bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5819 HAEMODIALYSIS EFFECT ON METABOLIC THERAPY WITH [131INA]: A COMPARATIVE STUDY
Authors: Arias-Camisón Paloma Livianos , Repetto Alessandra , Valeriano Juan Rey , Chamizo Sandra , Talens Antonio Cherino , Viloria María Cristina Peña , Mendez Isabel Garcia 
Published: June 2023

Abstract

Background and Aims
The use of [131INa] therapy in patients undergoing haemodialysis (HD) is still controversial. Considering that the main elimination of 131I is urinary and the sessions of HD take place in wards full of other patients, various modifications should be made in the therapy. Due to the limited bibliography and the lack of consensus in clinical guidelines we developed this comparative study between two patients on HD treated with [131INa]. External dose rate measurement (EDRM), time of hospitalization, timing of dialysis after the administration of [131INa] and the status of contamination of dialysis machine were considered.

Method
Two patients on HD were treated with [131INa] in June 2021. A 74years old women with hyperthyroidism due to a multinodular goitre, resistant to antithyroid drugs (PT1). A 49years old man candidate to ablation treatment with low activity of [131INa] after a total thyroidectomy due to differentiated thyroid cancer (pT2N0) (PT2). The recommended activity was administered according to clinical indication. PT1 received 555MBq and PT2 received 1110 MBq of [131INa] in Metabolic Therapy Unit (MTU) after the first HD session in the nephrology ward. The following HD sessions were in MTU (Wed.-Fri.). High-flux dialysis was performed using a Reverse Osmosis portable system. The hospital stay was 5 days (Mo at Fri) for each patient. EDRM at 1 meter was measured three times a day. Liquid samples from HD machine (dialysis fluid, water wash) were obtained every day at the same time before and after each session and radioactivity was analysed.

Results
EDRM after second HD at discharge was 12 and 7,4mcSv/h in PT1 and PT2 respectively. After first HD both patients reached EDR &lt;40mcSv/h (22 and18 mcSv/h). Red bone marrow dose was 130,76mGy and 110,42mGy respectively. Radioactivity in dialysis fluid was: 0,00999MBq PT1- 0,00259MBq PT2 after first HD; 0,0022MBq PT1- 0,00074MBq PT2 after second HD. No radioactivity was detected in wash water of dialysis equipment in both patients during each HD session. There was no secondary complications due to overhydration or dyslectrolythemias.

Conclusion
External dose rate measurement is key to decide if patients undergoing HD are ready to be discharge. Once EDRM &lt;40mcSv/h at 1 meter has been reached, patients could immediately return to their dialysis centre following the protection radiology rules and so we must always respect the distance between the patients, if that cannot be performed the session will be in the hospital. There is no need to modify radioiodine activities neither timing of HD sessions as red bone marrow dose do not exceed recommended value (2Gy). There is no contamination of HD machine, it could be used after usual decontamination for other patients.
#5826 NEPHROPROTECTIVE EFFECTS OF SEMAGLUTIDE IN A MOUSE MODEL OF HYPERTENSION-ACCELERATED DIABETIC KIDNEY DISEASE
Authors: Christensen Michael , Dalbøge Louise S , Madsen Martin Rønn , Hansen Henrik Björk , Ida Rune , Østergaard Mette Viberg 
Published: June 2023

Abstract

Background and Aims
Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female db/db mice.

Method
Seven weeks after ReninAAV administration and six weeks post-UNx, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included tail-cuff blood pressure evaluation at week 1 and 10, plasma/urine biochemistry, kidney histopathology as well as RNA sequencing.

Results
Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, urine/renal kidney injury molecule-1 (KIM-1) levels. Furthermore, semaglutide suppressed gene expression markers of extracellular matrix modelling and immune system activation. Co-administration of lisinopril further ameliorated hypertension, glomerulosclerosis as well as markers of fibrogenesis and inflammation.

