bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0100CALORIC RESTRICTION ALLEVIATES AGING-RELATED FIBROSIS OF KIDNEY THROUGH MIR-21 DOWNREGULATION IN EXTRACELLULAR VESICLES
Authors: Cai Guang-Yan 
Published: June 2020

Abstract

Background and Aims
The mechanism of renal interstitial fibrosis occurs with kidney aging is unknown. Caloric restriction and caloric restriction mimetics (CRM) alleviate aging-related-fibrosis. The aim of this study is to investigate whether extracellular microvesicles (EVs) derived from senescent cells facilitate fibrosis development in aging kidney and the potential signalling pathway involved in the process.

Method
In this study, animal experiments included 3-mon-old ad libitum(YAL) rats, 24-mon-old ad libitum(OAL) rats and 24-mon-old caloric restriction(OCR) rats, which was given 70% of OAL’s for 8 months. Senescent cells were induced in proximal tubular epithelial cells(PTCs) by high glucose and further treated with resveratrol as CRM. The expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF1α) in the kidney of rats and PTCs were examined. Epithelial to mesenchymal transition (EMT) and the related signalling pathway were detected by up- or down-regulation of miR-21, respectively.

Results
Long-term caloric restriction ameliorated senescent changes and aging-related fibrosis in aged ad libitum rat kidney. Caloric restriction blunted the increased expressions of miR-21 and HIF1α, the decreased expression of PPARα in renal tissue of old rats. High glucose induced PTCs senesence phenotype and EMT. miR-21 was detected in extracellular vesicles secreted by senescent PTC cells. CRMs resveratrol prevented EMT through downregulation of miR-21 in extracellular vesicles from the senescent PTC cells. Further, inhibiting miR-21 of donor senescent cells prevented the occurrence of EMT in recipient PTC cells. Finally, miR-21 induced EMT mainly through targeting PPARα protein and enhancing HIF1α expression.

Conclusion
This study demonstrated that miR-21-containing extracellular microvesicles derived from the senescent cells could facilitate tubular phenotype transition of neighbouring PTC cells via PPARα-HIF1α signalling pathway. Long-term caloric restriction and caloric restriction mimetics alleviate aging-related renal fibrosis through downregulation of miR-21 excretion.
P0103ANALYSIS OF GLOMERULAR IGG SUBCLASSES SWITCH IN IDIOPATHIC MEMBRANOUS NEPHROPATHY CLASSIFIED BY GLOMERULAR PHOSPHOLIPASE A2 RECEPTOR ANTIGEN AND SERUM ANTIBODY
Authors: Cui Haoyuan , Li Chao , Li Hang , Wen Yu-bing , Yan Xi-wei , Hu Yu-ting , Li Xuemei , Chen Limeng , Qin Yan , Li Xuewang 
Published: June 2020

Abstract

Background and Aims
IgG subclass switch phenomenon in early pathological stage of idiopathic membranous nephropathy (IMN) was reported recently. However, the profile of serum anti-phospholipase A2 receptor (PLA2R) antibody and glomerular PLA2R antigen was not reported in previous studies. The objective of our study was to testify whether glomerular IgG subclass switch phenomenon was present in PLA2R-related and PLA2R-unrelated IMN, respectively.

Method
This was a retrospective study including 157 Chinese patients with biopsy-proven IMN in a tertiary referral hospital between September 2017 and November 2019. IMN patients were classified into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroups. We compared the immunofluorescence intensity of glomerular IgG subclass between two groups among different electron microscopic (EM) stages.

Results
Positive rate of anti-PLA2R antibody was 56.0% (88/157) and glomerular PLA2R deposition was 75.8% (119/157). The intensity of IgG4 deposition in PLA2R-related group was stronger than that in unrelated group (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001). In stage I, IgG4 showed difference in predominant or co-dominant rate (pre/co rate) between two groups (P = 0.015). IgG4 was predominant in early stage (stage I) of both groups (pre/co rate 97% vs 57%). IgG1 was the less predominant subtype in stage I (pre/co rate 39% vs 43%). Pre/co rate of IgG3 declined with EM stage (P = 0.013).

