bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3534 ASSOCIATION OF STOPPING RENIN–ANGIOTENSIN SYSTEM INHIBITORS DURING AN ACUTE KIDNEY INJURY EPISODE WITH CARDIOVASCULAR AND ALL-CAUSE MORTALITY
Authors: LI Yanqin , Nie Sheng , Xin Xu , Hou Fan Fan 
Published: June 2023

Abstract

Background and Aims
The management of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with ongoing acute kidney injury (AKI) during hospitalization is debated. This study is aimed to explore whether the use of ACEI or ARB (ACEI/ARB) during an AKI episode is associated with adverse clinical outcomes.

Method
This nationwide, retrospective cohort study included 10,559 patients aged 18–100 years who had a hospital-acquired AKI (HA-AKI) episode and who were using ACEI/ARB at the time of AKI detection during the hospitalization between January 1, 2000 and May 26, 2021 from 19 medical centers across China. The primary exposure was stopping or continuing the use of ACEI/ARB after HA-AKI detection during hospitalization. The primary outcome was all-cause mortality (30-day, 180-day, and in-hospital mortality) after HA-AKI. Secondary outcomes included cardiovascular death and new-onset chronic kidney disease (CKD). Propensity scores were used to construct a matched-pairs cohort of patients who stopped or continued the use of ACEI/ARB during the HA-AKI episode.

Results
This study included 10,559 adults (mean [standard deviation] age, 67.4 [14.4] years; 6,606 [62.6%] male). A total of 2,015 (19.1%) participants stopped the usage of ACEI/ARB within 1 day after AKI detection. Among 1,915 matched-pairs, compared with those continued the using of ACEI/ARB, stopping the use of ACEI/ARB was associated with lower risks of 30 day all-cause mortality (adjusted hazard ratio (aHR), 0.67; 95% confidence interval [CI], 0.51-0.87), 180 day all-cause mortality (aHR, 0.77; 95%CI, 0.63-0.94) and in-hospital all-cause mortality (aHR, 0.64; 95%CI, 0.46-0.87). Similar results were found between stopping the use of ACEI/ARB and the risks of 30-day cardiovascular death (aHR, 0.58; 95%CI, 0.49-0.69), 180-day cardiovascular death (aHR, 0.57; 95%CI, 0.36-0.90), in-hospital cardiovascular death (aHR, 0.41; 95%CI, 0.19-0.86), and new-onset CKD after discharge (aHR, 0.76; 95%CI, 0.61-0.96). These protective effects were consistent in multiple sensitivity analyses.

Conclusion
Our study for the first time demonstrates that stopping the use of ACEI/ARB during an AKI episode is associated with lower risks of mortality and new-onset CKD. These findings provide strong evidence for the recommendation of avoiding renin-angiotensin system inhibitors during AKI from clinical guidelines.
#3571 GROWTH PATTERNS IN PEDIATRIC KIDNEY TRANSPLANT RECIPIENTS: A RETROSPECTIVE SINGLE CENTER STUDY
Authors: Askiti Varvara , Malakasioti Georgia , Gole Evangelia , Mitsioni Andromachi 
Published: June 2023

Abstract

Background and Aims
Attainment of a normal adult height remains a great challenge in the care of children with end stage kidney disease. Moreover, the incidence of overweight and obesity increases post kidney transplantation (KT). We aimed to describe growth parameters and predictive factors in children post KT.

Method
We retrospectively reviewed the records of 28 children who underwent KT in our center between 2002-2022. Height (hSDS) and body mass index (BMISDS) z-scores at various time points and possible predictors were assessed.

