bluuebunny/crossref_metadata_2025_split huggingface dataset:
#6465 MIR-451B AND CHRONIC KIDNEY DISEASE: A NOVEL TARGET TO MODULATE RENAL VEGF SIGNALING
Authors: Chade Alejandro , Sitz Rhys , Eirin Alfonso 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is a progressive disorder that affects over 15% of adults worldwide. A major component of CKD pathophysiology is renal microvascular rarefaction and loss that pairs the progression of the disease and complications. We developed a translational swine model of CKD and showed that loss of renal function associates with a significant decrease in renal vascular endothelial growth factor (VEGF) signaling and progressive microvascular (MV) rarefaction. VEGF is a key endogenous cytokine for MV proliferation and repair, but underlying mechanisms of renal VEGF downregulation in CKD are unknown. We hypothesized that micro-RNA (miRNA)-mediated processes contribute to the downregulation of renal VEGF signaling in CKD.

Method
Unbiased renal micro-RNA (miRNA)-seq was performed in a swine model of CKD stage 3 (14 weeks of bilateral renal artery stenosis + atherogenic diet) and normal controls (n = 5/group). Micro-RNAs up- (&gt;1.4 FC, p&lt;0.05) and down-regulated (&lt;0.7 FC, p&lt;0.05) were identified, followed by target prediction analysis (miRwalk 3.0, Target Scan 7.2). Renal gene and protein expression of VEGF was measured by qPCR and western blot, respectively, and renal MV architecture was studied by 3D micro-CT.

Results
Unbiased miRNA-seq and target prediction analysis identified four miRs upregulated in the kidney of CKD pigs vs. controls, of which miR-451b (validated by qPCR), broadly conserved among species, was capable of targeting VEGFA (FC = 4.46, p = 0.04). Renal gene and protein expression of VEGF was downregulated in CKD vs. controls, associated with significant cortical and medullary microvascular rarefaction (Figure 1).

Conclusion
Our data suggest that post-transcriptional modulation of renal VEGF signaling may serve as a prominent mechanism of VEGF downregulation, which leads to MV rarefaction and disease progression in CKD. Furthermore, this work in progress identified a novel candidate (miR-451b) and may set the stage for its targeted modulation to preserve VEGF signaling as a potential strategy to protect the renal microvasculature in CKD.
#6566 A STUDY OF CLINICAL PRESENTATION AND OUTCOME OF COVID 19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Parry Manzoor , Alam Shahzad 
Published: June 2023

Abstract

Background and Aims
Novel coronavirus 19 (coronavirus disease-19 [COVID-19]) disproportionately affects patients with various kidney diseases. Patients with kidney transplant are at higher risk of complications of COVID-19 infection. Our aim of this analysis was to study the clinical profile and outcome of COVID-19 infections in KTRs from Kashmir.

Method
Here we present a cohort study of 122 KTRs with polymerase chain reaction-confirmed COVID-19 positivity from March 31, 2020 to October 31, 2022. We detailed demographics, immunosuppression regimen, clinical profile, Covid 19 vaccination status, treatment given, and outcomes (acute kidney injury, graft failure and death) of our study population.

Results
Median age of the patients was 41 years and median age of disease was 2.9 years after transplant. Most common comorbidities included hypertension (65.6%) and diabetes (35.3%); presenting symptoms at the time of COVID-19 included fever (82.7%) and breathlessness (66.4%). Covid-19 vaccination was given to 81 patients (66.4%) with two doses in 26 patients and 55 patients received one dose. Clinical severity ranged from asymptomatic (4.1%), mild (36.1%), and moderate (28.7%), to severe (31.1%). Acute kidney injury developed in 46.7% of patients and mortality in 21 patients. Risk factors for mortality included higher age, severe disease, allograft dysfunction before COVID-19 infection, Obesity, acute kidney injury, absence of covid-19 vaccination (Table 1). At 3 months of follow-up, loss of graft function was seen in 19 patients of survivors.

