bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO234: Ubiquitin C-Terminal Hydrolase L1 (UCHL1) Antibody Production in Nephrotic Syndrome
Authors: Chebotareva Natalia , Vinogradov Anatoliy , Cao Wenjing 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Recently, evidence has emerged that the ubiquitin system, which is involved in extracellular protein degradation, is most susceptible to damage in podocytes in cases of severe nephritis. We studied anti-ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) antibodies in patients with glomerulonephritis and proteinuria.

METHOD
Sixty-five patients with CGN were included in our study. Forty-two patients had nephrotic syndrome, and twenty-three did not. Serum levels of anti-UCHL1 antibodies were measured by ELISA.

RESULTS
The levels of anti-UCHL1 antibodies were significantly higher in FSGS patients than in MCD, IgA nephropathy, membranous nephropathy or membranoproliferative glomerulonephritis patients and healthy people. The levels of UCHL1 antibodies in serum did not correlate with 24-h proteinuria, eGFR, blood pressure, glomerulosclerosis percentage or area of tubulointerstitial fibrosis. During the development of the ROC curve {[AUC = 0.839 [95% confidence interval (CI) 0.740–0.937]} for FSGS versus other forms of nephritides, a readjustment of the sensitivity of 81.3% and specificity of 72.7% were established (Fig. 1). A former increase in anti-UCHL1 antibody levels above 0.749 ng/mL may be a marker of FSGS (Fig. 1).

CONCLUSION
An increase in the level of anti-UCHL1 antibodies in the serum was noted in FSGS, which suggests that these antibodies could be a potential biomarker for FSGS patients.
MO235: TGF-Β1/PSMAD3 Dependent Signaling in Glomerulonephritis and Its Association With Renal Injury and Progression
Authors: Chalkia Aglaia , Gakiopoulou Harikleia , Giannou Panagiota , Kourniotis Dimitrios , Kapota Athanasia , Mpora Margarita , Vasilopoulos Dimitrios , Petras Dimitrios 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Transforming growth factor-β1 (TGF-β1) has long been considered as a potent, multifunctional cytokine that is involved in the pathogenesis of fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad3 signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD).

METHOD
We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression and their role in progression to CKD.

RESULTS
TGF-β1 expression correlated positively with segmental glomerulosclerosis (P = .025) and creatinine level at diagnosis (p = .002), while pSmad3 expression with interstitial inflammation (P = .024). In glomerulus, we recorded different expression patterns of pSmad3 in crescents, while concomitant expressions of strong Smad7 and moderate pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (P = .011), intense interstitial inflammation (P = .029) and lower serum complement 3 (P = .028) and complement 4 (P = .029). We also reported a significant preferable expression between pSmad3 and glomerular endothelial cells of proliferative GN (P = .045) and podocytes of non-proliferative GN (P = .005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR = 5.08; 95% CI 1.133–22.78; P = .034) was emerged as independent predictor for CKD.

CONCLUSION
TGF-β1/Smad3 dependent signaling is upregulated, especially in proliferative GN, with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.
MO238: Erythroid ACKR1 Expression has a Protective Effect on the Development of Experimental Glomerulonephritis
Authors: Artinger Katharina , Novitzky-Basso Igor , Kirsch Alexander H , Schabhuettl Corinna , Hub Elin , Eller Philipp , Rosenkranz Alexander , Eller Kathrin , Rot Antal 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The overwhelming majority of individuals of West African ancestry carry an ‘erythroid silent’ FyB(ES) SNP in the promoter region of ACKR1 that causes a selective loss of ACKR1 in erythroid cells but does not affect its expression in endothelial cells. The FyB(ES) polymorphism is of a special interest for understanding human kidney disease as individuals of West African ancestry have higher incidence of chronic kidney disease. Moreover, multiple chemokine ligands of ACKR1 are known to contribute to the inflammatory pathology in experimental nephrotoxic serum nephritis (NTS), a murine model of immune complex glomerulonephritis.

