bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3759 URINARY DCR2/CR LEVEL PREDICTS RENAL OUTCOME IN PATIENTS WITH ACUTE KIDNEY INJURY
Authors: Yi Xiangling , Chen Kehong , Luo Jia , Chen Jia , He Yani 
Published: June 2023

Abstract

Background and Aims
Acute kidney injury (AKI) is a well-recognized complication of critical illness which increases the risk of morbidity and mortality. It has been reported that about 30% of AKI patients developed to chronic kidney disease (CKD), and even to end-stage renal disease (ESRD). It is urgent to explore novel biomarkers to evaluation the renal outcome of AKI. Decoy receptor 2 (DcR2), a senescent marker, is expressed specifically in senescent tubular epithelia. And urinary DcR2 (uDcR2) is associated with renal fibrosis in chronic kidney disease. The aim of study is to investigate the association of urine DcR2 with renal outcome of AKI.

Method
153 biopsy-proven AKI patients were included from Daping Hospital, Army Medical University from January 2018 to October 2022. A composite renal endpoint included creatinine more than 50% higher than the baseline or ESRD after 90 days. All patients were divided into positive endpoints (n = 75) and negative endpoints (n = 78). The clinical characteristics were collected, and the pathological injury was scored. uDcR2 levels were measured using enzyme-linked immunosorbent assay and normalized to urinary cre (uDcR2/Cr). The correlation of uDcR2/Cr levels with renal function and renal pathological scores were analyzed. The logistic regression analysis was used to investigate the association of uDcR2/Cr with endpoint positive, after adjustment for probable causes of both exposure and outcome. The association of uDcR2/Cr with the composite renal endpoint using Kaplan-Meier curves were calculated.

Results
The level of uDcR2/Cr was positively correlated with cystatin C, and negatively correlated with estimated glomerular filtration rate (eGFR). And uDcR2/Cr was positively associated with renal pathological acute scores. Univariate logistic regression results increase the risk factors for poor kidney prognosis are age, female, with hypertension or (and) CKD, eGFR, Cystine C and uDcR2/Cr. Multivariate logistic regression analysis showed that the effect of uDcR2/Cr on renal outcome was statistically significant. After a median follow-up of 16 months, 75 participants achieve endpoint and there were 16 patients with end-stage renal disease. The ROC curve was used to analyze the value of uDcR2/Cr for predicting kidney prognosis in AKI with an area under the curve of 0.72 and the cut-off value of 365ng/g Cr. The median time from at the time of AKI to endpoint in the uDcR2/Cr≥365ng/g Cr group (7.6 months) was significantly shorter compared to the uDcR2/Cr&lt;365ng/g Cr group (36.6 months).

Conclusion
Urinary DcR2/Cr is closely associated to kidney injury and renal prognosis of AKI, suggesting that uDcR2/Cr could sever as a novel biomarker for predicting adverse outcomes in patients with AKI.
#3768 CDYL IS A THERAPEUTIC TARGET FOR ACUTE KIDNEY INJURY BY REGULATION PYROPTOSIS
Authors: Xiang Ting , LI Lingzhi , Yiting Wu , Fu Ping , MA Liang 
Published: June 2023

Abstract

Background and Aims
Pyroptosis as a necrosis type related to inflammation, is involved in various diseases, including acute kidney injury (AKI). Here, we report that Chromodomain Y-like (CDYL) is critical for pyroptosis regulation in AKI.

Method
Cisplatin-induced mouse model and cisplatin-induced TCMK-1 cell model of AKI were established, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured to evaluate kidney function, and renal tissue lesions were observed by HE staining. The expression of gene/protein in relation to inflammation and pyroptosis were measured by qPCR and western blot. The CDYL was overexpression in mice by rapid injection of a volume of naked plasmid DNA solution (30 ug) through the tail vein 2 hours before intraperitoneal injection of cisplatin.

Results
The results indicate that CDYL was increased in cisplatin-induced and sepsis-induced AKI, and overexpression of CDYL in mice would significantly increase the expressions of NGAL, NLRP3, Caspase-1, GSDMD, IL-1β, MCP-1, TNFα and IL-6 (Fig. 1). RNA-seq shown that the genes were mainly enriched in fatty acid metabolic process when CDYL overexpression, and FABP4 was finally identified as the key downstream factor (Fig. 2). Overexpression of CDYL in cisplatin-induced AKI further aggravated renal injury compared with the model mice, as indicated by the increased inflammation and pyroptosis protein expression, and worse tissue architecture, while the knockout of FABP4 will attenuate the injury (Fig. 3). In addition, treatment with CDYL inhibitors could attenuate inflammation and pyroptosis in cisplatin-induced renal injury (Fig. 4) and cisplatin-stimulated TCMK-1 cells (Fig. 5).

