bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4948 ROLE OF REGENERATING PROTEIN 1A IN THE PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Huang Nan , Zhu Xiangyun , Chen Sheng , Wu Xiaodong , Wang Bin , Li Ling 
Published: June 2023

Abstract

Background and Aims
Regenerating protein 1a (Reg 1a) is a secretory protein mostly produced by the pancreas. Serum levels of Reg 1a has been found increased in patients with diabetic nephropathy, which may be a potential indicator of renal dysfunction. Here, we investigated whether Reg 1a was associated with renal function in chronic kidney disease (CKD) and further to evaluate its predictive value of progress in renal dysfunction.

Method
Serum Reg 1a levels were measured by a double antibody sandwich ELISA enzyme-linked immunosorbent assay. Demographics information and clinical biochemical parameters such as blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) and urinary albumin-to-creatinine ratio (UACR) were collected. Correlations between serum Reg 1a and other factors were presented by Spearman's correlation coefficient and partial correlation analysis. Multivariate logistic regression analysis was utilized to identify the independent risk factors for chronic renal dysfunction and the progress in CKD. Draw the receiver operating characteristic curve (ROC curve) and calculate the area under the curve (AUC) to analyze the effectiveness of the individual serum Reg 1a. Statistical analyses were conducted using SPSS 20.0 software, Med-Calc statistical software.

Results
A total of 640 participants were enrolled in this study including non-CKD subjects (n = 240) and patients with CKD (n = 400). Compared with non-CKD group, participants in CKD group had higher level of serum reg 1a (188.2 [66.7∼387.6] ng/ml vs 23.8 [14.7∼35.1] ng/ml, P&lt;0.001). Serum reg 1a level elevated with increasing grades of CKD. Serum reg 1a was negatively correlated with eGFR and positively associated with age, hypertension, Scr, BUN, UA and UACR (P&lt;0.001). In multiple logistic regression analysis, serum reg 1a was one of independent risk factors to predict renal dysfunction (OR = 1.010 [1.003, 1.018], P = 0.008). The AUC for serum reg 1a to predict CKD was 0.889 [0.862, 0.913], and the AUC for serum reg 1a to screen the eGFR lower than 30 ml/min/1.73 m2 in CKD groups was 0.919 [0.888, 0.944]. Subgroup analysis showed that serum reg 1a is an independent risk factor to predict early progress of UACR (OR = 1.012 [1.002, 1.022], P = 0.016) in CKD patients.

Conclusion
The study provides clinical evidence that serum reg 1a may a meaningful biomarker of early kidney impairment and a useful supplementary factor in the progression of CKD.
#4967 GASDERMIN D IS REQUIRED FOR CONTROL OF NECROPTOTIC CELL DEATH IN AKI
Authors: Tonnus Wulf , Brucker Anne , Linkermann Andreas 
Published: June 2023

Abstract

Background and Aims
Contradicting previous reasoning, it is now established that necrotic rather than apoptotic cell death pathophysiologically drives acute tubular necrosis during AKI. Whereas involvement of necroptosis and ferroptosis has been demonstrated by various groups, the role of pyroptosis, a highly immunogenic form of cell death requiring proteolytic activation of gasdermin protein family members, remains uncertain upon AKI. Thus, we aimed to investigate the role of pyroptosis and its mechanism of action in AKI.

Method
We set to detect gasdermin D (GSDMD) expression in murine renal samples after ischemia/reperfusion injury (AKI) by immunohistochemistry. Furthermore, we investigated GSDMD-deficient mice in IRI and cisplatin-induced AKI. To conclude on mechanisms, we isolated fresh murine renal tubules and measured LDH release over time. We generated MLKL/GSDMDdko mice to investigate the interplay of these caspase-dependent forms of regulated necrosis in AKI.

Results
After IRI, we detected a specific GSDMD signal in areas surrounding necrotic tubules, whereas no such signal could be detected within necrotic areas. Whereas interference with other forms of regulated necrosis leads to reduced injury, GSDMD-deficient mice demonstrated higher levels of serum creatinine and urea as well as more severe tubular injury compared to wildtypes. In line with the findings of immunohistochemistry, we only found GSDMD protein expression in whole kidney lysates but not isolated renal tubules; and no difference in spontaneous cell death propagation was detectable. Co-deletion of MLKL (effector protein of necroptosis) reversed the sensitization to AKI by GSDMD-deficiency. These results could be reproduced in cisplatin-induced AKI.