Conclusion
Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Renal outcomes were further improved by combined antihypertensive standard-of-care. These data display the translatability of the db/db UNx-ReninAAV mouse model of DKD.
#5834 ALBUMINURIA AND RENAL RESISTIVE INDEX ARE ASSOCIATED WITH MICROVASCULAR REMODELING IN PATIENTS WITH SEVERE OBESITY
Authors: Moriconi Diego , Mengozzi Alessandro , Nannipieri Monica , Bruno Rosa Maria , Virdis Agostino 
Published: June 2023

Abstract

Background and Aims
Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in severe obesity, its noninvasive assessment with ultrasound still fails to provide pathophysiologic and clinical meaningfulness. The aim of the study is to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity.

Method
We enrolled forty-eight patients affected by severe obesity with an indication for bariatric surgery referring to our Clinic. Patients underwent an extensive renal examination with evaluation of eGFR with EPI-Cr formula, albuminuria and urinary TGF-β as indirect markers of kidney fibrosis, paired with Doppler ultrasound to measure renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L), wall-cross sectional area (WCSA) and vascular response to acetylcholine (ACh), alone or co-incubated with L-NAME, were measured.

Results
Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower eGFR and higher RRI compared to NT. The presence and extent of albuminuria were similar between the two groups, while TGF-β was slightly higher in the HT group (p = 0.059). Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT (p = 0.039). Multivariable analysis showed a relationship between M/L and RRI (p = 0.022, St.β 0.38) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation (p = 0.039, St. β = -0.36). Notably, all these correlations were consistent also after adjustment for confounding factors.

Conclusion
The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal hemodynamics and microcirculatory disruption.
#5835 A LOW DOSE GLUCOCORTICOID, LOW DOSE CYCLOPHOSPHAMIDE, RITUXIMAB TREATMENT PROTOCOL AS INDUCTION THERAPY IN ANCA ASSOCIATED VASCULITIS PATIENTS
Authors: Spanos Georgios , Paschou Styliani , Bakou Marianna , Atalla Alexandros , Bantis Christos , Fragidis Stylianos , Armetzoiou Livia Karmen , Bamichas Gerasimos 
Published: June 2023

Abstract

Background and Aims
There has been a considerable improvement in the survival of patients with ANCA associated vasculitis (AAV) since the introduction of immunosuppressive therapy. Nowadays early deaths are attributable to infection while cardiovascular disease, infection and malignancy are the most common causes in long term mortality in these patients. High-dose glucocorticoids and cyclophosphamide have numerous dose-dependent adverse effects and are associated with those events. The aim of this study is to investigate the efficacy and safety a low dose glucocorticoids, low dose cyclophosphamide, rituximab treatment protocol in AAV patients.

Method
This is a single-centre cohort study of patients on a combination of reduced-dose oral glucocorticoids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of rituximab and tapered steroid for the treatment of AAV (table). Data shown as median (IQR).

Results
Nine patients (3 women) aged 62.4 (55/67.8) years, with serum creatinine (sCre) 2.15 (1.8/2.5) mg/dL, eGFR CKD-EPI 28 (20/39) ml/min/1.73 m2, albuminuria 0.98 (0.57/1.45) gr/24 h and BVAS 14 at baseline were treated with the mentioned protocol. Seven patients had MPO and 2 had double MPO/PR3 positivity. Two were already on dialysis and 4 had pulmonary involvement. The median follow-up was 19 (12.5/39) months. One patient required the addition of plasma exchange and extended treatment due to aggressive disease and one was lost to follow-up after four months. The rest of the 7 patients were dialysis free with a sCre 2.15 (1.8/2.5) mg/dL, eGFR 28 (20/39) ml/min/1.73 m2 at the end of follow-up. Patient and renal survival were 88% and 100% respectively. 85.7% of patients achieved ANCA-negative status and all remained B cell deplete at 6 and 18 months. There were no major relapses, while two patients had infection related hospitalization. No unexpected side effects were observed during follow-up.