Conclusion
IgG subclass switch were not found in PLA2R-related or unrelated IMN. IgG4 was the predominant IgG subtype in all stages of PLA2R-related IMN. The positive rate of glomerular PLA2R antigen was higher than serum PLA2R antibody.
P0111AN UPDATE ON EPIDEMIOLOGY AND CLINICOPATHOLOGIC CORRELATION OF RENAL BIOPSY FINDINGS - A TERTIARY KIDNEY CENTRE REPORT
Authors: Bagherzadegan Hadia , Ossareh Shahrzad , Mehrazma Mitra 
Published: June 2020

Abstract

Background and Aims
Several studies have reported the results of renal biopsies from different registries and single centres. In most series focal and segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), membranous glomerulopathy (MG) and lupus nephritis (LN) have been reported as the most common primary and secondary glomerulonephritis (GN). This study was conducted to update the reports of our hospital, as the main referral kidney centre of the country.

Method
Data from 4713 patients, who had undergone renal biopsy between Sept-1999 to Sept.-2019 were extracted from the GN data registry of our centre. Demographic data, renal syndrome at presentation and laboratory findings were studied. Almost all kidney specimens had been studied with light and immunofluoroscent microscopes and in selected cases with electron microscope. Nephrotic syndrome (NS) was defined as proteinuria &gt;3.5 g/day or &gt;3 g/day, if associated with hyperlipidemia, hypoalbuminemia and edema. Nephritic syndrome was defined as proteinuria &gt;500 mg/day and hematuria, with or without hypertension and/or serum Cr (SCr) ≥1.4 mg/dl. Subnephrotic (SN) proteinuria was defined as proteinuria of 200 -3000 mg/day. Acute kidney injury (AKI) was defined as increase in SCr &gt;1.4 during the past few days to weeks before admission.

Results
The most frequent type of renal pathology was MG (25.2%) followed by FSGS (13.6%), IgAN (12%), LN (8.9%), minimal change disease (MCD) (7%), crescentic GN (6.2%) and paraprotein associated GN (4.3%). The prevalence of different renal pathologies changed significantly over time (p-value:0.000) (figure).The most common clinical presentation was NS (60.2%), followed by SN proteinuria (15.2%), nephritic syndrome (12%) and AKI (7.5%). Age, sex, clinical syndrome at presentation and hypertension were significantly different between major pathological diagnostic groups (p=0.000). Table shows the detailed clinical features of the most important glomerulonephritides in our centre. Figure shows the changes in prevalence of each pathologic diagnosis over 21 years.

Conclusion
In our series the most common types of GN were MG, FSGS and IgAN, which are the most frequent glomerulonephritides in other biopsy series with various orders. Most of our patients presented with NS, followed by SN proteinuria. The relative frequency of MPGN and LN have reduced and FSGS has increased over time.
P0113STANDARDIZED GRADING OF CHRONIC CHANGES IN MINIMAL CHANGE DISEASE: A VALIDATION STUDY IN NATIVE KIDNEY BIOPSY SPECIMENS
Authors: Stefan Gabriel , Stancu Simona , Hoinoiu Madalina , Petre Nicoleta , Zugravu Adrian Dorin , Mircescu Gabriel 
Published: June 2020

Abstract

Background and Aims
Recently, a group of pathologists and nephrologists devised a simple scoring system for chronic changes based on the grading of glomerulosclerosis (GS), tubular atrophy (TA), interstitial fibrosis (IF) and arteriosclerosis (AS). We aimed to validate for the first time this score in patients with minimal change disease.

Method
We included 79 adult patients (age 50.3 (46.3, 54.3) years, 57% male, eGFR 54.7 (44.2, 63.5) mL/min) with biopsy proven MCD between 2010-2015 who were followed up until January 1, 2017. The extent of GS, TA and AS was scored from 0 to 3, 0 to 3 and 0 to 1, respectively. The scores were then added (total renal chronicity score) to grade the overall severity of the chronic lesions into minimal (0–1 total score), mild (2–4 total score), moderate (5–7 total score) and severe (&gt;8 total score). The outcomes were: patient survival; kidney survival defined as doubling of serum creatinine or ESRD; partial (proteinuria 0.3 to 3.5g/24h) or complete remission (proteinuria &lt;0.3g/24h) - whichever came first. Variables related to renal outcome were further evaluated in a multivariate Cox proportional hazard (CPH) model.

