bluuebunny/crossref_metadata_2025_split huggingface dataset:
FC 050THE PREDICTIVE ABILITY OF URINARY BIOMARKERS FOR PROGRESSION OF ACUTE KIDNEY INJURY IN CRITICAL ILLNESS
Authors: Duff Stephen , Irwin Ruairi , Cote Jean Maxime , Doran Peter , Murray Patrick 
Published: May 2021

Abstract

Background and Aims
Acute Kidney Injury (AKI) is a common hospital complication associated with high morbidity, mortality and the risk of progression to CKD. Despite globally increasing rates of AKI and a shortage of critical care beds, clinicians currently lack the tools to predict progression of early AKI. The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective multi-center observational study with a heterogenous cohort of critically ill patients (n= 717). We hypothesised that a panel of 14 novel urinary biomarkers would predict progression of AKI.

Method
Biomarker values were measured daily for 7 days from ICU admission, including on the day of Stage 1-2 AKI diagnoses occurring within 48 hours of ICU admission. The primary outcome was progression to the composite outcome of increased AKI KDIGO Stage, Renal Replacement Therapy (RRT) or Death within 7 days of ICU admission. AUC-ROC values and adjusted Odds Ratios were calculated using multivariate logistic regression, and the additional value of biomarkers over the clinical model (serum creatinine and urine output at time of diagnosis) was assessed. In a secondary analysis,all AKI events within 7 days (including those diagnosed at Stage 3, and/or on days 3-7) were included, with the endpoint of progression to RRT/Death within 30 days of ICU admission.

Results
AKI developed in 268 patients (37%) within 7 days of ICU admission. 95 patients were diagnosed with AKI at Stage 1or2 AKI within 48 hours, of whom 32 (33.7%) progressed to the primary outcome. Adjusted odds ratios for the prediction of AKI progression were significantly higher for the highest tertile, versus the lowest, of eight biomarkers including uCystatin C (OR 5.2, 95% CI; 1.3-23.6), uAlbumin (OR 4.9, 95% CI; 1.5-18.3), uNGAL (OR 4.6, 95% CI; 1.4-17.9) and uIGFBP-7 (OR 4.7, 95% CI; 1.2-21.5). LFABP-1, KIM-1, IL-18 and Alpha-1-M also significantly improved prediction (Table 1). In ROC analysis of the primary outcome, uCystatin C (AUC 0.75, 95% CI; 0.63-0.87), uNGAL (AUC 0.72, 95% CI;0.61-0.84), uAlbumin (AUC 0.70, 95% CI; 0.59-0.82) and IL-18 (AUC 0.70, 95% CI; 0.58-0.82) had moderate accuracy; the others did not.

Conclusion
In this cohort study of AKI progression within 7 days of ICU admission, eight novel urinary biomarkers improved the prediction of AKI progression after multivariate adjustment. Similarly, ROC analysis found that several biomarkers had moderate accuracy for the prediction of AKI progression in the ICU.
FC 098MESENCHYMAL STEM CELL EXOSOMES AMELIORATE MICE PERITONEAL FIBROSIS INDUCED BY HUMAN PERITONITIS DIALYSIS EFFLUENT
Authors: Chen Kehong , He Yani 
Published: May 2021

Abstract

Background and Aims
Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies for it. The purpose of this study was to investigate the protective effect of exosomes secreted by mouse bone marrow mesenchymal stem cells on peritoneal fibrosis and to reveal the mechanism.

Method
Forty-two male C57BL/6 mice were randomly divided into a normal group, a control group (2.5% glucose dialysate), a peritonitis-effluent group (The overnight 2.5% glucose dialysate of patients with peritonitis), a high glucose dialysate group (4.25% glucose concentration), a peritonitis-dialysate + exosome group, and a high glucose dialysate + exosome group. The mouse model of peritoneal fibrosis was constructed by intraperitoneal injection of human peritonitis effusion continuously for 42 days. The mice in the exosome treatment group received intraperitoneal injection of mesenchymal stem cell (MSC)-exosomes twice. The level of peritoneal structural and functional damage, inflammation, fibrosis and mesothelial cell damage of peritoneum were detected. Furthermore, the effect of MSC-exosomes was validated in vitro.