METHOD
We developed two humanized transgenic mouse strains that are genetically deficient for mouse ACKR1 but instead carry either West African FyB(ES) or Caucasian FyB human polymorphic ACKR1 variants. These strains as well as ACKR1-deficient and WT mice were subjected to NTS. The parameters of immunopathogenesis and kidney disease were evaluated after 14 days after the induction of NTS.

RESULTS
Albuminuria, PAS and tubular injury scores were significantly increased in FyB(ES)tg and ACKR1-deficient mice as compared with their respective control strains. While monocytes were unchanged in peripheral blood, we found significantly increased numbers of macrophages and neutrophils infiltrating the kidneys of FyB(ES)tg and ACKR1-deficient mice. Interestingly, T cell numbers in the draining lymph nodes were comparable between FyB(ES)tg and ACKR1-deficient mice and their respective controls.

CONCLUSION
We found that NTS was more severe in ACKR1-deficient and FyB(ES) mice as compared with their respective controls. Our results show that ACKR1 expression in the erythroid compartment has a significant impact on the development of kidney disease. These findings have important implications for the pathomechanisms of glomerulonephritis in individuals of West African ancestry who lack ACKR1 selectively in the erythroid lineage.
MO244: PCSK9 Inhibitors are Efficient in Treatment of Resistant Hypercholesterolemia in Nephrotic Syndrome
Authors: Vukovic Brinar Ivana , Ivandic Ema , Gellineo Lana , Jelakovic Ana , Fistrek Prlic Margareta , Jelakovic Bojan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Hypercholesterolemia in nephrotic syndrome is commonly resistant to statin therapy and represents an important clinical challenge both for cardiovascular risk prevention and to eliminate lipotoxic effect on podocytes. Serum PCSK9 level is elevated in nephrotic syndrome and has a key pathophysiologic role in development and persistance of hyperlipidemia. Thus, we aimed to investigate the role of PCSK9 inhibitors in control of hypercholesterolemia in patients with neprotic syndrome.

METHOD
Consecutive patients with nephrotic syndrome and elevated atherogenic Lp (a) (n = 4) and patients with resistant secondary glomerulonephritis with nephrotic proteinuria (n = 2) were included. In all patients, in addition to full dose statin therapy, evolocumab 420 mg s.c. monthly was introduced. Lipid levels were measured after a median of 4 (range 2–9) months after starting evolocumab.

RESULTS
Nephrotic syndrome was caused by focal segmental glomerulosclerosis in four patients (66.7%) and membranous nepropathy was the cause in two patients (33.3%). Median age of included patients was 49.5 (range 24–70) years. Four patients with primary cause of glomerulonephritis received specific imunosupressive treatment. During follow-up, we observed descrease in glomerular filtration rate (eGFR median 58.5 interquartile range (IQR) [46.7–98.7] mL/min/1.73 m2 versus median 47 IQR [38.25–89.25] mL/min/1.73 m2; P = .046) and persistence of proteinuria [median 11 970 IQR (3862–13 765) mg/dU versus median 10 847 (5407–14 340) mg/dU; P = .753]. However, despite persistent proteinuria and decrease in eGFR, significant decrease in total cholesterol [median 9.10 IQR (6.92–10.87) mmol/L versus median 6.81 (5.4–8.45) mmol/L; P = .028] and LDL cholesterol [median 5.40 IQR (4.12–7.25) versus median 4.04 IQR (2.70–4.60); P = .046] was observed. There was no significant difference in Lp (a) and triglyceride levels.

CONCLUSION
PCSK9 inhibitors are a promising new therapeutic option for hyperlipidemia in patients with nephrotic syndrome. Further research, including a larger number of patients, is needed to correctly position PCSK9 inhibitors in treatment of hyperlipidemia in patients with nephrotic syndrome.
MO251: Renal Glucocorticoid Receptor Expression and Clinical Course in Patients with IGA Nephropathy
Authors: Tekin Ala Bilge , Paydas Saime , Kaya Bülent , Eren Ateş Kıvılcım , Gönlüşen Gülfiliz , Sertdemİr Yaşar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Glucocorticoids are used as primary treatment in IgA nephropathy (IgAN), and they manifest their effects by binding to intracellular glucocorticoid receptors. Studies have shown that GCR expression correlates with the degree of steroid response in various diseases. Therefore, we aimed to evaluate renal GCR expression, Oxford MEST score in clinical course of IgAN patients.