Results
Minimal chronic lesions were found in 77%, mild in 18% and moderate in 5% of the studied patients. Fifty percent had a null score of chronicity; they were younger (44 (29-53) versus 62 (44-66) years, p&lt;0.001), had higher eGFR (65.0 (42.1-83.2) versus 43.4 (25.8-63.9) mL/min, p&lt;0.01) but similar proteinuria (4.8 (1.9-8.2) versus 4.5 (1.1-6.7) g/g, p=0.3). Patients with a score higher than one had higher mortality (18% versus 0%, p&lt;0.001) and started RRT more often (15% versus 0%, p=0.01). There were no differences regarding the presentation as acute kidney injury, and in reaching complete or partial remission. Moreover, there were no clinical or pathology features that predicted remission. 17% of the patients reached the composite endpoint of kidney survival; mean kidney survival time was 5.7 (5.2, 6.3) years. In the CPH analysis the only independent predictors of decreased renal survival were elevated chronicity score (HR 1.56 (95%CI 1.14-2.14), p&lt;0.01), lower serum albumin (HR 0.27 (95%CI 0.08-0.88), p=0.03) and the presence of hypertension (HR 0.18 (95%CI 0.03-0.93), p=0.04).

Conclusion
To the best of our knowledge, this is the first study to validate the standardized grading of chronic changes as an independent predictor of renal survival in patients with minimal change disease.
P0115EFFECT OF CARDIOPULMONARY BYPASS ON THE DEVELOPMENT OF ACUTE KIDNEY INJURY AFTER OPEN-HEARD SURGERY
Authors: Molchan Nikolai , Akmalova Regina , Sokolov Dmitriy , Galkina Olga , Polushin Yuri , Levykina Elena 
Published: June 2020

Abstract

Background and Aims
Assessment of factors associated with cardiopulmonary bypass (CPB) in acute renal dysfunction in patients in the early postoperative period after cardiac surgery.

Method
Monocentric observational study in patients (n = 97) who underwent elective open-heart cardiac surgery (coronary artery bypass grafting -50.44%, aortic valve prosthetics - 31.04%, mitral valve prosthetics - 12.61%) using cardiopulmonary bypass. Inclusion criteria: the study included patients not younger than 18 years old, undergoing cardiac surgery with CPB lasting up to 95 minutes (coronary bypass surgery, valve replacement), without signs of end-stage chronic kidney disease (CKD).
Using nonparametric correlation analysis, we evaluated the effect on the development of acute kidney injury (AKI) of the following extracorporeal circulation factors: duration of CPB, aortic cross-clamp, mean arterial pressure (MAP), cardiac index (CI), perfusion flow rate (PFR), transport, consumption and oxygen extraction variables. The diagnosis of AKI was made on the basis of the KDIGO classification, the studied parameters were recorded initially (before the operation), 15 minutes after the start of general anesthesia, 30 minutes after the start of cardiopulmonary bypass and 15 minutes after the end of general anesthesia.

Results
The frequency of AKI in 24 hours after surgery was 56.3% (58 cases): including stage 1 in 37 (35.9%), stage 2 in 17 (16.5%), stage 3 - in 4 (3.9%) patients. In the 48th hour of the postoperative period signs of AKI regressed, and were presented in only 26 people (25.2%), including the stage 1 in 18 (17.5%), the stage 2 - in 5 (4.8%), stage 3 - in 3 (2.9%). Among the risk factors for AKI in cardiac surgery with CPB, the main effect of of the anemia was revealed, especially a decrease in hemoglobin levels of less than 90 g / l and hematocrit of less than 25%.

