bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO098HUMAN STOOL METABOLOME DIFFERS UPON 24-HOUR BLOOD PRESSURE LEVELS AND THE NON-DIPPING BLOOD PRESSURE PROFILE
Authors: Huart Justine , Cirillo Arianna , Taminiau Bernard , Descy Julie , Saint-Remy Annie , Daube Georges , Krzesinski Jean-Marie , Melin Pierrette , De Tullio Pascal , Jouret François 
Published: May 2021

Abstract

Background and Aims
Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of food-derived short chain fatty acids (SCFAs). Among the clinical manifestations of HT, the absence of a significant drop in blood pressure (BP) overnight (i.e. non-dipping BP profile) has been associated with poor cardiovascular outcomes. The link between GM and non-dipping BP profile is unknown.

Method
After informed consent, 16 male patients and their female partners (n=10) were subjected to 24-hours ambulatory BP monitoring and were categorized in 2 groups: HT (n=7; 6 men) and normotension (NT) (n=19). According to the conventional night–day systolic BP ratio &gt;0.9, 15 individuals (8 men and 7 women) were categorized as non-dippers. Metabolomics using Nuclear Magnetic Resonance was performed on stool samples, including the quantification of the 3 main SCFAs (i.e. acetate, propionate and butyrate).

Results
Multivariate analysis (principal component analyses (PCA) and partial least squares (PLS-DA)) of stool metabolomics were not able to statistically separate HT versus NT groups. However, this approach discriminated dippers versus non-dippers groups in both male and female cohorts (Q²=0.87 and 0.98, respectively), as well as in the entire cohort (Q²=0.68). As previously described, fecal amounts of acetate, propionate and butyrate were higher in HT patients than in NT patients in the entire cohort (p=0.027; p=0.015 and p=0.015, respectively). Fecal amounts of acetate, propionate and butyrate were also significantly higher in non-dippers versus dippers in the entire cohort (p=0.027; p=0.038 and p=0.036, respectively). Significant correlations between stool metabolomes and the 24h-mean BP levels were found in male and female cohorts (R²=0.63 and 0.79 respectively) as well as in the entire cohort (R²=0.54).

Conclusion
In conclusion, this 26-patient cohort highlights significant correlations between stool metabolome and (i) BP levels and (ii) non-dipping BP profile in both men and women.
MO100WNT/Β-CATENIN SIGNALING PATHWAY IS ASSOCIATED WITH HYPERTENSIVE CARDIAC AND RENAL FIBROSIS
Authors: Bogdanova Evdokia , Semenova Natalia , Galkina Olga , Zubina Irina , Beresneva Olga , Ivanova Galina , Parastaeva Marina , Dobronravov Vladimir 
Published: May 2021

Abstract

Background and Aims
Arterial hypertension (AH) causes a cardiac remodeling and renal fibrosis which considered to be mediated by reactivation of fetal and pro-fibrotic signaling pathways. Signal transduction of canonical Wnt (β-catenin expression) evaluation in the settings of heart and kidney hypertensive alterations was the subject of the study.

Method
Systolic blood pressure (BP), serum and urinary creatinine (Cr), proteinuria (uTP), inorganic phosphate (sPi), intact parathyroid hormone (PTH), intact fibroblast growth factor 23 (FGF23), Klotho protein, were estimated in spontaneously hypertensive rats after 1 (SHR1, n=6), 2 (SHR2, n=6), 4 (SHR4, n=6) и 6 (SHR6, n=6) months of exposure. Perivascular and interstitial fibrosis (Masson's trichrome), and β-catenin expression (IHC) were analyzed by light microscopy of myocardium and kidney tissues and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test. The association between biochemical and morphological variables was estimated by Spearman’s correlation.

Results
In all groups BP increased compared to baseline values (p = 0.011). The decline of renal function was obvious in SHR6 (vs SHR2, p=0.001). Klotho level decreased in SHR2 vs SHR1 (p = 0.026) and in SHR4-6 vs SHR2 (p &lt; 0.013). There were no differences in sPi (p = 0.50), PTH (p = 0.63), FGF23 (p = 0.62) between experimental groups. Perivascular myocardial fibrosis was already increased in SHR2 (vs SHR1, p=0.026, Figure 1a), renal interstitial fibrosis - since 6mo exposure (p = 0.012, Figure 2a). Both cardiac and renal fibrosis were associated with redistribution of β-catenin in cardiomyocytes and tubular epithelial cells (Figure 1a, 2a: decrease in membrane and increase in cytoplasm) without significant changes in tissue β-catenin expression. In heart β-catenin expression correlated with to perivascular fibrosis (Figure 1 b). Renal β-catenin expression correlated with interstitial fibrosis (Figure 2b), but not with sCr (r=-0.03, p&gt;0.05) и uTP (r=0.04, p&gt;0.05).