Conclusion
CDYL played a role in inflammation and pyroptosis regulation in AKI. Inhibition of CDYL could suppress renal inflammatory response and pyroptosis, and improve kidney function via modulation of FABP4 expression. The results highlighted that CDYL might represent a potential therapeutic target against AKI.
#3829 ARTERIAL STIFFNESS AND METABOLIC SYNDROME INDICES IN RENAL TRANSPLANTATION PATIENTS
Authors: Guliyev Orkhan , Mamedzade Ayten , Ismayilova Shalala , Jabrayilov Jabrayil 
Published: June 2023

Abstract

Background and Aims
Although renal transplantation improves survival, cardiovascular morbidity and mortality still remain as a significant problem compared with nonrenal populations. In end stage renal disease metabolic cardiovascular risk factors such as hypertension, hyperuricemia, obesity and diabetes mellitus have been confirmed to be positively correlated with arterial stiffness. Arterial stiffness is an important characteristic of the arterial wall and can be assessed noninvasively by the measurement of carotid-femoral pulse wave velocity (PWv). The aim of this study is to evaluate the risk factors for arterial stiffness in kidney transplant recipients.

Method
One hundred and forty nine kidney transplant recipients from our renal transplant outpatient clinic were enrolled into the study. All patients were evaluated for their standard clinical (age, gender, duration of hemodialysis, post-transplant time), biochemical parameters. Anthropometric and body composition analyses were performed for all patients. Body compositions were analyzed by using the Body Composition Analyzer (Tanita BC- 420MA). PWv was determined from pressure tracing over carotid and femoral arteries using the SphygmoCor system.

Results
Patients were divided into two groups according to PWv levels. The frequency of patients with PWv ≥ 7 m/s was higher in patients with new onset diabetes (55.9%), hyperuricemia (uric acid level type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical"&gt; 7 mg/dl) (p:0.029, 0.05). Higher carotid-femoral PWv was significantly related with systolic (p:0.003) and diastolic blood pressure (p:0.002), uric acid (p:0.0001) and fasting glucose (p: 0.02) levels. According to body composition analyses, muscle mass, visceral fat ratio and body weight were significantly higher in patients with PWv ≥ 7 m/s (p &lt; 0.005). In patients with high PWv, sagittal abdominal diameters and waist circumferences were significantly higher than patients with PWv &lt; 7 m/s. When criteria for metabolic syndrome were assessed there were a significant increase in pulse wave velocity in patients with 0-1; 2-3; and 4-5criteria (p &lt; 0.01).

Conclusion
In post transplantation period, metabolic syndrome indices as high blood pressure, hyperuricemia, hyperglycemia and increased waist and hip circumferences are closely related with arterial stiffness. For cardiovascular risk reduction after renal transplantation; blood pressure, serum glucose and uric acid levels should be under strict control.
#3831 TRIMER FORMATION ASSAY SUCCESSFULLY EVALUATES THE EFFECTS OF COL4A VARIANTS IN FSGS PATIENTS
Authors: Isaranuwatchai Suramath , Sratongjoung Wannika , Ingrungruanglert Praewphan , Chanakul Ankanee , Suphapeetiporn Kanya , Praditpornsilpa Kearkiat , Israsena Nipan 
Published: June 2023

Abstract

Background and Aims
Variants in COL4A3, COL4A4 and COL4A5 genes were the most common variants associated with focal segmental glomerulosclerosis (FSGS). Split-luciferase-based trimer formation assay of α345 collagen is a technique that test collagen structure formation by transfect COL4A3/4/5 plasmids into cells. This method was recently used to successfully determine the pathogenicity of variants in COL4A5 gene in Alport syndrome patients. We used the trimer formation assay to evaluate the variants found in our FSGS patients and correlate with genomic variants of COL4A gene.

Method
We transfected wild-type COL4A3-SmBiT, COL4A4-LgBiT and COL4A5 plasmids into human embryonic kidney cells. In wild-type plasmids, α345 collagen will be formed, then SmBiT and LgBiT will properly fuse, and luminescence will be measured (Figure 1A). We selected the pathogenic and likely pathogenic variants in three FSGS patients from our FSGS cohort, which are two missense variants in COL4A4 (c.1805G&gt;A, p.Gly602Glu and c.2752G&gt;A, p.Gly918Arg), and a deletion in COL4A4, leading to frameshift and premature stop codon (c.905delG, p.Gly302ValfsTer32). We also used COL4A4, c.2906C&gt;G, p.Ser969Ter and COL4A4, c.1396G&gt;A, p.Gly466Arg as nonsense and missense mutation negative controls, respectively. We did the mutagenesis in COL4A4-LgBiT plasmid and repeat the steps as in wild-type plasmids. If the variants caused abnormal protein structure, SmBiT and LgBiT will not properly fuse, and luminescence will be measured less than wild-type (Figure 1B).