Conclusion
Here, we found an unexpected protective role for GSDMD, the effector protein of pyroptosis, in two different models of AKI. Mechanistically, our studies indicate the effect of GSDMD to function outside the tubular compartment, specifically surrounding areas of tubular necrosis. These infiltrating innate immune cells appear to interfere with tubular necroptosis in a non-cell autonomous manner. Alongside with these mechanistic insights, our data urge caution when inhibition of pyroptosis is therapeutically considered.
#4977 ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH COVID-19 DURING ANTIOXIDANT THERAPY
Authors: Egamberdieva Dano , Ruzmetova Iroda , Raimkulova Narine 
Published: June 2023

Abstract

Background and Aims
In connection with the coronavirus pandemic of 2020, there have been recent discussions about the role of endothelial function in the course and prognosis of the disease. Purpose of the study. study of endothelial function in patients who have had a coronavirus infection.

Methods
Under observation were 60 patients who underwent COVID-19 of moderate severity on the 14th day of therapy at the age of 57 to 67 years. Patients of the 1st group (30 patients), against the background of standard basic therapy, were prescribed L-carnitine at a dose of 5 g/day for 5 days, followed by a maintenance dose of 1 g/day for 5 days. Group II consisted of 30 patients who met the inclusion criteria for the study, were treated for COVID-19 and did not receive metabolic agents. The state of endothelial function was assessed according to Doppler sonography of the brachial artery using the D.S. Celemajer (1992) using a reactive flush test. Changes in the diameter of the right brachial artery were assessed using a 7.5-12 MHz linear transducer with a phase grating ultrasound system En Visor C Philips. The results of the study were processed statistically using Student's t test for paired and unpaired variables. Differences were considered significant at p&lt;0.05.

Results
After analyzing the data of samples with RG in combination with blood flow velocity indicators, we noted that in response to an increase in blood flow velocity in the control group, the diameter of the brachial artery increased by almost 12%, in patients with COVID-19, the blood flow velocity increased significantly, and the diameter of the artery practically did not change. Thus, with an increase in the mechanical stimulus, i.e. blood flow velocity in patients with COVID-19 did not occur a commensurate increase in the diameter of the vessel. The results obtained indicate a pronounced dysfunction of the endothelium in patients with COVID-19, in particular, EDVD, the indicators of which were two times lower than the control values.

Conclusions
The inclusion of L-carnitine in the regimen of standard therapy for patients with COVID-19 significantly improves the values of EVR compared to the standard basic therapy.
#4983 THE UNEXPECTABLE BALANCE OF PROINFLAMMATORY CELLS IN PERITONEAL DIALYSIS PATIENTS
Authors: Grilo João , Santos Catarina , Monteiro Andreia , Chorão Raquel , Coutinho Joana , Ribeiro Lígia , Filipe Rui , Rocha Ernesto 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is a complex and heterogeneous disease and is increasingly becoming a global public health concern. It is is characterized by a persistent inflammation state which appear to be caused by cytokines, grown factors and hormones. Peritoneal dialysis (PD) accounts for 9% of all kidney replacement therapy (KRT) and over time, some changes are expected to occur in the peritoneal membrane mainly due to exposure to PD solutions, infectious processes and non-infectious complications. This inflammatory process is poorly understood and needs further clarification, but Th17 cells and Th1 cells seem to be involved. Therefore, we aimed to quantify the frequency of peripheral immune cells and the concentration of IL-17A in peripheral blood (PB) and peritoneal effluent (PE) and compare to a healthy control group.

Method
In a cross-sectional study of 26 PD patients and 10 healthy, age and sex-matched controls we evaluated PB and PE frequencies of T lymphocytes, T CD4, T CD8 and Th1 cells by flow cytometry as well as IL-17 concentrations using enzyme-linked immunosorbent assay. Comparisons were performed between PD patients and controls and between the different groups of PD patients according to PD modality, number of exchanges, dialysate tonicity, extraneal use, infusion and daily total volumes, type of peritoneal transport and volume indexes. Statistical analyses were performed using the SPSS statistics version 26.