Results
Peritoneal transport was significantly impaired and peritoneal thickness was significantly increased in the peritonitis-effluent group and the high glucose dialysate group after 42 days. The degree of peritoneal inflammation and fibrosis in the two groups was significantly higher than the control group. The results suggested that human peritonitis dialysis effluent could be used to construct a mouse model of peritoneal fibrosis. Masson staining results showed that the fibrosis degree of peritonitis - effluent + exosome group was significantly less than the peritonitis - effluent group. Immunohistochemical analysis showed that the expression levels of mesothelial markers E-cadherin and ZO-1, neutrophil granulocytes (MPO) and macrophages (F4/80), and fibrosis markers collagen I and a-SMA in the peritonitis - effluent + exosome group were significantly lower than those in the peritonitis - effluent group. Similarly, the high glucose dialysate + exosome group mice showed significantly lower levels of peritoneal inflammation and fibrosis than the high glucose dialysate group mice. In vitro experiments showed that exosomes could down-regulate the secretion of IL-1, IL-6 and TGF- by renal tubular cells stimulated by high glucose dialysate, maintain the expression of mesenchymal cell marker (E-cadherin), and inhibit the mesenchymal marker (-SMA), suggesting that exosomes could inhibit the transdifferentiation of peritoneal mesenchymal cell-mesenchymal cells (MMT).

Conclusion
MSC-exosomes can alleviate peritoneal fibrosis by inhibiting peritoneal mesothelial cell-mesenchymal cell transdifferentiation.
FC 086GLOMERULI PROTEOME ANALYSIS REVEALS EARLY DIFFERENCES BETWEEN PRE-EXISTING AND DE-NOVO TYPE 2 DIABETES IN HUMAN RENAL ALLOGRAFTS
Authors: Kipp Anne , Marti Hans-Peter , Babickova Janka , Nakken Sigrid , Leh Sabine , Halden Thea A S , Jenssen Trond , Vikse Bjørn Egil , Åsberg Anders , Furriol Jessica 
Published: May 2021

Abstract

Background and Aims
Diabetes mellitus, either preexisting or developing after kidney transplantation remains a crucial clinical problem. The aim of this study is to compare the proteome of histologically normal glomeruli from normoglycemic (NG), T2DM, and PTDM patients one year after kidney transplantation to identify novel early biomarkers detectable prior to the development of histologically visible diabetic nephropathy.

Method
We comparatively analyzed the proteome of histologically normal glomeruli from normoglycemic (NG) recipients, and recipients with pre-existing type 2 diabetes mellitus (T2DM), or post-transplant diabetes mellitus (PTDM), in protocol biopsies obtained one year after kidney transplantation. Glomerular cross-sections were microdissected in core biopsies from 8 NG, 8 PTDM and 8 T2DM kidney transplant recipients. Proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analyzed.

Results
Proteins related to immune response and inflammation, transport regulation and cell organization and communication, including the nephrin family, were more abundant in NG, as compared to the combined groups of diabetic patients. Proteins involved in cell morphogenesis and adhesion were less abundant in PTDM, as compared to T2DM. In contrast, CCT3, CCT4 and CNDP2 diabetic nephropathy markers, LDHB and tacrolimus binding protein FKBP1A were significantly overrepresented in glomeruli from PTDM, as compared to T2DM patients.

Conclusion
These data suggest that glomerular proteome profile differentiates PTDM from NG and T2DM, and disruption of cell-cell interactions at molecular level represents an early event in PTDM development.
FC 088DUAL BLOCKADE OF ENDOTHELIN A RECEPTOR (ETA) AND SODIUM-GLUCOSE COTRANSPORTER 2 (SGLT2) TO PREVENT DIABETIC KIDNEY DISEASE PROGRESSION ON A TYPE 2 MURINE MODEL
Authors: Vergara Arana Ander , Molina Mireia , Jacobs Cachá Conxita , Dominguez Pamela , Benito Begoña , Agraz Irene , Seron Micas Daniel , Soler María José 
Published: May 2021

Abstract

Background and Aims
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and endothelin A receptor (ETA) antagonist have shown nephroprotective effects in diabetic kidney disease (DKD) through blood pressure and urinary albumin loss reduction. The protective impact and the pathways through which they exert this protection have not yet been elucidated. This study aimed to investigate the effects of the add-on therapy of SGLT2i and ETA antagonists on a type 2 diabetes murine model.

Method
12 weeks-old db/db mice were treated for 8 weeks with different combinations of empagliflozin 10 mg/Kg/day (SGLT2i), atrasentan 7 mg/Kg/day (ETA antagonist) or ramipril 8 mg/Kg/day. A group of non-diabetic mice (db/m) was included as negative control. In vivo variables were recorded during treatment, including transdermal measured glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR). After treatment kidneys were preserved for histopathological studies.

