bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0689LINACLOTIDE, THE GUANYLATE CYCLASE C AGONIST LIMITS CARDIAC FIBROSIS FORMATION IN MICE WITH CHRONIC KIDNEY DISEASE AFTER ISCHEMIA-REPERFUSION INJURY
Authors: Isoyama Naohito , Nakayama Yuki , Nakamura Kimihiko , Hiroyoshi Toshiya , Fujikawa Kouki , Matsuyama Hideyasu 
Published: June 2020

Abstract

Background and Aims
Cardiovascular disease (CVD) is a major cause of mortality in patients with chronic kidney disease (CKD). Renal ischemia-reperfusion injury (IRI) is a clinically significant condition that progress to CKD after acute kidney injury (AKI). We have reported that the suppression of Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine, by linaclotide could prevent renal fibrosis and improve renal function in the chronic phase after renal IRI.
TMAO has been linked directly with progression of CVD too. We investigated whether the reduction of TMAO by linaclotide limits cardiac fibrosis in mouse model of CKD after IRI.

Method
Linaclotide (100μg/kg) was administered for 2weeks before IRI and continued for 2weeks after IRI. After 2weeks since IRI, removed hearts sections were performed Azan stain to evaluate the level of fibrosis and western blotting to evaluate the expression level of fibronectin.

Results
The administration of linaclotide significantly improved cardiac fibrosis area (Fig1). Additionally, western blotting showed linaclotide suppress the expression level of fibronectin (Fig2).

Conclusion
The reduction of TMAO by linaclotide could prevent cardiac fibrosis in the chronic phase after renal IRI. Linaclotide may be a powerful tool for prevention of the cardiorenal syndrome after renal IRI.
P0694ALTERATION OF PHYSICAL ACTIVITY AND ITS ASSOCIATION WITH CARDIOVASCULAR OUTCOMES AMONG PRE-DIALYSIS CKD PATIENTS
Authors: Lee Soojin , Lee Yeonhee , Park Sehoon , Kim Yaerim , Han Kyungdo , Kim Jung-Hyun , Joo Kwon Wook , Kim Dong Ki 
Published: June 2020

Abstract

Background and Aims
Cardiovascular disease is major cause of mortality among chronic kidney disease (CKD) patients, and it is fundamental to focus on reducing the potential risk factors. Regular physical activity is known to reduce the risk of cardiovascular disease in general population. However, whether the change of physical activity habits is beneficial for pre-dialysis CKD patients had not been examined thoroughly.

Method
We performed a nationwide population based cohort study using the database of Korean National Health Insurance System. Among adult patients who received national health screening program ≥2 times between 2012 and 2016, CKD patients were identified using the serum creatinine and dipstick albuminuria measurements. Those who previously underwent dialysis or diagnosed cardiovascular disease were excluded. The frequency and the intensity of the physical activity were obtained at least twice, from self-reported questionnaire during the health examination. The study groups were divided according to the status of physical activity habit alteration; active, quit exercise, start exercise, and inactive group. Then, the development of myocardial infarction (MI), stroke or death was assessed using the multivariate Cox regression analysis.

Results
During the median follow up of 3.18 years, 549,187 CKD patients were examined for adverse outcomes. Compared to those who remained inactive, the active group patients who consistently continued physical activity exhibited lower risk of MI (hazard ratio (HR); 0.76, 95% confidence interval (95% CI); 0.69-0.85), stroke (HR (95%CI) 0.69 (0.62-0.78)), and death (HR (95%CI) 0.62 (0.57-0.67)). Moreover, those who newly started physical activity also showed lower risk of adverse outcomes, compared to the inactive group (HR (95%CI) 0.83 (0.76-0.89)).

Conclusion
Continuation of physical activity in pre-dialysis CKD patients is beneficial to reduce the risk of cardiovascular disease development. Therefore, clinicians should encourage even mild intensity of physical activity to CKD patients.
P0695ANALYSIS OF HOSPITALIZATION EVENTS IN NON-DIALYSIS CKD PATIENTS
Authors: Mandreoli Marcora , Gibertoni Dino , Santoro Antonio 
Published: June 2020

Abstract

Background and Aims
Data are limited about rates and causes of hospitalization in patients with Chronic Kidney Disease (CKD) during maintenance period. In the present study, we investigate the amount, characteristics and trends of hospital admissions in a large cohort of pre-dialysis CKD patients followed within the Emilia-Romagna Region (Italy) PIRP project.

