bluuebunny/crossref_metadata_2025_split huggingface dataset:
FC 081ULTRA-PROCESSED FOOD CONSUMPTION AND RISK OF INCIDENT CHRONIC KIDNEY DISEASE: THE LIFELINES COHORT
Authors: Cai Qingqing , Duan Minjie , Dekker Louise H , Bakker Stephan , De Borst Martin , Navis Gerjan 
Published: May 2021

Abstract

Background and Aims
Ultra-processed foods (UPF), that are widespread in Western-style diet, are risk factors for the development of cardiovascular disease, diabetes, obesity, hypertension, and all-cause mortality. The role of UPF in kidney function decline, however, is still unknown. The aim of this study was to investigate the associations of UPF consumption with incident CKD and estimated glomerular filtration rate (eGFR) decline. Additionally, we considered the heterogeneity of UPF by identifying different patterns of UPF consumption.

Method
The study was performed in a prospective general population-based cohort in the Northern Netherlands. A total of 78 346 participants who were free of CKD at baseline were included in this study. The dietary information was assessed at baseline using a 110-item food frequency questionnaire. The proportion (in weight) of UPF in the total diet was calculated and UPF consumption patterns were identified by principle component analysis (PCA). Multivariable logistic regression analyses were used to evaluated the associations of the proportion of UPF consumption and UPF patterns, respectively, with risk of incident CKD and a ≥20% eGFR decline.

Results
Average UPF consumption was 37.7% of total food intake in grams. After a mean (SD) follow-up of 7.9±1.1 years, 2 072 participants developed CKD and 7 611 had a ≥20% eGFR decline. The consumption of UPF was independently associated with a higher risk of incident CKD (OR for an absolute increment of 10 % of UPF in the diet 1.07 [95% CI 1.01-1.13], P=0.026) and with a higher risk of ≥20% eGFR decline (OR10% increment 1.07 [95% CI 1.05-1.10], P&lt;0.001). PCA revealed four habitual UPF consumption patterns. The “warm savory snack” pattern was associated with both incident CKD (OR 1.13 [1.04-1.23], P=0.003) and a ≥20% eGFR decline (OR 1.08 [1.05-1.11], P&lt;0.001). The “sweet snack” pattern was associated with eGFR decline (OR 1.06 [1.03-1.09], P&lt;0.001) only, whereas the “Dutch traditional” and the “cold snack” were not associated with CKD or eGFR decline.

Conclusion
A higher UPF consumption was associated with higher risks of incident CKD and eGFR decline in the general population. Different UPF consumption patterns were identified, with different impact on renal risk. The “warm savory snack” pattern and the “sweet snack” pattern were associated with kidney function decline. Our findings suggest that UPF need to be considered in designing future dietary strategies for CKD prevention.
FC 083PROBIOTIC L.CASEI ZHANG SLOWS THE PROGRESSION OF ACUTE AND CHRONIC KIDNEY DISEASE
Authors: Zeng Rui 
Published: May 2021

Abstract

Background and Aims
The relationship between gut microbial dysbiosis and acute or chronic kidney disease is currently acknowledged to be a health concern which is characterized by immune dysregulation and metabolic disorder. However, the therapeutic strategies remain to be developed. In the present study, we examined the protective effects and mechanisms of action of probiotic Lactobacillus casei Zhang (L. casei Zhang) on bilateral renal ischemia-reperfusion (I/R)-induced injury in mice.

Method
We orally gavaged male C57BL/6 mice with or without L. casei Zhang and probiotic Lactobacillus acidophilus (L. acidophilus) for 4 weeks (1 × 109 CFU per day) prior to being subjected to ischemia-reperfusion (I/R)-induced injury. Serum, colons and renal samples were collected after 5 days and 28 days. The composition and abundance of gut microbiota was investigated by using 16S rRNA. LC-MS metabolomic analysis technology and GC-MS analysis technology were used to investigate the metabolic alterations. To define the intra-renal cell subsets that are involved in L. casei Zhang-induced renoprotection, we performed single-cell RNA-sequencing (scRNA-seq) of kidney samples dissected from L. casei Zhang pretreated mice at day 5 after I/R along with samples from non-treated controls.

Results
Compared to L.acidophilus, L. casei Zhang demonstrated superior capacity in restoring intestinal flora homeostasis, protecting intestinal mucosal barrier function and improving the disrupted metabolomic profile. L. casei Zhang not only elevated the short chain fatty acids (SCFAs) in serum and kidney, but also significantly increased nicotinamide, by which L. casei Zhang inhibited renal inflammatory response and alleviated the damage of renal tubular epithelial cells (TECs) via interacting with SCFAs receptors on macrophages and TECs, and activating NAD+ metabolism in injured kidneys.