Results
After 8 weeks of treatment empagliflozin decreased fasting blood glucose alone or in combination with atrasentan or ramipril (234.2 mg/dL mean reduction in three treated groups when compared to db/db). Ramipril decreased blood pressure (BP) in monotherapy or in add-on therapy. Empagliflozin or atrasentan alone did not have any effect on blood pressure, but combination of atrasentan and ramipril had a synergistic effect and reduced both systolic (9.0 mmHg, CI 95%: -16.3 to -1.1; P=0.028) and diastolic BP (11.9 mmHg, CI 95%: -17.7 to -3.1; P=0.005) when compared to ramipril alone. The combination of atrasentan and ramipril significantly reduced UACR (1002 ug/mg, CI 95%: -2312.0 to -32.4; P=0.043). Empagliflozin treatment alone or in combination also reduced UACR (686.0 ug/mg mean reduction in three treated groups), although this reduction was not statistically significant. In the kidney, empagliflozin in monotherapy or combination reduced glomerular mesangial matrix expansion (4.85% mean mesangial reduction in three treated groups). Treatments with atrasentan and ramipril also reduced measangial matrix expansion.

Conclusion
Both empagliflozin and atrasentan demonstrated possible beneficial effects in DKD by reducing BP, UACR, and mesangial matrix expansion. The add-on therapy did not show greater protective effects in the analysed variables. Further studies are needed to characterize these protective effects and pathways involved.
FC 026COVID-19 IMPACT ON ELDERLY HEMODIALYSIS POPULATION: RESULTS FROM THE SPANISH COVID-19 CKD WORKING GROUP REGISTRY
Authors: Vergara Arana Ander , Molina Mireia , Villegas Andrés , Sã¡nchez Cã¡mara Luis Alberto , De Sequera Ortiz Patricia , Toapanta Néstor , Manrique Joaquín , Shabaka Amir , Aragoncillo Ines , Ruíz María Carmen , Benito Silvia , Sanchez-Alvarez Jose Emilio , Soler María José 
Published: May 2021

Abstract

Background and Aims
Age and chronic kidney disease have been described as mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an important percentage of patients in hemodialysis are elderly. This study aimed to investigate the impact of COVID-19 in this population and to determine risk factors associated with mortality.

Method
Data was obtained from the Spanish COVID-19 CKD Working Group Registry, that included patients in renal replacement therapy (dialysis and kidney transplantation) infected by COVID-19. From March 18, 2020, to August 27, 2020, 1165 patients on hemodialysis affected by COVID-19 were included in the Registry. A total of 328 patients were under 65 years-old and 837 were 65 years old or older (elderly group).

Results
Mortality was 18.6% higher (95% confidence interval (CI): 13.8%-23.4%) in the elderly hemodialysis patients compared to the non-elderly group (see figure). Death from COVID-19 infection was increased 5.5-fold in hemodialysis patients compared to mortality in the general population for a similar period, and there was an age-associated mortality increase in both populations (see figure 1). In multivariate Cox regression analysis, age (hazard ratio (HR) 1.58, 95% CI: 1.31-1.92), dyspnea at presentation (HR 1.61, 95% CI: 1.20-2.16), pneumonia (HR 1.76, 95% CI: 1.12-2.75) and admission to hospital (HR 4.13, 95% CI: 1.92-8.88) were identified as independent mortality risk factors in the elderly hemodialysis population. Treatment with glucocorticoids reduced the risk of death (HR 0.71, 95% CI: 0.51-0.98) in aged patients on hemodialysis.

Conclusion
Mortality is dramatically increased in elderly hemodialysis patients affected by COVID-19. Age, dyspnea at presentation, pneumonia or hospitalization are factors associated with a worse prognosis, after adjusting dialysis population to other confounding factors. Treatment with glucocorticoids could be a therapeutic option for this specific population.
FC 121THE UPTAKE OF PET RADIOTRACER 18 F-FLUORODEOXYGLUCOSE BY THE RENAL ALLOGRAFT SIGNIFICANTLY CORRELATES WITH THE ACUTE BANFF SCORES OF CORTEX INFLAMMATION
Authors: Weekers Laurent , Lovinfosse Pierre , Pottel Hans , Bouquegneau Antoine , Bonvoisin Catherine , Bovy Christophe , Grosch Stéphanie , Hustinx Roland , Jouret François 
Published: May 2021

Abstract

Background and Aims
Acute T-cell mediated rejection (TCMR) is associated with the recruitment of mononuclear leukocytes into the renal transplant, which corresponds to the core of the conventional Banff classification. The boosted metabolism of these inflammatory cells can be assessed by positron emission tomography (PET) quantifying the renal uptake of 18F-fluorodeoxyglucose (18FDG). The correlation of biopsy-based Banff versus PET-based scores of acute inflammation in the renal transplant is unknown.

