) and the Cochrane Library were searched systematically for trials up to October 2021. RCTs assessing the effects of uric acid-lowering agents on renal and/or cardiovascular outcomes in CKD patients complicated with asymptomatic hyperuricemia were included. Both the fixed-effect and the random-effect models were used.

Results
A total of 17 RCTs (one trial1 divided patients into two groups according to CKD stages). including CKD patients with asymptomatic hyperuricemia were included in this meta-analysis. Compared with placebo or no treatment group, ULT group showed a higher estimated glomerular filtration rate (eGFR) with a weighted mean difference (WMD) of 3.679 mL/min/1.73 m2, 95%CI [1.592, 5.766] (p = 0.001) and a lower serum creatinine (Scr) with a WMD of -46.131umol/L, 95% CI [-65.643, -26.619] (p&lt;0.0001). Subgroup analysis demonstrated a significant benefit from ULT in patients with CKD stage 1-3 (p = 0.035), from Asian countries (p = 0.005) and those younger than 60 years (p = 0.002). At the same time, ULT was associated with lower incidence of events of doubling of Scr without dialysis (relative risk (RR) 0.314[0.203, 0.485] (p&lt; 0.0001)). However, no difference was found for all-cause mortality, incidence of AKI, progression to end-stage kidney disease (ESKD), and cardiovascular events. In addition, ULT with allopurinol was associated with lower cardiovascular events (RR 0.678[0.473, 0.971] (p = 0.034)).

Conclusion
ULT could slow down the progression of renal impairment in CKD patients complicated with asymptomatic hyperuricemia, especially for patients under 60 years old, early CKD stage(1-3) and the Asian descent.
#5342 ASSOCIATION BETWEEN LONGITUDINAL GFR TRAJECTORIES AND BMD DECLINE RATE IN PATIENTS WITH CKD STAGE 2­–4
Authors: Kang Dong Hoon , Kim Hyung Woo , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Yoo Tae-Hyun 
Published: June 2023

Abstract

Background and Aims
Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD). However, there are few studies regarding BMD decline rates in CKD population. In this study, we investigated whether BMD decline rate is associated with baseline estimated glomerular filtration rate (eGFR) and further evaluated with longitudinal eGFR trajectories.

Method
A prospective cohort study of 1,006 patients with CKD stages 2 through 4 who enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and year 4. Estimated GFR was measured 2–5 times during 4 years of follow-up. Mixed linear regression model was used for the longitudinal analysis and trajectory analysis was performed using semiparametric group-based modeling using maximum likelihood.

Results
Declined renal function was associated with increased rate of decline in total hip BMD (Stage 2: −0.23, Stage 3A: −0.39, Stage 3B: −0.80, Stage 4: −1.20 in men; −0.86, −1.19, −1.20, −1.58% change/year respectively in women). Trajectory analysis revealed two distinct trajectories of eGFR for each CKD Stages 2 through 4: Class 1, stable group; Class 2, rapid decline group. Trajectory group that represented rapid eGFR decline showed consistent trends of increased rate of decline in total hip BMD. There was significant difference between stable and rapid decline group in Stage 3A, 3B (Stage 3A: −0.18 vs. −0.67 [p = 0.009], Stage 3B: −0.36 vs. −1.10 [p = 0.031] in men; Stage 3A: −0.79 vs. −1.67 [p = 0.006], Stage 3B: −0.60 vs. −1.52% change/year [p = 0.001] in women; p for interaction).

Conclusion
Declined renal function and faster GFR decline is associated with rapid BMD decline in CKD stage 2–4.
#5348 THE EFFECTS OF RITUXIMAB IN NON-HCV-RELATED MIXED CRYOGLOBULINEMIC VASCULITIS
Authors: Guarino Annalisa , Caruso Nunziante , Geraci Giovanni , Longo Roberta , Amore Giorgio , Rabajoli Gianluca , Fenoglio Roberta , Sciascia Savino , Roccatello Dario 
Published: June 2023

Abstract

Background and Aims
Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking.

Method
This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome

Results
The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p &lt; 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p &lt; 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively.

Conclusion
In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.