Conclusion
Reactivation of Wnt/ β-catenin signal transduction is possibly a basic molecular mechanism of cardiac and renal fibrosis in arterial hypertension. The data suggests involvement of Klotho decline mediated activation of canonical Wnt. Targeting these signaling molecules is promising therapeutic strategy for protecting both organs in cardiorenal pathology and requires further research.
MO112SYSTEMIC OXALOSIS IN PRIMARY HYPEROXALURIA TYPE 3 – ARE THE PATIENTS AT RISK?
Authors: Hoppe Bernd , Martin Higueras Cristina , Herberg Ulrike , Birtel Johannes , Born Mark 
Published: May 2021

Abstract

Background and Aims
Primary Hyperoxaluria type 3 (PH3) is said to be the less problematic form of PH and with low risk of chronic kidney disease (CKD) and end stage renal disease. However, a recent OxalEurope registry evaluation reported both urine and plasma oxalate levels in a comparable range as in PH1 and PH2 patients. In addition, PH3 patients remain symptomatic with recurrent kidney stones, even in adulthood, and 24% of the 95 patients evaluated were on CKD ≥ 2 at last follow up. Hence, it was speculated, that PH3 patients may also be on risk to develop systemic oxalate deposition.

Method
We retrospectively analyzed the imaging procedures performed so far in patients regularly seen at the German Hyperoxaluria Center, which included: eye exams; x-rays of the hand; bone MRI (3 Thesla of the left knee and proximal tibia); and Speckle tracking echocardiography using 2D Cardiac Performance Analysis VC (TomTec Imaging Systems GmbH, Germany), which measures changes in global longitudinal strain (GLS), an index of left ventricular contractibility. The normal range for GLS is ≤18%. All patients or parents signed an informed consent.

Results
From the 49 PH3 patients registered at the German Hyperoxaluria center, 12 pediatric and 4 adult patients are seen on a regular basis, at least twice a year, and the rest are followed in other centers. All the 16 patients were in stable kidney function and in no less than CKD 2. Eye examination was performed in six patients and was normal in all. Four patients received an x-ray of the left hand, which was normal in 3, but in one patient with a problematic clinical course (multiple stone removal procedures, decline in GFR), tiny sclerosing areas, although no true metaphyseal bands, were seen at caput MCP IV and the thumb. Therefore, MRI of the left knee and proximal tibia was performed in this and another patient, which showed no signs of systemic oxalate deposition. Speckle tracking echocardiography was done in 6 patients and was abnormal in one (GLS – 17.3 and left ventricular hypertrophy) and borderline in the twin sibling (GLS – 18.6). The patient with the abnormal GLS also had salivary stones in the parotid gland, as were also found in his other, older sibling in a routine x-ray of the jaw before orthodontic treatment.

Conclusion
Although this is currently only data of a small cohort of patients, the parameters available so far show, that systemic oxalate deposition may also occur in PH3. Based on our experience on PH1, we regard Speckle tracking echocardiography as the best parameter to detect early systemic calcium-oxalate depositions. Hence the reduction in global longitudinal strain, thus ventricular contractability, is a clear proof of such deposits. Of course, data in more patients are needed to elucidate the true risk of systemic oxalate deposition and we are therefore currently screening all our PH3 patients.
MO121ASSOCIATION BETWEEN BONE MINERAL DENSITY, BODY COMPOSITION AND SERUM SCLEROSTIN IN MALE STONE-FORMERS
Authors: Guedes Rodrigues Fernanda , Pietrobom Igor , Subtil Ormanji Milene , Ligeiro Gonçalves Esper Priscila , Matos Ana Cristina , Ribeiro da Rocha Daniel , Dos Santos Dutra Adriana , De Borst Martin , Pfeferman Heilberg Ita 
Published: May 2021

Abstract

Background and Aims
Reduced bone mineral density (BMD) has been observed in stone-formers (SF). Although obesity is considered a protective factor for bone health due to increased mechanical load, the role of muscle mass (lean) or body fat remains controversial. Sclerostin, an antagonist of the Wnt signaling pathway, is secreted by osteocytes and its actions involve the inhibition of bone formation, FGF23 stimulation, and increased urinary calcium and phosphorus excretion. Recent studies also indicate its association with body composition. The aim of the present study was to evaluate the relationship between BMD and body composition with serum sclerostin levels in male SF.