Conclusion
These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline.
FC 051PREDICTIVE VALUE OF PLASMA NGAL:HEPCIDIN-25 FOR MAJOR ADVERSE KIDNEY EVENTS AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS: A PILOT STUDY
Authors: Elitok Saban , Haase-Fielitz Anja , Ernst Martin , Haase Michael 
Published: May 2021

Abstract

Background and Aims
Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 appear to be involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We aimed to explore the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events after cardiac surgery.

Method
We compared the predictive value of plasma NGAL, hepcidin-25, and NGAL:hepcidin-25 with those of serum creatinine (Cr), and urinary output and urinary protein for primary endpoint major adverse kidney events (MAKE; acute kidney injury [AKI] stages 2 and 3, persistent AKI &gt; 48 hrs, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses.

Results
At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77 [95% confidence interval (CI) 0.60–0.94], 0.79 [0.63–0.95], 0.74 [0.51–0.97]) and AKI (0.73 [0.53–0.93], 0.89 [0.81–0.98], 0.70 [0.48–0.93]). For AKI prediction, NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC &lt; 0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients for MAKE or AKI (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥ 0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P = 0.014), whereas Cr did not.

Conclusion
NGAL:hepcidin-25 is a promising plasma marker for predicting postoperative MAKE.
FC 052ACID-BASE BALANCE DURING IN-SERIES EXTRACORPOREAL CARBON DIOXIDE REMOVAL AND CONTINUOUS VENOVENOUS HEMOFILTRATION: PREDICTIONS FROM A MATHEMATICAL MODEL
Authors: Leypoldt John (Ken) , Kurz Joerg , Echeverri Jorge , Storr Markus , Harenski Kai 
Published: May 2021

Abstract

Background and Aims
Critically ill acute kidney injury (AKI) patients may require treatment by extracorporeal carbon dioxide removal (ECCO2R) devices to allow protective or ultraprotective mechanical ventilation and avoid hypercapnic acidosis. Continuous venovenous hemofiltration (CVVH) and ECCO2R devices can be arranged in series to form a single extracorporeal circuit; such a circuit has been proposed to be optimal, based carbon dioxide removal efficacy, if the ECCO2R device is placed proximal to the CVVH device (Allardet-Servent et al, Crit Care Med 43:2570-2581, 2015).

Method
We developed a mathematical model of whole-body, acid-base balance during extracorporeal therapy using in-series ECCO2R and CVVH devices for treatment of mechanically ventilated AKI patients. Equilibrium acid-base chemistry in blood was assumed as reported previously (Rees and Andreassen, Crit Rev Biomed Eng 33:209-264, 2005). Published clinical data from Allardet-Servent et al of mechanically ventilated (6 mL/kg predicted body weight or PBW) AKI patients treated by CVVH without ECCO2R were used to adjust model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO2) and arterial plasma bicarbonate concentration ([HCO3]). The effects of applying ECCO2R at an unchanged tidal volume and a reduced tidal volume (4 mL/kg PBW) on PaCO2 and [HCO3] were then simulated assuming carbon dioxide removal rates from the ECCO2R device measured in the clinical study (91 mL of CO2/min when ECCO2R was proximal and 72 mL of CO2/min when CVVH was proximal).

Results
Agreement of model predictions with the clinical data was good, and model predictions were relatively independent of the in-series position of the devices (see Table). Total carbon dioxide removal from the CVVH device via ultrafiltration predicted by the model was lower after applying ECCO2R at both the unchanged tidal volume (25 mL of CO2/min when ECCO2R was proximal and 39 mL of CO2/min when CVVH was proximal) and the reduced tidal volume (30 mL of CO2/min when ECCO2R was proximal and 44 mL of CO2/min when CVVH was proximal). The reduced removal of total carbon dioxide via ultrafiltration when ECCO2R was proximal resulted from the lower total carbon dioxide concentration in blood entering the CVVH device. Thus, independent of the in-series position of the devices, the magnitude of this difference in total carbon dioxide removal by the CVVH device (14 mL of CO2/min) approximately cancels out the relative greater efficacy of the ECCO2R device (19 mL of CO2/min).

