bluuebunny/crossref_metadata_2025_split huggingface dataset:
SO014CHANGES IN CHARACTERISTICS OF CRYSTALLURIA IN PATIENTS WITH RECURRENT NEPHROLITHIASIS
Authors: Di Maio Federica , Barbarini Silvia , Baccaro Rocco , Grandaliano Giuseppe , Ferraro Pietro Manuel 
Published: June 2020

Abstract

Background and Aims
The study of crystals in the urinary sediment finds application in the diagnosis of hereditary or metabolic nephrolithiasis and in the identification of crystals from drugs.

Method
We conducted a thorough microscopic urine examination, focused on the determination of crystalluria, associated with the metabolic study at baseline and about 6 months after the start of a metaphylactic therapy, in 21 patients with recurrent nephrolithiasis, followed at the Metabolic Stone Clinic of our Institution. The analysis of the crystals was performed in parallel and blind through direct microscopic examination (MD) and automated instrumentation (SA) (SediMax analyzer - Menarini Diagnostics) of our institution. We used a semi-quantitative approach for both methods.

Results
We examined 42 sediments (21 at baseline and 21 after an average follow-up of 196±88 days) from 21 patients (8 females, 13 males), all of them showing calcium oxalate crystalluria. The analysis on baseline evaluation and follow-up on both Crystalluria MD and crystalluria SA through spaghetti plots showed a tendency to reduction of severity for the first one only. This trend is consistent with the data obtained from the metabolic studies: urinary oxalate and calcium excretions, the main drivers of calcium oxalate crystallization, which showed decreasing levels. The same examination for urinary citrate excretion showed a rising trend, again in accordance with the on-going changes in urine lithogenic profile.

Conclusion
The study of crystals in the urinary sediment, repeated over time, may represent a further indicator of the effectiveness of metaphylactic therapy and an indicator of patient adherence to the prescription in metabolic calcium oxalate nephrolithiasis.
SO019A PREDICTIVE MODEL OF MORTALITY IN ACUTE RENAL FAILURE IN THE CRITICAL PATIENT: USEFULNESS OF ARTIFICIAL INTELLIGENCE
Authors: Ibeas Jose , Lleal Elia , Macias Edwar , Rubiella Carolina , Morell Antoni , Serrano Javier , Vicario Jose 
Published: June 2020

Abstract

Background and Aims
Patients with Acute Renal Failure (ARF) have a high risk of mortality, especially those who enter the Intensive Care Unit (ICU). In this population, predictive models of mortality on prognostic scales, such as SAPS-II (Simplified Acute Physiology Score II), linearly relate risk factors without taking into account the complex relationship's variables can have. There are models where Machine Learning (ML) techniques have been used, but there is still room for improvement. The implementation of deep artificial neural networks (DANN) can be challenging.
The literature models, using SAPS-II report an accuracy, f1 and ROC area (receiver operating curve) in ranges of 0.538-0.621, 0.333-0.377 and 0.781-0.809 respectively. The best results with ML are improved in neural networks of a hidden layer or random forest, being the best performance in the latter: accuracy 0.715-0.741, F1 0.449-0.470 and ROC between 0.862-0.870.
The aim is to evaluate and improve the predictive capacity of ML techniques for the prediction of mortality in patients with ARF admitted to the ICU, through the use of the open database MIMIC-III (Medical Information Martfor Intensive Care III).

Method
Design: Retrospective analysis of historical cooperation of 20,928 patients with ARF from Beth Israel Deaconess (Boston), from 2001 to 2012.
Method: ML algorithm based on DANN. Creation of a model to predict in-hospital mortality after discharge from the ICU with the variables of the first 24 hours after admission to the ICU.
To evaluate the robustness of the model has been performed cross-validation by separating the samples into different combinations of training and test data (k-folds). The unavailable variables haematological with means extracted from the training set of the respective fold. The DANN trained with the complex relationship's variables folds, two hidden layers of 75 and 40 neurons respectively.
Inclusion criteria: &gt; 16 years, AKI according to KDIGO criteria and predictive variables based on SAPS-II.
Variables: Age, sex, type of admission, number of admissions in ICU, heart rate, blood pressure, temperature, PaO2, FiO2, sodium, potassium, bilirubin, bicarbonate, urea, leukocytes, diuresis and diagnosis of ICD-9 (metastatic cancer, haematological malignancies).

