bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0704PROTECTIVE EFFECT OF DUAL ACTING LIGAND TARGETING A2A AND A3 ADENOSINE RECEPTOR ON OBSTRUCTION-INDUCED KIDNEY INJURY IN MICE
Authors: Pak Eun Seon , Lee Jiyoun , Ha Hunjoo 
Published: June 2020

Abstract

Background and Aims
Chronic kidney disease (CKD) has been a worldwide public health problem, and the current therapeutic strategies against CKD are limited. Adenosine plays a significant role in protection against cellular damage in the regions with high metabolism. All 4 known subtypes of adenosine receptors such as A1AR, A2AAR, A2BAR, and A3AR are expressed in the kidney. While A2AAR agonists protect the kidney against inflammation, our previous study has demonstrated that an A3AR regulator effectively prevented diabetic kidney injury. The present study examined the preventive effect of LJ-4459, a newly synthesized dual acting ligand targeting A2AAR and A3AR, on unilateral ureteral obstruction (UUO)-induced kidney injury in mice.

Method
UUO surgery was performed in 6-week-old male C57BL/6 mice. LJ-4459 was administered by oral gavage at dose of either 1 or 10 mg/kg per day. The control group was administered an equal volume of vehicle (0.25% carboxymethyl cellulose).

Results
LJ-4459 effectively prevented tubular damage presented by significantly reduced NGAL expression and tubular necrosis in the obstructed kidney. LJ-4459 effectively inhibited elevation of a-SMA, collagen I, and collagen IV protein expression as well as picro sirius red staining in the obstructed kidney, suggesting antifibrotic effect of LJ-4459. LJ-4459 also inhibited inflammation as estimated by significantly reduced F4/80 positive-stained area and protein expression of p-NF-kB and ICAM1.

Conclusion
The results suggest that LJ-4459 may become a potential therapeutic agent against interstitial fibrosis, a common feature of CKD.
P0715SUPERB MICROVASCULAR IMAGING: AN INNOVATIVE ULTRASOUND TECHNIQUE FOR EARLY DETECTION OF KIDNEY DYSFUNCTION AND RENAL FIBROSIS
Authors: Abu-rahme Munai , Artul Suheil , Kinaneh Safa , Abassi Zaid , Armaly Zaher 
Published: June 2020

Abstract

Background and Aims
Superb microvascular imaging (SMI) is an innovative ultrasound image processing technique that shows greater details and better visualization of small branching vessels by using a unique algorithm that offer high frame rates, less clutter, and fewer tissue motion artefact that were not previously possible without the use of contrast agent. We assume that SMI provides superb information regarding the severity of chronic kidney disease (CKD) and associated the fibrotic changes. Therefore, the present study was designed to examine whether SMI can detect early renal fibrosis as compared with the reference standard renal biopsy.

Method
The SMI was performed in patients (n=47) with CKD stage 2-4, where some of them underwent biopsy proven chronic renal dysfunction and fibrosis as part of the diagnosis and therapeutic judgment as needed. In addition, biochemical tests were performed in order to obtain the serum parameters of kidney function (BUN, Serum Creatinine), a urine collection test for the assessment of proteinuria, and estimation of GFR by MDRD formula in patients with CKD of various severity and healthy controls (n=17). In addition, all patients underwent SMI US imaging, where vascularity is expressed as SMI index (low index reflects low vascularity/fibrosis and vice versa).

Results
As expected, SMI vascular index was significantly lower in CKD patients as compared with healthy control (72.2±3.1 Vs 49.1±2.6 %, P&lt;0.001). Interestingly, strong correlation between the SMI index and eGFR was found among the CKD patients (r=0.595, P&lt;0.001). Similarly, a keen correlation was found between the SCr and SMI index of the diseased subjects. Among those who underwent renal biopsy, SMI index corresponds with the histological alterations as well as CKD staging.

Conclusion
This study demonstrates that in patients with CKD of various stages, SMI imaging may be utilized as a simple and practical method for evaluation of the chronic renal morphological changes and for the differentiation between CKD grades.
P0718HEALTH CARE COSTS IN CHRONIC KIDNEY DISEASE: A LONGITUDINAL STUDY FROM THE PIRP COHORT
Authors: Rucci Paola , Gibertoni Dino , Voci Claudio , Fantini Maria Pia , Mandreoli Marcora , Santoro Antonio 
Published: June 2020

Abstract

Background and Aims
Health care costs in patients with chronic kidney disease (CKD) vary widely according to patients’ severity. In patients followed up in a community-based project, it is of interest to determine cost variations over time, as a result of treatment and CKD progression. The aim of the study was to estimate the costs incurred by the health care system for CKD patients in an Italian region.