Conclusion
Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients. Risk factors for mortality included higher age, severe disease, allograft dysfunction before COVID-19 infection, Obesity, acute kidney injury, absence of covid-19 vaccination.
#6573 ASSOCIATION BETWEEN SERUM TOTAL PROTEIN-TO-ALBUMIN RATIO AND PROGNOSIS IN SEPTIC ACUTE KIDNEY INJURY PATIENTS
Authors: Yin Ting , Wei Wei , Huang Xiaorong , Zhao Yuliang , Fu Ping , MA Liang 
Published: June 2023

Abstract

Background and Aims
Sepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as inflammation- and nutrition-based prognostic score. The purpose of this study was to assess the effect of TAR on predicting the clinical outcomes of septic AKI patients.

Method
A retrospective study between August 2015 and August 2021 was performed at West China Hospital of Sichuan University. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI.

Results
A total of 309 eligible patients with a median age of 58 years were enrolled. Among the patients, 70.2% were males. In multivariate analysis, after adjustments for age, sex, and other confounding factors, higher baseline TAR was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95% CI 1.18–3.09, P = 0.008; HR 1.54, 95% CI 1.01-2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. We found no relationship between TAR and secondary outcomes. The Youden index of TAR was larger than total protein or albumin alone in predicting both 30-day and 90-day all-cause mortality.

Conclusion
Increased TAR is an independent predictor for 30-day and 90-day all-cause mortality in septic AKI patients. The predictive performance of TAR outperformed those of total protein and albumin. Further research is needed to corroborate our findings in other cohorts and to compare the predictive ability of baseline TAR and the change in TAR under treatments.
#6600 ASSOCIATION BETWEEN ADVANCED GLYCATION END-PRODUCTS AND SARCOPENIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Molinari Paolo , Caldiroli Lara , Vettoretti Simone 
Published: June 2023

Abstract

Background and Aims
In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD patients.

Method
We enrolled 117 patients. The AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. As for the sarcopenia definition, we used the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria.

Results
The average age was 80 ± 11 years, 70% were males, and the mean eGFR was 25 + 11 mL/min/1.73 m2. Sarcopenia was diagnosed in 26 patients (with a prevalence of 22%). The sarcopenic patients had higher levels of circulating AGEs (3405 ± 951 vs. 2912 ± 722 A.U., p = 0.005). AGEs were higher in subjects with a lower midarm muscle circumference (MAMC) (3322 ± 919 vs. 2883 ± 700 A.U., respectively; p = 0.005) and were directly correlated with the gait test time (r = 0.180, p = 0.049). The total sRAGE and its different isoforms (esRAGE and cRAGE) did not differ in patients with or without sarcopenia.

Conclusion
In older CKD patients, AGEs, but not sRAGE, are associated with the presence of sarcopenia. Therefore, AGEs may contribute to the complex pathophysiology leading to the development of sarcopenia in CKD patients.
#6635 ARNT AND ALK3 MEDIATE RENO PROTECTION AFTER ISCHEMIC PRECONDITIONING
Authors: Rapp Gregor Christof , Zeisberg Michael , Nyamsuren Gunsmaa 
Published: June 2023

Abstract

Background and Aims
Ischemia and following hypoxia are a common cause of acute kidney injury (AKI). Strategies for prevention and treatment of AKI are limited. In several animal models, ischemic preconditioning (IPC) has been established as an effective intervention to prevent ischemic organ injury. An IPC protocol of ischemia and reperfusion mediates organ protection for a few hours. This first phase of organ protection is followed by a second, protective phase occurring after 24–48 h. The second phase, named second window of protection (SWOP), persists for 3–4 d. Mechanisms and transcriptional mediators during SWOP are mostly unknown. The aim of the underlying study was to investigate effectors and target genes during SWOP and to identify a potential pharmacological therapeutic target.

Method
6–8-week-old C57BL/6 mice were undergoing an IPC intervention; five minutes of renal sinistra artery ischemia was followed by five minutes of reperfusion. This cycle was performed five times. Mice were sacrificed 2, 4, 8, 12, 25, 48, 72 h after IPC. Two additional groups of mice were pharmacologically preconditioned for 48 h with low dose FK506 and small molecule GPI1046. Analysis of murine kidneys were performed by SDS-Page and Western blot.