Method
This is a retrospective study, based on medical records of SF with available data of BMD and body composition, serum and urinary biochemistry and hormonal measurements including sclerostin. BMD had been assessed at lumbar spine (L1-L4), femoral neck (FN) and total femur (TF) and body composition (fat and lean mass) in a dual energy X-ray absorptiometry (DXA).

Results
Fifty-five male SF (37.2 ± 9.3 years) were included. Patients were divided into tertiles according to the percentage of body fat (T1, n = 19, 8.7-20.0 %; T2, n = 20, 20.1-26.0 %; T3, n = 16, 26.1-38.0 %). There was no statistical difference in BMD in any of the sites between these tertiles. Higher urinary sodium and serum sclerostin were observed in T3 versus T1 (280 ± 93 vs 199 ± 75 mEq/day, p &lt;0.05; 33.6 ± 14.7 vs 24.7 ± 8.3 pmol/L, p&lt;0.05, respectively). There was an inverse association between serum sclerostin and lean mass (β= -0.30, p=0.001) and direct association with fat mass (β=0.40, p=0.001), urinary calcium and phosphorus (β=0.29, p=0.02; β=0.32, p=0.01). In a multivariate linear regression model, lean mass was an independent predictor of BMD at L1-L4, FN and TF (β= 0.70, p&lt;0.001; β=0.70, p&lt;0.001; β=0.57, p=0.00, respectively) and at the TF there was also an inverse association between body fat and PTH (β= –0.51, p= 0.03; β= –0.25, p= 0.03).

Conclusion
These data suggest that male SF with a higher percentage of body fat had higher levels of serum sclerostin, which were directly associated with calciuria and phosphaturia but not with BMD. In addition, lean mass was an independent predictor of BMD. Further studies are needed to determine long-term effects of serum sclerostin levels upon bone formation in SF.
MO122SEX DIFFERENCES IN THE RISK OF KIDNEY STONES
Authors: Ferraro Pietro Manuel , Taylor Eric N , Curhan Gary C 
Published: May 2021

Abstract

Background and Aims
Kidney stone disease is a highly prevalent condition. Men are at higher risk of developing stones compared with women, however recent data suggest a changing epidemiology with women being relatively more affected than in the past. The reasons for such differences and changes over time are not clear.

Method
We analyzed the association between sex and the first symptomatic incident kidney stone using data from three large, longitudinal cohorts. Incidence rates for men and women overall and across categories of age and calendar time were computed and hazard ratios (HRs) and 95% confidence intervals (CIs) generated with age-adjusted Cox proportional hazards regression models. Mediation analysis was performed in order to estimate the amount of excess risk for men explained by established risk factors, including BMI, waist circumference, history of high blood pressure, history of diabetes, use of thiazides, dietary intakes of animal protein, caffeine, fructose, potassium, sodium, oxalate, phytate, dietary and supplemental intakes of calcium, vitamin C and vitamin D, sugar-sweetened beverages and total fluid intake.

Results
The analysis included data from 268,616 participants, contributing 5,876,205 person-years of follow-up, during which 10,303 incident stone events were confirmed. The overall incidence rate of kidney stones was 271 and 158 per 100,000 person-years for men and women, respectively. The age-adjusted HR for men compared with women was 2.32 (95% CI 2.20, 2.45). About 18% of the difference in rates was explained by the risk factors included in the analysis. The risk of stones was consistently higher across categories of age among men compared with women. With regard to calendar time, the risk remained higher among men, but tended to decrease over time while it increased among women, resulting in a relative risk reduction of 38% for after 2009 compared with before 1990.