Results
Table 1 summarizes the main characteristics of PD patients and controls. Overall, in comparison with the control group, the frequency of Th1 cells in PB of PD patients was significantly lower (P = 0.001). On the other hand, frequency of Th1 cells substantially expanded in the PE, as compared to the PB (P = 0.001). PD patients also presented lower Th17 cells frequencies (P = 0.061) and those prescribed Extraneal had the lowest frequencies of Th17 (P = 0.030). IL-17A concentration was significantly higher in PE vs PB of PD patients (P = 0.012). Finally, the frequency of total lymphocytes in high PD transporters was significantly higher in comparison with high-average transporters (P = 0.021).

Conclusion
In our cohort, PE presented high concentrations of proinflammatory cells and cytokines. Th1 cells rather than Th17 cells were increased, pointing to a predominant cytolytic activity but IL-17 was also increased. Treatment with Extraneal associated with a lower frequency of these cells, somehow counterbalancing the inflammatory millieu associated with high glucose concentrations.
#4990 OMEGA-3 FATTY ACID ACTIVATES MITOCHONDRIAL BIOGENESIS AND PINK1 DEPENDENT MITOPHAGY IN KIDNEY AND HEART OF ADENINE INDUCED UREMIC RATS
Authors: Yang Dong Eun , Lee Su MI , Kim Jun Chul , An Won Suk 
Published: June 2023

Abstract

Background and Aims
Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FA) are beneficial for cardiovascular disease. We aimed to investigate whether omega-3 FA regulates the expression of mediators of mitochondrial biogenesis, dynamics, and mitophagy in kidney and heart of adenine-induced uremic rats.

Method
Sprague-Dawley rats were divided into three groups: normal control, adenine control, and omega-3 FA. Uremia was induced by feeding diets containing 0.75% adenine and 2.5% protein for the first 3 weeks. During next 4 weeks, they were received 2.5% protein with or without omega-3 FA (300 mg/kg/day). The renal and cardiac expression of PGC-1α, SIRT1/3, Nrf2, DRP-1, OPA1, Mfn1/2, PINK1, BNIP3 and NIX were examined by western blot analysis. The qPCR was used to determine mitochondrial DNA (mtDNA).

Results
Compared to normal, serum creatinine and heart weight/body weight in adenine control was increased and improved in omega-3 FA group. Compared with normal, PGC-1α, SIRT1/3 and Nrf2 were down-regulated in kidney and heart of adenine control. PGC-1α expression of kidney and heart was recovered in omega-3 FA group. DRP-1 of kidney was up-regulated but DRP-1 of heart was down-regulated in adenine control. DRP-1 of heart was recovered in omega-3 FA group. PINK1, BNIP3 and NIX were down-regulated in heart of adenine control and recovered in omega-3 FA group. PINK1 was down-regulated but BNIP3 and NIX were up-regulated in kidney of adenine control and those were mitigated in omega-3 FA group. MtDNA was decreased in kidney and heart of adenine control group but mtDNA of heart was recovered in omega-3 FA group.

Conclusion
DRP-1 related with mitochondrial fission may oppositely work in uremic kidney and heart. Omega-3 FA is beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1 dependent mitophagy in kidney and heart of uremic rats.
#4991 IMMUNE MODULATING DRUGS AND ORAL ANTICOAGULATION IN KIDNEY TRANSPLANT: COMPARISON OF DIRECT ORAL ANTICOAGULANTS VERSUS ANTAGONIST OF VITAMIN-K
Authors: Casanova Annalisa , Santoro Francesco , Simone Simona , Alfieri Carlo Maria , Fancone Adele , Strologo Andrea Dello , Grandaliano Giuseppe , Busutti Marco , Comai Giorgia , Grandinetti Valeria , Gesualdo Loreto , Pesce Francesco 
Published: June 2023

Abstract

Background and Aims
Direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs pharmacokinetic. Our study evaluates safety and efficacy profile of direct oral anticoagulants (DOACs) compared to avK in kidney transplant recipients (KTRs) treated with immune modulating agents.

Methods
A multi-center retrospective observational study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-six patients on DOACs were compared with fifty patients on avK with similar clinical features. Serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed.

Results
Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73 m2. Immune-modulating therapy included tacrolimus (n = 47, 71%), cyclosporin (n = 13, 20%), everolimus (n = 10, 7%) and sirolimus (n = 4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p = 0.80) and cyclosporine (+0.12±0.25 p = 0.94) not statistically significant. Only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p = 0.99), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs or avK therapy (-3.9±1 vs −3.8±2 p = 0.82).

