bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0516DCR2 PROMOTES RENAL FIBROSIS BY ACCELERATING TUBULAR CELL SENESCENCE AFTER ISCHEMIA REPERFUSION INJURY
Authors: Chen Jia , He Yani 
Published: June 2020

Abstract

Background and Aims
Cell senescence of renal tubular epithelial cells (RTECs), which is involved in renal fibrosis, is a key event in the progression of acute kidney injury (AKI). However, the underlying mechanism remains unclear. This study aims to investigate the role and mechanism of decoy receptor 2 (DcR2) in renal fibrosis and cell senescence of RTECs.

Method
KSP-creDcR2f/f mouse (Tubular DcR2 KO) and Ischemia-Reperfusion (I/R) Injury models were constructed. The models were divided into moderated (ischemia 20min) and severe (ischemia 35min) injury. The expression of renal DcR2, senescent markers (P16, P21, SA-β-gal) and senescent phenotype (IL-6, TGF-β1) were detected. Furthermore, wild type (WT) mice and KSP-creDcR2f/f mice were used to compare the degree of renal tissue and functional damage and the senescence of renal tubular cells after I/R injury. In vitro, knockdown and overexpression experiments were performed by transfected DcR2 siRNA or overexpressed adenovirus in hypoxia-reoxygenation stimulated mouse primary RTEC. The cell senescence and phenotype markers were further detected.

Results
The levels of Scr, BUN and urinary DcR2 and renal injury scores were significantly increased in I/R group at the early stage (1d) of renal injury compared with sham group. Renal fibrosis was observed in the later stage (21-42d) in severe injury. DcR2 was mainly expressed in renal tubules, and the percentage of tubular DcR2 was increased after I/R injury. DcR2 was co-expressed with P16 and SA-β-gal, and urinary DcR2 levels were related to senescent makers, suggesting that DcR2 was associated with cell senescence. The renal function and renal injury scores were lower in KSP-creDcR2f/f mice than that of WT after renal reperfusion. And the area of renal fibrosis was significantly decreased in KSP-creDcR2f/f mice compared with WT, indicating DcR2 inhibited renal fibrosis. Furthermore, the expression of senescent phenotype were suppressed in tubular DcR2 KO mice after I/R injury, suggesting that DcR2 could promote the senescence of renal tubule cells.

Conclusion
DcR2 promotes renal fibrosis by accelerating tubular cell senescence after ischemia-reperfusion Injury, suggesting that DcR2 may be a potential intervention target during the progression of AKI.
P0872EFFECT OF PARATHYROID HORMONE OSCILLATIONS ON BONE HEALTH: FROM OSTEO-ANABOLISM TO CATABOLISM
Authors: Cherif Alhaji , Kotanko Peter 
Published: June 2020

Abstract

Background and Aims
In patients with chronic kidney disease or primary hyperparathyroidism, chronically elevated parathyroid hormones (PTH) levels exert catabolic effects on the bone. In contrast, PTH oscillations (as seen in healthy subjects) or daily application of teriparatide (a form of PTH consisting of the N-terminal 34 amino acids; it is used to treat osteoporosis) promote bone formation. These differential responses have important clinical and therapeutic implications. Although the anabolic effects of PTH (and teriparatide) cycling are widely accepted, the underlying osteo-anabolic dynamics are not well understood.

Method
A recently developed mechanistic physiology-based model quantitating the interrelations of osteoclasts, osteoblasts and osteocytes on bone remodeling is used (Cherif et al., ΝΔΤ 2018, 33 (συππλ. 1): 165–166). The model incorporates cell-to-cell signaling pathways (i.e., RANK-RANKL-OPG), intracellular pathways, cytokines (i.e. TGFβ), PTH, sclerostin, and endocrine and paracrine feedbacks. Using the validated model, we explore the effect of altered PTH (teriparatide) administration regimen (e.g., dosing frequency and amplitude) on bone catabolism and anabolism, respectively.

Results
As in previous studies, the model accurately predicts differential responses of osteo-anabolic and catabolic effects of continuously and intermittently elevated PTH (teriparatide) levels, respectively. In addition, we observe that intermittent administration of PTH with a high frequency and amplitude induces bone catabolism similar to that seen in pathologies with continuously elevated PTH (i.e. primary or secondary hyperparathyroidism). We see a more than 3-fold change from baseline in osteoclastic over osteoblastic activities, resulting in a bone efflux of calcium and phosphate. Low PTH frequency with high dosing amplitude induces both osteoclastic and osteoblastic activities, but the net result is bone anabolism. Further, Fig. 1 shows a nonlinear region where high osteoblastic activities exceed osteoclastic resorption. These findings suggest the existence of optimal PTH (teriparatide) frequency-amplitude combinations that enhance anabolic gains, beyond which there can be a detrimental effect on bone.