Method
From January 2013 to December 2019, we prospectively performed 114 18FDG-PET/CT in 105 adult KTR who underwent per cause transplant biopsy for suspected TCMR. Biopsy-proven polyoma-BK nephropathies (n=7) and uninterpretable PET images (n=2) were excluded. PET/CT was performed 194±19 minutes after administration of 243±35 MBq of 18FDG, before any immunosuppression change. The mSUVs were measured in both upper and lower poles of the renal allograft. The acute Banff score was conventionally defined as the sum (from 0 to 15) of g (glomerulitis), ptc (peritubular capillaritis), t (tubulitis), i (inflammation in non-scarred cortex) and v (endarteritis). The Banff “total i” score (from 0 to 3) corresponds to the total cortical inflammation, including scarred and non-scarred cortex. Regression of mSUV against the acute Banff score was performed, and Pearson correlation coefficients were calculated. The distribution of mSUV between “total i” groups was assessed by the non-parametric Kruskal-Wallis test followed by Dunn’s post hoc test.

Results
The mean age of the cohort was 51.5±14.3 years, with M/F ratio of 67/38. The prevalence of biopsy-proven TCMR and borderline was 20.9% and 16.2%, respectively. The mean mSUV of the 105-case cohort was 1.82±0.45. The highest value of acute Banff score was 12, while 55.2% of biopsies were scored as 0. The distribution of “Total i” score was: 0 (58.8%); 1 (20.6%); 2 (8.8%); 3 (11.8%). Regression showed a significant correlation between mSUV and acute Banff score (p&lt;0.0001), with adjusted R² of 0.38. The mSUV value was significantly different between subgroups of “Total i” (p, 0.0047), with 2.33±0.76 in score 3 versus 1.68±0.24 in score 1.

Conclusion
18FDG-PET/CT may help noninvasively assess the degree of allograft inflammation in KTR with suspected TCMR.
FC 125DIURETIC USE IS ASSOCIATED WITH INCREASED RISK FOR POSTTRANSPLANTATION DIABETES MELLITUS IN RENAL TRANSPLANT RECIPIENTS
Authors: Sokooti Oskooei Sara , Tye Sok Cin , M. Douwes Rianne , Lambers Heerspink Hiddo , Bakker Stephan 
Published: May 2021

Abstract

Background and Aims
Posttransplantation diabetes Mellitus (PTDM) is one of the major medical problems in renal transplant recipients (RTRs). Diuretic-induced hyperglycemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in RTRs.

Method
We included 486 stable outpatient RTRs (with a functioning graft ≥1 year) without diabetes from a prospective longitudinal study (the Transplantlines Food and Nutrition Study [NCT02811835]). Participants were classified as diuretic users and non-diuretic users based on their medication use recording at baseline. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable Cox proportional-hazards regression analyses were performed to assess the prospective association between diuretic use and the risk of PTDM development.

Results
Median time since transplantation was 5.4 (2.0-12.2) years and 168 (35%) RTRs were taking diuretics. After 5.2 (IQR, 4.0 5.9) years of follow up, 54 (11%) RTRs developed PTDM. In Kaplan-Meier (log-rank test, p&lt;0.001) and Cox regression analyses, diuretic use was found to be associated with incident PTDM after adjustment for age, sex, fasting plasma glucose (FPG), and HbA1c (hazard ratio[HR] 3.28, 95% CI 1.84-5.83; p&lt;0.001). The association remained independent of further adjustment for potential confounders, including lifestyle, use of other medication, kidney function, transplantation-specific parameters, BMI, lipids, and blood pressure. Exploratory analyses further indicates that, in Cox regression analyses, both thiazide (n=74) and loop diuretics (n=76) as two main types of diuretics used among RTRs appeared to be associated with the development of PTDM, independent of age, sex, FPG, and HbA1c ([HR 2.70, 95% CI 1.24-5.29; p=0.012], and [HR 5.08, 95% CI 2.49-10.34; p&lt;0.001], respectively).