Results
Accuracy: 76.7% 0 ± 1.7%, f1: 86.6% ± 1.9%, RO area: 0.859 ± 0.006, sensitivity: 75.7% ± 2.8%, specificity: 80.5% ± 2.9%.

Conclusion
The use of Machine Learning techniques based on deep artificial neural networks can improve the predictive ability of mortality in acute renal failure of the critically ill patient of traditional clinical risk scales and even current Machine Learning models.
SO034A NEW MARKER OF RESISTANT HYPERTENSION IN CKD PATIENTS
Authors: Gembillo Guido , Siligato Rossella , Cernaro Valeria , Satta Ersilia , Conti Giovanni , Salvo Antonino , Romeo Adolfo , Calabrese Vincenzo , Sposito Giovanna , Ferlazzo Guido , Santoro Domenico 
Published: June 2020

Abstract

Background and Aims
Monocytes -HDL ratio (MHR), has emerged as a possible marker of inflammation and oxidative stress (OS), demonstrating its possible use in the population with Chronic Kidney Disease (CKD). These effects seem to be modulated by an increased lipid production, by reduced cellular catabolism of fatty acids and by the alteration of the antioxidant, anti-inflammatory mechanisms and the reverse cholesterol transport of HDL. The latter to exert favorable effects on inflammatory and oxidative pathway. The purpose of our research is to evaluate the link between MHR and resistant hypertension (RH) which, together with inflammation, OS and atherosclerosis, represents a widespread feature in the population with CKD and carries a greater risk of premature death due to cardiovascular disease.

Method
A retrospective study has been performed on 251 hypertensive patients, admitted in the last 6 months to the Unit of Nephrology and Dialysis of the Policlinic G. Martino of Messina, Italy. 80 patients were diagnosed with RH, defined as blood pressure that remains above 140/90 mmHg despite use of three different classes of antihypertensive medications (one of which must be a diuretic) at the maximum tolerated doses.
We evaluated the distribution of data with Kolmogorov-Smirnov test and, considering that MHR had a non-normal distribution, we expressed the values as medians and interquartile ranges (IQR). Moreover, differences between groups with Mann-Whitney test, correlations with Rank Correlation and Spearman's Rho coefficient were also considered in the analysis. Finally, we assessed the differences of variables between the means of different groups with ANOVA test using multiple regression to valuate independent relations between variables.

Results
MHR appeared to be positively correlated with serum creatinine levels (ρ=0.24; P=0.0001) (Figure 1). MHR correlated with the number of antihypertensive drugs per patient in the entire cohort of patients (F = 18.23; P &lt;0.001) (Figure 2). Patients with RH had a significantly higher MHR than patients without resistant hypertension (0.1493 [IQR 0.12 - 0.18] versus 0.11 [IQR 0.0 - 0.13], P &lt;0.0001) (Figure 3).

Conclusion
MHR has proven to be an accurate tool in quantifying inflammatory status and OS, whose effectiveness lies in the close correlation that exists between HDL and monocytes. HDL prevent and reverse the recruitment of monocytes in the arterial wall and their activation through a decrease in their F-actin content, thereby reducing the expression of CD11b on monocytes, and modulating their adhesion to the endothelium. Our study showed that MHR could be a useful and immediate tool to evaluate OS and inflammatory status in order to select high-risk patients and identify earlier and appropriate treatment strategies.
SO036THE EFFECT OF DAPAGLIFLOZIN ON AMBULATORY AORTIC BLOOD PRESSURE AND ARTERIAL STIFFNESS PARAMETERS IN PATIENTS WITH TYPE-2 DIABETES MELLITUS: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL
Authors: Papadopoulou Eirini , Loutradis Charalampos , Kotsa Kalliopi , Karras Spiros , Sambanis Christos , Tzatzagou Glyceria , Karakozoglou Anastasios , Didangelos Triantafillos , Theodorakopoulou Marieta , Minopoulou Ioanna , Tsapas Apostolos , Karagiannis Asterios , Sarafidis Pantelis 
Published: June 2020

Abstract

Background and Aims
Arterial stiffness is a prominent risk factor for heart failure and overall mortality in patients with type-2 diabetes mellitus (DM). Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce the incidence of heart failure and death in these patients. The aim of this study is to evaluate the effects of dapagliflozin on ambulatory central blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 DM.