Results
The luminescence of nonsense control and missense control were at 22.50% and 23.58% of relative light unit (RLU) from cells expressing wild-type, respectively. The luminescences of cells expressing mutated plasmid were at 33.68%, 30.94% and 19.74% of RLU from cells expressing wide type for c.905delG, c.1805G&gt;A and c.2752G&gt;A, respectively. (Figure 1C) The lower luminescence means cells with mutated plasmids produced less normal α345 collagen than cells with wild-type plasmids. The results confirmed that these three variants could really cause abnormal α345 collagen in cell model.

Conclusion
This is the first study to demonstrate that split-luciferase-based trimer formation assay of α345 collagen can be used as a functional study to evaluate the effect of COL4A3/4/5 variants in FSGS.
#3862 TGF-β1/ SMAD SIGNALLING IN ANCA ASSOCIATED GLOMERULONEPHRITIS
Authors: Chalkia Aglaia , Gakiopoulou Harikleia , Bora Margarita , Aggelis George , Vasilopoulos Dimitrios , Petras Dimitrios 
Published: June 2023

Abstract

Background and Aims
The transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine, with distinct roles both in fibrosis and inflammation and acts through the Smad signalling in renal injury. We sought the expression of TGF-β1/Smad signalling in ANCA associated glomerulonephritis (AAGN) and we assessed this expression in correlation with the renal injury at diagnosis as well as the renal progression.

Method
We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semi-quantitatively and quantitatively using computerized image analysis program in different compartments of 11 renal biopsies with AAGN and the results were statistically analysed with clinicopathological parameters. We also used healthy controls and disease controls with other types of Glomerulonephritis (GN).

Results
The expression of TGF-β1, pSmad3 and Smad7 were higher in AAGN, compared to healthy controls and other types of GN. The glomerular pSmad3 presented preferable expression at mesangial and endothelial cells and its intensity was correlated with higher chronicity index [global glomerulosclerosis (p&lt;0.001) and interstitial fibrosis (p = 0.03)] (Figure 1). We also reported that the intensity of Smad7 was correlated with higher activity index [cellular crescents (p = 0.03), and fibroid necrosis (p&lt;0.001)] (Figure 2). TGF-β1 expressed at peritubular capillaries around the areas of tubulitis and its expression was correlated with more severe renal injury at diagnosis [higher creatinine (p = 0.019) and proteinuria (p = 0.008)]. At last follow-up (median time 5 years) we reported a significant worst renal function with higher intensity pSmad3 (p = 0.05) and TGF-β1 (p = 0.005), while the expression of Smad7 tended to be beneficial in the maintenance of eGFR (p = 0.055).

Conclusion
The TGF-β1/Smad signalling is activated in AAGN and its expression is correlated with renal injury both at diagnosis and renal progression.
#3932 INSULIN RESISTANCE IN PEDIATRIC CKD PATIENTS
Authors: Sallam Dina E 
Published: June 2023

Abstract

Background and Aims
Pediatric chronic kidney disease (CKD) is associated with disturbance of glucose metabolism & insulin receptor sensitivity leading to impaired glucose tolerance & insulin resistance (IR), which are potential risk factors for cardiovascular disease (CVD). Hyperinsulinemia and IR are not extensively investigated in children with CKD, especially in different stages of CKD. The aim of our study was to detect hyperinsulinemia & IR in pediatric CKD patients.

Method
A total of 87 children and adolescents; 58 with chronic kidney disease (CKD); (29 CKD stage 2-4, pre-dialysis group & 29 CKD stage 5 on regular hemodialysis, CKD5d group) & 29 age & gender matched controls were enrolled in the current cross-sectional study. Homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin & glucose, where IR was considered if HOMA-IR was 4.39.

Results
Fasting insulin & glucose hadn't significantly changed between CKD patients & controls (p = 0.7, 0.3 respectively), while IR represented by HOMA-IR was found in a total of 11 (12.6%) CKD patients (6, 6.89% CKD5d & 5, 5.74% CKD 2-4) with no significant difference between pre-dialysis & dialysis groups (p&gt;0.05), while it was significant with controls (p = 0.039), meanwhile, the total means of HOMA-IR between were no statistically significant between all CKD patients & (p = 0.64). HOMA-IR correlated positively to dialysis durations (p = &lt;0.001, &lt;0.001 respectively), but hadn't changed with BMI.