Method
Patients recruited in the Emilia-Romagna (Italy) PIRP project in the years 2007-2014 with CKD stage 3a to 5 were included in the study. Patients were stratified at baseline into 7 groups at different risk of progression according to the CT-PIRP classification (Rucci et al., A clinical stratification tool for chronic kidney disease progression rate based on classification tree analysis, NDT 2014). To calculate the annual medical costs, we multiplied the number of services used by the respective unit cost. Per capita costs were obtained dividing overall costs by person-years. We used DRG tariffs as a proxy of costs for hospital admissions, the regional nomenclator for outpatient visits and lab tests, and cost unit for prescribed drugs. Mixed effects generalized linear models were used to estimate the annual direct costs of CT-PIRP groups, adjusted for calendar year of entry in PIRP and local health authority of residence.

Results
The study cohort includes 7737 CKD patients, aged 73.2±11.6 years, 64.5% males, mostly in CKD stage 4 (3136, 40.5%) and 3b (2799, 36.2%); 697 patients (9.0%) entered the study at stage 5. The CT-PIRP classification and frequency distribution is shown in Tab.1. After 4 years, 5017 (64.8%) were still alive, 1743 (22.5%) died, 546 (7.2%) were on ESKD and 422 (5.5%) were lost. The overall direct costs of patients while still enrolled in the PIRP project decreased from 36.89 million € in the first year to 32.22 in the fourth year, while the per capita annual median costs were stable around 2200 €. The cost breakdown showed a decrease of hospitalization and drugs costs and an increase in specialty visits costs (Fig.1).
The model-estimated average annual costs were significantly higher for proteinuric, low GFR patients of CT-PIRP groups 2 and 3 (7239 € and 8825 € respectively), while non-diabetic, younger patients of group 5 determined a significantly lower burden (3350 €).
P0721PPAR-GAMMA ACTIVATION INHIBITS TGF-BETA INDUCED RENAL COMPLEMENT AND GALECTIN-3 EXPRESSION IN VIVO AND IN VITRO
Authors: Popovics Helga , Mikone Krisztina , Mozes Miklos , Kwon JiYeon , Hansmann Georg , Kokeny Gabor 
Published: June 2020

Abstract

Background and Aims
Reduced peroxisome proliferator-activated receptor-γ (PPARγ) activity has been observed in chronic kidney disease and fibrosis. We have recently shown that the PPARγ agonist pioglitazone dampens TGF-β induced renal pro-fibrotic transcription factors in vivo. Several studies have shown that renal complement expression is associated with fibrosis, yet the role of galectin-3 (Lgals3) remains controversial. However, the effect of PPARγ agonists on renal complement (C3, C4b) and Lgals3 expression has not been studied. We investigated how pioglitazone treatment affects TGF-β–driven renal inflammatory molecule expression in transgenic mice and in primary tubular epithelial cell (PTEC) culture.

Method
Ten weeks-old male C57Bl6 control (CTL) and TGF-β transgenic mice (with elevated circulating TGF-β1 level) were divided in two sets. The first set of mice received regular chow (CTL and TGFβ, n=4/group). The second set of mice were treated orally with pioglitazone (20mg/kg/day) for 5 weeks (CTL+Pio and TGFβ+Pio, n=5/group), when the kidneys were analyzed for mRNA and protein expression. PTEC were isolated from 4-weels old CTL mouse kidneys using graded sieving and characterized by immunoblot. Isolated cells were maintained in DMEM/F12 medium supplemented with 2% FBS and insulin/transferrin/selenium, and cells of passage 4-6 were used in triplicate for the experiments. Cells were treated for 24h with 10 ng/ml TGF-β and/or 5 µM pioglitazone, then mRNA expression levels were assessed. Statistical significance was verified using Mann-Whitney test.

Results
TGFβ kidneys depicted 13-fold and 4-fold overexpression of C3 and C4b mRNA (p&lt;0.05), respectively, accompanied by a 1.7-fold Lgals3 expression (p&lt;0.05). Oral treatment with the PPARγ agonist pioglitazone inhibited the TGF-β1 induced overexpression of C3, C4b, Lgals3, as well as IL-6 and CCL2 (MCP-1) mRNA (p&lt;0.01). This was accompanied by reduced alfa-SMA (Actca2) and fibronectin mRNA expression. Renal Lgals3 showed significant correlation with alfa-SMA expression (p&lt;0.01, see Figure). PTEC treated with TGF-β also depicted increased C3aR, alfa-SMA and collagen-1 mRNA expression by 1.7-fold, 2-fold and 2.1-fold, respectively (p&lt;0.01), that were reduced to control levels by pioglitazone treatment (p&lt;0.05).