Method
This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 DM on monotherapy or combination therapy with two of: metformin, sulphonylurea, DDP-4 inhibitor, or insulin. Patients were randomized in a 1:1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end.

Results
Baseline demographic, clinical and laboratory parameters were similar in the two groups (age 61.74±6.73 vs 60.64±9.35; p=0.534). During follow-up, 24-hour central SBP/DBP significantly decreased in dapagliflozin (117.41±10.52/78.88±7.25 vs 113.30±8.75/77.25±6.54; p=0.002/p=0.047), but not in the placebo group. Corresponding reductions of 24-hour central SBP (-4.12±8.00 vs -0.65±7.77; p=0.046) were greater with dapagliflozin than placebo. Aortic pulse pressure (PP) decreased only in the dapagliflozin group (38.53±7.44 vs 36.05±6.59 mmHg; p=0.004). 24-hour heart-rate adjusted augmentation-index significantly decreased with dapagliflozin. Importantly, there was a significant difference in the change of 24-hour PWV (-0.16±0.32 vs 0.02±0.27; p=0.007) favoring dapagliflozin.

Conclusion
Treatment with dapagliflozin significantly reduces ambulatory central BP and PWV levels in type-2 diabetics. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.
SO038A TRANSLATIONAL KIDNEY ORGANOID SYSTEM BOLSTERS HUMAN RELEVANCE OF CLINICAL DEVELOPMENT CANDIDATE
Authors: Westerling-Bui Amy , Soare Thomas , Venkatachalan Srinivasan , DeRan Michael , Fast Eva , Fanelli Alyssa , Kyrychenko Sergii , Hoang Hien , Corriea Grinal , Zhang Wei , Yu Maolin , Malojcic Goran , Pan-Zhou Xin-Ru , Ledeboer Mark , Harmange Jean-Christophe , Emani Maheswarareddy , Tibbitts Thomas T , Reilly John , Mundel Peter 
Published: June 2020

Abstract

Background and Aims
A major challenge in drug discovery is gaining confidence in the human relevance of pre-clinical animal studies. While human iPSC-derived organoids offer exciting opportunities to address this, concerns about applicability and scalability remain. Here, we report a high-throughput human organoid platform for assessment of kidney disease targeting compounds.

Method
In vitro & in vivo transplanted under athymic rat kidney capsule, differentiated organoids were characterized using single cell RNA sequencing (scRNA-Seq), NanoString, & immunofluorescence techniques. Immunofluorescence quantitative analysis of aggregated actin per in vitro organoid in a protamine sulfate (PS) podocyte injury model was used to evaluate efficacy of GFB-887, a sub-type selective, small molecule transient receptor potential canonical 5 (TRPC5) inhibitor. In pharmacokinetic studies, GFB-887 was orally administered into rats, then the presentation of GFB-887 was measured in rat plasma, rat kidney, & in vivo transplanted human organoids. In pharmacodynamic studies of transplanted human organoids, rats were co-perfused with GFB-887 & PS or orally dosed with GFB-887 prior to PS, then immunofluorescence quantitative analysis of mean synaptopodin intensity in podocytes of the in vivo transplanted organoids was used to evaluate efficacy of GFB-887.

Results
We confirmed platform reproducibility by scRNA-Seq and derived a NanoString panel for efficient quality control. Organoid transplantation in rats for 2 to 4 weeks promoted organoid maturation and vascularization. In functional studies, cyclosporine A (CsA), a calcineurin inhibitor clinically utilized for the treatment of nephrotic syndrome, and GFB-887, a novel sub-type selective TRPC5 inhibitor currently in clinical development, protected in vitro kidney organoids from injury. Pharmacodynamic studies with GFB-887 delivered orally to rats were also successfully performed in human transplanted organoids.

