bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0317EARLY MARKERS OF RENAL INJURY AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH METABOLIC SYNDROME
Authors: Abdullaev Sherzod 
Published: June 2020

Abstract

Background and Aims
The definition of subclinical renal damage markers in patients with metabolic syndrome (MS) and evaluation the relations between the indicators of subclinical renal injury and endothelial dysfunction.

Method
The study included 62 patients with MS, 32 (51.6%) men and 30 (48.4%) women aged 51.2±5.4 years. The control group included 25 practically healthy individuals, 13 (52.0%) men and 12 (48.0%) women, aged 47.3±6.1 years. All patients were underwent clinical and laboratory examination, calculation of glomerular filtration rate (GFR) using the formula CKD-EPI, ultrasound of the carotid arteries, determination of the insulin resistance index (IR) (HOMA-IR), as well as determination of the content of endothelin-1 (ET-1) in serum and albumin excretion in a single portion of urine by IFA.

Results
When calculating GFR, hyperfiltration was detected in 10 (16.1%), optimal filtration - in 23 (37.1%), slightly reduced - in 29 (46.8%). At the same time, in patients with MS, a statistically significant excess of urinary albumin excretion (UAE) in a single dose was revealed compared with the control group (26.6±5.8 mcg/ml and 9.2±3.4 mcg/ml, respectively; p &lt;0.001).
Based on the increase in level (ET-1) in patients of the main group, compared with the control (6.3±3.2 fmol/ml and 3.4±1.0 fmol/ml, respectively; p=0.03) may indicate the development in patients of the main group of endothelial dysfunction. A correlation analysis revealed a direct correlation between the level of UAE and ET-1 (R = 0.45; p = 0.005).
A direct correlation was found between UAE and IR-HOMA (R = 0.68; p &lt;0.007), interventricular septum thickness (R = 0.71; p &lt;0.001), and intima–media thickness (IMT) (R = 0.49; p &lt;0.008) and systolic blood pressure (R = 0.47; p = 0.026). Similar associations were noted also for the ET-1 level: IR-HOMA2 (R = 0.78; p &lt;0.001), with the thickness of the interventricular septum (R = 0.76; p = 0.001), IMT (R = 0.46; p &lt;0.033) and systolic blood pressure (R = 0.45; p = 0.035).

Conclusion
In patients with metabolic syndrome, in addition to the well-known manifestations, in the early stages, may be a violation of renal function and endothelium, manifested by the change of glomerular filtration rate, increased levels of UAE and increased concentration of ET-1 in the blood. Direct correlation of the level of UAE and ET-1 level, and the coincidence of the correlation relationships of these indicators with a number of clinical and laboratory indicators of the metabolic syndrome will make it possible to consider an increasing of the level of UAE as one of the markers of endothelial dysfunction.
P0318HYPERKALEMIA: EPIDEMIOLOGY AND MANAGEMENT
Authors: Felah Eya , Samia Barbouch , Mariem Hajji , Ben amor Shedha , Chargui Soumaya , Amiri Mohamed lotfi , Trabelsi Raja , Goucha Rym , Ben Hmida Fethi , Ounissi Mondher , Ben abdallah Taieb 
Published: June 2020

Abstract

Background and Aims
Hyperkalemia is a dreadful biological event that can immediately compromise the vital prognosis. Etiologies are many and varied. The aim of our study is to better characterize the epidemiological and clinical aspects of this disorder in order to establish adequate diagnostic and therapeutic strategies in order to intervene effectively and in the shortest possible time.

Methods
Cross-sectional study carried out over a period of 12 months [January-December 2017] including all emergency calls for hyperkalemia greater than 5.5 mmol / l and undergoing hemodialysis in the nephrology department.