Conclusion
Pre-dialysis & dialysis CKD pediatric patients are at a high risk of IR & hence CVD. CKD & dialysis durations are independent risk factors for IR.
#3935 AUDIOLOGICAL ASSESSMENT IN PEDIATRIC CKD PATIENTS
Authors: Sallam Dina E 
Published: June 2023

Abstract

Background and Aims
Many similarities exist between the nephron & ear infrastructures, making them vulnerable to same risk factors. Idiopathic sensory neural hearing loss is frequent in pediatric patients with chronic kidney disease (CKD). Our aims were to determine the prevalence, type, & degree of hearing impairment in pediatric CKD patients.

Method
This cross-sectional study was carried out at pediatric dialysis & nephrology unit at Children's hospital & Audiology unit, Faculty of Medicine Ain Shams University, included 45 CKD patients’ stage 2-4, 45 CKD patients’ stage 5 on hemodialysis, & 90 children as controls. Detailed history, physical, otological examinations & audiological assessment by standard pure tone audiometry, speech audiometry & tympanometry, IQ test, in addition to some laboratory investigations were done for all our studied patients.

Results
The mean IQ was significantly lower in CKD patients than the controls, however, it was significantly higher in dialysis than non-dialysis groups (p = 0.05). Pure tone audiometry showed 16.6% of out CKD patients had hearing loss, which was mainly sensory neural (SNHL); (53.3%), that was significantly higher compared to the control group (p &lt; 0.001). A mild degree of high-frequency hearing loss was frequently reported. These findings weren't significantly different between dialysis & non-dialysis patients, but were significant compared to control group (P&lt;0.001). Regarding speech discrimination scores, controls had a higher significant change compared to CKD patients. Regarding Tympanometry test results, most of CKD patients & the controls had normal middle ear pressure. The most determining factor affecting the hearing loss in our patients was the IQ.

Conclusion
High-frequency SNHL is not uncommon in CKD pediatric patients, in addition to low IQ. It's recommended to do a routine audiological evaluation & follow up for early diagnosis & intervention.
#3999 PROTEINURIA AND PROGRESSION OF IGA NEPHROPATHY. HAVE WE REACHED THE POINT OF NO RETURN?
Authors: Echeverri Carolina Isabel Movilla , Gómez Cristina Andrades , Arellano Macarena Naranjo , Garcelán Carmen Alarcón , Cárdenas Fátima Cazalla , Chaves Virginia Cabello , Mendoza Manuel López , Couñago Inmaculada Gómez , Batalha Paula , Valdivia Miguel Ángel Pérez 
Published: June 2023

Abstract

Background and Aims
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, associated with an incidence of 2.5/100.000 cases per year and progression to end-stage kidney disease (ESKD) in 20% patients within 10 years. Proteinuria has been identified as the greatest risk factor for ESKD in IgAN. The aim was to evaluate the correlation between proteinuria and major adverse renal events (MARE). We define MARE as 40% decline in glomerular filtration rate (eGFR), initiation of kidney replacement therapy (either dialysis or kidney transplantation) or death whether from renal cause or cardiovascular-related.

Method
In this retrospective observational single-center study, we included all biopsy-proven IgAN patients older than 18 years with proteinuria &gt;500 mg/24h, diagnosed between 2006-2017 and followed up to January 2022. Clinical, analytical, and histological findings were collected at time of diagnosis and during follow-up. Uni and multivariable Cox regression were performed to establish correlation between our data and the main event. A linear mixed-effects model was used to estimate eGFR slope.

Results
A total of 124 patients were included. Mean age and eGFR were 40 ±15 years and 59 ml/min (IQR: 33-94 ml/min) respectively, with a median proteinuria of 1.44 g/24h (IQR 0.7-2.3). 64% of patients were treated with corticosteroids. In the multivariate analysis, we found that IFTA &gt;25% had a statistically significant risk of MARE (IFTA T1 HR 3.1; 95% CI 1.52-6.6; p = 0.002; IFTA T2 HR 6.6; 95% CI 1.46-16.12; p&lt;0.001), history of cardiovascular disease presented 3.7 times higher risk of MARE (HR 3.7; 95% CI 1.46-9.6 p = 0.015). Patients with proteinuria &gt;3 g/24h showed significantly higher hazard ratio (HR 2.36 95%CI 1.16-4.8 p = 0.01) for MARE. In the 3-year linear mixed-effects model, patients with proteinuria above 3 g/24h had an annual eGFR slope of -6.3 ml/min (-9.6 to -3.1 95%CI). Nevertheless, proteinuria between 1.5 to 3 g/24h had an annual eGFR slope of -2.1 ml/min (-4.9 to 0.62 95% CI), finding no statistical difference in comparison to patients with proteinuria &lt;1.5 g/24h.