Conclusion
DOACs are a potential therapeutic option among kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, thromboembolic events and renal function decline was found when comparing with avK therapy.
#5012 THE EFFECT OF GLOMERULAR C3 DEPOSITION ON RENAL OUTCOME IN PATIENTS WITH MEMBRANOUS NEPHROPATHY: DATA OF THE TSN-GOLD STUDY
Authors: Gursu Meltem , Cebeci Egemen , Turkmen Aydin , Dervisoglu Erkan , Sezen Mehmet , Turgutalp Kenan , Sahin Gulizar Manga , Trablus Sinan , Kutlay Sim , Uzun Sami , Üstündağ Sedat , Dursun Belda , Ayli Deniz , Tatar Erhan , Oztop Kenan Evren , Basturk Taner , Cevher Simal Koksal , Yilmaz Zulfikar , Tunca Onur , Sevinç Mustafa , Yadigar Serap , Duranay Murat , Arikan Izzet Hakki , Elcioglu Omer Celal , Karakan Şebnem , Turkmen Kultigin , Torun Dilek , Gungor Ozkan , Artan Ayse Serra , Ozturk Savas , Unsal Abdülkadir , Seyahi Nurhan 
Published: June 2023

Abstract

Background and Aims
We aimed to evaluate the effect of glomerular C3 deposits on clinical and laboratory findings and outcome in patients with idiopathic membranous nephropathy (MN) included in the Primary Glomerular Diseases Study of Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD).

Method
The data of 1595 patients with MN in the database has been evaluated. 114 patients were excluded due to lack of data about C3 staining, 54 patients due to secondary MN and 523 due to lack of data about the follow-up. Patients with glomerular C3 deposits were compared with those with no C3 staining.

Results
Glomerular C3 deposits were detected in kidney biopsy specimens of 601 patients of the 888 patients analysed. The demographic data, clinical and laboratory findings at the time of diagnosis of C3 (+) and C3 (-) groups are presented in Table 1. They were similar except serum albumin level that was lower in C3 (+) group. Subepithelial deposits and interstitial fibrosis was more prominent, IgG, Kappa and Lambda staining more intense, positivity for C1q and IgA was more frequent in C3 (+) group (Table 2).
The study groups were similar regarding remission rates after the first imuunosuppressive treatment (p = 0.582). 155 patients (25.8%) had partial, 152 (25.3%) had complete remission while no remission was detected in 92 patients (15.3%) in C3 (+) group. 69 patients (24.0%) had partial and 81 patients (28.2%) had complete remission; 40 patients (13.9%) had no remission in C3 (-) group. The relapse rates were 17.6% and 19.9% in C3 (+) and C3 (-) groups (p = 0.360). The percentage of patients who died or needed renal replacement therapy (RRT) were higher C3 (+) group (p = 0.013) (Figure 1).

Conclusion
Need for RRT and mortality is higher in patients with C3 deposition showing the importance of C3 deposition in the prognosis of MN. More prominent interstitial fibrosis may be related with the worse outcome.
#5019 MORTALITY FOR COVID-19 IN UNDERGOING MAINTENANCE DIALYSIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Wu Chen , Xie Guoqiang , Chen Junzhe , Liu Qin , Wang Honglei , Tang Ying 
Published: June 2023

Abstract

Background and Aims
Since December 2019, patients undergoing maintenance dialysis have been significantly affected by COVID-19, facing higher risk of death than general population. However, current evidences assess the mortality of patients with COVID-19 remains incomplete. We performed meta-analyses of overall mortality in dialysis patients after SARS-CoV-2 infection. In addition, this study investigated the differences among different races,viral variants, hemodialysis and peritoneal dialysis with COVID-19. At the same time, the mortality rate of dialysis patients with the COVID-19 after vaccination was also observed.

Method
We performed a meta-analysis with literature searching in PubMed, EMBASE, Web of Science and Cochrane databases, published between December 1, 2019 and January 10,2023. Two authors separately screened the titles and abstracts of the documents and ruled out irrelevant articles. Fixed effects model and random effects model were used for calculating heterogeneity.

