bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1011ATHE SGTL-2 INHIBITORS DECREASE THE MORTALITY AND PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD) IN TYPE 2 DIABETES PATIENTES. SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE
Authors: Cabrera Sebastian , Torres Ruben , Elgueta Leticia , Segovia Erico , Sanhueza Maria Eugenia , Boltansky Andres , Alvo Miriam 
Published: June 2020

Abstract

Background and Aims
Diabetic nephropathy is one of the main causes of chronic kidney disease (CKD) in the world. In the past years new studies using SGLT-2 inhibitors in diabetic patients have shown benefit in both mortality and progression of CKD. However, these works show heterogeneity between studies regarding the severity of CKD of patients included. All above complicates the interpretation of the benefits of SGLT-2 inhibitors.

Method
We did a systematic search of the literature in PUBMED, EMBASE, Cochrane CENTRAL trials database and in references of the selected studies. Terms used for the search were Canaglifozin, Dapaglifozin, Ertuglifozin, Empaglifozin, diabetes, mortality and CKD. Search included studies in all languages. We selected only randomized and controlled studies that reported mortality and relevant renal outcomes (doubling serum creatinine or decrease in eGFR&gt; 40%, need for renal replacement or renal death). We included studies until September 30, 2019. For the meta-analysis, a Mantel-Haenszel model of random effects was used. The software Review Manager, Version 5.3 The Cochrane Collaboration, 2014 was used.

Results
We obtained results from 142 studies, fifteen studies met the selected criteria, but only four reported mortality and renal outcomes (EMPA-REG, CANVAS, CREDENCE AND DECLARE-TIMI 58). A total of 38,721 patients (SGTL2 inhibitors n = 21,264 and control n = 17,457) were included for the analysis. The EMPA-REG study used Empaglifozin, the CANVAS and CREDENCE studies used Canaglifozin and the DECLARE-TIMI 58 used Dapaglifozin. All studies were funded by pharmaceutical laboratories.The average age range of the studies was between 62 to 67 years. The percentage of patients with eGFR &lt;60ml/min were 26%, 20%, 60% and 7% for the EMPA-REG, CANVAS, CREDENCE and DECLARE-TIMI 58 studies respectively.Mortality was lower in patients who used SGTL2 inhibitors OR 0.86 (CI 0.80-0.94) Figure 1. Renal outcomes were also lower in patients who used SGTL-2 inhibitors OR 0.69 (CI 0.60-0.78) Figure 2. We assessed whether the effect was related to the severity of the CKD taking out the work with patients with more severe CKD (CREDENCE study), the effect on mortality did not change OR 0.87 (CI 0.80-0.95) as well as renal outcome OR 0.66 (CI 0.52- 0.83).

Conclusion
The SGTL-2 inhibitors decrease mortality and improve renal outcomes in patients with diabetic nephropathy. These benefits remain in patients with less severe CKD.
P1019CANAGLIFLOZIN AND RISK OF SKIN AND SOFT TISSUE INFECTIONS IN PEOPLE WITH DIABETES MELLITUS AND KIDNEY DISEASE - A POST-HOC ANALYSIS OF THE CREDENCE TRIAL
Authors: Kang Amy , Smyth Brendan , Neuen Brendon , Lambers Heerspink Hiddo , Di Tanna Gian Luca , Neal Bruce , Zhang Hong , Hockham Carinna , Agarwal Rajiv , Bakris George , Charytan David M , De Zeeuw Dick , Greene Tom , Levin Adeera , Pollock Carol , Wheeler David , Zinman Bernard , Mahaffey Kenneth W , Perkovic Vlado , Jardine Meg 
Published: June 2020

Abstract

Background and Aims
The skin’s hypertonic microenvironment has a hypothesized protective antimicrobial function that may be disrupted by SGLT2i. The association between sodium glucose cotransporter inhibitors (SGLT2i) and genital mycotic infections is well established, but it is not known if these agents increase the risk of other skin and soft tissue infections (SSTI). We aimed to describe SSTI in the CREDENCE trial, and determine whether canagliflozin affects the risk of skin and soft tissue infections (SSTIs) overall and in subgroups.

Method
We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Infections reported as adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with a sensitivity analysis conducted in the intention-to-treat population. Univariable time-to first-event regression models were assessed.