Results
The first phase after IPC (2–4 h) was characterized by an increasing expression of hypoxia inducible factor-1α (HIF1α); 48 h after intervention a significant increase of expression of aryl hydrocarbon receptor nuclear translocator (ARNT) and consecutive activin receptor-like kinase 3 (ALK3) was observed. Comparable induction of ARNT and ALK3 expression was obtained by pharmacological preconditioning with FK506 or GPI1046.

Conclusion
Affected by hypoxia, HIF1α activates transcriptional upregulation of ARNT 48 h after IPC. The increasing expression of ARNT, follows an increased ARNT homodimerization. ARNT homodimer binds to the palindromic E-box 5′-CACGTG-3′ of the proximal ALK3 promoter. By this it induces the expression of the renoprotective ALK3 during SWOP. The organ-protective effects of constitutively expressed ARNT during SWOP can be mimicked pharmacologically by administration of FK506 or GPI1046 and may be used as a future therapeutic target.
#6641 BONE MATERIAL STRENGTH INDEX AND DUAL ENERGY X-RAY ABSORPTIOMETRY IN EVALUATION OF BONE HEALTH IN AUTOSOMAL POLYCYSTIC KIDNEY DISEASE
Authors: Jankowska Magdalena , Wiśniewski Piotr , Evenepoel Pieter , Lindholm Bengt , Debska-Slizien Alicja , Stenvinkel Peter , Haarhaus Mathias Loberg 
Published: June 2023

Abstract

Background and Aims
Bone material strength measured with the use of impact microindentation technique (OsteoProbe®) has emerged recently as potentially beneficial tool in evaluating bone quality in metabolic bone disorders. Patients with autosomal polycystic kidney disease (ADPKD) carry an increased risk of skeletal complications, both due to deficiency of polycystins and development of chronic kidney disease-mineral bone disorder (CKD-MBD). In our preliminary study, we found that bone material strength index (BMSi) associated with bone mineral density (BMD) measured with the use of dual energy X-ray absorptiometry (DXA) in chronic kidney disese patients (CKD). The aim of the present study was to find if the same applies to patients with ADPKD. We evaluated bone health by measuring BMSi and performing DXA in patients with ADPKD.

Method
BMSi was measured (OsteoProbe®, Active Life Scientific, USA) in 64 adult patients (37 men, mean age 43 years) with ADPKD in CKD stages G1-4. The measurement of BMSi compared the resistance to impact of microindentation in bone and reference material. After applying local anaesthesia, we impacted the cortical bone in the midshaft tibia in 10 different points. BMD was measured using Hologic Discovery Wi densitometer in multiple sites: lumbar spine, hip, 1/3 distal non-dominant forearm and whole-body. Trabecular bone score (TBS) was calculated using Medimaps TBS iNsight software.

Results
Mean values of BMSi, TBS and BMD are presented in the Table 1. BMSi in ADPKD patients was lower than average value observed in healthy individuals (85 men and 80 women). A positive linear relationship between BMSi and BMD was found in all of the examined sites with the highest standardized regression coefficient for 1/3 distal forearm (R2 = 0.315, beta = 0.57, p &lt; 0.001) and weakest for lumbar spine (R2 = 0.003, beta = 0.33, p = 0.003). There was no association between BMSi and TBS.

Conclusion
This is the first report on BMSi in ADPKD patients. In agreement with the notion of a distinct bone phenotype in ADPKD, we observed a median bone material strength index in patients with ADPKD that was lower than the reference value. BMSi associated with BMD, but not with TBS. However, the association with BMD overall is weak, with BMD explaining only 3 to 31% of the variability of BMSi. This observation suggests complementarity and warrants additional studies investigating whether BMSi associates with hard bone endpoints, independent of BMD.
#6690 THE ASSOCIATION BETWEEN SERUM CHEMERIN AND PERITONEAL MEMBRANE TRANSPORT FUNCTION IN INCIDENT PERITONEAL DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY
Authors: Zang Zhiyun , Wu Xiaofang , Xia Xiaoxiao , Li Zi 
Published: June 2023

Abstract

Background and Aims
Some biomarkers in drained dialysate or peritoneal membrane have been found related to the dialysate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays roles in inflammation, adipogenesis and metabolism. In this study, we intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients.