Conclusion
Our results suggest that both frequency and amplitude of PTH (teriparatide) cycling affect the balance of osteo-catabolic and -anabolic effects. Understanding the underlying mechanism of differential osteo-anabolic and -catabolic responses induced by intermittent and continuous levels of PTH, respectively, may provide new therapeutic options for patients and minimize unintended consequences of intervention protocols.
P0876THE ROLE OF TRPM7 IN VASCULAR CALCIFICATION: COMPARISION BETWEEN PHOSPHATE AND UREMIC TOXIN
Authors: Lee Chien-Te , Ng Hwee-Yeong 
Published: June 2020

Abstract

Background and Aims
Vascular calcification is a common complication in patients with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Pathogenesis of vascular calcification in CKD is multiple and phenotypic transformation of vascular smooth muscle cell (VSMC) is of critical importance. TRPM7 is a magnesium channel that regulate magnesium transport. The role of TRPM7 in VSMC transformation during vascular calcification is not clear. We aim to investigate the effects of phosphate and indoxyl sulphate on the expression of TRPM7 in VSMC and 2-APB, the TRPM7 blocker was used to evaluate the alteration of calcification-related molecules.

Method
Human aortic smooth muscle cells (HASMC) were used and treated either with phosphate (3.3mM) or indoxyl sulphate (500uM) for 7 days. 2-APB, a channel blocker of TRPM7 was added simultaneously in blocking experiment. Cells were then examined grossly and alizarin red solution was employed for calcification staining assessment. For calcification process study, cells were harvested for gene expression and protein abundance analysis.

Results
Gross examination did not find evidence of cell death during experiment on both treatments. Alizarin staining revealed apparent calcification in phosphate-treated HASMC but it was unremarkable in indoxyl sulphate. Phosphate treatment induced significant increase in RUNX2(151±35.8% of control), BMP2(124±10.1%), BMP7(155±9.3%), vitamin D receptor (VDR, 138±21%), calcium sensing receptor (CaSR, 185± 39%) and TRPM7(172±33.7%, all p&lt; 0.05), but DKK1 and sclerostin were not changed. The addition of 2-APB prevented the increase of RUNX2(107±31.2%), BMP2(80±4.9%), BMP7(72±32.9%), VDR (94±43.2%), CaSR (83±17%) and TRPM7(118±23.9%). Indoxyl sulphate treatment was associated with decrease in TRPM7 (45±22%, p&lt;0.05), but increase in BMP2(136±10.4%), VDR (154±53.5%) were noted. There were no significant alterations in CaSR (108±43.7%) and sclerostin (110±27.1%). Co-administration with 2-APB partially reduced the increase in RUNX2(158±55.1%), VDR (149±35.9%). The abundance of BMP2/7were not changed. TRPM7 was decreased significantly (33±23.1%).

Conclusion
We concluded that both phosphate and indoxyl sulphate induced calcification in VSMC but it was less in indoxyl sulphate. TRPM7 was upregulated by phosphate but decreased in indoxyl sulphate treatment. Blocking TRPM7 with 2-APB can prevent phosphate-induced calcification but partially attenuated calcification during indoxyl sulphate administration.
P1313CHANGES IN VASCULAR ACCESS AND HEALTH-RELATED QUALITY OF LIFE
Authors: Chen Chen , Jiao Yue , Winter Anke , Larkin John , Usvyat Len A , Stauss-Grabo Manuela , Maddux Franklin 
Published: June 2020

Abstract

Background and Aims
The patient’s reported perception of their health-related quality of life (HRQOL) are important patient-centered metrics that associate with outcomes in hemodialysis (HD) populations. Patients using an arteriovenous (AV) access (fistula or graft) tend to report better HRQOL compared with those dialyzing via a catheter (Wasse et al. 2007; Moura et al. 2014). However, these differences might be due to distinct characteristics of patients who have an AV access placed, or not. For example, catheter-dependent patients are typically older and have more comorbidities than those with an AV access. We considered a different way to evaluate the impact of vascular access on HRQOL in HD patients by assessing whether a change from a catheter to an AV access, and vice versa, associates with changes in HRQOL.