Results
Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious. Drug was continued in 290/373 (78%) of first events, with similar frequency of subsequent events between groups (31/133 (23%) and 33/157 (21%) for those continuing canagliflozin and placebo respectively). In both cases of necrotising fasciitis, drug was withdrawn and the participants recovered.Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11) (Figure 1). Results were similar in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33), and in the predefined subgroups.

Conclusion
Although other studies suggest that SGLT2i may reduce the sodium content of the skin, we found that canagliflozin does not increase the risk of skin and soft tissue infections, overall or in any subgroup, in people with type 2 diabetes mellitus and albuminuric chronic kidney disease.
P1021MARKERS OF “METABOLIC MEMORY” AND KIDNEY GRAFT FUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION
Authors: Larina Irina , Severina Anastasia , Shamhalova Minara , Shestakova Marina , Nikankina Larisa , Artemova Ekaterina , Egorova Darya , Musaeva Gulya , Dmitriev Ilya , Pinchuk Aleksey , Kaabak Michael 
Published: June 2020

Abstract

Background and Aims
To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT).

Method
The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy.

Results
SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE & creatinine (R=0.50, p=0.02), RAGE & KIM-1 (R=0.43, p=0.047), 3-NT& eGFR (R= - 0.40, p=0.046), IL-18 & SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE & HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline & RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”.

Conclusion
SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.
P1039BARIATRIC SURGERY AND RISKS OF RENAL DISEASES, CARDIOVASCULAR DISEASES AND MORTALITY AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Wong Carlos , Wu Tingting , Wong Simon , Law Betty , Grieve Eleanor , Wu Olivia , Lam Cindy 
Published: June 2020

Abstract

Background and Aims
To measure and compare the risks of end-stage renal diseases (ESRD), cardiovascular diseases (CVD), all-cause mortality between obese type 2 diabetes mellitus (T2DM) patients with and without bariatric surgery.

Method
A retrospective population-based cohort of 1,690 obese T2DM patients who were free of ESRD and CVD were assembled based on 2006-2017 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IR) of stage 4/5 chronic renal diseases, ESRD, CVD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for stage 4/5 chronic renal diseases, ESRD, CVD events were assessed using Cox proportional hazard models. Changes in estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) were measured up to 60 months.

Results
Over a mean follow-up period of 34 months with 863 person-years, cumulative incidences of mortality, stage 4/5 chronic kidney diseases, ESRD and CVD for surgical patients were 0, 0.050, 0.017, and 0.036, respectively. Surgical patients had reduced IR of all-cause mortality, stage 4/5 chronic kidney diseases, ESRD and CVD (IR=0, 1.784, 0.587 and 1.321 per 100 person-years, respectively) than control patients (IR=1.954, 2.028, 0.914 and 2.814 per 100 person-years, respectively). Surgery group had a significant reduction in risk of CVD events (HR=0.464, P=0.015), and no occurrence of mortality events. However, the IR of stage 4/5 chronic kidney diseases and ESRD of the two groups were not significantly different. Surgical patients had significantly higher eGFR within 12 months, and had significantly lower until 48 months.

Conclusion
Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes of eGFR up to 36 months.
P1060USING ARTIFICIAL INTELLIGENCE TO PREDICT HOME THERAPY CANDIDATES
Authors: Yu Jerry , Long Andrew , Hanson Maria , Ellis Aleetha , Macarthur Michael , Chatoth Dinesh , Turk Joseph , Buck Michael , Usvyat Len A , Kossmann Robert J , Maddux Franklin 
Published: June 2020

Abstract

Background and Aims
There are many benefits for performing dialysis at home including more flexibility and more frequent treatments. A possible barrier to election of home therapy (HT) by in-center patients is a lack of adequate HT education. To aid efficient education efforts, a predictive model was developed to help identify patients who are more likely to switch from in-center and succeed on HT.

Method
We developed a model using machine learning to predict which patients who are treated in-center without prior HT history are most likely to switch to HT in the next 90 days and stay on HT for at least 90 days. Training data was extracted from 2016–2019 for approximately 300,000 patients. We randomly sampled one in-center treatment date per patient and determined if the patient would switch and succeed on HT. The input features consisted of treatment vitals, laboratories, absence history, comprehensive assessments, facility information, county-level housing, and patient characteristics. Patients were excluded if they had less than 30 days on dialysis due to lack of data. A machine learning model (XGBoost classifier) was deployed monthly in a pilot with a team of HT educators to investigate the model’s utility for identifying HT candidates.