Conclusion
Hemodilution below the "threshold" values of hemoglobin and hematocrit during the CPB provoke acute kidney injury in patients undergoing open-heart surgery.
P0116DISCOVERY OF A NOVEL ANTIMICROBIAL COMPOUND AGAINST PSEUDOMONAS AERUGINOSA FROM URINE OF KTX PATIENTS
Authors: Knafl Daniela , Mitulovic Goran , Pichler Peter , Reiter Thomas , Wagner Ludwig , Winnicki Wolfgang 
Published: June 2020

Abstract

Background and Aims
The urinary microbiome harbors a great repertoire of bacteria, which possess an immense potential for the biosynthesis of different biochemical products such as polyketide synthases. Traditionally such compounds have been utilized as pharmaceutical drugs, for example as antibiotics or cytostatic substances or agrochemical agents. While examining the urinary microbiome of KTX-patients during AKI and concomitant antibiotic treatment a remarkable decrease of Candidatus solibacter usitatus in one patient attracted our attention. Surprised about detecting a putative close relative of a bacterium, which originally has been found in Australian soil in our patient’s urine, we examined the genome and protein coding regions of Candidatus solibacter usitatus. Thereby we identified a biosynthetic pathway, which allowed us to clone and produce an up-to-now unknown polyketide type 1 synthase, which we named Dananase.

Method
The dananase gene was synthesized, cloned into the pEX-A258 for replication and inserted into the p-TOPO-entry-D gateway vector following PCR amplification. The resultant insert was shifted into the pEXP1- DEST gateway vector. E. coli transformants were selected for dananase expression. BAP1-E. coli was transformed with the dananase-pEXP1- DEST expression plasmid and grown in liquid culture under induction with IPTG. The supernatant was filtered and utilized for antimicrobial activity testing against Pseudomonas aeruginosa. Metabolome analysis of BAP1- pEXP1-DEST-dananase following induction with IPDG was performed and compared to LB-media alone and supernatants of dummy plasmid transformed BAP1-E. coli. In addition, the molecular structure of dananase product was determined using trans-AT polyketide synthase predictor web application genome mining tool.

Results
The 1646 amino acid long polyketide synthase type 1 named dananase was cloned into pEXP1 expression vector and expressed in BAP1. The supernatant contained specific antimicrobial activity against clinical isolates of Pseudomonas aeruginosa. This highly active compound could be further purified by HPLC but not yet identified in its structure. In silico prediction analysis suggested a polyketide as follows CC(C(O)*)C=CC(CC(NC([K])C(CC(O)=O)=O)=O)=O. Mass spectrometric analysis revealed several Dananase-specific peaks representing most likely its product in the supernatant.

Conclusion
The dananase gene of Candidatus solibacter usitatus consists of 4941bp and encodes a polymodular polyketide synthase type-1, its product successfully inhibits growth of Pseudomonas aeruginosa in vitro.
P0118ANEMIA AS A RISK FACTOR FOR CONTRAST-INDUCED NEPHROPATHY
Authors: Chaabouni Emna , Jbali Hela , Mariem Najjar , Khadija Mzoughi , Karim Zouaghi 
Published: June 2020

Abstract

Background and Aims
Contrast-induced nephropathy is a potentially serious complication following coronary angiography and percutaneous coronary intervention .
The association between severity of anemia and Contrast-induced nephropathy following coronary angiography is not well-established. In this prospective study, we aimed at assessing the association of anemia of various severity with the risk of Contrast-induced nephropathy in patients who underwent coronary angiography

Method
We prospectively enrolled 158 patients who underwent coronary angiography with or without percutaneous coronary intervention from December 2017 to February 2018 at a cardiology department .
CIN was defined as an increase in serum creatinine level &gt;25% or 0.5 mg/dL after 48 hours and anemia was defined as a value of Hb level ≤ 13 g/dl in male patients or ≤ 12 g/dl in female patients.
Patients were stratified into three subgroups—mild (11.1 to 13.0 g/dL) in male patients and (11.1 to 12.0 g/dL) in female patients, moderate (9.1 to 11.0 g/dL) and severe anemia (7.0 to 9.0 g/dL).
we used a multivariable logistic-regression model.