Conclusion
The risk of kidney stones is higher among men compared with women. This difference is only partly explained by modifiable risk factors.
MO113CALCULATED URINARY CALCIUM-OXALATE SATURATION (ßCAOX) IS NOT SPECIFICALLY ELEVATED IN PATIENTS WITH PRIMARY HYPEROXALURIA
Authors: Hoppe Bernd , Böhm Wolfgang , Martin Higueras Cristina 
Published: May 2021

Abstract

Background and Aims
In the primary hyperoxalurias (PH; types 1-3) recurrent urolithiasis (UL) and/or progressive nephrocalcinosis (NC) are the clinical hallmarks. Three different enzyme defects lead to endogenous oxalate overproduction and to extremely elevated urinary oxalate excretion (UOx). Thus, it seems logical that urine is supersaturated for calcium-oxalate (CaOx). It was, hence, speculated that urinary CaOx saturation (ßCaOx), calculated by computed programs, is significantly higher as compared to that of patients with idiopathic CaOx stones. We now aimed to evaluate and calculate urinary ßCaOx in PH patients according to type, as well as in non-PH patients with UL or NC.

Method
The computed equilibrium program EQUIL2 was used for the calculation of ßCaOx. For this, 24 h urine specimen of 70 patients with non-PH NC (46 male, 24 female, median age 6.06 (range 0.3-31.4 years)), of 149 idiopathic CaOx UL (90/59 m/f, age 8.5 (0.1-68.6)), of 51 PH 1 patients (31/21, age 12.33 (0.8-63.8)), of 5 PH 2 patients (3/2, age
5.41 (4.3-12.9)) and of 14 PH 3 patients (8/6, age 8.5 (2.9-29.3)) were analyzed for all necessary components. All patients were in stable kidney function (eGFR &gt; 45 ml/min).

Results
Uox was higher in the PH patients as compared to the non-PH UL or NC patients (p &lt; 0.05). However, there was no statistical difference between the Uox in PH 1 vs PH 2 or PH 3 patients, although, a clear effect of B6 medication was visible in PH1 patients. Urinary calcium excretion was lower (not significant) in PH patients as compared to NC/UL. There was no difference in ßCaOx when PH were compared to non-PH patients and it mostly remained in the normal range.

Conclusion
Urine ßCaOx is similar in PH and non-PH stone formers. Therefore, calculation of ßCaOx using computed programs is not a reliable parameter to define the definitively extreme CaOx supersaturation of urine from PH patients. This miscalculation is related to a rather lowish urinary calcium excretion in PH as compared to other UL/NC patients. Therefore, we recommend not to use such programs to express the risk of recurrent stone disease or nephrocalcinosis in PH.
MO1156,7-DIHYDROXYCOUMARIN AMELIORATE EXPERIMENTAL NEPHROLITHIASIS BY INHIBITING MLKL PHOSPHORYLATION
Authors: Prajapati Smita , Tomar Bhawna , Srivastava Anjali , Mulay Shrikant Ramesh 
Published: May 2021

Abstract

Background and Aims
Intrarenal deposition of organic and inorganic minerals attributes towards the pathogenesis of nephrolithiasis. Various current studies implicates crystal mineralization involves necroinflammation for the progression of crystal induced chronic kidney diseases (CKD). We hypothesized that 6,7-dihydroxycoumarin (6,7-DHC) inhibits calcium oxalate (CaOx) induced necroptosis and ameliorates nephrolithiasis.

Method
We used an in vitro unbiased high content screening for identifying natural compounds that inhibits CaOx induced necroptosis. Molecular docking and molecular dynamic simulations were done to study the interaction between 6,7-DHC - MLKL. Further, for in vivo studies mice and rats models of nephrolithiasis were used. Renal injuries, CaOx deposition and fibrosis were evaluated using histological analysis. Protein expressions were assessed using immunoblots. Data was analysed using one way ANOVA.

Results
An unbiased in vitro high content screening of a library of 24 natural compounds identified 6,7-DHC as a potential candidate. Further, pretreatment with 6,7-DHC protected human and mouse cells from CaOx crystal mediated necroptosis in vitro. Treatment with 6,7-DHC also protected both mice and rats from nephrolithiasis. Computational modelling have revealed 6,7-DHC interacts with MLKL and inhibits its phosphorylation by ATP which is a key event in necroptosis signaling cascade.