METHOD
This study included 110 patients with biopsy-proven IgAN. Patients were treated with ACEI/ARB, methylprednisolon (80% patients). In renal biopsies, Oxford-MEST score was calculated and GCR expression was determined immunohistochemically. KDIGO criteria (2020) were accepted for remission. Clinical course, eGFR, proteinuria and other biochemical tests test were recorded during 1-year follow-up period.

RESULTS
Demographic and laboratory data did not correlate with renal GCR staining rate. İn patients with M1 of the MEST score, GCR staining was more prominent than those with M0. GFR values were higher and proteinuria was lower in patients with T0 compared with patients with T1 and T2 (P &lt; .05 for all) . Patients with E1 had significantly higher systolic blood pressure (BP), increased proteinuria and lower eGFR than patients with E0. Poor prognostic factors for achieving remission were higher systolic/diastolic BP, increased levels of white blood cell (WBC) count/neutrophil count, PTH, BUN, creatinine, uric acid, potassium, magnesium, MCV, Mentzer index, total cholesterol, LDL and higher sclerosis in biopsy at baseline during follow up period for 1 year.

CONCLUSION
Clinical presentation and outcome at 1 year in IgAN patients were well predicted by the Oxford-MEST score, but not by renal GCR expression. GCR staining intensity was only correlated with M1 score. Baseline higher BP, increased serum creatinine, uric acid and PTH were poor prognostic factors. Interestingly higher WBC and neutrophils counts, increased serum LDL and Mentzer index at baseline were also correlated with clinical course.
MO259: Maintenance Therapies for Anti-Neutrophil Cytoplasmic Antibody Small-Vessel Vasculitis: A Network Meta-Analysis
Authors: Bellos Ioannis , Boletis Ioannis , Karagiannis Minas , Lionaki Sophia 
Published: May 2022

Abstract

BACKGROUNDS AND AIMS
Over the past two decades, considerable progress has been made in maintaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA) vasculitis using a variety of medications, including rituximab, azathioprine, mycophenolate, methotrexate, and glucocorticoids. However, although survival has improved dramatically over the last decades, relapse rates remain significant for certain patients, stressing the need for advocation of new therapeutic strategies. The aim of this study was to compare the efficacy and safety of different regimens used for maintenance of remission in patients with ANCA-vasculitis.

METHOD
This network meta-analysis studied adult patients with ANCA-vasculitis in complete remission, who were maintained with various regimens, excluding patients with eosinophilic granulomatosis with polyangiitis, and those who have ended up in end-stage kidney disease. Outcomes of interest included relapse (any/major), relapse-free survival and adverse effects. PubMed, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception.

RESULTS
Overall, the meta-analysis was based on 10 reports, describing the outcomes of 7 RCTs including 752 patients with ANCA-vasculitis. Compared with rituximab, relapse-free survival was significantly worse with the use of azathioprine {HR 2.11 [95% confidence interval (CI) 1.19–3.74]}, methotrexate [HR 2.51 (95% CI 1.24–5.08)] and mycophenolate mofetil [HR 3.57 (95% CI 1.70–7.46)]. Compared with mycophenolate mofetil, better outcomes were estimated for azathioprine [HR 0.59 (95% CI 0.37–0.94)], cyclophosphamide [HR 0.39 (95% CI 0.20–0.75)] and leflunomide [HR 0.30 (95% CI 0.11–0.84)]. Compared with rituximab a higher relapse risk was estimated for azathioprine [OR 2.15 (95% CI 1.00–4.59)] and mycophenolate mofetil [OR 4.42 (95% CI 1.63–11.94)]. A higher risk of major relapse was calculated for azathioprine [OR 2.39 (95% CI 1.10–5.19)], methotrexate [OR 3.18 (95% CI 1.14–8.89)] and mycophenolate mofetil [OR 5.20 (95% CI 1.65–16.37)] compared with rituximab. The rates of serious adverse effects did not differ significantly among interventions.