Results
We collected 185 patients (Sex ratio= 1.43) aged on average 61.8 ± 16.1 years [18-94 years].
70.3% had serum potassium between 5.5 and 7 mmol / l and 29.7% greater than 7. Patients mainly came from emergencies in 71.4% of cases. Main symptoms consisted in oligoanuria, vomiting, chest pain, and febrile syndrome in 38.9%, 10.8%, %, and 5.9% of cases, respectively. Of these patients, 76.2% are known to be chronic renal failure whose 29.7% are in chronic dialysis. Acute renal failure (ARF) was diagnosed in 30.3% of patients. Of these, 39.4% were functional AKI, 41% were obstructive and organic AKI in 19.6% of cases. Mean serum potassium was 6.7 ± 0.9mmol / l [5.5-11] associated with metabolic acidosis in 52.4% of cases. Mean serum creatinine was 988umol /l[184-3270]. The electrical signs of hyperkalemia were noted in 40% (n = 74) of patients: large T in 28.6% of cases, atrioventricular block (AVB) in 3.8% of cases including a 3rd BAV degree in 1.6% of cases, QRS wide in 11.4% of cases and sinus bradycardia in 7% of cases, Ventricular Extrasystoles and a branch block found respectively in 3.2% of cases. 30.8% (n = 57) of the patients were under hyperkalaemic treatment. In fact, 27 % of patients took a blocker of the renin-angiotensin system, 7% were on aldoactone, 13.5% of patients on þetabloquant,1.6 % of whom were on kaleoride and / or admitted to intensive care and infused with KCl. Medical treatment was started urgently in 42.7 % of cases and included the administration of twenty ml 10% ca gluconate that was given intravenously over 5-10minutes, insulin with glucose ,sodium polystyrene sulfate (Kayexalete) and salbutamol, sodium bicarbonate indicated for severe metabolic acidosis (pH&lt;7.20). Overall mortality was 21.1% of cases .

Conclusion
Hyperkalemia remains a frequent metabolic disorder. Renal failure and acidosis were the main factors associated to hyperkalemia in our study. The clinical and therapeutic subtleties must be known by any caregiver in order to effectively mitigate the harmful effects of this disorder, mainly in the cardiac function.
P0352P-SELECTIN BLOCKADE AMELIORATES RENAL HYPOXIA OF LUPUS NEPHRITIS IN MRI/LPR MICE
Authors: Li Xiao 
Published: June 2020

Abstract

Background and Aims
Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus, of which poor prognosis is indicated by aggravated renal hypoxia and tubulointerstitial fibrosis. Cell adhesion molecules play a key role in the progression of lupus nephritis tubulointerstitial lesion, including P-selectin, which mediates the rolling of leukocytes and subsequent adhesion and infiltration and then initiates the inflammatory immune response and ischemia and hypoxia injury. However, the effects and mechanisms of P-selectin in lupus nephritis remain to be investigated, and a noninvasive measurement of lupus nephritis tubulointerstitial hypoxia and fibrosis remains to be explored.

Method
Thirty-four MRL/lpr mice were randomly divided into the following three groups: MRL/lpr, saline, and anti–P-selectin, which consisted of no treatment, treatment with normal saline, and treatment with anti–P-selectin monoclonal antibody (mAb) from 12 to 16 weeks of age, respectively. Ten male C57BL/6 mice of the same age served as normal controls. Twenty-four-hour urinary protein, urinary albumin–creatinine ratio, and periodic acid–Schiff were used to assess kidney damage; Western blot or immunohistochemical staining of the hypoxia probe HypoxyprobeTM-1, hypoxia-inducible factor 1α (HIF-1α), and CD31 were used to evaluate hypoxia in renal tissue; and NADPH oxidase subunit gp91phox and p22phox were used to examine renal oxidative stress. The correlation between kidney injury and blood oxygen level–dependent magnetic resonance imaging (BOLD-MRI) was calculated to assess the clinical value of BOLD-MRI.

Results
P-selectin is upregulated in lupus nephritis. Blocking P-selectin with mAb alleviated renal tubulointerstitial fibrosis, renal hypoxia, and peritubular capillary loss, without alteration of the levels of lupus activity indicators, anti-dsDNA antibody, or complement C3. BOLD-MRI showed that the reduced R2* values in the renal cortex and medulla of lupus mice were increased when treated with anti–P-selectin mAb as compared with those treated with normal saline, which were negatively correlated with HypoxyprobeTM-1 hypoxia probe and the expression of HIF-1α.

Conclusion
Early intervention of lupus nephritis with anti–P-selectin mAb can significantly improve the hypoxic state of the kidney and reduce the severity of tubulointerstitial lesions. BOLD-MRI techniques are noninvasive and can dynamically evaluate the changes in renal lesions and intrarenal oxygenation levels before and after treatment in lupus nephritis.
P0364A NOVEL INTERPLAY BETWEEN INTESTINAL BACTERIA AND METABOLITES IN IGA NEPHROPATHY IDENTIFIED VIA INTEGRATED MICROBIOME AND METABOLOME APPROACHES
Authors: Wu Hongwei , Dai Yong , Liu Fanna , Yin Lianghong 
Published: June 2020

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Intestinal bacteria and their metabolites have been implicated in various diseases. Improved understanding of the gut microbiota and its metabolic capabilities will facilitate development of diagnostic, therapeutic, and prognostic methods for IgAN

Method
We identified gut microbiota and metabolite biomarkers of IgAN by analyzing microbiomes and metabolomes of fecal and serum samples of IgAN patients and healthy controls using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches

Results
We found that relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. The changes in gut microbiota affected metabolism and absorbance of microbiota-associated metabolites of IgAN patients, in particular polyunsaturated fatty acids, free amino acids and oligopeptides, and activated the phenylalanine metabolism pathway. Also, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were proved to be associated with the classification of segmental glomerular sclerosis but not 24h urine protein and estimated glomerular filtration rate.