Conclusion
All together our studies indicates that 6,7-DHC owns a novel pharmacological inhibitory property towards MLKL and it could serve as a lead molecule for further development of novel coumarin based MLKL inhibitors. Moreover, our findings also suggests that 6,7-DHC could be used as a therapeutic strategy for combating nephrolithiasis.
MO116COMPARISON OF THE CHARACTERISTICS BETWEEN UNILATERAL AND BILATERAL RENAL STONES AND THEIR ASSOCIATION WITH KIDNEY INJURY IN CHINESE POPULATION
Authors: Fan Xiaohong , Ye Wenling , Ma Jie , Wang Liang , Li Xuemei 
Published: May 2021

Abstract

Background and Aims
Urinary stone disease (USD) has been associated with increased risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) in Western populations. However, the comparison of metabolic disorders between unilateral and bilateral renal stones and their association with CKD have not been fully examined. It is also unclear whether there is an increased risk for kidney tubular injury makers such as N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG) in different stone formers.

Method
We performed a cross-sectional study of 10,281 participants in rural China in 2014. All subjects underwent a renal ultrasound to detect USD; stone formers were grouped into one or two sides of USD by ultrasound exams. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, &lt;60mL/min/1.73m2) and/or albuminuria (ACR≥30mg/g). Increased urine NAG and α1-MG were defined as the values of NAG and α1-MG above the 75th percentile of the sample distribution.

Results
The mean age of the study population was 55.4±10.0 years; 47.1% were males. Among all participants, 4.9% (n=507) had unilateral renal stone, and 0.7% had bilateral renal stones. The proportion of CKD in non-stone formers, unilateral and bilateral renal stones were 11.0%, 19.2%, and 29.7%, respectively (p for trend&lt;0.001). Bilateral renal stone formers tend to have a higher proportion of hypertension and diabetes. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased NAG (OR 1.95; 95% CI 1.21-3.16) and α1-MG (OR 2.54; 95% CI 1.56-4.12) compared with non-stone formers.

Conclusion
In the present study, bilateral renal stone formers tend to have a higher proportion of metabolic disorders and are also associated with a higher risk of CKD and kidney tubular injury. Further studies are needed to confirm the increased risk for ESRD.
MO118ROLE OF DUAL ENERGY COMPUTED TOMOGRAPHY IN PREDICTING THE CHEMICAL COMPOSITION OF STONES
Authors: Bhat Dr Sanjay , Kaul Anupma 
Published: May 2021

Abstract

Background and Aims
Dual-energy CT (DECT) has shown excellent outcomes in differentiating the chemical composition of the urinary stones with a great accuracy. A reliable determination of the chemical type of the stone help the clinician to better satisfy treatment options for the patient- medical versus surgery We used the DECT in our study to assess the accuracy of non-invasive differentiation of renal stones using the 3rd generation dual-source computed tomography (CT) scanner in determining the chemical composition of renal stones and to determine appropriate management based on DECT determined chemical composition of stones.

Method
This prospective study was conducted in the Department of surgery and radiodiagnosis and Imaging, Era Medical College and RML institute of Medical Sciences , Lucknow over the study period, i.e., November 2016 to May 2018 . The patients were those referred for non-contrast/contrast CT for the diagnosis/evaluation of urolithiasis from the department of Surgery admitted for PCNL/ESWL/therapeutic ureterorenoscopy. DECT ratios of the various stones were noted and compared with the post extraction analysis of stones for composition. A total of 100 patients were included in the study, and their DECT results were compared with the post-extraction analysis (by infrared spectroscopy as the standard comparative method).

Results
Mean age of patients was 41.15+/- 10.08 years with 64% being males. DECT was highly sensitive and specific in the diagnosis of various types of calculi based on their dual-energy ratio. It was found to be 100% sensitivity and 97.2% specificity for differentiating UA stones with level of agreement between chemical and DECT was almost perfect (k= .951) .However for hydroxyapatite stones was substantial (k=.889). Most of the stones belonged to non-UA category (72%), and only 28% were UA calculi. The sensitivity and specificity in differentiating a calcium oxalate from non-calcium oxalate calculus was 94.1% and 95.5%, respectively.

Conclusion
DECT highly sensitive and effective in characterizing chemical composition of the urinary stones and can help in determining the management plan and reduce the unnecessary burden of surgical interventions.