Method
We used data from adult in-center HD patients (age ≥18 years) treated at a large dialysis organization in the United States from 2016-2017. Patients who had one vascular access conversion and used the corresponding access for at least 12 months before and after the conversion were included in the analysis. HRQOL was assessed by Kidney Disease Quality of Life (KDQOL-36) surveys (0-100 scale) performed over the 12 months preceding and following the change. We computed the mean score for each of the five KDQOL domains in each time period and compared the score differences between pre- and post-access change using Student’s t-tests for each conversion type.

Results
A total of 1088 HD patients (mean age 59.2 years, 52.6% male, and 59.3% white race) switched from a catheter to an AV access and 3427 patients (mean age 61.8 years, 47.8% male, and 50.7% white race) switched from an AV access to a catheter over the analysis period. After conversion from a catheter to an AV access, patients reported significantly higher physical component summary (+0.5, p&lt;0.05), mental component summary (+0.8, p&lt;0.001), symptoms and problems of kidney disease (+0.7, p&lt;0.05), and effects of kidney disease (+1.2, p&lt;0.05) scores (Figure 1). No significant difference was observed for four out of the five domains following the change from an AV access to a catheter, except for physical component summary, where the score dropped by 1.2 points (p&lt;0.01) (Figure 2).

Conclusion
Our results suggest switching from a catheter to an AV access may associate with patients perceiving an improved physical and mental HRQOL. In contrast, changing from an AV access to a catheter might associate with a diminished perception of physical HRQOL. Albeit distinctions in HRQOL are statistically significant, absolute differences were below two points and the clinical meaning needs to be assessed in further adjusted analyses considering the underlying reasons for vascular access conversions. Nonetheless, these findings may be of importance to provide more patient focused care.
P1317THE PREVALENCE OF CENTRAL VENOUS CATHETERS AND LOWER ARM ARTERIOVENOUS FISTULAS DEPENDS ON DIFFERENT VASCULAR ACCESS MANAGEMENT POLICIES: A MULTICENTER ITALIAN STUDY
Authors: Finocchiaro Pietro , Alberti Antonino , Tripepi Rocco , Versace Maria Carmela , Garozzo Maurizio , Milone Filippo , Battaglia Giovanni Giorgio , La Rosa Sandra , Maccarrone Rosario , Granata Antonio , Sessa Concetto , Pocorobba Barbara , Musso Salvatore , Bolignano Davide , Pazzano Dario , Volpe Pietro , Mallamaci Francesca 
Published: June 2020

Abstract

Background and Aims
According to local resources, different vascular access (VA) procedures are employed in every country. In Italy, high variability exists in VA management among different dialysis units. In 2018, the DOPPS 5 study showed a declining prevalence of lower arm arteriovenous fistulas (AVF) in Europe with an increasing tendency of making upper arm AVFs and placing central venous catheters (CVCs). Accordingly, an Italian Survey in 2013 confirmed an increasing trend in CVCs use among different Italian regions.
Hence, we made an epidemiologic, multicenter study to evaluate a possible relation between this trend and the variability of local VA management policies.

Method
VA data from 236 patients of prevalent patients were collected from five dialysis centers in the South of Italy. The prevalence of the various types of VAs was analyzed in relation to the following different VA surgery policies adopted in the participant centers:

Results
Age of patients was comparable among all centers while dialysis vintage was higher in center A (P&lt;0.001). The prevalence of lower arm AVFs was significantly reduced In Center A (50.6%) and the prevalence of CVCs (25.8%) was significantly increased as compared to the Centers D-E. On the contrary the Centers D-E had the highest prevalence of lower arm AVF (70.8%) and the lowest of CVCs (12.3%), with a statistically significant difference as compared to Center A (Table 1 ). Conversely, no differences were noticed when comparing data from Centers B-C vs. Center A and vs. Centers D-E, although the prevalence of lower arm AVFs was slightly higher, but the difference was not significant, and that of CVCs was slightly lower as compared to Center A ,fully supported by the vascular surgeon (Figure 1 ).