CONCLUSION
Rituximab appears predominant in maintaining remission in patients with ANCA-vasculitis with no cost in adverse events.
MO268: Use of Corticosteroids in a Norwegian Cohort of Patients with IGA Nephropathy and Rapid Progression to End-Stage Renal Disease
Authors: Lunde Haaskjold Yngvar , Rivedal Mariell , Gjærde Lura Njål , Bjorneklett Rune , Knoop Thomas 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Despite several clinical trials, treatment with corticosteroids in patients with Immunoglobulin A nephropathy (IgAN) remains controversial [1, 2]. The recently updated KDIGO guidelines suggests that treatment with corticosteroids could be considered in patients with persistent proteinuria above 0.75 to 1.0 g per day in patients with estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m2 despite intensive supportive care [3]. This is a more liberal approach compared with the 2012 guidelines, which suggested that patients selected for treatment with steroids should have eGFR above 50 mL/min/1.73 m2 [4]. It could be valuable to identify clinicians decision on when to initiate immunosuppressive treatment, since this could have implication on how future therapeutics might be used in patients with IgAN [5]. Our aim is to describe the use of corticosteroids and evaluate the effect of this treatment using a Norwegian cohort of patients with IgAN.

METHOD
We identified patients with biopsy-proven IgAN from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, who all had progressed to end-stage renal disease (ESRD) and collected clinical, treatment and biochemical data from patient records.

RESULTS
A total of 151 patients with a diagnostic kidney biopsy performed between 1988 and 2010 were included. The median time from biopsy to ESRD was 5 years. A majority of 94% of the patients received supportive treatment with Renin–Angiotensin–Aldosterone System blockade. A total of 40 patients (27%) received treatment with corticosteroids, with a median eGFR and proteinuria at time of biopsy at 49.5 mL/min/1.73 m2 and 5.1 g per day, respectively. Median time from biopsy to steroid treatment was 12 months. Patients treated with corticosteroids had a significant decrease in proteinuria from 5.6 to 3 g per day (P = .02), but there was no difference in time to progression to ESRD between the two groups (P = .58). The vast majority (87.5%) of the patients treated with corticosteroids reported on adverse events.

CONCLUSION
We found that the use of corticosteroids had significant impact on proteinuria but did not delay progression to ESRD. Adverse events were common in patients treated with corticosteroids. The patients were treated according to the current guidelines
MO284: Dipeptidyl-Peptidase-4 Inhibitor, Teneligliptin, Ameliorates Folic Acid-Induced Acute Kidney Injury in Mice
Authors: Ema Chiemi , Iwakura Takamasa , Tsuchida Miyuu , Fujikura Tomoyuki , Yasuda Hideo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Acute kidney injury (AKI) is histologically characterized by tubular cell death and inflammation. It has demonstrated that cell death in renal tubule cells on AKI could be introduced by regulated necrosis or apoptosis, but the molecular mechanisms are reported to be different between AKI models [1]. Recently, Dipeptidyl -peptidase-4(DPP4) inhibitors have been reported to ameliorate cisplatin-induced AKI and ischemia-reperfusion-induced AKI [2, 3]. In this study, we examined the effect of teneligliptin, a DPP4 inhibitor, on folic acid (FA)-induced AKI(FA-AKI) model in mice, which is reported to be mainly induced by ferroptosis, one of the regulated necrotic pathways [4].

METHOD
C57BL/6J mice (12–14 weeks old) received a single intraperitoneal injection of FA of 250 mg/kg in 0.3 mol/L sodium bicarbonate, and were euthanized 48 h later. Teneligliptin or vehicle were orally administered just before and 24 h after FA infusion, respectively. Blood samples and renal tissue samples were collected at the time of euthanasia for evaluation.