Results
Median age at KT was 11.2 years (5.3-14), 20 were male, mean time on dialysis was 5.95 years. KT from a living donor (LRD) was performed in 18 patients. Mean follow-up time was 4.88 (1-10) years. rhGH was administered pre-KT in 15/28 patients and in 3 post KT. Following the first year post KT, steroid free, alternate day and daily steroid regimes were adopted for 9, 11 and 8 patients, respectively. Mean hSDS at the time of KT, one year after and at last visit were -1.76, -1.87, and -1.77 (p&gt;0.05). Mean BMISDS at the respective time points were 0.13, 0.65 and 0.05 respectively (p&gt;0.05). At last visit, 29% and 17% of children showed moderate and severe height deficit. hSDS at last visit was associated with preoperative hSDS, whereas difference between hSDS pre and last visit post KT (ΔhSDS) was associated with the type of KT [mean ΔhSDS for LRD and DDT -1.45 (95%CI -1.87, -1.03) and -2.66 (95%CI -3.4, -1.93) respectively, p = 0.002] and steroid regime [mean ΔhSDS for daily and alternate day steroid treatment -0.39 (95%CI -0.77, -0.003) and 0.55 (95%CI -0.07, 1.17) respectively, p = 0.037]. Τhere was no association between ΔhSDS and rejection episodes or rhGH administration pre-KT. At the time of KT and at last visit 25% and 10.7% were overweight, respectively, whereas only 1 patient was obese preoperatively but none at last visit. The overall incidence of overweight and obesity had reduced at last visit compared to pre-KT (p = 0.01).

Conclusion
Linear growth post KT remained limited, resulting in short stature in nearly half of children. Strategies to improve height post pediatric KT could include height optimization pre-KT, steroid withdrawal/avoidance protocols, and LRD KT.
#3581 ACSS2-INDUCED FATTY ACID SYNTHESIS PROMOTES NLRP3 INFLAMMASOME AND PYROPTOSIS OF RENAL TUBULAR CELLS IN SEPSIS-INDUCED ACUTE KIDNEY INJURY
Authors: Lu Jian , Jiang Chun-Ming 
Published: June 2023

Abstract

Background and Aims
Cellular fatty acid metabolism was supposed to be tightly associated with immune responses. Pyroptosis is a form of programmed cell death dependent on the NLRP3 inflammasome activation. Previous studies have revealed that acyl-CoA synthetase 2 (ACSS2) promoted fatty acid synthesis under metabolic stress. However, whether ACSS2-mediated fatty acid metabolism can regulate pyroptosis and inflammatory responses of renal tubular cells in AKI remain unclear.

Method
lipopolysaccharide (LPS) was intraperitoneally injected to establish the sepsis mouse model, and in vitro HK-2 cell culture model was achieved by LPS stimulation. HE and PAS staining were carried out to evaluate pathological injury of kidneys in mice. The renal tissue immunostaining was conducted to detect IL-1β expression and macrophage distribution in kidney tissues of mice. Gene expression of inflammatory factors was evaluated by real-time PCR. Western Blot was conducted to the activation of the NLRP3 pathway and pyroptosis in vivo and in vitro.

Results
Here, we demonstrated that the expression of ACSS2 was significantly increased in the renal epithelial cells of mice with Lipopolysaccharide (LPS)-induced AKI when compared to wild-type mice. ACSS2 regulates NLRP3-mediated caspase-1 activation and IL-1β production through the stimulation of fatty acid synthase (FASN) in renal epithelial cells. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model. Consistently, ACSS2-deficient mice displayed impaired FASN-mediated lipid synthesis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and decreased fatty acid synthesis through the downregulation of FASN. The treatment with the chemical inhibitor C75 suppressed NLRP3-mediated caspase-1 activation and pyroptosis of HK-2 cells under LPS treatment in renal tubular cells.

Conclusion
Our results suggested that ACSS2 regulated the NLRP3 inflammasome activation and pyroptosis by inducing the FASN-mediated fatty acid synthesis pathway in renal epithelial cells. These results identified ACSS2 as a potential therapeutic target in AKI.
#3595 DIALYSIS MODALITY AFFECTS SENESCENCE-RELATED PHENOTYPE OF T AND B LYMPHOCYTES
Authors: Lioulios Georgios , Fylaktou Asimina , Tourountzis Theodoros , Christodoulou Michalis , Moysidou Eleni , Giamalis Panagiotis , Tsouchnikas Ioannis , Papagianni Aikaterini , Stangou Maria 
Published: June 2023

Abstract

Background and Aims
Hemodiafiltration (HDF) is characterized by enhanced clearance of middle molecular weight toxins and therefore, it is considered superior to hemodialysis (HD), especially in higher hemofiltration volumes. Although proinflammatory cytokines are lower in HDF, its impact on immune phenotype has not been studied, so far. In this study we compared the lymphocytes’ senescent phenotype between HD and HDF patients.

