bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3056 IMPACT OF ALBUMIN BINDING FUNCTION ON PHARMACOKINETICS AND PHARMACODYNAMICS OF FUROSEMIDE
Authors: Klinkmann Gerd , Klammt Sebastian , Reuter Daniel , Mitzner Steffen 
Published: June 2023

Abstract

Background and Aims
Albumin binding of furosemide forms the basis for its transport to the kidney and subsequent tubular secretion, which is a prerequisite for the effect of furosemide. Accordingly, high albumin concentrations should result in higher efficacy of furosemide. However, study results on the combination of furosemide in conjunction with albumin and on the efficacy of furosemide in hypoalbuminemia did not confirm this hypothesis. The aim of this study was to determine the efficacy of furosemide not only in relation to concentration, but also to take albumin function into account.

Method
In a prospective and non-interventional clinical observational trial, blood and urine samples from 50 intensive care patients receiving continuous intravenous furosemide therapy were evaluated. Albumin binding capacity (ABiC) determination allowed conclusions to be drawn about the binding site-specific loading state of albumin by quantifying the unbound fraction of the fluorescent marker dansylsarcosine. In addition, assessment of the total concentration of furosemide in plasma and urine as well as the concentration of free furosemide fraction in plasma was performed by HPLC-MS. The efficacy of furosemide was evaluated by the ratio of urine excretion to fluid intake.

Results
In patients with an ABiC ≥ 60% free furosemide fraction was significantly lower compared to patients with a lower ABiC (p &lt; 0.001), urinary furosemide concentration was higher (p = 0.136), and a significantly higher proportion of infused furosemide was excreted renally (p = 0.010). ABiC was positively correlated (r = 0.908, p = 0.017) with the increase in urine excretion to fluid input ratio after initiation of furosemide therapy.

Conclusion
ABiC could serve as a marker for individual response to furosemide and could be used to generate patient-specific therapeutic regimens. In view of the relatively low number of patients in this study, the relationship between furosemide efficacy and albumin function should be investigated in larger studies in the future.
#3065 INVESTIGATION OF NOTCH PATHWAY ACTIVATION AND ITS RELATION TO GREMLIN IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Tejedor Lucia , González Laura Núñez , Marquez-Exposito Laura , Cordido Adrian , Marchant Vanessa , Basantes Pamela Estefanía , Diez Raul Rodrigues , Tejera Antonio , Rayego-Mateos Sandra , Sanz Ana Belen , Ortiz Alberto , Gonzalez Miguel Angel Garcia , Ruiz-Ortega Marta 
Published: June 2023

Abstract

Background and Aims
Activation of the NOTCH signalling pathway has been described in several progressive kidney diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease caused by PKD1 or PKD2 mutations, which codify for the Polycystin-1 and Polycystin-2 proteins, respectively. ADPKD prevalence is among 1:800 and 1:1000 of live births and is characterized by fluid-filled renal cysts. During this process the production of chemokines, cytokines and growth factors by epithelial cells, interstitial fibroblasts and inflammatory cells, such as macrophages, increases, leading to end-stage renal disease (ESRD). GREMLIN has been proposed GREMLIN as an important mediator of chronic kidney disease in preclinical studies. In addition, urinary levels of GREMLIN may be a biomarker in any renal disease. However, there are no studies on GREMLIN in polycystic kidney disease.

Method
We have done the studies in an orthologous murine model of polycystic kidney disease (Pkd1cond/cond;Tam-Cre−/+) where we investigated the role of GREMLIN and its related mechanisms (its receptor VEGFR2 and the Notch signalling pathway) in different stages of renal cystic progression. The polycystic phenotype was induced in lactating mice by administering tamoxifen to the mother on postnatal days 10 and 11, causing a deletion in Pkd1 gene. Studies were performed considering different sacrifice points: at 18, 30 and 45 days. Furthermore, in urine and renal tissue from ADPKD patients, we studied the expression of GREMLIM.