Conclusion
Our data indicate that PPARγ activation exert strong anti-inflammatory effects in the renal tubular epithelial cells, implicating its possible therapeutic benefit by attenuating renal EMT and fibrosis in CKD patients.
P0723CHRONIC KIDNEY DISEASE AS AND INDICATION FOR MINIMIZATION OF IMMUNOSUPPRESSION IN LIVER TRANSPLANT RECIPIENTS
Authors: Mucha Krzysztof , Knioła Emilia , Foroncewicz Bartosz , Moszczuk Barbara , Zieniewicz Krzysztof , Pac Michaå‚ , Pączek Leszek 
Published: June 2020

Abstract

Background and Aims
Liver transplantation (LT) requires patients to take immunosuppression (IS). Long term IS leads to hypertension and chronic kidney disease (CKD). Calcineurin inhibitors (CNi) are known to have nephrotoxic effects. Thus, liver transplant recipients (LTRs) that are taking either long-term or high cumulative doses of CNi are at a significantly higher risk of developing CKD. This study aimed to find predictive factors for development of CKD post-LT. Furthermore, it introduced IS minimization protocol in LTRs with clinical or laboratory indications with the aim to prevent the CKD progression and decrease the burden of other comorbidities.

Method
212 out of all 870 LTRs from our center were screened for eligibility and 93 were recruited in 2018 for IS minimization after obtaining informed consent. They were deemed eligible if the primary cause of LT was a non-autoimmune disease and the graft function was stable. At the time of screening, patients were on IS either triple-, dual- or monotherapy (Table 1). The IS were reduced in 3 months intervals and was minimized until monotherapy with subtherapeutic serum levels (tacrolimus &lt;5mg/ml or cyclosporine &lt;50mg/ml).

Results
The indications for IS minimization were hypertension (73.87%), CKD (35.87%), cardiovascular diseases (32%), diabetes mellitus (23.91%) or malignancies (6.52%). It was found that LTRs with CKD were older (61.8 CKD vs. 49.6 non-CKD) and predominantly male (84.85% male; 15.15% female) when compared to non-CKD patients (33.9% male; 66.1% female). Another risk factor for post-LT CKD development was higher BMI (27.57 vs. 25.35). Time from transplantation of LTR with CKD was 129.12 months while for non-CKD was 150.19 months, suggesting that longer time since transplantation is not a predictive factor for development of CKD after LT. LTRs with CKD concomitantly had hypertension (84.85% vs. 67.80%) and DM (48.48% vs. 27.12%) more often than non-CKD LTRs. It was found that CKD-LTRs at the beginning of the IS minimization were more commonly taking IS polytherapies (triple 6.06% and dual 45.45% vs. triple 0% and dual 33.9%) than monotherapy (48.48% vs. 67.80%). In the first 12 months of the study, 22 out of the 33 patients with CKD safely reached monotherapy, 11 of those reached subtherapeutic levels of CNi (50,0%). Moreover, when kidney function was compared before and after IS reduction any progression of CKD was observed. Liver function tests were elevated in 4 patients with CKD, but return to the previous dose of IS resulted in normalization of liver function.

Conclusion
Minimization of IS should be considered in patients after LT who suffer from IS related comorbidities, particulary CKD. Its incidence post-LT was found to be associated with male gender, BMI and IS polytherapy. Our protocol of IS minimization seems to be safe in respect to graft rejection.
P0724ASSOCIATIONS OF URINARY POLYMERIC IMMUNOGLOBULIN RECEPTOR PEPTIDES IN THE CONTEXT OF CARDIO-RENAL SYNDROM
Authors: He Tianlin , Siwy Justyna , Metzger Jochen , Mullen William , Mischak Harald , Schanstra Joost , Zürbig Petra , Jankowski Vera 
Published: June 2020

Abstract

Background and Aims
The polymeric immunoglobulin receptor (pIgR) which transports immunoglobulins from the basolateral to the apical surface of epithelial cells was recently shown to be associated with kidney dysfunction. The immune defense is initiated at the apical surface where the N-terminal domain of pIgR, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to immunoglobulins. The aim of our study was to show the association of pIgR peptides with the cardio-renal syndrome in a large cohort and to get information on how the SC will be released.

Method
We investigated urinary peptides of 2707 individuals available in the Human Urine Proteome Database using capillary electrophoresis coupled to mass spectrometry.