Results
A total of 83 studies included 7278 died from confirmed COVID-19 cases in a pool of 42925 dialysis patients. Overall mortality of COVID-19 in dialysis patients was 22% (95%Confidence Interval [CI]:19%-25%, p&lt;0.01; I2 = 96.74%) from 2020 to 2022. In subgroup analysis, compared with ancestral COVID-19 (23%,95%CI:20%-25%,p&lt;0.01; I2 = 93.01%) and alpha variant (30%, 95% CI:21%-54%,p&lt;0.01;I2 = 95.35%),omicron variant (4%,95%CI:0-14%,p = 0.09; I2 = 0) had a lower morality significantly (Figure 1). The mortality for Asian and non-Asian were 20% (95% CI:16%-25%,p&lt;0.01;I2 = 96.6%) and 24% (95%CI:20%-27%,p&lt;0.01; I2 = 96.32%) respectively. The odds of death for maintenance hemodialysis and peritoneal dialysis were similar (odd ratio [OR] 1.30,95%CI:0.88-1.93,p = 0.191,I2 = 0). Furthermore, we also compared vaccination with unvaccination, and found out that vaccination was associated with lower mortality (OR = 0.18, 95%CI:0.11-0.28,p&lt;0.01;I2 = 71.4%) (Figure 2).

Conclusion
Patients undergoing maintenance dialysis with COVID-19 have a higher morality. These findings suggest that the mortality of omicron variant may be lower than other variants. In our study, there's no significant difference in mortality between hemodialysis and peritoneal dialysis patients with COVID-19. Moreover, vaccines have a good protective effect on dialysis patients.
#5036 THE OUTCOME OF LUMASIRAN TREATMENT IN 10 PAEDIATRIC PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1
Authors: Saffe Sina , Büscher Anja , Doerry Katja , Habbig Sandra , Hansen Matthias , John-Kroegel Ulrike , Kanzelmeyer Nele , Latta Kay , Oh Jun , Kemper Markus 
Published: June 2023

Abstract

Background and Aims
In primary hyperoxaluria type 1 (PH 1) a rare enzymatic defect in the liver leads to a hepatic overproduction of oxalate. The resulting hyperoxaluria can cause nephrocalcinosis, urolithiasis and renal failure. Conservative treatment options such as hyperhydration, citrate and pyridoxine aim to slow the progression of the disease with a liver transplant currently being the only curative treatment. Since November 2020 Lumasiran is approved for use in patients with PH 1. Lumasiran reduces the hepatic oxalate production by RNA interference and may hence reduce hyperoxaluria. To date there is limited real world data available on the effectiveness of the treatment with Lumasiran.

Method
This observational study looked at the outcome of Lumasiran treatment in 10 patients under the age of 18 years with genetically confirmed PH 1. The primary end point was percentage reduction in plasma oxalate in the two patients on haemodialysis and percentage reduction of urinary oxalate excretion in the patients with preserved renal function. Secondary end points were change in nephrocalcinosis, urolithiasis and renal function. The follow up time was 6 months in one patient and 12 months in the other nine patients.

Results
Four of the patients were girls and the median age at the start of treatment was 5.25 years (range 0.3-17.9 years). One of the two patients on haemodialysis showed a decrease in plasma oxalate which allowed for a reduction of dialysis frequency from 5x/week to 3x/week whilst the other patient's dialysis had to be intensified due to worsening systemic oxalosis. In the patients with preserved renal function the median reduction of urinary oxalate was 71% (range 10–91%) after 6 months and 78% (range 61–86%) after 12 months. Two patients reached values in the age specific normal range (Matos et al.). Lumasiran was discontinued after 4 months in one patient and after 8 months in another one due to treatment failure. An improvement in nephrocalcinosis was seen in three patients and two patients showed a subjective reduction in urolithiasis. Renal function improved slightly in one patient and remained stable in the others. Injection site reactions were the only observed side effects.

Conclusion
Our data highlights the heterogeneity of the disease and treatment response to Lumasiran. Despite promising data regarding the benefits of Lumasiran 2 of 10 patients did not benefit from Lumasiran injections. Hence, it is imperative to regularly re-evaluate hyperoxaluria during treatment with Lumasiran. Ideally the data should be entered into a registry for PH 1 patients to monitor the effectiveness and side effects of this novel drug not only in the short- but also the long term.