Conclusion
These findings confirm the literature that a combined regimen provides early disease control with low relapse rates, without significant adverse effects from immunosuppression. A regimen like this may provide the basis for further refinement of remission induction protocols in AAV, potentially allowing early withdrawal of corticosteroids.
#5842 ULTRASOUND AND 3D IMAGING CHARACTERISATION OF A RAT MODEL OF POLYCYSTIC KIDNEY DISEASE
Authors: Christensen Michael , Porsgaard Trine , Perens Johanne , Sembach Frederikke Emilie , Hansen Henrik Björk , Ougaard Maria 
Published: June 2023

Abstract

Background and Aims
Polycystic kidney disease (PKD) is a congenital fibrocystic disorder where cysts are primarily forming within the kidneys causing enlargement, loss of kidney function and resulting in chronic kidney disease for which there is no curative treatment. Consequently, PKD is classified as a medical condition with high unmet therapeutic need. Animal models with improved clinical translatability can optimally inform about potential clinical efficacy of novel drug candidates for PKD. The polycystic kidney (PCK) rat is an established genetic model of PKD with natural history and renal histologic abnormalities that resemble the human disease. Gubra has established a PCK rat breeding program to enable fast turnaround time of preclinical drug discovery studies for PKD. In this study, we have characterised disease progression in the PCK rat to aid in designing future pharmacological intervention studies.

Method
Male PCK (PCK/CrljCrl-Pkhd1pck/Crl) and control (CRL:CD(SD)) rats (Charles River) were randomised into groups based on body weight at the age of 10 weeks. At the age of 17 and 25 weeks, rats underwent ultrasound assessment of kidney volume, urine collection for quantification of albuminuria, and plasma sampling for analysis of urea and creatinine levels. At termination, whole kidneys were harvested and total kidney volume, cyst number and cyst volume were analysed using quantitative 3D light sheet imaging.

Results
Compared to age-matched control rats, PCK rats displayed marked albuminuria which was significantly increased at week 25 of age. Whereas plasma urea was progressively increased at both time points, plasma creatinine increased at week 25. Ultrasound measurements revealed that total kidney volume progressive increased compared to control rats. 3D Light sheet imaging enabled whole-kidney counting of cysts and quantification of cyst volume as wells as the total kidney volume that closely correlated to kidney ultrasound results.

Conclusion
The PCK rats displays histological hallmarks of PKD, characterized by age-dependent progressive increases in biomarkers of kidney injury, kidney hypertrophy and cyst formation. In vivo ultrasound and ex vivo quantitative whole-kidney 3D light sheet imaging is highly instrumental for detailed assessment of progressive disease in the PCK rat. The renal histopathological markers may serve as key histological endpoints for assessment of therapeutic effects of preclinical drug candidates in this translational rat model of PKD.
#5848 ROLE OF STATINS IN THE CONTRAST-INDUCED ACUTE KIDNEY INJURY PREVENTION AFTER COMPUTED TOMOGRAPHY WITH CONTRAST MEDIA
Authors: Vasin Andrey , Pahlevani Elham , Biryukova Valentina , Mironova Olga , Fomin Victor 
Published: June 2023

Abstract

Background and Aims
Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast media (CM). A number of researches have shown that statins have a protective role in the prevention of CI-AKI due to their pleiotropic effects. The aim of the study was to assess the influence of statins on the incidence of CI-AKI after intravenous CM administration.

Method
A randomized controlled open-label prospective study was conducted. Statin naive patients with cardiovascular diseases referred for contrast-enhanced computed tomography (CT) were included. Exclusion criteria were the use of statins and chronic kidney disease (CKD) stages 4-5. Acute kidney injury was defined as an increase in serum creatinine level by more than 44 μmol/L (0.5 mg/dL) or 25% from baseline within 48 hours after CM administration according to KDIGO guidelines. Glomerular filtration rate was calculated using the CKD-EPI formula. Overall, 181 patients were included in the study and divided into two groups. The first group (120 people) received high doses of atorvastatin (80mg or 40mg) 24 hours after and before the CM administration, while the second group (61 people), the control group, did not receive any statin therapy. Low-osmolar solutions in an amount of 100 ml were used. All patients were given intravenous hydration with saline before the study and 24 hours later. The statistical analysis was done using IBM SPSS Statistics v26.0.

Results
The patients in both groups did not significantly differ in age, BMI, coexisting conditions, and medications taken (Table 1). Both groups showed an increase in average creatinine levels after CT with intravenous CM administration, however, in the group of patients receiving high doses of statins, the average level increased less, p = 0.092 (Table 2). AKI developed in 12 individuals (6.7%), 9 of them were in the control group, and 3 were in the group receiving high doses of statins, p = 0.003. The chances of AKI development in the group receiving high doses of statins were 6.95 times lower compared to the control group (OR = 6.05, 95% CI: 1.7-21.5). Most of the patients had preserved kidney function and did not suffer from diabetes mellitus. There were statistically significantly more patients with preserved kidney function in the statin group, p = 0,007, OR: 2,374 (CI 95% 1,258 - 4,479), and fewer patients with CKD 3a stage, p = 0,05, OR: 0,406 (CI 95% 0,195 – 0,844).