Results
The mean abundance of 23 different pIgR peptides correlates negatively with the estimated glomerular filtration rate (eGFR, r=-0.314, p&lt;0.0001). Furthermore, pIgR peptides are significantly increased in coronary artery disease after adjustment for eGFR. We further predicted the proteases involved in urinary peptide generation using the Proteasix tool. Peptide cleavage site analysis suggests that several, and not one, proteases are involved in the generation of the SC.

Conclusion
In this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and provide more detailed insights on how pIgR can be potentially cleaved to release the SC.
P0730ALTERATION OF BRAIN CONNECTIVITY IN NEUROLOGICALLY ASYMPTOMATIC PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Kim Yang Wook , Lee YOO JIN , Park Bong Soo , Park Sihyung , Heo Chang min , Lee Yoojin 
Published: June 2020

Abstract

Background and Aims
Our previous study demonstrated that patients in End stage renal disease had decreased structural and functional brain connectivity, and there was significant association between brain connectivity and cognitive function. The aim of this study was to evaluate the alterations of structural and functional connectivity using graph theoretical analysis in the neurologically asymptomatic patients with relatively early stage chronic kidney disease (CKD).

Method
We prospectively enrolled neurologically asymptomatic 20 patients with CKD stage 3 and 20 healthy controls, and all of the subjects underwent diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI). Using data from the structural and functional connectivity matrix based on DTI and rs-fMRI, we calculated network measures, including global efficiency, local efficiency, mean clustering coefficient, characteristic path length, and small-worldness index, and investigated the differences between the patients with CKD and healthy controls.

Results
The patients with CKD had altered global structural connectivity and preserved functional connectivity compared to healthy controls. The all of the measures of global structural connectivity were significantly different between the patients with CKD and healthy controls. However, all of the measures of global functional connectivity in the CKD patients were not different from those in healthy participants. In the CKD patients, the functional betweenness centrality of the right insular cortex, right occipital pole, and right thalamus was significantly different from that in healthy subjects. The structural betweenness centrality of the left calcarine, right posterior cingulum was significantly different from that in healthy subjects.

Conclusion
There were significant alterations of global structural connectivity between patients with CKD and control. However, functional connectivity of brain network was preserved in contrast to ESRD patients.
P0742ASSOCIATION BETWEEN EOSINOPHILIA AND RENAL PROGNOSIS IN PATIENTS WITH CHOLESTEROL CRYSTAL EMBOLISM
Authors: Mochida Yasuhiro , Ohtake Takayasu , Morota Marie , Ishioka Kunihiro , Moriya Hidekazu , Hidaka Sumi , Kobayashi Shuzo 
Published: June 2020

Abstract

Background and Aims
Approximately, 20%-70% of patients with cholesterol crystal embolism (CCE) have eosinophilia. However, it remains unknown how eosinophilia influences on renal prognosis in patients with CCE. In this study, we investigated an association between eosinophil count (Eo) and renal prognosis in CCE patients on steroid therapy.

Method
The present study is a single-center retrospective cohort study in patients with pathological proven CCE and Chronic kidney disease from April 2007 to May 2018. This study included the patients who are not treated with maintenance dialysis nor steroid, and moreover followed until November 2019. We analyzed the validity of eosinophil counts using receiver operating characteristic (ROC) curve analysis. In the statistical analysis, renal survival was calculated with the Kaplan– Meier method, and comparisons between higher and low Eo groups were made with the log-rank test.

Results
Thirty-two patients with pathological diagnosed CCE were enrolled and followed-up for 11.0 (4.7-43.6) months. There were significant differences in the white blood cell (p=0.03), hemoglobin (p=0.007), serum creatinine levels (p=0.03), phosphate (p=0.045), Calcium×Phosphate (p=0.03), and Eo (p=0.016) between the renal survival and renal death groups. Using the receiver operating characteristic curve analysis with Youden index, Eo of 810/µL showed the sensitivity and specificity 71% and 88% for detecting renal death, respectively (area under the carve; 0.789). Comparing the outcomes in patients having Eo ≥ and &lt;810/µL by using the log-rank test, there are significantly higher renal death rate in CCE patients with Eo ≥810/µL (p=0.004).

Conclusion
Higher eosinophilia was a prognostic risk factor for renal death in the patients with CCE.
P0747STRESS ERGOMETRY PERFORMANCE AND ABDOMINAL AORTIC CALCIFICATION PREDICT PATIENT OUTCOMES IN CKD STAGE 4-5
Authors: Lankinen Roosa , Hakamäki Markus , Metsarinne Kaj Peter , Pärkkä Jussi , Hellman Tapio , Kartiosuo Noora , Raitakari Olli , Järvisalo Mikko 
Published: June 2020

Abstract

Background and Aims
Patients with chronic kidney disease (CKD) stage 4-5 have an increased risk of cardiovascular morbidity and mortality.