Results
We have been able to see how in Pkd1−/+ mutant mice, grem-1 renal expression (that encoding GREMLIN protein), was increased from 18 days, with a significant increase at 30 days. This increase was associated with progressive cysts expansion and detriment in renal function measured by BUN. These results were confirmed at the protein level by western blot. Immunohistochemistry revealed positive GREMLIM staining since pre-cystic tubuloepithelial cells, which remained elevated in the tubules at later times. Positive GREMLIN expression was observed in biopsy samples of cysts from ADPKD patients as well as GREMLIN protein presence in urine samples. In the polycystic model, GREMLIN induction was correlated with VEGFR2 activation in the same tubular segments. Cyst formation was associated with activation of the NOTCH pathway, characterized by NOTCH1 and NOTCH3 activation.

Conclusion
Thus, we can suggest that GREMLIN expression may be an important mediator of renal damage progression in ADPKD and this protein would act through the Notch pathway.
#3101 LOW CIRCULATING LEVELS OF CARDIO-REGULATORY MIRNAS PREDICT WORSE OUTCOMES IN HEMODIALYSIS PATIENTS
Authors: Zicarelli Mariateresa , Greco Marta , Presta Pierangela , Duni Anila , Vita Caterina , Pappas Efthymios , Mirabelli Maria , Lakkas Lampros , Naka Katerina , Brunetti Antonio , Foti Daniela , Andreucci Michele , Coppolino Giuseppe , Ntounousi Evangelia , Bolignano Davide 
Published: June 2023

Abstract

Background and Aims
Patients with end stage renal disease (ESKD) on hemodialysis (HD) have a high risk of cardiovascular (CV) events, this being mostly related to the presence of uraemic cardiomyopathy. A deregulation in the expression of various microRNAs (miRNAs: non-coding RNAs that regulate post-transcriptional gene expression) has previously been implied in pathological cardiac remodelling. Nevertheless, scarce evidence has accrued so far on a possible significance in CV morbidity and mortality in HD patients, in relationship with the presence of uremic cardiomyopathy.

Method
We run a pilot, prospective, multicentre cohort study involving 74 ESKD patients undergoing chronic HD from 3 different hospitals in Italy and Greece. HD patients underwent a thorough clinical, laboratory and echocardiography assessment and were then prospectively followed for 24 months or until the occurrence of a composite endpoint of (CV and all-cause) mortality or non-fatal CV events. Through a systematic review of the literature, we identified a small panel of miRNAs (30a-5p, 23a-3p,451a and let7d-5p), which levels are known to be altered in either major CV disorders and kidney failure. miRNAs were then measured in the blood of HD patients and in a small group of matched healthy controls.

Results
miRNAs 23a-3p (p&lt;0.0001), 451a (p = 0.001), 30a-5p (p = 0.003) and let7d-5p (p &lt;0.0001) were all reduced in HD patients as compared with controls. Significant correlations were found between miRNAs and indexes of cardiac dysfunction such as Vmax, TAPSE and E/E’, as well as with some other laboratory parameters such as uric acid, sodium, potassium, HDL and CRP. During follow-up, 30/74 patients (40.5%) reached the composite endpoint. In these individuals, all miRNAs but let7d-5p were significantly reduced at baseline (p&lt;0.0001). As showed by multivariate Cox-regression analyses, miRNAs 23a-3p, 451a, 30a-5p were all predictors of the composite endpoint (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) and Kaplan-Meier analyses confirmed a faster progression to the endpoint in subjects with miRNAs levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to &lt;0.0001; crude HRs 7.95 to 8.61; Figure 1).