Conclusion
Typically, the threshold of proteinuria &gt;1 g/24h has been marked as the start of immunosuppression in this nephropathy. Several studies published in recent years (as example STOP IgAN) question this paradigm. According to our data, there is a strong association between proteinuria &gt;3 g/24h and major adverse renal events. Patients with proteinuria between 1.5 to 3 g/24h had a similar behaviour as our reference group (proteinuria &lt;1.5 g/24h). These results might provide new evidence supporting a more conservative approach and start receiving glucocorticoids if proteinuria is &gt; 3 g/24h.
#4074 FRACTIONATED PLASMA SEPARATION AND ADSORPTION INTEGRATED WITH CONTINUOUS VENO-VENOUS HEMOFILTRATION IN PATIENTS WITH ACUTE LIVER FAILURE
Authors: Dong Jianhua , Huang LI , LI Chuan , Wu Bian , Yang XI , Ge Yongchun 
Published: June 2023

Abstract

Background and Aims
To observe the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF).

Method
In this retrospective study, we enrolled patients with ALF (serum total bilirubin&gt;10mg/dl or Model for End-Stage Liver Disease (MELD) Score&gt;18) hospitalized from 2017 to 2022.All patients received the treatment of FPSA-CVVH.The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH.

Results
8 patients (68 males and 10 females) with ALF were enrolled. 66 patients (84.6%) exhibited acute kidney injury and required renal replacement therapy (RRT). The score of MELD at baseline was 22.9±7.5. The concentration of serum total bilirubin was 22.05±5.94mg/dL, direct bilirubin was 16.33±4.60mg/dL and indirect bilirubin was 3.43±1.60mg/dL.187 sessions of FPSA-CVVH treatment with 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs was 52.0±7.6% for total bilirubin, 59.4±13.0% for direct bilirubin and 36.9±15.4% for indirect bilirubin. 2 patients changed the filters due to blood coagulation. And other 2 patients exhibited bleeding, including gastrointestinal bleeding and Oozing bleeding. 29 patients (37.2%) survived in discharging from hospital, 12 patients recovered with their liver function, and the remaining 17 patients still needed intermittent artificial liver support therapy.

Conclusion
FPSA-CVVH therapy was a novol and effective artificial liver support therapy in patients with ALF. It may be considered as a “bridge technique” to the recovery of liver function in critical ill patients with ALF.
#4089 SARCOPENIA AS A PREDICTOR OF MORTALITY IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Kosoku Akihiro , Iwai Tamoaki , Kabei Kazuya , Nishide Shunji , Machida Yuichi , Uchida Junji 
Published: June 2023

Abstract

Background and Aims
Sarcopenia is a risk factor for adverse outcomes in older adults and dialysis patients, but this has yet to be confirmed in kidney transplant recipients. This study aimed to investigate the association of sarcopenia with all-cause mortality in kidney transplant recipients.

Method
In this single-center prospective cohort study, kidney transplant recipients were evaluated at baseline muscle mass, muscle strength, and physical performance using a hand dynamometer, 10-m walk test, and bioelectrical impedance analysis, respectively. Sarcopenia was defined according to the Asia Working Group for Sarcopenia 2019 criteria. Propensity score matching was used to reduce bias between the sarcopenia and non-sarcopenia groups, adjusted for three potential confounding variables including age, sex, and body mass index. After a 5-year follow-up, patient survival was assessed by the Kaplan-Meier method and Cox proportional hazards model in the matched cohort.

Results
Out of 212 patients (median age, 54 years; median transplant vintage, 79 months) enrolled in this study, patients who had sarcopenia at baseline was 33 (16%). After 1:1 propensity score matching, a matched cohort with 62 patients was generated. In the matched cohort, the overall incidence density rates of mortality were 48.8 and 6.75 per 1000 person-years in the sarcopenia and non-sarcopenia groups, respectively. The survival curves estimated using the Kaplan-Meier method indicated that the sarcopenia group was significantly lower cumulative survival than the non-sarcopenia group (log-rank test, p = 0.025). Moreover, the sarcopenia group had a significantly higher mortality risk than the non-sarcopenia group (hazard ratio = 7.59, 95% confidence interval = 1.93–61.7).

Conclusion
Sarcopenia was a significant predictor of mortality in kidney transplant recipients.