Results
158 patients (females = 36.1%, mean age 60.0 ± 11 years) who underwent coronary angiography, 15 (9,5%) developed Contrast-induced nephropathy .
Presence of anemia was associated with increased risk of developing Contrast-induced nephropathy (OR = 3.04, 95% confidence interval [CI] = 1.03 to 8.96, p= 0,043).
Risk of Contrast-induced nephropathy was increasingly higher with increasing severity of the anemia; mild (OR = 1.67, 95% CI = 1.38 to 2.17, p=0,036), moderate (OR = 3.3, 95% CI = 0.61 to 10.6, p=0,028) .There was no patient with severe anemia.

Conclusion
In conclusion, severity of anemia is a strong predictor of CIN following coronary angiography.
P0123THE IMPORTANCE OF PPAR-ALPHA IN AKI TO CKD TRANSITION IN NEPHROPATHY INDUCED BY FOLIC ACID
Authors: Estrela Gabriel , Arruda Adriano , Freitas-Lima Leandro , Barrera-Chimal Jonatan , Araujo Ronaldo 
Published: June 2020

Abstract

Background and Aims
PPAR-alpha is a nuclear receptor which plays major role in the regulation of lipid metabolism, activation of PPAR-alpha has been shown to have beneficial effects in renal diseases. Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of PPAR-alpha in AKI to CKD transition in folic acid induced nephropathy.

Method
Male C57/Bl6 and PPARKO (C57Bl6 background) mice were divided in 4 groups, Control, Folic Acid, Gemfibrozil + Folic Acid and PPARKO + Folic Acid. Animals has been treated with single dose of Folic Acid (250mg/kg i.p) and Gemfibrozil (150mg/kg gavage) euthanized after 48 hours for AKI assessment and 28 days for CKD. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis.

Results
After 48 hours of folic acid inducing AKI, PPARKO mice showed decreased urea levels (Folic Acid: 178,9±25,2 PPARKO: 92,4±15,5), less tubular injury (Folic Acid: 0,61±0,05 PPARKO: 0,21±0,03), lower mRNA expression of NGAL (Folic Acid; 32,2±7,67 PPARKO 3,74±1,71), KIM-1 (Folic Acid: 671,8±170,2 PPARKO: 43,4±29,7) and TNF-alpha (Folic Acid: 2,81±0,58 PPARKO: 0,67±0,14), while PPAR-alpha activation with gemfibrozil showed to have no effects in AKI. After 28 days of folic acid inducing CKD. PPARKO showed same levels of injury than folic acid alone treated mice, however PPAR-alpha activation with gemfibrozil decreased urea levels (Folic Acid: 79,2±3,2 Gemfibrozil: 46,1±3,8), showed less tubulointerstitial fibrosis (Folic Acid: 0,60±0,05 Gemfibrozil: 0,18±0,02) and lower urine protein/creatinine ratio (Folic Acid: 5,48±0,58 Gemfibrozil: 2,53±0,12),

Conclusion
PPAR-alpha deletion protects against AKI induced by folic acid but did not showed protection in chronic phase, in the other hand ppar-alpha activation with gemfibrozil did not protect in AKI but show to be effective in CKD.
P0124PREDICTIVE VALUE OF RENAL RISK SCORE AND CHRONICITY SCORE IN PREDICTING RENAL OUTCOME IN ANCA ASSOCIATED GLOMERULONEPHRITIS
Authors: Chen Yong-Xi , An Xiao-Ning , Wei Zhao-Nan 
Published: June 2020

Abstract

Background and Aims
Renal Risk Score (RRS) and Chronicity Score (CS) are both newly proposed tools to predict End stage renal disease (ESRD) which could be applicable in Antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (AGN) patients. Their predictive value has not been fully studied and compared.

Method
Patients with newly biopsy-proven AGN at Department of Nephrology, Ruijin Hospital were retrospectively studied. Patients were evaluated with RRS and CS for clinical factors, pathological lesions and outcome. Their predictive value of renal survival was also compared with 2010 histological classification.