Conclusion
Our study demonstrated that the evaluation of a very small panel of circulating miRNAs (30-5p, 23a–3p and 451a) may impart important prognostic information in chronic HD patients with respect to mortality and CV risk. Although the biological meaning of their deregulation remains unanswered, these preliminary findings may set the stage for larger investigation to generalize their usefulness as biomarkers, as well as possible therapeutic targets.
#3122 30-DAY COMPLICATIONS IN PERITONEAL DIALYSIS CATHETERS INSERTED PERCUTANEOUSLY VERSUS SURGICALLY IN A SECOND LEVEL HOSPITAL IN MERIDA, YUCATAN, MEXICO
Authors: Tapia Leticia , Álvarez Naomi 
Published: June 2023

Abstract

Background and Aims
Peritoneal dialysis (PD) catheter insertion technique has an impact on the health outcomes and technical success in PD. The percutaneous technique allows for a bedside, minimally invasive and faster insertion without the need of using an operating room and general anesthesia. In 2021, Agarwal et. al reported that percutaneous insertion was associated with a 64% relative risk reduction (RRR) of early exit site infection and a 48% RRR of early peritonitis with no difference in terms of mechanical complications compared to the surgical technique [1]. The aim of our study was to describe the frequency of mechanical and infectious complications within the first 30 days of PD catheter insertion between the percutaneous and surgical technique.

Method
We conducted a descriptive and prospective study in our Hospital from January 1st to December 31st, 2022. Patients who were candidates for renal replacement therapy with PD and who had no previous history of abdominal surgery or only minor abdominal surgery, underwent percutaneous insertion of PD catheter by a nephrologist with a bedside blind technique, whereas patients with previous abdominal surgery underwent surgical insertion with a mini laparotomy. Informed consent and preoperative blood tests were obtained before the procedure in both techniques. Patient preparation for the percutaneous insertion included fasting the night before, colonic enema and the placement of a urinary catheter, patients received antimicrobial prophylaxis as well as analgesia and light sedation. Mechanical and infectious complications within the first 30 days after insertion of double cuff Tenckhoff catheters were registered.

Results
During the study period, 155 PD catheter insertions took place in our hospital, the majority of insertions were surgical (53.5% versus 46.4%) and happened in women (60.6%). The mean age of the population was 51.5 years and 70.3% of the participants were diabetic. Exit-site infection was significantly more frequent in the surgically placed PD catheters (10% versus 1%, p = 0.02), there was a tendency for more mechanical dysfunction in the surgical technique versus the percutaneous technique (14.4% versus 5.5%, p = 0.07) and transfer to hemodialysis was more frequent in the surgical insertion group (10.8% versus 1.3%, p = 0.01). There was no difference between peritonitis in both groups and the frequency of uncomplicated PD catheters (catheter survival without any complication) was similar in both techniques.

Conclusion
Bedside PD catheter insertion by the nephrologist using a percutaneous technique can be an easy, timely, safe and adequate procedure with comparable success to the surgical insertion. It may have the advantage of more efficient control of infectious and mechanical complications and what is more, this approach could reduce the cost of kidney failure treatment as it allows for the use of minimal material and human resources.
#3153 HEMOPERFUSION WITH CYTOSORB AND RENAL REPLACEMENT THERAPY IN PATIENTS WITH ACUTE KIDNEY INJURY IN THE INTENSIVE CARE UNIT
Authors: Kobal Barbara , Korošec Tea , Jakopin Eva , Svenšek Franc , Bevc Sebastjan , Hojs Radovan , Ekart Robert 
Published: June 2023

Abstract

Background and Aims
Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a substantial proportion of critically ill patients. The aim of our single centre retrospective observational study was to analyse the outcomes of patients admitted to a non-surgical ICU and treated with RRT and with/without continuous hemoperfusion with Cytosorb.

Method
One hundred critically ill patients (mean age, 64.3 years; 69 men) admitted to the ICU and requiring RRT for AKI were analysed. Patient demographics, concomitant diseases, type of RRT, and survival were obtained from the medical record. APACHE II and Sofa Scores on admission were calculated. 30-day mortality was assessed using Kaplan-Meyer or Cox proportional hazards models.