Method
This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test (PET) after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay (ELISA). The patients’ CVDs were recorded during the follow-up period.

Results
151 eligible patients with a mean age of 46.59±13.52 years were enrolled. And the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was found to be positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (HDL) (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 vs 27.37 ng/mL, p = 0.000). And there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (&lt;29.09 ng/mL) (42% vs 21%, p = 0.009).

Conclusion
Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of peritoneal membrane. And serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.
#6697 HIGHER PRO-INFLAMMATORY CYTOKINES IL-6 AND IFN-γ ARE ASSOCIATED WITH A HIGHER SEROCONVERSION RATE AGAINST SARS-COV-2 VIRUS SPIKE PROTEIN
Authors: Prasad Narayan , Yadav Brijesh 
Published: June 2023

Abstract

Background and Aims
Maintenance of Immunosuppressive regimen in renal transplant recipients (RTR), leads to a decreased immunogenic response to SARS-CoV-2 infection and vaccination than in the general population. In contrast, healthy people with SARS-CoV-2 infection often developed neutralizing antibodies and secrete copious quantities of cytokines leading to virus clearance and sometimes more severe immune-related complications. Associations of cytokines with seroconversion rate in immunocompromised renal transplant recipients are not clear. Therefore, in this study, we have determined the association of cytokines with seroconversion.

Method
In this study, 210 living-related RTRs who either acquired SARS-CoV-2 infection or were vaccinated with two doses of vaccine against SARS-CoV-2.Thirty-five healthy controls, who were non-vaccinated and had no anti-SARS-CoV-2 spike protein-specific antibodies, were also included as controls. Cytokines IL-6, IFN-γ, TGF-β, and IL-10 were measured using the enzyme-linked immunosorbent assay, and SARS-CoV-2 spike protein-specific IgG titer by chemiluminescent microparticle immunoassay methods.

Results
We found a seroconversion rate of 115/132 (87.12%), with a median antibody titer of 706.40 au/ml (IQR, 215.45-1844.42) in the infection group and 63/78 (80.76%) with a median titer 1454.20 (IQR, 80.52-3838.75) au/ml in the vaccinated group. The IL-6, IFN-γ, TGF-β, and IL-10 levels were significantly higher in both, the infection and vaccination groups as compared to the healthy control Fig. 1A-D. In the infection group, the proinflammatory cytokines IL-6 (55.41±24.30 vs. 31.64±16.98 pg/ml; p&lt;0.001); IFN-γ (91.21±33.09 vs. 61.69±33.28 pg/ml; p = 0.001), were significantly high in the seroconverter group as compared to non-seroconverter. Anti-inflammatory cytokines TGF-β (730.48±400.47 vs. 765.47±366.39 pg/ml; p = 0.92), and IL-10 (91.31±48.54 vs. 96.73±59.53 pg/ml; p = 0.88) were not significantly different between the seroconverter and non-seroconverter group respectively. Similarly, in the vaccination group, the pro-inflammatory cytokines IL-6 (50.31±25.67 vs. 30.00±11.19 pg/ml; p = 0.002), and IFN-γ (65.70±39.78 vs. 32.14±17.48 pg/ml; p = 0.001) were significantly high in seroconverter post-vaccination compared to non-seroconverter. In contrast, TGF-β (820.96±415.78 vs. 1045.57±204.66; p = 0.046) was elevated in non-seroconverter, and although IL-10 (93.18±35.45 vs. 112.90±59.61 pg/ml; p = 0.11) was not significantly high in non-converter.

Conclusion
Inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination.
#6792 VASCULAR ACCESS SURVIVAL OUTCOME IN ELDERLY HEMODIALYSIS PATIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: Surattichaiyakul Bongkod 
Published: June 2023

Abstract

Background and Aims
Elderly hemodialysis patients usually have lower life patency of vascular access than another age-group. Our center, elderly patients are the most of population of hemodialysis patients. Prior to initiate hemodialysis, planning of first vascular access has been established by patients, nephrologist, and vascular surgeon. The canulation technique for arteriovenous fistula (AVFs) has been determined by experienced hemodialysis-nurse and patient preferences. The aim of this study was to analyze the survival outcome of the access depending on the vascular type in the elderly.