Conclusion
The described mathematical model has quantitative accuracy. It suggests that overall acid-base balance when using ECCO2R and CVVH devices in a single, combined extracorporeal circuit will be similar, independent of their in-series position.
FC 084LIPOTOXICITY MEDIATED BY GPR43 ACTIVATION CONTRIBUTES TO PODOCYTE INJURY IN DIABETIC NEPHROPATHY THROUGH MODULATING ERK/EGR1 PATHWAY
Authors: Lu Jian , Zhang Jia Xiu , Chen Pei Pei , Li Xue Qi , Liu Bicheng , Ma Kun Ling 
Published: May 2021

Abstract

Background and Aims
The G-protein-coupled receptor 43 (GPR43) is a post-transcriptional regulator involved in cholesterol metabolism. Our previous studies demonstrated that intracellular cholesterol accumulation contributed to podocyte injury in diabetic nephropathy (DN). This study aimed to investigate possible roles of GPR43 activation in lipid nephrotoxicity in DN and to explore its potential mechanisms.

Method
The experiments were conducted by using diabetic GPR43 knockout mice and cell culture model of podocytes. Renal pathological changes were checked by periodic acid schiff staining, immunohistochemical staining and transmission electron microscopy (TEM). The lipid deposition and free cholesterol contents in kidney tissues were detected by Oil Red O staining, BODIPY staining, and cholesterol quantitative assay. The protein expressions of GPR43, LC3II, p62 and related molecules of LDLR pathway in kidney tissues and podocytes were detected by real-time PCR, immunofluorescent staining, and Western blotting.

Results
There were decreased plasma level of LDL-cholesterol and cholesterol accumulation in kidney tissues of diabetic GPR43 knockout mice. In vitro study demonstrated that acetate, a stimulator of GPR43, increased LDLR-mediated cholesterol uptake in podocytes, accompanied with reduced cholesterol autophagic degeneration, characterized by inhibited LC3 maturation, p62 degradation, and autophagosome formation. These may evoke synergistic effects attributing to cellular cholesterol accumulation in podocytes. While genetic knockdown or pharmacological inhibition of GPR43 inhibited this effect in podocytes. Furthermore, the activation of GPR43 led to the activation of ERK1/2/EGR1 pathway in podocytes, whereas blocking ERK1/2 activity or reducing EGR1 expression reversed cholesterol influx and the inhibition of autophagy mediated by GPR43 activation in podocytes. Meanwhile, deletion of the GPR43 improved autophagy and inhibited the ERK1/2-EGR1 pathway of podocyte in diabetic mice in vivo.

Conclusion
Activation of the GPR43 mediated lipid nephrotoxicity contributes to podocyte injury in DN, which was mainly through the activation of ERK/EGR1 pathways. These findings suggested that the GPR43 receptor could be a potential therapeutic target for the prevention of DN progression.
FC 027COVID-19 IN PATIENTS ON KIDNEY REPLACEMENT THERAPY - CLINICAL CHARACTERISTICS AT TRIAGE ASSOCIATED WITH ADMISSION, READMISSION AND SHORT-TERM OUTCOMES
Authors: Mitra Sandip , Jayanti Anu , Vart Priya , Coca Armando , Gallieni Maurizio , Altern Øvrehus Marius , Midtvedt Karsten , Abd ElHafeez Samar , Gandolfini Ilaria , Büttner Stefan , Franssen Casper , Hemmelder Marc 
Published: May 2021

Abstract

Background and Aims
Patients on kidney replacement therapy (KRT) are at high risk of developing severe COVID-19 illness and often require high intensity care and utilisation of hospital resources. During the ongoing pandemic, the optimal care pathway and triage for KRT patients presenting with varying severity of COVID-19 illness is unknown. We studied clinical factors and outcomes associated with admission, readmission and short-term outcomes.

Method
Data from the European Renal Association COVID-19 Database (ERACODA) was analysed. This database includes granular data on dialysis patients and kidney transplant recipients with COVID-19 from all over Europe. The clinical and laboratory features at first presentation of hospitalized and non-hospitalized patients and those who returned for second presentation were studied. In addition, possible predictors of outcome in those who were not hospitalized at first presentation were identified.