Results
Reasons for ICU admission were acute respiratory failure (39%), cardiopulmonary resuscitation (14%), shock (13%), acute coronary syndrome (9%), sepsis (3%), acute pancreatitis (3%), and other (19%). Prior comorbidities were hypertension (70%), diabetes (43%), heart failure (32%), chronic kidney disease (CKD) (30%), coronary artery disease (CAD) (27%), chronic obstructive pulmonary disease (COPD) (15%), malignancies (12%). Eighty-six patients were treated with continuous RRT (CRRT) and 14 with intermittent hemodialysis (IHD). Twenty-four (24%) of patients treated with CRRT were also treated with hemoperfusion with Cytosorb. Using an independent-samples T test, we compared the two groups of patients with respect to the use of Cytosorb (Table 1). 30-day mortality was 82% in all patients and 87.5% in patients treated with CRRT and Cytosorb. Among concomitant diseases, only patients with previous heart failure had worse survival (p = 0.032), previous CKD, CAD, COPD, malignancy had no statistically significant impact. We found no statistically significant differences in 30-day mortality between patients treated with CRRT+Cytosorb and patients treated with CRRT or IHD alone. Multivariate Cox proportional hazard regression showed that of all the variables in the statistical model (age, sex, body mass index, previous diabetes, C-reactive protein, lactate, procalcitonin, serum creatinine, mean arterial pressure, APACHE II, ultrafiltration between CRRT), only lactate levels on admission (p = 0.002; 95%CI 1.08-1.38) were significant predictor of survival.

Conclusion
The use of hemoperfusion with Cytosorb in ICU patients with AKI did not reduce 30-day mortality. Patients with prior heart failure had a worse outcome. Serum lactate levels at ICU admission were an independent highly prognostic factor for death within 30 days of admission.
#3161 CLINICAL EFFICACY AND OPTIMAL REGIMEN OF BNT162B2 VACCINE IN CHRONIC DIALYSIS PATIENTS
Authors: Hagai Keren Cohen , Hornik-Lurie Tzipi , Einbinder Yael , Nacasch Naomi , Grupper Ayelet , Wand Ori , Shashar Moshe , Benchetrit Sydney 
Published: June 2023

Abstract

Background and Aims
Highly effective vaccines against severe acute respiratory syndrome virus 2 (SARS-CoV-2) have been developed and administered worldwide. Protection from coronavirus disease 2019 (COVID-19), however, is not absolute, and optimal vaccination regimens need to be established. Concerns regarding breakthrough COVID-19 disease in vaccinated patients are increasing, as vaccine efficacy appears to gradually decline in the months following vaccination. The emergence of highly infective variants, escalates these issues. This study assessed the clinical efficacy of the BNT162b2 vaccine and all-cause mortality among dialysis patients receiving varying numbers of vaccine doses.

Method
This study was conducted using the electronic database of Clalit Health Services in Israel. Patients receiving chronic hemodialysis or peritoneal dialysis during COVID-19 pandemic were included in the analysis. The control group consisted of age-and sex-matched individuals, in a 4:1 ratio to the dialysis group. The study included the pre- and post-vaccination periods.

Results
A total of 14,230 people were included; 2,846 on chronic dialysis and 11,384 controls. Mean age was 66.2±14.3 years (range 18-97). Before the vaccine was available in Israel, 223 dialysis patients were infected with SARS-CoV2. Their mortality rate was 18.4% compared to 10.8% among uninfected, unvaccinated patients in the same period (p = 0.001). On post-vaccination period, we compared the clinical efficacy of a fourth dose to patients who received only 3 doses of BNT162b2 vaccine. SARS-CoV-2 infection rates, hospitalizations due to severe COVID-19, COVID-19–related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after adjusting for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, an additional booster dose was associated with reduced COVID-19–related mortality (1.7% vs. 3.8%, p = 0.04, HR 0.44 (95% CI 0.2–0.98) in patients who received 4 doses compared to 3 doses.