RESULTS
The increase of serum creatinine (mean 0.297 mg/dL in teneligliptin-treated mice versus 0.833 mg/dL in vehicle-treated mice; P &lt; 0.01) and blood urea nitrogen (mean 72.22mg/dL in teneligliptin-treated mice versus 177.7mg/dL in teneligliptin-treated mice; P = 0.016) were suppressed in teneligliptin-treated mice, compared to vehicle-treated mice (Fig. 1A and B). Histologically, teneligliptin treatment reduced tubular injury score, tubular cell death evaluated with the terminal uridine nick-end labeling (TUNEL) and kidney injury molecule-1 (kim-1) expression in the kidney (Fig. 2A-C). In addition, number of infiltrating Ly6G + neutrophil and number of infiltrating F4/80 + macrophages were decreased in the kidney of teneligliptin-treated mice, compared with that of vehicle-treated mice (Fig. 2D and E).

CONCLUSION
We found that teneligliptin ameliorated FA-AKI in mice by suppressing necroinflammation in the kidney. Further studies are needed to clarify the underlying mechanisms of the renoprotection.
MO305: COVID-19 in Elderly Patients with Acute Kidney Injury
Authors: Ayar Yavuz , Deniz Olgun , Doner Baris , Kilic İsa , Demir Canan , Sahin Abdulkadir 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Coronavirus disease 2019 (COVID-19), which started in China in December 2019 and spread all over the world, is more progressive in patients who are elderly and with chronic diseases. Especially, kidney involvement affects the survival of patients. In this study, we analysed COVID-19 patients who developed acute kidney injury treated in our unit, retrospectively.

METHOD
The clinical and laboratory data of 610 patients who were hospitalized due to COVID-19 pandemic between 1 June 2020 and 30 June 2021 in the intensive care and other clinics of our hospital were evaluated from the records, retrospectively. A total of 140 patients were diagnosed with AKI according to the criteria of Kidney Disease Global Outcomes (KDIGO). The patients were divided into two groups as KDIGO stages 1 and 2 and 3.

RESULTS
The median age in both groups was 70 (35–92) and 73 (35–90) years. Approximately 70% of them were &gt;65 years old. Almost all of the patients had hypertension. Most of the patients were using angiotensin converting enzyme inhibitors (ACE inh) or angiotensin receptor blockers (ARB) (84%). AKI was present at the time of admission (61.9%) in the KDIGO 1 group and at the time of hospitalization (64.3%) in the KDIGO 2, 3 groups. The mortality rate was higher in stage 2–3 AKI patients (35.7%). Ferritin and fibrinogen levels were high in the KDIGO 2, 3 group, while lymphocyte levels were low.

CONCLUSION
AKI can be seen at the time of admission and during treatment in patients who are hospitalized and treated due to COVID-19. COVID-19 is more mortal in patients with advanced AKI.
MO308: Urinary Biomarkers to Predict Acute Kidney Damage and Mortality In COVID-19
Authors: Racovitan Diana , Hogeweg Maximilian , Doevelaar Adrian , Seidel Maximilian , Rohn Benjamin , Bettag Sebastian , Rieckmann Sonja , Babel Nina , Henning Westhoff Timm , Seibert Felix S 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Acute kidney injury (AK) is a frequent condition in patients hospitalized for COVID-19. There are only few reports on the use of urinary biomarkers in COVID-19 and no data comparing the prognostic use of individual biomarkers in the prediction of adverse outcome so far.

METHOD
We performed a prospective monocentric study on the value of urinary biomarkers to predict the composite endpoint of a transfer to the intensive care unit (ICU), the need for renal replacement therapy (RRT), mechanical ventilation and in-hospital mortality. A total of 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission in order to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin and vanin-1.

RESULTS
We identified calprotectin as a predictor of a severe course of the disease, requiring intensive care treatment (AUC 0.728, P = .016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19 associated AKI without reaching statistical significance (AUC 0.669, P = .053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, P = .077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints.

CONCLUSION
While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, this study shows that urinary calprotectin and NGAL concentrations are independent predictors of an adverse course of the disease. Calprotectin and NGAL may thereby constitute helpful adjuncts in the identification of patients at increased risk who may benefit from upcoming antiviral agents to SARS-CoV-2.