Conclusion
Our findings demonstrate an interplay between intestinal bacteria and metabolites in IgAN. The identified metabolites may have diagnostic and therapeutic applications.
P0390THERAPEUTIC EFFECTS AND SERUM METABOLOMIC VARIATIONS IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS MICE ON TREATMENT WITH HUMAN UMBILICAL MESENCHYMAL STEM CELLS
Authors: Wang Caili 
Published: June 2020

Abstract

Background and Aims
Focal segmental glomerulosclerosis (FSGS) mediates the kidney podocyte dysfunction and leads to chronic renal diseases worldwide. Current treatment options are limited, owing to the poor understanding of the metabolic pathologic variations and regeneration of FSGS. Mesenchymal stem cells (MSC) offer the better insights to prevent renal injury and could promote the recovery of renal structure and function through complex mechanisms. Due to the safe, feasible, and therapeutic features, we first designed to investigate the role of human umbilical mesenchymal stem cells (HUMSCs) on FSGS mice and explored the potential serum metabolomic variations.

Method
Nephropathy was induced by adriamycin (ADR) in male Balb/C mice to study FSGS via intravenous administration. 2*106 HUMSCs are provided to treat FSGS model for 3 times. Renal function was measured by urine protein, serum urea nitrogen (BUN) and serum creatinine (SCr) in the study. Serum metabolic profiles from three groups of Balb/C mice were analysed using ultra- performance liquid chromatography coupled with a triple quadrupole-linear ion trap mass spectrometer and a novel mass spectrometry (UPLC-MS/MS) data collection technique.

Results
The concentrations of SCr and BUN were apparently decreased after HUMSCs injection for three times compared with the FSGS model and body weight from HUMSCs group was improved significantly. A total of 532 differential metabolites were identified between FSGS group and the normal control group. Bile acid dysregulation and valine/leucine/ isoleucine metabolism pathway, especially, N-acetylvaline and L-valine, were positively associated to ADR-induced FSGS. A panel of identified specific metabolites (pyrrole-2- carboxylic acid, urocanic acid and 6-hydroxynicotinic acid) as well as valine/leucine/isoleucine metabolism pathway rather than bile acid metabolism were related to the renal repair after HUMSCs treatment.

Conclusion
The administration of HUMSCs in FSGS induced ADR provides the promising protection owing to the improvement of metabolomics.
Figure 2. The distribution of DiR-HUMSCs in vivo.
Figure 3. Kidney pathology using periodic acid-Schiff (PAS) and Masson staining.
Figure 4. Metabolome profiling analysis and Venn diagram for comparisons of numbers from each group.
Figure 5. Metabolic pathway analysis results from FSGS + Saline and FSGS + HUMSCs groups.
Figure S1. The quality control (QC) of serum metabolomics was designed and performed as follows.
Figure S2. Metabolic pathway analysis results from FSGS + Saline and Normal + Saline groups.
Figure S3. Metabolic pathway analysis results from FSGS + HUMSCs and Normal + Saline groups.
P0401RITUXIMAB VESUS CYCLOPHOSPHAMIDE AS FIRST STEROID SPARING AGENT IN CHILDHOOD FREQUENTLY RELAPSING OR STEROID DEPENDENT NEPHROTIC SYNDROME
Authors: Kari Jameela , Albanna Amr , Alhassan Khalid , Safdar Osama , Shalaby Mohamed , Bockenhauer Detlef , El-Desoky Sherif 
Published: June 2020

Abstract

Background and Aims
Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications

Method
A prospective open label randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months

Results
46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR: 0.36; 95% CI: 0.09 – 1.45; p=0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N=10) and 6.3 months in the rituximab group (N=3). Both treatments were associated with a significant (p=?) reduction in prescribed dose of oral alternate days steroid from 1.02 to 0.36mg/kg (Cyclophoshamide) and 0.86 to 0.08mg/kg (Rituximab). Importantly, a significantly (P = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group.
Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity beside severe leucopenia and neutropenia on the 7th week of treatment although she showed complete recovery with withdrawal of cyclophosphamide and maintained remission. A minor infusion related reaction was observed in 1 patient (5%) in the rituximab group.