Method
Senescent and exhausted related lymphocyte markers, including CD45RA, CCR7, CD28, CD57 and PD1 on T cells and CD27 and IgD on B cells, were assessed by flow cytometry in 35 ESRD patients on HD and 25 ESRD patients on HDF of similar age, sex, and ethnicity. Moreover, we evaluated the association of these markers with hemofiltration volume.

Results
Patients on HDF had significantly reduced CD4+CD28- T lymphocytes, 31(18-74) vs 50(36-131)cells/μL, respectively, p = 0.019, which was restricted only in the CD28-CD57- T cells compartment, [17(9-25) vs 31(19-50)cells/μL, p = 0,002], while terminally differentiated CD28-CD57+ did not differ between the two groups [14(4-49) vs 23(7-52)cells/μL, p = 0,22]. Expression of CD57 molecule on CD4+ T cells depended on dialysis vintage (r = 0.27, p = 0.03). Moreover, HDF patients had lower percentage of CD4+PD1+ exhausted T cells [8.5(6.8-11.7) vs 13.7(8.7-19.5) % for HDF and HD respectively, p = 0.006]. CD8+PD1+ T cells were also lower in HDF patients, without reaching statistical significance [17.4(8.5-41) vs 34(12,7-52.9) % for HDF and HD respectively, p = 0.06]. Hemofiltration volume was negatively correlated to effector memory CD8+ T cells re-expressing CD45RA count (CD8+ EMRA), (r = -0.46, p = 0.027) and positively correlated to total B cells count (r = 0.46, p = 0.025). However, not all B cell subsets were equally affected, with only naïve IgD+CD27- B cells and switched memory IgD-CD27+ B cells count showing positive correlation with hemofiltration volume (r = 0.53, p = 0.008 and r = 0.5, p = 0.015, respectively).

Conclusion
Hemodiafiltration and high filtration volumes may have beneficial effects on adaptive immunity, predisposing to less senescent and exhausted T and B cell phenotypes.
#3620 AGING-RELATED RENAL FIBROSIS WAS ALLEVIATED VIA CONSERVING MITOCHONDRIAL FUNCTION AND AUTOPHAGY IN NLRP3 KO MICE
Authors: Kim Yang-Gyun , Lee Sang-Ho , Moon Ju-Young , Jung Su Woong , Jeong Kyung Hwan , Hwang Hyeon Seok , Kim Jin Sug , Cho Minhae 
Published: June 2023

Abstract

Background and Aims
Nod-like receptor family, pyrin domain containing-3 (NLRP3) activation in kidney diseases contributes to aggravating disease progression and fibrosis. However, the role of NLRP3 in renal aging is not clear. This study was designed to identify whether the NLRP3 KO mice could be protected from renal aging.

Method
NLRP3 KO and counterpart wild-type (WT) mice were used at different ages (3 months, 12 months, and 24 months). Plasma, urine, and kidneys were collected.

Results
Plasma creatinine and blood urea nitrogen (BUN) increased with aging, while BUN was significantly decreased in NLRP3 KO old mice (24M) compared with WT old mice. NLRP3 ablation contributed to decreasing tubular vacuolization, tubulointerstitial fibrosis, and atypical autophagosomes with aging. In line with it, renal fibrosis markers, such as connective tissue growth factor, and fibronectin were alleviated in RT-PCR tests. Immunoblot results showed that autophagy with mitochondrial biogenesis increased in old NLRP3 KO mice. In addition, phosphorylated AMP-activated protein kinase and persoxisome proliferator-activated receptor gamma coactivator 1α were increased in old NLRP3 KO mice. Transcriptional expression data using kidney RNA bulk sequencing showed augmentation of autophagy and mitochondrial biogenesis in old NLRP3 KO mice.