Conclusion
This study demonstrates that diuretics overall, associated with the risk of developing PTDM in RTRs, independent of established risk factors for PTDM development. The association was consistent for thiazide and loop diuretics.
FC 128NON-HLA ANTIBODIES AND EPLET MISMATCHES IN KIDNEY TRANSPLANT RECIPIENTS WITH A HISTOLOGICAL PICTURE OF ANTIBODY-MEDIATED REJECTION WITH AND WITHOUT HLA DONOR-SPECIFIC ANTIBODIES
Authors: Crespo Marta , Llinas Laura , Redondo Pachon Dolores , Butler Carrie L , Gimeno Javier , Perez-Saez Maria Jose , Buxeda Anna , Arias-Cabrales Carlos , Folgueiras Montserrat , Sanz Sara , Valenzuela Nicole M , Reed Elaine F , Pascual Santos Julio 
Published: May 2021

Abstract

Background and Aims
Correlation between antibody-mediated rejection (ABMR) and HLA donor-specific antibodies (DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of other detrimental antibodies contributing to ABMR. The role of non-HLA antibodies on outcomes is not well known.

Method
We retrospectively assessed KT biopsies scored according to Banff’15 classification. Pre- and post-KT serum samples were checked for HLA and non-HLA antibodies (MICA-Ab, angiotensin II type 1 receptor (AT1R)-Ab, endothelin-1 type A receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)). We also analyzed HLA epitope mismatches between donors and recipients.

Results
One-hundred eighteen patients with normal (n=19), ABMR histology (n=52) or IFTA (n=47) in their biopsy were studied. Graft survival was worse in ABMR patients (p=0.003). Pre-KT HLA-DSA were more frequent in ABMR cases (p=0.006). At biopsy, 73% ABMR patients had HLA-DSA (p&lt;0.001). Pre-KT AT1R-Ab were more frequent in ABMR compared with IFTA and normal cases (p=0.003), without differences in other non-HLA antibodies. Fourteen patients with histological ABMR (27%) had no detectable HLA-DSA post-KT and only 3 had non-HLA Ab. However, these ABMR-DSA- cases showed similar biopsy changes and graft survival compared with ABMR-DSA+. Pre- or post-KT non-HLA antibodies other than AT1R-Ab were detected similarly in ABMR and in normal or IFTA cases. Both total class II and DRB1 epitope mismatches were associated with postransplant DSA and ABMR-DSA+. Multivariate analysis showed that both pre-KT HLA-DSA and AT1R-Ab (DSA: OR: 3.39 [1.20-9.59], p=0.021; AT1R-Ab: OR: 5.31 [1.75-16.10], p=0.003) were strong independent predictors of postransplant ABMR-DSA+ (Table 1).

Conclusion
Despite highly prevalent HLA-DSA before and after transplantation in KT with histological ABMR, 27% of cases did not show circulating HLA-DSA. Pre-KT AT1R-Ab associated with ABMR-DSA+, but not MICA-Ab, ETAR-Ab or EC-XM+. Any of them associated significantly with ABMR-DSA-. Epitope mismatch predicted both postransplant DRB-DSA and ABMR-DSA+. Detection of pre-KT HLA-DSA and/or AT1R-Ab, together with HLA epitope mismatch assessment, are valuable tools for better DSA and ABMR prediction in KT patients.
High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients
Authors: Longlune Nathalie , Nogier Marie Béatrice , Miedougé Marcel , Gabilan Charlotte , Cartou Charles , Seigneuric Bruno , Del Bello Arnaud , Marion Olivier , Faguer Stanislas , Izopet Jacques , Kamar Nassim 
Published: May 2021

Abstract

Background
Patients with chronic kidney disease, dialysis patients and kidney transplant patients are at high risk of developing severe coronavirus disease 2019 (COVID-19). Data regarding the immunogenicity of anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (anti-SARS-CoV-2 mRNA) vaccines in dialysis patients were published recently. We assessed the immunogenicity of anti-SARS-CoV-2 mRNA vaccine in dialysis patients.

Patients and methods
One hundred and nine patients on haemodialysis (n = 85) or peritoneal dialysis (n = 24) have received two injections of 30-μg doses of BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) that were administered intramuscularly 28 days apart. Those who were still seronegative after the second dose were given a third dose 1 month later. Anti-SARS-CoV-2 antibodies were tested before and after vaccination.

Results
Ninety-one out of the 102 patients who had at least a 1-month follow-up after the second (n = 97) or the third (n = 5) vaccine doses had anti-SARS-CoV-2 antibodies. The seroconversion rate was 88.7% (86 out of 97 patients) among SARS-CoV-2 seronegative patients at the initiation of vaccination. Receiving immunosuppressive therapy was an independent predictive factor for non-response to vaccination.

Conclusion
Due to high immunogenicity and safety of mRNA vaccines, we strongly recommend prioritizing a two-dose vaccination of dialysis patients. A third dose can be required in non-responders to two doses. When possible, patients waiting for a kidney transplantation should be offered the vaccine before transplantation.