Method
The study was collected retrospective data between Jan 1, 2013, and December 31,2022. We identified elderly patient (age ≥65) who initiate in-center hemodialysis and first-use vascular access in our center, including arteriovenous fistulas, graft, tunnel-catheter. Outcomes were vascular access patency and subgroup analysis for non-extreme elderly group and extreme (age ≥80) elderly group. A χ2 test, Kaplan-Meier analysis were performed.

Results
Overall number of elderly patients who initiated hemodialysis are 170: 63 AVFs-first (74% buttonhole cannulation technique), 21 grafts-first and 86 for tunnel-catheters. Mean survival of vascular accesses are higher in AVFs group (78 months in AVFs, 52.5 months in grafts, 53.3 months in tunnel-catheter P = 0.012). The outcome was consistency in the subgroup age 65-80 (80.9 months in AVFs, 47.3 months in grafts, 47.2 months in tunnel-catheter P = 0.005). However, mean vascular access survival did not differ in subgroup age &gt;80 (56.3 months in AVFs, 58.4 months in grafts, 56.4 months in tunnel-catheter P = 0.98).

Conclusion
In our single center data, vascular access patency of elderly patients was highest in AVFs-first group and AVFs should be the first choice for elderly patients who would initiate hemodialysis especially non-extreme elderly group.
#6817 ROLE OF THE CGAS-STING PATHWAY IN THE PROGRESSION OF DIABETIC NEPHROPATHY
Authors: Khedr Sherif , Palygin Oleg , Staruschenko Alexander 
Published: June 2023

Abstract

Background and Aims
Diabetic kidney disease (DKD) is the leading cause of chronic renal pathology. Understanding the molecular underpinnings of DKD is critical to designing tailored therapeutic approaches. We have demonstrated previously that type 2 diabetic nephropathy (T2DN) rats develop renal and physiological abnormalities similar to clinical observations in humans with DKD, indicating these rats are an excellent model for studying the progression of renal injury in type 2 DKD [1]. Furthermore, our recent studies revealed sexual dimorphism in this model, indicating that while both male and female T2DN rats developed non-obese DKD phenotype, females had significant protection from the development of severe forms of glomerular and tubular damage [2]. The potential role of the cyclic GMP-AMP synthase (cGAS) / Stimulator of interferon genes (STING) pathway in renal inflammation and fibrosis was also uncovered [3]. Here we focused on sex differences in DKD and the potential mechanisms leading to the progression of DKD.

Method
To explore the sexual dimorphisms in the development of DKD, we utilized young (12-week-old) and aged (&gt;48 weeks old) type 2 diabetic nephropathy (T2DN) rats. To delineate transcriptional changes, RNA-Seq analysis was performed in the kidney cortex of T2DN rats of both sexes at a younger and older age. Western blotting, immunohistochemistry, and flow cytometry analyses were further used to identify specific pathways contributing to sexual dimorphism and disease progression in T2DN rats.

Results
We have revealed that the cGAS/STING signaling pathway is upregulated in T2DN rats compared to non-diabetic Wistar rats and in type 2 diabetic human kidneys. The expression of key proteins in the cGAS-STING pathway, such as cGAS, STING, phospho-IRF, mtTFA, and TREX1, was significantly different between male and female T2DN rats and following the progression of DKD. Proinflammatory genes were also upregulated in male T2DN rats compared to female rats of the same age, and their levels were further elevated in aged rats. RNA-Seq analysis also identified significant changes in genes participating in the cGAS-STING inflammatory pathway. Flow cytometry revealed a significantly greater number of infiltrating leukocytes in the male kidneys compared to their age-matched females. Moreover, the leukocytic count was significantly higher in old males versus young males, while it was almost the same in females of different ages. Approximately 50% of the renal leukocytic population was monocytes/macrophages (CD11b/c+), with fewer CD3+ T cells, both CD3+CD4+ T helper and CD3+CD8+ cytotoxic T cells, and CD45R+ B cells.

Conclusion
Our study provides critical insights into the sexual dimorphism and progression of DKD and identifies the cGAS-STING pathway as an essential contributor to disease development.