Conclusion
These data show how human organoids can deliver confidence in taking development candidate compounds to the clinic, fulfilling their promise to revolutionize drug discovery.
SO045DOES MALNUTRITION INFLAMMATION SCORE MAINTAINS ITS PREDICTIVE RISK ASSESSMENT IN THE MODERN HEMODIALYSIS ERA?
Authors: Sá Martins Vitor , Adragao Teresa , Aguiar Leila , Dias Catarina , Lourenço Pedro , Figueiredo Rita , Pascoal Tania , Pereira Juliana , Pinheiro Tatiana , Ramião Inês , Velez Brígida , Papoila Ana Luisa , Pinto Iola , Borges Nuno , Calhau Conceição , Macário Fernando 
Published: June 2020

Abstract

Background and Aims
Malnutrition Inflammation score (MIS) is a risk score published in 2001 (Kalantar-Zadeh, 2001) and validated in 2008 (Rambod, 2009). It is associated with a high mortality and morbidity risk in hemodialysis (HD) patients (pts).
Currently, HD pts population is composed of much older individuals, submitted to a high efficient treatment with access to pharmacological and nutritional therapy, assured by a bundled payment, when comparing with the validation study population.
The objective of this study is to evaluate if MIS maintain its predictive risk assessment.

Method
Cross sectional analysis of HD pts from 25 outpatient clinics. MIS was evaluated at the study baseline. Univariable and multivariable Cox additive regression models were used to analyze the data. C-index was estimated to assess the performance of the final model. A level of significance of α= 0.05 was considered.

Results
A total of 2444 pts were analyzed (59.0% males; 32.0% diabetic) during a median period of 48 months (P25=31; P75=48), 875 patients registered MIS&lt;5, corresponding to 35.8%. All-cause mortality was observed in 860 pts (35.2%). There were 202 (35.8%) events in the group of patients with MIS&lt;5, while in the group with MIS≥5, the number of deaths was higher (658 pts, 41.9%).
In univariable analysis using Cox additive model, the main results were:
In multivariable analysis, adjusting for age, nPNA, IDWG, Kt/V and diabetes, a MIS ≥ 5 and ≥ 7 showed, respectively, a HR of 1.761 (IC 95%, p&lt;0.001) and 1.822 (IC 95%, p&lt;0.001).

Conclusion
The findings of this analysis confirms that MIS maintains a discriminative power to identify higher risk of mortality. In this model, age and diabetes also correlate with mortality risk increase, while nPNA, IDWG and Kt/V have the opposite effect.
SO059ASSOCIATION OF ALL-CAUSE MORTALITY WITH PRE-HEMODIALYSIS PULSE PRESSURE IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Zhang Hanjie , Cherif Alhaji , Kotanko Peter 
Published: June 2020

Abstract

Background and Aims
Chronic and end-stage kidney disease patients experience significantly increased risk of cardiovascular morbidity and mortality due to multitude of interlinked pathophysiological processes inducing metabolic and inflammatory conditions. Pulse pressure (PP) reports cardiac and vascular conditions, where consistently high PP values are associated with atrial fibrillation, aortic insufficiency, arterial stiffness or arteriovenous malformation, and low PP values may be associated with aortic valve stenosis, cardiac insufficiency or cardiac tamponade. However, the association of pre-hemodialysis (pre-HD) PP with mortality among hemodialysis patients is not well understood. In this study, we aim to explore the extent to which PP is associated with mortality.

Method
We analyzed pre-HD PP (calculated as pre-HD SBP minus pre-HD DBP) between 1/2001 and 12/2012 in hemodialysis patients treated in U.S. Fresenius Medical Care facilities. A 3-months baseline period was defined as months 4 to 6 after hemodialysis initiation, all-cause mortality was noted during follow-up. Only patients who survived baseline were included. Censoring events were renal transplantation, modality change, or study end. We built Cox proportional hazards models with spline terms, allowing us to model nonlinear effects of pre-HD PP as a continuous variable and its relationship with all-cause mortality.

Results
We included 152,625 patients. Mean age was 60.8 years, 59% were white and 56% were male. During a median follow-up of 26.0 months 40.4% patients died. We found that for patients with pre-HD PP between 49.2 mmHg and 74.7 mmHg, were associated with better survival. In contrast, a PP below 49.2 mmHg and above 74.7 mmHg were associated with higher mortality. Similar nonlinear effects are seen in SBP for a given pre-HD PP value (see Fig. 1).