Results
There were approximately 1,200 patients starting a home therapy per month in a large dialysis provider, with approximately one-third being in-center patients. The prevalence of switching and succeeding to HT in this population was 2.54%. The predictive model achieved an area under the curve of 0.87, sensitivity of 0.77, and a specificity of 0.80 on a hold-out test dataset. The pilot was successfully executed for several months and two major lessons were learned: 1) some patients who reappeared on each month’s list should be removed from the list after expressing no interest in HT, and 2) a data collection mechanism should be put in place to capture the reasons why patients are not interested in HT.

Conclusion
This quality-improvement initiative demonstrates that predictive modeling can be used to identify patients likely to switch and succeed on home therapy. Integration of the model in existing workflows requires creating a feedback loop which can help improve future worklists.
P1061ACID-BASE MODELLING AND TREND IN CENTRAL VENOUS OXYGEN SATURATION IN HEMODIALYSIS
Authors: Mauro Pietribiasi , Leypoldt John (Ken) , Waniewski Jacek 
Published: June 2020

Abstract

Background and Aims
Central venous oxygen saturation (sO2cv) is commonly used as a proxy of cardiac output in non-uremic populations. Recently, the decrease in sO2cv commonly observed in many hemodialysis (HD) sessions was correlated with ultrafiltration volume (UFV) and was suspected to be linked with a treatment-induced decrease in cardiac output (Zhang et al, NDT 2018). High variability in sO2cv has also been associated with all-cause mortality in this group of patients (Zhang et al, Blood Purif 2019). We adapted a comprehensive mathematical model of whole body oxygen (O2) and carbon dioxide (CO2) biochemistry, storage and transport and applied it to simulate the changes in sO2cv during bicarbonate hemodialysis to test their connection with changes in CO.

Method
The original model of biochemistry and transport of base excess, CO2 and O2 was originally developed by Rees and Andreassen (Crit Rev Biomed Eng 2005), and describes in detail the chemical and respiratory mechanisms that regulate the biochemical status in different physiological compartments of the patients’ body (venous blood, arterial blood, tissue cells, interstitial fluid). The model was modified to include the effect of the HD treatment on these systems, allowing to calculate the variations in venous and arterial sO2. Treatment perturbations included the removal via ultrafiltration of interstitial fluid and plasma volume (and consequent hemoconcentration), and infusion of bicarbonate. Simulation experiments of 4h HD sessions were carried out with bicarbonate dialysate concentration = 35 mmol/L and dialysance = 198 mL/min, and various ultrafiltration volumes (UFV); CO was assumed to decrease by 2% for each 1% change in blood volume. The initial biochemical status of the patient was defined assuming 20 mEq/L bicarbonate concentration, 7.4 pH, and 97% oxygen saturation in the arterial compartment, resulting in initial sO2cv equal to 66.6%. Both artero-venous and veno-venous access were simulated.

Results
The model predicted a negative linear trend for sO2cv with variable slope depending on UFV, as shown in the table:
The trend in sO2cv was directly proportional to the decrease in CO during HD and inversely proportional to UFV. In case of constant CO, the simulated sO2cv would actually increase during the session. Although the type of vascular access determined changes in other simulated quantities, partial pressures of CO2 and O2 and oxygen saturation in both arterial and venous blood were practically unchanged.

Conclusion
Our model confirmed the correlation between the trend in sO2cv and UFV already highlighted in previous works. Moreover, it showed that the decrease in cardiac output is a major determinant of the decrease in sO2cv during the HD session. The developed mathematical model may provide physiological insights in the development of new technologies to monitor changes in cardiac performance during HD.
P1064HEPARIN-FREE DIALYSIS: A PHASE II PILOT STUDY USING ASYMMETRIC TRIACETATE (ATA) CELLULOSE DIALYZERS
Authors: Meijers Björn , Vandenbosch Ines , Bammens Bert , De Vusser Katrien , Van Craenenbroeck Amaryllis , Claes Kathleen , Evenepoel Pieter 
Published: June 2020

Abstract

Background and Aims
Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers.

Method
We performed a phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis (SAFE study)’ was a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting.