Method
We recruited 174 consecutive patients with CKD stage 4-5 between 2013 and 2017 into a prospective follow-up study assessing arterial disease, quality of life, mortality and their predictors. Together with baseline medical data, standard maximal bicycle ergometry stress testing, abdominal aortic calcification score (AAC) and echocardiography was collected. Patients were followed up for mean 42 months.

Results
Mean age at recruitment was 61 years, 54 (31%) were women and estimated glomerular filtration rate (eGFR) was 12.9 ml/min. Altogether, 36 (21%) patients died during follow-up with a mean time to death of 835 days. At baseline, all but one patient were hypertensive, 75 patients had diabetes and 21 patients had coronary artery disease. Mean AAC was 6.27±5.68 and work load of the last 4 minutes of maximal stress (WMAX) was 83.7±36.5W, respectively. In the multivariate proportional hazard models pro-BNP [1.98 (95% CI 1.36 – 2.90), p=0.0004], WMAX [HR 0.45 (95% CI 0.27 – 0.77), p=0.0033], AAC [HR 2.51 (95% CI 1.37 – 4.61), p=0.0030], E/e’ –ratio [HR 1.66 (95% CI 1.08 – 2.56), p=0.0221] and albumin [HR 0.59 (95% CI 0.39 – 0.90), p=0.0134] were significant predictors for mortality when adjusted with age, sex, diabetes and previous coronary artery disease. Patients who perished, especially those who died in less than 2 years, within follow-up had significantly higher AAC and lower WMAX compared to those surviving to the end of the study (Figure 1).

Conclusion
Maximal stress ergometry test work load and AAC are associated with patient survival in severe CKD.
P0748CLINICAL OUTCOMES OF JAPANESE ANTI-MYELOPEROXIDASE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-RELATED RAPIDLY PROGRESSIVE GLOMERULAR NEPHRITIS
Authors: Nishida Yoshihiro , Ito Kenji , Yasui Yuki , Takahashi Koji , Yasuno Tetsuhiko , Himuro Naoko , Miyake Katsuhisa , Masutani Kosuke 
Published: June 2020

Abstract

Background and Aims
Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related nephritis constitutes 60% of rapidly progressive glomerular nephritis (RPGN). In 2014, Japanese Society of Nephrology (JSN) created RPGN clinical guidelines for Japanese MPO-ANCA-related RPGN patients, and proposed the clinical grading system for predicting their prognosis, which took into consideration factors such as age, renal function, lung involvement, and serum CRP (Yoshihiro Arimura et al. Clin Exp Nephrol. 2016). However, evidence regarding clinical outcomes is still limited. In the study reported here, we conducted a single-center retrospective study to evaluate the outcomes of MPO-ANCA-related RPGN patients and to establish an efficacy of RPGN guidelines of JSN.

Method
We retrospectively investigated 54 patients (female, n=32; average age ± 13.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukuoka University Hospital between 2009 and 2018. Their clinical grade determined by JSN guideline and method of treatment were retrospectively evaluated for prediction of survival, as well as laboratory data and clinical features.

Results
12 patients (22.2 %) has deceased during a median observation period of 17.1 months. 7 patients are died of infectious disease (Bacterial pneumonia 4, Sepsis 2, pulmonary aspergillosis 1), and 10 patients died within 1 year. Median estimated glomerular filtration rate (eGFR) was 15.5 mL/min/1.73m2 at admission. 14 patients (25.9%) presented with end-stage renal disease (ESRD) during the observation period, 8 of them were died. The distribution of clinical grade of JSN guideline was grade I for 10, II for 27, III for 10 and IV for 7. (grade IV is the most severe) Patients with high clinical grade showed significantly high mortality (Log Rank test, p&lt;0.05; figure 1). Multivariate Cox proportional hazards model analysis revealed that high clinical grade was a significant risk factor for all-cause death (Hazard ratio (HR), 7.09; 95% confidence interval (CI), 2.01-15.69, p&lt;0.05) and for infectious disease death (HR, 16.9; 95% CI, 2.56-121.5, p&lt;0.05). On the other hands, the preventive administration of Trimethoprim-Sulfamethoxazole (TS) decreased the risk of infectious disease death (figure 2).

Conclusion
The MPO-ANCA-related RPGN clinical grading system created by JSN was a useful tool for prediction of prognosis. Furthermore, TS should be administrated for all immune-suppressive patients to prevent variable infections not only Pneumocystis.