Conclusion
NLRP3 absence prevented aging-related renal fibrosis via maintaining renal mitochondrial biogenesis and autophagy.
#3635 THERAPEUTIC STRATEGIES TARGETING RAGE IMPROVES RENAL OUTCOME IN LUPUS NEPHRITIS
Authors: Taguchi Kensei , Yokota Yunosuke , Kodama Gou , Itou Sakuya , Fukami Kei 
Published: June 2023

Abstract

Background and Aims
Lupus nephritis (LN) occurs in up to 60% of patients with systemic lupus erythematosus (SLE). Despite of current development of immunosuppressant agents, LN still impairs the survival and quality of life in SLE patients. Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that belongs to the immunoglobulin superfamily, which is strongly associated with innate immune system. In the present study, we examined whether RAGE is involved in the development of LN. Further, we explored the therapeutic impact of DNA-aptamer directed against RAGE on lupus-related kidney injury.

Method
[Protocol 1] RAGE expression in kidneys and urinary RAGE excretion (uRAGE) were determined at 8, 12, 16, 18, 20-week-old by real-time PCR and ELISA, respectively in MRL/lpr, SLE-prone mice. [Protocol 2] LN was induced by peritoneally injecting pristane in wild type and RAGE globally knockout mice. [Protocol 3] MRL/lpr mice were subcutaneously administrated with DNA-aptamer raised against RAGE (RAGE-apt) or Control-aptamer (Ctrl-apt) for 10weeks.

Results
[Protocol 1] uRAGE, but not urinary protein excretion, was increased in 8-week-old MRL/lpr mice when compared to that of the control of MRL/MPJ mice. uRAGE is positively correlated with urinary NAG, a tubular injury marker, suggesting that uRAGE can predict the onset and the progression of LN. Immunofluorescence staining demonstrated that RAGE was upregulated in distal tubules but not in glomerulus in early stage, meanwhile RAGE started to be extensively expressed in nephron at late stage of LN. Not only tubules, but RAGE was also found in infiltrated macrophages in glomerulus. In proximal tubules (PTC), RAGE was co-localized with cathepsine D, a lysosomal aspartyl protease, and Rab7, a marker of late endocytosis, suggesting that PTC RAGE is involved in endosome-related protein degradation. [Protocol 2] Pristane-induced the increase in systolic blood pressure was reduced with improvement of renal dysfunction in RAGE knockouts. RAGE knockouts also showed less fibrosis with the decrease in macrophage infiltration when compared to wild type mice in pristane-induced lupus nephritis. [Protocol 3] Similar to RAGE knockouts, administration of RAGE-apt reduced systolic blood pressure and attenuated the renal dysfunction. RAGE-apt also ameliorated mesangial expansion, crescent formation, and macrophage infiltration into glomerulus in MRL/lpr mice. The level of pro-inflammatory cytokines gene expression including IL-6, TNF-a, and MCP-1 was reduced by RAGE-apt, but not Ctrl-apt, in MRL/lpr mice.

Conclusion
RAGE could be involved in the pathogenesis of LN, and RAGE-DNA aptamer might be one of the promising therapeutic strategies for preventing the development of LN.
#3650 LINACLOTIDE IS PROTECTIVE AGAINST RENAL ISCHEMIA-REPERFUSION INJURY
Authors: Hitaka Yukihiro , Nakamura Kimihiko , Isoyama Naohito , Shiraishi Koji 
Published: June 2023

Abstract

Background and Aims
Renal ischemia-reperfusion injury is associated with delayed graft function and poor long-term graft survival following transplantation. Linaclotide is a guanylate cyclase C (GC-C) receptor agonist that increases intracellular cGMP concentrations and promotes intestinal transport capacity by activating the GC-C receptor. Since CKD is a deficiency of cGMP in the kidney, increasing cGMP in the kidney by linaclotide would suppress fibrosis, protecting the kidney.