Conclusion
The reduced tendency of lower arm fistulas and the increasing prevalence of CVCs showed by the DOPPS 5 study might not be applicable to all Italian regions. In our study of 5 dialysis units in the South of Italy, the stability of the nephrologist’s surgical activity probably played a crucial role in explaining the observed decreased use of CVCs with a steadily high prevalence (over 70%) of the lower arm fistulas, regardless of aging.
P1734INFORMATION AND COMMUNICATION TECHNOLOGY-BASED CENTRALIZED MONITORING SYSTEM TO INCREASE ADHERENCE TO IMMUNOSUPPRESSIVE MEDICATION IN KIDNEY TRANSPLANT RECIPIENTS: A RANDOMIZED CONTROLLED TRIAL
Authors: Jung Hee-Yeon , Jeon Yena , Seong Sook Jin , Seo Jung Ju , Choi Ji-Young , Cho Jang-Hee , Park Sun-Hee , Kim Chan Duck , Yoon Young-Ran , Yoon Se-Hee , Lee Jong Soo , Kim Yong-Lim 
Published: June 2020

Abstract

Background and Aims
Innovative strategies to promote adherence to immunosuppressants in kidney transplant recipients (KTRs) is imperative. This study aimed to evaluate the efficacy and stability of the information and communication technology (ICT)-based centralized monitoring system in increasing medication adherence in Korean KTRs.

Method
A prospective, multicenter, randomized controlled study was conducted (ClinicalTrials.gov Identifier: NCT03136588). All KTRs were randomized into the ICT-based centralized monitoring or the control group and had follow-up visits every 4 weeks during 6 months. The ICT-based centralized monitoring system alerted both patients and medical staff with texts and pill box alarms if there was a dosage/dosing time error or a missed dose. Medication adherence and transplant outcomes were compared between the two groups, and patient satisfaction on the ICT-based monitoring system was evaluated.

Results
Among enrolled 114 KTRs, 57 patients were assigned to the ICT-based centralized monitoring group and 57 patients to the control group. Mean adherence at each follow-up visit was not significantly different between groups. No differences in intrapatient variability of tacrolimus and mycophenolic acid levels, renal function, and adverse transplant outcomes were observed between the intervention and control groups, as well as between the intervention group with feedback generation and the intervention group without feedback generation. Overall patient satisfaction with the ICT-based centralized monitoring system was high and significantly improved during the study period (P = 0.012).

Conclusion
Although the ICT-based centralized monitoring system did not maximize mediation adherence or enhance transplant outcomes in Korean KTRs due to high baseline adherence, patient satisfaction with the system was high. We identified the future possibility that the ICT-based centralized monitoring system could be successfully applied in clinical trials targeting other disease groups with impaired adherence.
P0168FRUCTOSE IS A CAUSE OF CALCIUM PHOSPHATE UROLITHIASIS IN RATS
Authors: Flisiński Mariusz , Brymora Andrzej , Skoczylas-Makowska Natalia , Stefańska Anna , Manitius Jacek 
Published: June 2020

Abstract

Background and Aims
Excessive consumption of fructose (Fr) leads to obesity, metabolic syndrome and insulin resistance, which are known risk factors for kidney stones. Along with the epidemic of obesity and diabetes there is also a growing incidence of kidney stones in both adults and children. The epidemiological studies have shown that the relative risk of nephrolithiasis significantly increases with fructose intake in diet.
The aim of the study was to assess the effect of high-fructose diet on kidney tubules disorders and predisposition to the development of kidney stones.

Method
Male Wistar rats were assigned for 8 weeks to 3 groups differing in the content of Fr in the diet: RD - regular diet with a fructose content &lt;3%; F10 - regular diet with an addition of 10% Fr in drinking water; F60 - 60% Fr as a solid feed. Serum concentration of Fr, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (Hcs), uric acid (UA), calcium (Ca), phosphorus (P), magnesium (Mg) were measured. Based on a 24-hour urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (UAE), phosphorus (PE), calcium (CaE), magnesium (MgE) and sodium (NaE). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using H+E and von Kossa staining. Statistical analysis was performed using one-way analysis of variance ANOVA. Statistical significance was considered as p&lt;0,05.

Results
The results are presented in table as mean ± SD.
The rats did not differ in total calories intake in their diet.

Conclusion
The high-fructose diet, in a dose-dependent manner, exacerbated inflammation and induced damage to the proximal tubules. Both F10 and F60 led to hypouricosuria, hypercalciuria and hyperphosphaturia. Those disturbances, in turn, caused precipitation of calcium phosphate deposits in kidney tubules and parenchyma.
P0179ECULIZUMAB USE IN A TERTIARY CARE NEPHROLOGY CENTER
Authors: Aigner Christof , Stemer Gunar , Gaggl Martina , Haninger-Vacariu Natalja , Prohaszka Zoltán , Sunder-Plassmann Raute , Kain Renate , Alice Schmidt , Sunder-Plassmann Gere 
Published: June 2020

Abstract

Background and Aims
Practice patterns of Eculizumab use in patients with thrombotic microangiopathies (TMA) and C3-glomerulopathy (C3G) are not well described.