Results
Among 1,423 KRT patients (haemodialysis; 1017/kidney transplant; 406) with COVID-19, 25% (n=355) were not hospitalized at first presentation. Of them, only 10% (n=36), presented for a second time in the hospital. The median interval between the first and second presentation was 5 days (Interquartile interval: 2-7 days). Patients who re-presented had worsening of pulmonary symptoms, a fall in oxygen saturation (97% to 90%), and an increase in C-reactive protein (26 mg/L to 73 mg/L) between their attendances. Patients who re-presented after initial assessment were older (72 vs. 63 years) and initially more often had pulmonary symptoms and abnormalities on lung imaging compared with those who did not present for a second time. The 28-day mortality rate of patients admitted at the second presentation was similar to that of patients admitted at first presentation (26.5% vs. 29.7%, p=0. 61). Among patients who were not hospitalized at first presentation (mortality 6%), age, prior smoking, clinical frailty scale, and shortness of breath at first presentation were identified as predictors of mortality.

Conclusion
KRT patients with COVID-19 and mild pulmonary abnormalities and no signs of pulmonary insufficiency can be safely returned without hospitalization. These patients should be advised to seek immediate contact when they develop respiratory distress. Our findings provide support for a risk-stratified clinical approach to admissions of KRT patients presenting with COVID-19. The study findings may be valuable for clinical triage and optimising hospital capacity utilisation during the ongoing pandemic.
FC 028COVID-19 RELATED MORTALITY IN KIDNEY TRANSPLANT AND DIALYSIS PATIENTS: A COMPARATIVE, PROSPECTIVE REGISTRY BASED STUDY
Authors: Candellier Alexandre , Goffin Eric Jean , Vart Priya , Noordzij Marlies , Arnol Miha , Covic Adrian , Lentini Paolo , Malik Shafi , Reichert Louis , Sever Mehmet Sukru , Watschinger Bruno , Jager Kitty J , Gansevoort Ronald 
Published: May 2021

Abstract

Background and Aims
Studies examining kidney failure patients with COVID-19 reported higher mortality in hemodialysis patients than in kidney transplant recipients. However, hemodialysis patients are often older and have more comorbidities. This study investigated the association of type of kidney replacement therapy with COVID-19 severity adjusting for differences in characteristics.

Method
Data were retrieved from the European Renal Association COVID-19 Database (ERACODA), which includes kidney replacement therapy patients diagnosed with COVID-19 from all over Europe. We included all kidney transplant recipients and hemodialysis patients who presented between February 1st and December 1st 2020 and had complete information reason for COVID-19 screening and vital status at day 28. The diagnosis of COVID-19 was made based on a PCR of a nasal or pharyngeal swab specimens and/or COVID-19 compatible findings on a lung CT scan. The association of kidney transplantation or hemodialysis with 28-day mortality was examined using Cox proportional-hazards regression models adjusted for age, sex, frailty and comorbidities. Additionally, this association was investigated in the subsets of patients that were screened because of symptoms or have had routine screening.

Results
A total of 1,670 patients (496 functional kidney transplant recipients and 1,174 hemodialysis patients) were examined. 16.9% of kidney transplant recipients and 23.9% of hemodialysis patients died within 28 days of presentation. In an unadjusted model, the risk of 28-day mortality was 33% lower in kidney transplant recipients compared with hemodialysis patients (hazard ratio (HR): 0.67, 95% CI: 0.52, 0.85). However, in an age, sex and frailty adjusted model, the risk of 28-day mortality was 29% higher in kidney transplant recipients (HR=1.29, 95% CI: 1.00, 1.68), whereas in a fully adjusted model the risk was even 43% higher (HR=1.43, 95% CI: 1.06, 1.93). This association in patients who were screened because of symptoms (n=1,145) was similar (fully adjusted model HR=1.46, 95% CI: 1.05, 2.04). Results were similar when other endpoints were studied (e.g. risk for hospitalization, ICU admission or mortality beyond 28 days) as well as across subgroups. Only age was found to interact significantly, suggesting that the increased mortality risk associated with kidney transplantation was especially present in elderly subjects.

Conclusion
In this study, kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients when adjusted for age, sex and comorbidities.
FC 123RENAL TRANSPLANTATION MITIGATES INCREASED BIOLOGICAL (EPIGENETIC) AGE IN CHRONIC KIDNEY DISEASE
Authors: Neytchev Ognian , Witasp Anna , Nordfors Louise , Qureshi Abdul Rashid Tony , Wennberg Lars , Erlandsson Helen , Ebert Thomas , Selman Colin , Shiels Paul , Stenvinkel Peter 
Published: May 2021

Abstract

Background and Aims
Chronic kidney disease (CKD) shares important features of a dysregulated ageing process with other common “burden of lifestyle” diseases, which aggregates into the diseasome of ageing. Typically, this is hallmarked by an acceleration of epigenetic (DNA methylation-based) clocks. It remains to be determined if current therapeutic interventions, such as renal transplantation or dialysis, can slow this clock, and thus the rate of biological ageing, in CKD. We therefore assessed the rate of biological ageing in CKD patients and whether these therapies impact on it, by measuring epigenetic age before and 1 year after treatment.