Conclusion
As seen in the general population, and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19 hospitalization and mortality among chronic dialysis patients. This study strengthens the recommendation to administer a fourth booster dose of vaccine to dialysis patients. Further studies are needed to establish the exact dose and schedule of the COVID-19 vaccine in the vulnerable population patients on chronic maintenance dialysis.
#3163 SARS-COV-2 OMICRON INFECTIONS AMONG VACCINATED MAINTENANCE HEMODIALYSIS PATIENTS: OUTCOMES AND COMPARISON TO DELTA VARIANT
Authors: Hagai Keren Cohen , Wand Ori , Drori Idan , Einbinder Yael , Nacasch Naomi , Benchetrit Sydney 
Published: June 2023

Abstract

Background and Aims
Infections with the B.1.1.529 Omicron variant of SARS-CoV-2 became predominant worldwide in late 2021, replacing the previously dominant B.1.617.2 Delta variant. While these variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes after infection with Omicron variant were better than with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron vs. Delta variants are limited.

Method
This retrospective, cohort study included all patients with end-stage kidney disease treated with MHD at Meir Medical Center, Kfar Saba, Israel, who were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022.

Results
Twenty-six MHD patients were diagnosed with the Delta variant and 71 with Omicron. SARS-CoV-2 infection severity was significantly worse among those infected with the Delta variant: 50% developed severe or critical COVID-19 vs. 5% in the Omicron group (p&lt;0.001). Among MHD infected with Omicron, 57% were asymptomatic during their illness. For the entire cohort, 30-day mortality was 5.2%. It was higher among MHD in the Delta group (5/26, 19.2%) than in the Omicron group (0/71; p&lt;0.001), as was 90-day mortality (5/26, 19.2% vs. 3/71, 4.2%, respectively; p = 0.02). Mean age was comparable between groups. Patients infected with Omicron variant received a higher mean number of vaccine doses before infection, as compared to Delta group (p&lt;0.001).

Conclusion
Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among patients on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with significant 90-day mortality rate.
#3185 INFLUENCE OF COMBINED CYP 3A4/5 AND POR*28 GENETIC POLYMORPHISMS ON TACROLIMUS AND CCLOSPORINE DOSE REQUIREMENTS IN INCIDENT RENAL TRANSPLANT PATIENTS
Authors: Elsharkawy Magdy , Ismail Dina , Ebid Abdel-Hameed , Lotfy Neama , Mahmoud Mohamed 
Published: June 2023

Abstract

Background and Aims
Calcineurin inhibitors, cyclosporine and tacrolimus have a narrow therapeutic index and have wide intra- and inter individual pharmacokinetic variability. They are metabolized mainly by CYP3A4 and CYP3A5. The P450 oxidoreductase POR*28 variant allele has been associated with changes in cytochrome P450 enzymatic activity that can affect the therapeutic level of both medications. The aim of this study is to investigate the allelic frequency of the POR*28 in Egyptian renal transplant patients and to evaluate the effect of the presence of CYP3A5*1, CYP3A4*22, and POR*28 genetic polymorphism on calcineurins inhibitos dose requirements and adjustments.

Method
A prospective clinical trial that included 130 renal transplant patients placed on either tacrolimus or cyclosporine. Patients were genotyped for POR*28, CYP3A4*22, and CYP3A5*1. The relation between the present genetic polymorphisms and tacrolimus and cyclosporine doses and dose adjustments were studied at days 14, 30, and 90 post-transplantation.

Results
The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was highly statistically significant in the fast metabolizers group (CYP3A5*1/POR*28T carriers) than in the slow metabolizers group (CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) (p value 0.001, &lt;0.001, and 0.003, respectively). There was no significant effect for this gene combination on cyclosporine (C0/D).

Conclusion
Combining the CYP3A5*1, POR*28, and CYP3A4*22 genotypes can be of significant value in early tacrolimus dose requirements and adjustments. However, it does not have any influence on cyclosporine dose requirements.