Conclusion
Despite the presence of patients at risk, the incidence of CI-AKI was 6.7%, possibly due to additional prevention of this complication with intravenous saline before and after administration of the CM.
In this trial, we observed that periprocedural administration of atorvastatin in high doses for a short duration, reduced the incidence of CI-AKI.
#5852 EFFECT OF DIET ON THE COLLECTOR DUCT BEHAVIOUR: RELEVANCE IN PRECLINICAL DRUG DEVELOPMENT
Authors: Tejedor Marta , Gonzalez-Nicolas Maria Angeles , Uzun Baris , Álvarez-Sala-Walther Luis Antonio , Lázaro Alberto 
Published: June 2023

Abstract

Background and Aims
Drug induced syndrome of inadequate antidiuretic hormone secretion (SIADH) is a common problem in clinical practice. Early detection of this side effect at a preclinical level would improve safety and efficiency. We investigate the role of different diets in preclinical detection of SIADH.

Method
Animals were divided into two groups (n = 4 each), one receiving standard pellet based diet, and the other one a diluted hyposodic gelified liquid diet. After one week, both groups were administered daily intraperitoneal (i.p.) injections of desmopressin acetate (ddAVP; 0.4 μg/kg) and a volume of distilled water equivalent to 2.5% of body weight for 7 days. Animals were placed in metabolic cages for 24h at the end of each period to collect and analyse the urine, and a blood sample from the tail vein was obtained. Weight, water and food intake were measured on a daily basis.

Results
Differences in water and electrolyte balance are shown in Table 1. Pellet fed animals presented an increased water intake and produced a more concentrated urine compared to those on a hyposodic diet. When analysed in detail, urinary osmolality was mainly driven by ionic osmoles in pellet fed animals (42,25 ± 4,72 vs 266,30 ± 17,32 mOsm/kg, p&lt;0,005). Of note, there seems to be an occult osmole, especially prominent in the pellet group (osmol gap 20,40 ± 3,18 vs 99,89 ± 9,81 mOsm/kg, p = 0,017). All of the above suggest there is a net retention of water, sodium and potassium in those animals fed with a conventional pellet diet. Daily administration of ddAVP/water induced a mild transient hyponatremia that was recovered 24h later in both groups; this situation was repeated over a 7 day period. Pellet fed animals did not modify water intake, diuresis, free water clearance or urinary osmolality after ddAVP/water treatment, suggesting that hyperosmolar diets significantly increase urinary osmolality fixating urinary water losses and impairing further urinary concentration. On the contrary, animals on a hyposodic diet did present antiaquaresis, as shown by an increase in water intake, a decrease in diuresis and free water clearance and an increase in urinary osmolality. Animals fed with hyposodic diet progressively lost weight, while pellet fed animals did not. However, this trend was reversed after 4 days of treatment with ddAVP/water, again suggesting a degree of water retention. It is remarkable that we have found signs of water retention despite the fact that the induced hyponatremia is mild and transient.

Conclusion
The antiaquaretic effect of ddAVP is overridden by the amount of urinary osmoles excreted when on a pellet diet, which seem to fixate the amount of water in the urine. Therefore, the use of hyposodic diets in preclinical drug development is essential when SIADH is likely to be expected, as its effects will be unnoticed if a standard diet is used.
#5865 BET INHIBITION DIMINISHES CELLULAR SENESCENCE IN CULTURED TUBULAR EPITHELIAL CELLS
Authors: Basantes Pamela Estefanía , Rayego-Mateos Sandra , Tejedor Lucia , Marquez-Exposito Laura , Díez Raúl Rodrígues , Marchant Vanessa , Tejera Antonio , Ruiz-Ortega Marta 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) can be considered an age-related disorder. Recent studies have shown the involvement of the activation of cellular senescence mechanisms in the kidney and aging. Intensive research to develop pharmacological approaches targeting cellular senescence is under investigation. Among novel therapeutic options, epigenetic drugs, such as bromodomain and extra terminal BET inhibitors, are being widely explored in proliferative, immune and chronic inflammatory diseases, including CKD. These drugs regulate transcription activation of cell cycle control and proinflammatory factors. There are not studies about the potential effect of BET inhibitors on cellular senescence in the kidney despite the fact that tubular epithelial cells are frequently implicated in kidney senescence.