Results
We scheduled 240 dialysis sessions (120 per arm) in twenty patients. Ten patients were randomized to start in Arm 1, the others to Arm 2. All patients crossed to the other arm halfway the study. 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm 1 and 16 in Arm 2. Success rate in Arm 1 (ATA + citrate containing dialysate) was 90.8 / 94.0 % (intention to treat/ as treated). Success rate in Arm 2 (ATA + predilution HDF) was 83.3 / 86.2 % (intention to treat/ as treated). Therapy survival was borderline significantly better in Arm 1(Mantel-Cox log rank P = 0.05).

Conclusion
Asymmetric cellulose triacetate (ATA) dialyzers have a low clotting propensity. In combination with citrate-containing dialysate, asymmetric cellulose triacetate (ATA) may be a suitable alternative to heparin-coated membranes for systemic heparin-free hemodialysis.
P1065EXTRACORPOREAL CYTOKINE ADSORPTION IN PATIENTS WITH AKI AND SEPTIC SHOCK AFTER CARDIAC SURGERY
Authors: Boss Kristina , Jahn Michael , Wendt Daniel , Demircioglu Ender , Thielmann Matthias , Ruhparwar Arjang , Kribben Andreas , Tyczynski Bartosz 
Published: June 2020

Abstract

Background and Aims
Extracorporeal cytokine adsorption is a new option in septic shock as an additional measure to prevent severe cytokinaemia. The purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamics in patients with acute kidney injury (AKI) and septic shock after cardiac surgery.

Method
In this retrospective study 64 patients with AKI and septic shock after cardiac surgery were investigated for the effect of extracorporeal cytokine adsorption by CytoSorb® columns on hemodynamics. In all patients CytoSorb®-treatment was applied in addition to continuous renal replacement therapy (CRRT) with citrate anticoagulation. A paired t-test has been performed to determine statistical significance.

Results
Before treatment, the mean noradrenalin dose to reach a mean arterial pressure (MAP) &gt; 65 mmHg was 0.49 µg/kg bw/min, the mean adrenalin dose was 0.1 µg/kg bw/min. 24 h after treatment, significantly reduced catecholamine doses were necessary to maintain a MAP &gt; 65 mmHg (0.23 µg/kg bw/min noradrenalin; p***&lt; 0.0002 and 0.06 µg/kg bw/min adrenalin; p* &lt; 0.02). The mean SOFA-score for these patients with AKI and septic shock 24 h before CytoSorb®- treatment was 16.6 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.6 points was 77 % while the all-cause mortality rate of the patients in this study was 59.4 %.

Conclusion
In patients with AKI and septic shock after cardiac surgery, 24 h after extracorporeal cytokine adsorption by CytoSorb® the catecholamine dose required to maintain a MAP &gt; 65 mmHg was halved. Additionally, observed in-hospital mortality was lower than SOFA-score predicted mortality.
P1101A BIFUNCTIONAL ADSORBER PARTICLE FOR THE REMOVAL OF HYDROPHOBIC UREMIC TOXINS FROM WHOLE BLOOD OF RENAL FAILURE PATIENTS
Authors: Sternkopf Marieke , Speer Thimoteus , Göttsch Claudia , Jankowski Vera , Jankowski Joachim , Noels Heidi 
Published: June 2020

Abstract

Background and Aims
Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques may be an appropriate alternative to increase hydrophobic uremic toxin removal.

Method
We developed an extracorporeal, whole-blood bifunctional adsorber particle consisting of a porous, activated charcoal core with a hydrophilic polyvinylpyrrolidone surface coating. The adsorption capacity was quantified using analytical chromatography after perfusion of the particles with an albumin solution or blood, each containing mixtures of hydrophobic uremic toxins.

Results
A time-dependent increase in hydrophobic uremic toxin adsorption was depicted and all toxins showed a high binding affinity to the adsorber particles. Further, the particle showed a sufficient hemocompatibility without significant effects on complement component 5a, thrombin-antithrombin III complex, or thrombocyte concentration in blood in vitro, although leukocyte counts were slightly reduced.

Conclusion
In conclusion, the bifunctional adsorber particle with cross-linked polyvinylpyrrolidone coating showed a high adsorption capacity without adverse effects on hemocompatibility in vitro. Thus, it may be an interesting candidate for further in vivo studies with the aim to increase the efficiency of conventional dialysis techniques.