Conclusion
The association of pre-HD PP with mortality is nonlinear, and a better understanding of the nonlinearity will provide further insights into disentangling the associated mediators affecting its dynamics. Our findings may aid risk stratification in HD patients.
SO093LONGITUDINAL DATA ON TREATMENT DURATION AND COMPLIANCE FROM AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS WITH TOLVAPTAN
Authors: Zhou Xiaolei , Garbinsky Diana , Ouyang John , Davenport Eric , Agarwal Indra , Oberdhan Dorothee 
Published: June 2020

Abstract
Background and Aims : Observation of impactful clinical outcomes in a clinical trial setting for ADPKD is challenging due to the life-long progressive nature of ADPKD and longer-term associated outcomes of interest in this population (e.g., renal function decline, cardiovascular events, and mortality). Since 2004, the tolvaptan (TOL) clinical trial program enrolled subjects in multiple clinical studies with the opportunity to enroll in subsequent clinical trials for treatment and outcomes evaluation.
Method : Data from 6 ADPKD studies (protocols 156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271) were pooled and evaluated over time for overall treatment duration, treatment time, and treatment gaps. Treatment duration for the individual clinical trials ranged from 1 week to up to 3 years.
Results : Overall, 1,437 subjects received TOL in these ADPKD clinical trials. For these subjects, the mean overall treatment duration was 4.1 years (3.8 years on treatment) with a maximum of 9.7 years (9.0 years on treatment). In this cohort, 513 subjects (35.7%) received TOL treatment for more than 5 years. Mean treatment compliance was 94.1%. Overall, 723 subjects (50.3%) received TOL treatment in ≥2 trials, with a median treatment gap duration between trials of 0.1 years (maximum, 5.6 years). At least 7 years of follow-up data are available for estimated glomerular filtration rate in 241 subjects (mean at baseline, 78.6 mL/min/1.73m2) and for total kidney volume in 130 subjects (mean at baseline, 1,816.9 mL).
Conclusion : This analysis provides longitudinal follow-up over an extended timeframe in a large number of subjects treated with TOL, with the greatest number of subjects being enrolled in clinical trials enriched for rapidly progressing ADPKD. Treatment compliance over years was reasonably good despite treatment gaps.
MO006INFLAMMASOME ACTIVATOR NLRP3 HYPOMETHYLATION IS ASSOCIATED WITH GLUCOCORTICOID RESISTANCE IN PATIENTS WITH IDIOPATHIC NEPHROTIC SYNDROME
Authors: Granata Simona , Stocco Gabriele , Lucafò Marianna , Bonten Erik , McCorkle Robert , Decorti Giuliana , Gambaro Giovanni , Evans William E , Zaza Gianluigi 
Published: June 2020

Abstract

Background and Aims
We have previously shown that the Nod-like receptor protein-3 (NLRP3) gene is over-expressed in leukocytes of many patients with chronic kidney disease, and studies have also shown that hypomethylation and overexpression of NLRP3 are associated with glucocorticoid resistance in acute lymphoblastic leukemia. Therefore, we hypothesized that hypomethylation of the NLRP3 promoter my cause glucocorticoid resistance in patients with Idiopathic Nephrotic Syndrome (INS) associated with minimal change disease (MCD) or focal glomerulosclerosis (FSGS).

Method
We assessed NLRP3 and Caspase 1 (CASP1) promoter methylation by SNuPE reaction in germline DNA from leukocytes of 14 glucocorticoid-resistant and 18 glucocorticoid-sensitive adult INS patients (discovery cohort) and 7 glucocorticoid-resistant and 14 glucocorticoid-sensitive pediatric INS patients with MCD/FSGS (validation cohort). The effects of NLRP3 inflammasome on glucocorticoid resistance were validated in vitro in human monocytic cell lines (THP-1 and U937).

Results
Methylation of CpG islands in the CASP1 promoter was undetectable in both groups whereas NLRP3 promoter methylation was significantly lower in glucocorticoid-resistant compared to glucocorticoid-sensitive in both adults and children.
The AUROC curve was 81.2% (p=0.0003) in adults and 73.5% (p=0.0002) in children demonstrating the capability of NLRP3 methylation to discriminate glucocorticoid-resistant versus glucocorticoid-sensitive.
Activation of the NLRP3 inflammasome by LPS/ATP reduced glucocorticoid receptor expression and increased glucocorticoid resistance in U937. Consistently, knockdown of NLRP3 in THP-1 increased sensitivity to glucocorticoids.

Conclusion
Our findings demonstrate a novel mechanism whereby INS patients develop resistance to glucocorticoids via leukocyte epigenetic changes of NLRP3 and reveal a new potential clinical biomarker to early detect this condition.