Method
To study this, we evaluate the effect of JQ1, a BET inhibitor, on cellular senescence in primary cell culture of murine tubular epithelial cells (TECs) using Adriamycin as a senescence inducer verified by B-galactosidase assay. Next, we evaluated the effect of JQ1 on gene expression levels of cell cycle markers, components of senescence-associated secretory phenotype (SASP) as well as anti-apoptotic and antioxidant markers, all of them related to senescence program.

Results
Our results indicated that JQ1 significantly decreased Adriamycin-induced p21 gene upregulation, a primordial cell cycle arrest factor. This BET inhibitor also downregulated SAPS genes, such as Tgfb1, Il1b, Ctgf, Ccl2 and Il6 overexpression in Adriamycin-treated tubular cells. Likewise, anti-apoptotic Bcl-xl and antioxidant factors Cat, Hmox-1, Nox-4 and Nrf2 mRNA levels were significantly restored by JQ1.

Conclusion
In conclusion, the present study highlights the use of JQ1 as a therapeutic option to ameliorate tubular cellular senescence-associated markers. These data support the potential use of BET inhibitors in chronic kidney diseases.
#5876 ISLET TRANSPLANTATION VERSUS INSULIN ALONE IN TYPE 1 DIABETIC KIDNEY TRANSPLANT RECIPIENTS: A FRENCH NATIONWIDE STUDY ON BEHALF OF THE TREPID GROUP
Authors: Maanaoui Mehdi , Lenain Rémi , Foucher Yohann , Chetboun Mikael , Kerr-Conte Julie , Blancho Gilles , Buron Fanny , Lablanche Sandrine , Caillard Sophie , Kessler Laurence , Berney Thierry , Vantyghem Marie-Christine , Hazzan Marc , Pattou François 
Published: June 2023

Abstract

Background and Aims
Islet transplantation is associated with a benefit on glycaemic control compared to optimized insulin therapy in recent clinical trials. However, there is a lack of evidence concerning the long-term impact of islet transplantation on type 1 diabetic kidney transplant recipients’ prognosis.

Method
Every type 1 diabetic recipient transplanted with a kidney in France between 2000 and 2017 was included. Patients transplanted with pancreatic islets were compared to controls treated with insulin alone according to a matching method based on time-dependent propensity scores (using the following variables : yera of transplantation, donor age, and recipient age, serum creatinine, HBA1c, BMI, cardiovascular background) which allow to ensure patients comparability at the time of islet transplantation. The primary outcome was graft failure, defined by death or return to dialysis.

Results
Among 2393 type 1 diabetic patients transplanted with a kidney during the study period, 381 were eligible to islet transplantation, including 47 that were actually transplanted with islets. Median time for islet transplantation was 34.8 months [21.8-48.4]. Probabilities of insulino-independence and islet graft survival at 1, 5 and 10 years were respectively 63.8% [51.5-79.2], 46.3% [33.9-63.2], 38.7% [25.9-57.8] and 89.4% [81.0-98.6], 87.2% [78.2-97.3], 78.2% [66.2-92.4]. After matching, we observed a significant benefit of islet transplantation compared to insulin alone on graft failure, with a HR of 0.48 [0.20-0.94], mainly explained by a protective effect on the risk of death (HR = 0.38 [0.11-0.95]). We finally estimated the life-expectancy for a 10-year follow-up and found 9.61 years [9.02-10.00] in the islet transplantation group versus 8.85 years [7.97-9.56], with a difference of 8.88 months [-2.16-20.44]

Conclusion
We observe a significant benefit of islet transplantation on the risk of graft failure and death in type 1 diabetic kidney transplant recipients. These results provide incentives to promote islet transplantation in this population.