Methods
Whole blood samples were taken from CKD 5 patients at baseline and 1 year after renal transplantation (n=12) or dialysis (n=11; peritoneal dialysis n=7, haemodialysis n=4) as well as from age and sex-matched population-based controls (n=24). DNA methylation was measured using the Illumina Infinium Human Methylation 450K BeadChip and epigenetic age was calculated using three independent DNA methylation clocks: the Horvath, Hannum, and PhenoAge clocks. Additionally, a novel composite clock incorporating these three clocks was evaluated. We then calculated the age acceleration (difference between epigenetic and chronological age) for each clock and compared average age acceleration between groups and across time points.

Results
Incident dialysis patients displayed accelerated ageing versus chronologically age-matched controls (p&lt;0.001). We observed a PhenoAge age acceleration difference in both the transplant (8.5 years, p=0.001) and dialysis (9.7 years, p&lt;0.001) groups at baseline compared to control. After 1 year, we also observed a decrease of the age acceleration in the transplant group (mean reduced by 4.4 years, p=0.016), but not in the dialysis group (mean reduced by 0.7 years, p=0.668).

Conclusion
CKD 5 patients display an increased biological (i.e. epigenetic) age. This age acceleration is mitigated one year after renal transplantation, but not in patients undergoing dialysis. Neither therapy reverses high biological age.
FC 127SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (SGLT2I) SHORT-TERM OUTCOME IN DIABETIC KIDNEY TRANSPLANT RECIPIENTS
Authors: Yagan Jude , Mahmoud Tarek S H , Geith Osama 
Published: May 2021

Abstract

Background and Aims
The emergence of positive data on the use of sodium glucose co-transporter inhibitors (SGLT2i) in the last several years, begged the question of whether their positive outcomes can be seen in kidney transplant recipients, as they have the same and even more pronounced cardiovascular risk factors than the general population and in addition, we got better in improving graft and patients survival in the short term , but we lack the tools to improve long term patients and graft survival where so many patients die from cardiovascular disease with a functioning graft or lose their graft from chronic changes and chronic antibody mediated rejection with difficult to control blood pressure and proteinuria
For these reasons we need more powerful tools , like the SGLT2i bearing in mind the unique side effects that might be amplified in kidney transplant recipients receiving immunosuppression like urinary tract infection, and the dip in serum creatinine.

Method
We collected data retrospectively from transplant records of patients with type II diabetes mellitus (T2D) or post-transplant diabetes mellitus (PTDM) (n=79) who were receiving SGLT2i agents plus standard of care [SOC] management and compared them to (n=56) similar diabetic patients who were only on SOC management.

Results
The two groups were comparable regarding age, sex, type of donor, type of diabetes (T2D PTDM), post-transplant period, induction immunosuppression and use of CNI. Though improvement of HbA1c was not significantly different between the two groups, patients on SGLT2i showed better drop in HbA1c compared to the SOC group (0.7% versus 0.5% respectively). Reduction of BMI was equal between the two groups (-1.1%) and there was no significant difference in the number of blood pressure medications (average 2 drugs per patient). Kidney function was assessed by the eGFR using CKD-EPI equation and by urine albumin/creatinine ratio (ACR). The eGFR was calculated at start then at 1,3,6 and 12 months. In SGLT2i group, eGFR showed a dip at 3 months (from 66 to 63.35 ml/min) then started to improve gradually toward the end of the year and maintained at a level close to baseline (65.44 ml/min). The SOC group showed gradual drop in eGFR over the year from 65.76 to 63.19 ml/min. Urine ACR reduced in the SGLT2i group from 48.79 to 23.79 mg/mmol creatinine and increased from 42.84 to 63.16 mg/mmol creatinine in the SOC group. The incidences of graft rejection, urinary tract infection, genital infection, myocardial infarction, heart failure or cerebrovascular stroke were not different between the groups.

Conclusion
Use of SGLT2i in managing diabetic patients post kidney transplantation is safe and has better short-term outcomes on renal function with comparable safety compared to standard of care therapy.