Method
An AKI rat model of unilateral nephrectomy plus contralateral ischaemia (30 min) and impaired reperfusion (up to 14 days) was used. Linaclotide was administered before and after surgery for 2 weeks, and blood and renal tissue samples were collected to determine its effect on renal function and whether it was protective against the progression of CKD.

Results
In the I/R injury+ group, creatinine levels were lower in the linaclotide-treated group than in the non-treated group. Sirius red staining showed significant improvement in fibrosis. The hydroxyproline content of kidneys was determined by the basic hydroxyproline method. RNA seq showed that genes down-regulated in I/R injury+ were the oxidative stress markers SOD3 and Gpx1. The expression of genes down-regulated in I/R injury+ was up-regulated to a degree similar to that in I/R injury- by treatment with linaclotide. These data suggest that linaclotide may ameliorate renal fibrosis by suppressing renal dysfunction through its antioxidant effects.

Conclusion
The antioxidant effect of linaclotide was found to suppress the decrease in renal function caused by I/R. We would like to apply this finding to human renal transplantation in the future to prevent renal function deterioration due to I/R.
#3654 ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION LOWERS INCIDENCES OF DE NOVO DONOR-SPECIFIC ANTIBODIES AND CHRONIC ANTIBODY-MEDIATED REJECTION
Authors: Weidmann Lukas , Lopez Kai Castrezana , Schmid Nicolas , Mueller Thomas , Schachtner Thomas 
Published: June 2023

Abstract

Background and Aims
ABO-incompatible kidney transplantation has been associated with an increased risk for antibody-mediated rejection (ABMR) and early graft loss attributable to isoagglutinins. Its impact on the development of de novo donor-specific HLA antibodies (DSA) and DSA-induced chronic ABMR, however, remains less well studied.

Method
We analyzed 297 kidney transplant recipients (KTRs) who underwent living donor transplantation at the University Hospital Zurich from 2009 to 2021. 58 ABO-incompatible (iABO) KTRs were compared to 239 ABO-compatible (cABO) KTRs concerning the development of de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). ABO desensitization was performed using rituximab and antigen-specific immunoadsorption. The HLA-derived epitope-mismatches were calculated per HLA-locus and in total using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm. High-resolution re-typing was performed from protocol kidney allograft biopsies if necessary.

Results
The incidence of TCMR/ABMR in the first post-transplant year was comparable between iABO KTRs (19%) and cABO KTRs (13%; p = 0.207). De novo DSA were detected in only 1 of 58 iABO KTRs but 12 of 239 cABO KTRs in the first post-transplant year and 2 of 58 iABO KTRs but 50 of 239 cABO KTRs in the long-term follow-up (p = 0.001). ABMR was diagnosed in only 1 of 58 iABO KTRs but 28 of 239 cABO KTRs after the first post-transplant year (p = 0.021). iABO kidney transplantation decreased the risk of de novo DSA development (HR 7.222, CI 1.755-29.722, p = 0.006) and ABMR (HR 7.362, CI 1.000-54.239; p = 0.050) after the first-post-transplant year independent from the presence of preformed DSA. Total PIRCHE-II scores and PIRCHE-II scores per locus were not associated with the development of de novo DSA in all 297 living-donor KTRs (p&gt;0.05).

Conclusion
Our findings suggest that iABO kidney transplantation is associated with a lower incidence of de novo DSA and ABMR in the long term, independent from the HLA-derived epitope mismatch load. Whether this protective effect offers new therapeutic options against kidney allograft injury needs to be investigated in future studies.
#3706 EFFECT OF CHOLECALCIFEROL INTAKE ON NOVEL INFLAMMATORY INDICATORS IN HEMODIALYSIS PATIENTS
Authors: Ghazy Mona Alshahawey , Elwakeel Lamia , Sabri Nagwa , Said Tamer El , Maher Radwa 
Published: June 2023

Abstract

Background and Aims
Hemodialysis patients (HD) are in a chronic state of systemic inflammation, with vast majority of these patients are vitamin D deficient. Vitamin D appears to be a strong controller of inflammation. It's well known that C-reactive protein (CRP) is considered the gold of inflammatory markers. Recently, neutrophil- to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be inexpensive, readily available indicators of systemic inflammation. This study is to demonstrate the pleotropic effects, the efficacy and the safety of two dosing regimens of cholecalciferol; (weekly regimen vs monthly regimen) on novel inflammatory indicators in HD population.