Conclusion
Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide
P0411PREDICTORS OF RENAL AND PATIENT OUTCOME IN PATIENTS WITH IDIOPATHIC MEMBRANOUS NEPHROPATHY: FROM KOGNET DATA
Authors: Choi Ji-Young , Kim Ji Hye , Lee Ga Young , Noh Hee Won , Jeon Soojee , Lim Jeong-Hoon , Jung Hee-Yeon , Cho Jang-Hee , Kim Chan Duck , Kim Yong-Lim , Park Sun-Hee 
Published: June 2020

Abstract

Background and Aims
Idiopathic membranous nephropathy (iMN) is a leading cause of nephrotic syndrome and one of the major causes of end-stage renal disease (ESRD). Various factors can affect renal and patient outcome in patients with iMN. In this study, we analyzed the predictors of renal and patient survival in patients with iMN.

Method
We analyzed 1,776 patients diagnosed with iMN in Korean GlomeruloNEphritis STudy (KoGNET), a retrospective database of patients with renal biopsy from 1979 to 2018 from 18 centers in Korea. Student t-test for continuous variables and Chi-square test for categorical variables were performed for analyses. Cox proportional hazard regression was used to determine risk factors affecting renal and patient survival.

Results
The mean age of patients was 53.0 ± 14.7 years old and 1,075 (60.5%) were male. At the time of renal biopsy, 755 (46.0%) and 266 (16.2%) had hypertension and diabetes, respectively. Serum albumin level was 2.7 ± 0.8 g/dL and 871 (49.0%) had nephrotic range of proteinuria. When analyzed by dividing over 65 and under, the hemoglobin and serum albumin level were lower, more patients showed nephrotic ranged proteinuria, and higher prevalence of comorbidities such as hypertension, diabetes, coronary heart disease and cerebrovascular disease in the group over 65 than in the group under 65. Median duration of follow-up was 88.0 (38.0 – 115.1) months. Complete or partial remission rates were 48.5%, 63.8%, and 68.0% at 6 months, 12months after biopsy, and last follow-up, respectively. In Cox proportional hazard regression, high hemoglobin [HR 0.66 (0.47 – 0.93), p=0.017], high serum albumin level [HR 0.41 (0.18 – 0.94), p=0.034], and high estimated GFR by CKD-EPI equation [HR 0.94 (0.91 – 0.96), p&lt;0.001] at biopsy were good predictors for renal outcome, whereas presence of cerebrovascular disease at biopsy [HR 6.45 (1.16 – 35.71), p=0.033] were poor prognostic factors for ESRD. Age 65 and older [HR 3.26 (1.53 – 6.95), p=0.002] and presence of hypertension at biopsy [HR 2.45 (1.09 – 5.54), p=0.031] were significant risk factors for patient survival in multivariate Cox proportional regression analysis.

Conclusion
High hemoglobin and serum albumin, and good renal function at biopsy were good predictors for renal survival. Older age and hypertension at biopsy were poor prognostic factors for patient survival in iMN patients. Prognostic information of outcomes in this study might be helpful to optimize management in iMN patients.
P0415MONOCLONAL GAMMOPATHY-RELATED RENAL DISEASES: NEW CLINICAL AND HISTOLOGICAL PATTERNS
Authors: Schiavone Giulia , Santostefano Marisa , Fabbrizio Benedetta , Mancini Elena 
Published: June 2020

Abstract

Background and Aims
In the last few years new clinical-histopathological forms of paraproteinemia associated kidney disease have emerged: light chain proximal tubulopathies, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and C3-glomerulopathy.
It is now widely recognized that the pathogenic role of the monoclonal protein depends on the free light chain chemical-physical features, even in the case of “dangerous small B cell clones”.
Thus MGRS (monoclonal gammopathy of renal significance) associated disease is now considered a different entity from monoclonal gammopathy of undetermined significance (MGUS).

Method
We retrospectively evaluated the clinical-histopathological features of the biopsies performed in our Nephrological Unit on patients with MGUS in 2008-2018, in order to re-classify them in accordance with the recent scientific literature.