Results
There were 252 AGN patients enrolled in current study, including 212 MPA, 12 GPA, 4 EGPA and 24 renal limited vasculitis (RLV). In current study, the median serum creatinine of patients at diagnosis was 245.5 μmol/L (IQR 128-487.5 μmol/L) and median eGFR was 20.3 ml/min (IQR 9-45.3 ml/min). Fifty (19.8%) patients required dialysis at disease onset. The median RRS score at diagnosis was 6 (IQR 0-9) and CS score was 4 (IQR 3-7).
During up to 217 months of follow-up (mean 63.9 months), 71(28.2%) patients progressed to end stage renal disease (ESRD) and required renal replacement therapy. Significant differences were found regarding dialysis dependency within RRS and CS groups (p&lt;0.001 and p&lt;0.01 respectively).
The C statistic of the predictive models was 0.828 (95% CI, 0.775-0.880) for developing ESRD required renal replacement therapy. The addition of RRS or CS scoring scheme to the model significantly improved discrimination.
Compared with the 2010 histopathological classification, RRS and CS both showed adequate and similar discrimination, but significantly greater discrimination than 2010 histopathological classification.

Conclusion
Among AGN patients, RRS and CS achieved similar discrimination, but the discrimination of RRS was superior.
P0127ROUTINE USE OF COMBINATION CD3/PAS STAIN IN EVALUATING RENAL ALLOGRAFT BIOPSIES FOR REJECTION RESULTS IN MORE ACCURATE BANFF SCORES FOR TUBULITIS
Authors: Ziadie Mandolin , Abrahams Lauren , Freeman-Costin Katherine , Obregon Cecilia , Abrahams Neil 
Published: June 2020

Abstract

Background and Aims
The BANFF Classification of renal allograft rejection consists of scores for cellular rejection which rely primarily on the evaluation of lymphocytic infiltration into tubules (t), non-atrophic interstitial inflammation (i), total inflammation (ti), and endotheliatis (v.) CD3/PAS is a combination stain that highlights T lymphocytes (CD3) and basement membrane (PAS). The original BANFF scoring was developed using a hematoxylin and eosin (H&E) stain only. This study compares scores for (t) using H&E versus CD3/PAS.

Method
50 consecutive renal allograft biopsies were retrieved and on each case H&E and CD3/PAS combination stains (Ventana/Roche tissue Diagnostics Clone 2GV6 for CD3) were performed. One blinded group of matching CD3/PAS and H&E slides were evaluated and reviewed independently by two renal pathologists (Reviewer 1 and 2). Each case was graded in an identical manner following criteria designated for (t) as previously described in the Banff Classification for Renal Allograft Biopsies. Briefly (t)=0 no lymphocytes in 10 tubule cross section (tcx), (t)=1 between 1-4 lymphocytes per tcx, (t)=2 5-10 lymphocytes per tcx and (t)=3 greater than 10 lymphocytes per tcx. Cases were not graded for (v) as there were too few cases with endotheliatis to allow for statistical evaluation. The difference between CD3/PAS versus H&E scores were tested for significance using the Wilcoxon Signed Rank test. All p values were two-tailed and values of &lt;0.05 were considered statistically significant.

Results
Mean age was 44 years with a range of 9 -75 years. Standard deviation (SD) for age was 18 years. Gender distribution was 20% female and 80% male. 28 cases were graded as (t) = 0 in H&E versus 18 in the CD3/PAS group (59% versus 36%). 17 cases were graded as (t)=1 in H&E group versus 19 in the CD3/PAS group (36% versus 38% respectively). 2 cases were graded (t)=&gt;2 in H&E versus 12 cases in CD3/PAS groups (4% versus 24% respectively). In all categories of (t) there was a higher (t) score when using a CD3/PAS with 42% showing a one digit score increase and 8% showing a 2 digit increase. The difference in scoring for (t) between the H&E set versus the CD3/PAS set for both Reviewers 1 and 2 were statistically significant (p&lt;0.0001).

Conclusion
This study showed statistically significant higher tubulitis scores when using a CD3/PAS combination stain to grade allograft biopsies. Since (t) scores directly affect the diagnosis of cellular rejection, we propose routine use of CD3/PAS in addition to H&E when reviewing renal allograft biopsies. Compared with H&E, CD3/PAS makes recognition and quantification of lymphocytes crossing the tubular basement membrane easier to detect and therefore more accurate.