Method
A prospective, randomized trial was carried out to evaluate the effect of weekly versus, monthly oral cholecalciferol, on vitamin D (25(OH)D) levels, on inflammatory markers and secondary hyperparathyroidism in HD patients. Fifty eligible HD patients were randomly assigned to either Group A (Once weekly oral 50.000IU Cholecalciferol) or Group B (One monthly, oral 200.000IU Cholecalciferol), for 3 months’ period. Serum levels of high sensitive CRP (hsCRP), NLR, PLR, were all assessed at baseline and at the end of the study.

Results
Cholecalciferol significantly increased serum levels of 25(OH)D in both groups. A significant decrease in serum hsCRP levels (p &lt;0.001) and NLR was noted only in Group A. No significant difference in calcium or phosphorus levels was noticed. No side effects or adverse events were reported.

Conclusion
Weekly (50.000 IU) oral cholecalciferol appears to have a beneficial action on replenishing 25(OH)D levels in HD patients, with an ameliorative action on inflammatory status as well. NLR seems to be an effective, non-expensive inflammatory indicator in HD.
#3746 RISK OF PROGRESSIVE CHRONIC KIDNEY DISEASE WITH NEPHROSCLEROSIS ON KIDNEY BIOPSY DEFINED USING AGE-BASED VERSUS YOUNG ADULT-BASED THRESHOLDS
Authors: Asghar Muhammad , Denic Aleksandar , Mullan Aidan , Alexander Mariam , Rule Andrew 
Published: June 2023

Abstract

Background and Aims
The tissue pathology of both aging and chronic kidney disease (CKD) is nephrosclerosis defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA). We sought to determine if risk of CKD outcomes is better predicted by age-based or young adult-based thresholds for nephrosclerosis.

Method
Using the Aging Kidney Anatomy study, living kidney donors, kidney tumor patients, and native kidney disease patients had kidney biopsy images analyzed morphometric to quantify %GSG, %IFTA, and IFTA foci density (Figure 1). Using normotensive donors, young (18-29 y) thresholds and age-based (18-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70+y) 95th percentile thresholds were defined. Progressive CKD was defined as a 40% decline in serum creatinine based estimated GFR or kidney failure (dialysis or transplantation) from a 4-month post-biopsy baseline (due to the nephrectomy event in tumor patients and due to the common occurrence of acute kidney injury in the native kidney disease patients at the time of biopsy). The age-adjusted risk of progressive CKD in tumor patients and native kidney disease patients was compared between those with nephrosclerosis that was “normal compared to young”, “normal for age but abnormal compared to young”, and “abnormal for age” (Figure 2).

Results
There were 2583 normotensive living kidney donors, 1363 tumor patients, and 314 native kidney disease patients studied. The 95th percentiles for 18-29y to 70+y age groups among normotensive donors were 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm2 for IFTA foci density. The risk of CKD outcomes did not differ between tumor patients and native kidney disease patients with nephrosclerosis “normal compared to young” versus “abnormal compared to young but normal for age” in both cohorts. Thus, these two categories were combined into “normal for age”. The risk of progressive CKD over a median 5.5 years follow-up for tumor patients was higher with %GSG, %IFTA, and IFTA foci density that was abnormal for age vs normal for age (HRs 2.28, 2.41, and 3.11, respectively, p&lt;.0001 for all). The risk of progressive CKD over a median 7.2 years follow-up for native kidney disease patients was higher with %GSG, %IFTA, and IFTA density that was abnormal for age vs normal for age (HRs 1.87, 2.65, and 3.11, respectively, p&lt;.0001 for all).

Conclusion
There is a substantial increase in nephrosclerosis from aging alone in healthy adults that is not prognostic for CKD outcomes. Age-based thresholds better identify clinically relevant CKD.