Method
We used the “Vienna TMA cohort” and the hospital pharmacy database at the Medical University of Vienna to identify adult patients with a history of eculizumab use between 2012 and 2019. We describe clinical characteristics, details of eculizumab use, and outcomes of patients with complement gene variant mediated TMA (cTMA), secondary TMA (sTMA) and C3G.

Results
As of December 2019, 212 individuals were enrolled in the Vienna TMA cohort comprising 51 cTMA, 144 sTMA, and 17 TTP patients. We included also our cohort of 14 patients with C3G for this analysis. 47 patients (22 TMA and 2 C3G, 23 other indications, i.e. paroxysmal nocturnal haemoglobinuria) received at least one dose of eculizumab at the Medical University of Vienna (Figure 1). Table 1 indicates demographic and clinical details of 15 cTMA (29.4% of all cTMA), 7 sTMA (4.9% of all sTMA) and 2 C3G (14.3% of all C3G) patients treated with eculizumab. 60% of cTMA patients showed a rare complement gene variant, while sTMA was ruled out in the remaining 40%. Causes of sTMA were bone marrow transplantation (BMT) (n=2), malignant hypertension, malignoma, systemic lupus erythematodes, antiphospholipid syndrome and lung transplantation (each n=1). One sTMA patient, a BMT recipient, had a donor with a thrombomodulin gene variant. Patients with cTMA had a greater delay from first diagnosis to treatment with eculizumab than the other groups and received maintenance therapy for a longer period of time. More female patients received eculizumab as compared to male patients. Chronic kidney disease stage improved in 60% and 43% of cTMA and sTMA patients, respectively. TMA relapses did not occur during administration of eculizumab. The 2 patients with C3G didn’t respond to eculizumab in our center. Eculizumab therapy was stopped in 66% of patients with cTMA and in all patients presenting with sTMA or C3G. In general, eculizumab was well tolerated and we did not observe life threatening infections of our patients. Three adverse drug reactions included exanthema, liver injury, and hypertensive emergency. Two patients died during therapy with eculizumab (1 cTMA, 1 C3G,) and two after cessation of eculizumab therapy (1 cTMA, 1 sTMA) resulting in a mortality of 16.7%.

Conclusion
Improvement of CKD stage was achieved in 60% of patients with cTMA and in 43% of patients with sTMA. In our patients with C3G, eculizumab did not improve kidney function. In general, therapy with eculizumab was well tolerated.
P1129PERITONEAL DIALYSIS TECHNIQUE FAILURE IN A LARGE POPULATION IN COLOMBIA
Authors: Vesga Jasmin , Rodriguez Nelcy , Rivera Angela , Sanabria Mauricio 
Published: June 2020

Abstract

Background and Aims
Peritoneal dialysis (PD) is a renal replacement therapy widely used in the world; about 197,000 patients use it. The main limitation of the use is related to technique failure. Extending time free of technique failure remains a long-term challenge in PD.
To estimate the incidence of technique failure in PD and, describe the main reasons for failure.

Method
A historical, multicenter, observational cohort study of all adult patients starting PD between January 1, 2010, and December 31, 2015, with follow-up until December 31, 2018, at Renal Therapy Services (RTS) network. The definition of technique failure applied when a patient was switched to Hemodialysis (HD) for at least 30 days. Socio-demographic and clinical characteristics of all patients were summarized descriptively by PD modality. We estimate the failure rate with an analysis of Kaplan Meier and analysis that incorporate competing risks as death and transplant.

Results
6452 patients met the inclusion criteria for data analysis, 67% were in CAPD modality. The mean age was 59 years, 54% were male, and 53.7% had a history of diabetes, see Table 1. There were 1462 technique failures events with a rate of 10.67 events per 100 patients-year [95% CI, 10.14 – 11.24]. The median technique survival time was 5.8 years [ 95% CI: 5.11 to 5.45]. Technique failure rates did not differ by PD modality (Wilcoxon test = 0.4986), Figure 1.
In the presence of competing events, the cumulative incidence of technique failure for the first year was 6.9 events per 100 persons-risk [95% CI: 6.27 to 7.56], Table 2. The most common causes of technique failure were catheter complications, followed by psychological and medical indications, Table 3.

Conclusion
The incidence of PD technique failure is around ten events per 100 patient-year, and this is lower than the previous cohort reports in the literature. Catheter problems remain the leading cause of technique failure