Results
Nine patients (7 M/2 F; age 46-77 y) were analyzed: five of them suffering from CKD stage 2, four of them with AKI or rapidly progressive CKD, 7 with proteinuria &gt; 1 g/day, 2 with physiological proteinuria. Bone marrow biopsy: 7 patients with MGUS, 2 with smoldering multiple myeloma. Renal biopsy: 4 glomerulopathies (monoclonal fibrillary glomerulonephritis, cryoglobulinaemic (type I) glomerulonephritis, C3 glomerulonephritis, PGNMID), 5 proximal tubulopathies (2 LCPT with Fanconi syndrome, 1 LCPT without cytoplasmic inclusions and with interstitial inflammatory reaction, 2 LCPT with acute tubular necrosis) Table 1, Table 2, Light microscopy and IF of PGNMID.

Conclusion
MGRS is responsible for the pathogenesis of new histopathological renal lesions, based on new pathogenetic pathways. The clinical and histological features of the different disease states are dependent on the structure of FLCs. Our retrospective analysis of MGRS biopsies confirms how difficult and complex the diagnostic challenge of monoclonal renal injury really is.
The differentiation between MGUS and MGRS is based on renal biopsy and demonstration of monoclonality on kidney tissue even if serum/urine immunofixation is negative.
Early biomarkers of the pathogenetic role of monoclonal FLC should be identified both for diagnosis and therapeutical monitoring.
P0419AUTOANTIGEN-SPECIFIC TH17 AND TH22 INFLAME THE KIDNEY IN ANCA-VASCULITIS
Authors: Boschmann Erika , Hinkeldein Tanja , Kribben Andreas , Dolff Sebastian , Van Paassen Pieter , Witzke Oliver , Wilde Benjamin 
Published: June 2020

Abstract

Background and Aims
Anti-neutrophil-cytoplasmic-antibody (ANCA)-associated-vasculitis (AAV) is an autoimmune small-vessel-vasculitis. T-cells play a pivotal role in pathogenesis as drivers of autoantibody formation and vasculitic damage. However, the involvement of T-cells in renal vasculitis is understood poorly. IL-17C is secreted by epithelial parenchymal cells enhancing the pathogenicity of Th17 cells. Furthermore, IL-17C is a chemotactic factor for Th17 cells. The aim of this study was to assess the role of Th17 cells and IL-17C in the pathogenesis of ANCA-vasculitis in an animal model of AAV.

Method
Wistar-Kyoto-rats were immunized with myeloperoxidase (MPO) in Freunds Adjuvant to induce AAV. Control rats were immunized with Freunds Adjuvant only. Albuminuria was determined weekly and rats were culled after two, four and six weeks. At the time of harvest, renal T-cells were isolated and characterized by flow cytometry. Antigen-specificity was determined by ELiSPOT. Petechial bleedings on the lung surface reflecting pulmonary vasculitis were quantified after harvest. Gene expression in spleen, kidneys and lungs was studied by PCR and is expressed as fold change over controls. IL-17C levels were measured in sera by ELISA.

Results
MPO-rats developed detectable titres of anti-MPO by week two. By week six, all MPO-animals developed renal vasculitis with significant albuminuria and pulmonary vasculitis. Accordingly, MPO animals showed significant crescent formation as compared to the controls (% of affected glomeruli: 11.4 ±10.5% vs. 0.4 ±0.7%, p&lt;0.005). The petechial bleeding score on the lung surface was higher in MPO-immunized rats than in controls at week six (68 ±13 vs. 2 ±1, p&lt;0.05). From week two on, Th17 and Th22 cells inflamed the kidney as determined by PCR and/or flow cytometry in MPO-rats. The Th17 and Th22 infiltrate was heaviest at week six post-immunization. The intra-renal T-cell response was skewed towards Th17 as compared to the frequency of splenic Th17 cells in MPO-rats (9.1 ±4.3% vs. 1.9 ±0.6%, p&lt;0.005). The majority of intra-renal Th17 and Th22 cells was MPO-specific. Control rats did not show renal T-cell infiltration. Renal transcripts for IL-17C were slightly decreased in week 2 (0.88 ±0.1 fold), unchanged in week four (1.0 ±0.2) and slightly increased in week six after immunization (1.7 ±0.7 fold). Pulmonary IL-17C mRNA transcripts were decreased during weeks two and four after disease induction as compared to controls (0.29 ±0.07 fold, 0.98 ±0.2 fold). During week six, pulmonary IL-17C mRNA transcripts were slightly increased over controls (1.9 ±0.4 fold). Serum levels of IL17C were unchanged during weeks two to six after disease induction comparing MPO-immunized rats and controls.

Conclusion
Th17 and Th22 cells are drivers of renal inflammation in ANCA-vasculitis. The role of IL-17C in this cascade needs to be determined.