Method
Patients who were enrolled in the PIRP project in the period 1.4.2004-31.12.2018 constitute the study population. The PIRP database contains clinical and laboratory data collected at each follow-up visit. Hospitalization data regarding admissions occurred during patients’ follow-up in PIRP were obtained from the regional hospital discharges database through unique individual linkage. Day-hospital admissions and hospitalizations aimed at arteriovenous fistula creation and peritoneal catheter placement were excluded.

Results
In almost 15 years of observation, 27,886 patients were enrolled in PIRP, mostly males (65,3%) with baseline median age of 75 years and baseline median eGFR=32.3 mL/min/1.73m2. Among them, 19,288 (69.2%) generated 72,432 hospitalizations during their follow-up in the project. The number of hospitalizations per person/year was 1.06 overall, increasing from 0.38 for stage CKD 1 to 1.93 for stage CKD 5 (Fig.1). The median length of stay was 9 days. Overall, cardio-vascular diseases were the main cause of hospitalization (30.0% of admissions), with renal diseases, tumors and respiratory diseases each accounting for over 10% of admissions, although the distribution of causes of hospitalization varies according to CKD stage (Fig.2). About one fifth of patients had one or more hospitalizations for acute kidney injury. The trend analysis revealed a steadily decreasing hospitalization rate for patients that were on CKD stage 4 and 5 at baseline, a constant hospitalization trend over time for patients who began their follow-up in stages 1 to 3a, while hospitalization rate of patients in CKD 3b stage declined after 9 years (Fig 3).

Conclusion
The study broadens our knowledge on the hospitalizations “consumption” by the population with CKD in the non-dialysis phase. It confirms that patients with CKD represent a vulnerable population, needing about 1 hospitalization / year / patient. The trend towards a reduction in hospitalizations during the follow-up period could be traced back to the specific care model, which encourages a more frequent management of patients in the Nephrology clinics.
P0697IDENTIFYING PATIENTS SUITABLE FOR PRIMARY CARE FOLLOW-UP IN A LARGE NON-DIALYSIS CKD COHORT
Authors: Mohammed Sophia , Kalra Philip A , Chinnadurai Rajkumar 
Published: June 2020

Abstract

Background and Aims
Chronic Kidney Disease (CKD) is a growing public health concern, affecting approximately 13.4% of the global population. Due to the rising burden of CKD and its economic cost, there is a pressing need to identify the risk factors which can predict CKD progression and thereby enable us to manage these patients in the community under primary care follow-up. Our study aimed to identify risk factors that can predict outcomes in patients with stable CKD.

Method
The study was conducted on patients recruited in the Salford Kidney Study, (a large prospective CKD database recruiting patients since 2002). From a total of 2952 recruited between 2002 and the year 2016, 1023 patients with a diagnosis of hypertension, diabetes or pyelonephritis were sampled for this study. Based on the annual rate of progression of estimated glomerular filtration rate (delta eGFR), 140 patients were identified as stable CKD patients (delta eGFR -0.50 and 0.50 ml/min/1.73m2/year). The characteristics of this group was compared with 277 rapid progressors (RP) (delta eGFR&lt;-3) and 212 patients in the improved group (delta eGFR&gt;0.50).
Negative predictive value analysis was performed on all patients with an outcome of a GFR &lt; 30ml/min/1.73m2.

Results
Stable CKD patients had a significantly higher age compared to RP ( 69 vs 62, p&lt;0.001). Further patients in the stable CKD group had a comparatively lower median blood pressure (141.5 vs 137, p&lt;0.001). Other factors which were identified as risk factors for rapid progression included history of diabetes (177 vs 73, p=0.021), low albumin (41 vs 44, p&lt;0.001), raised urine protein creatinine ratio (154.6 vs 18.8, p&lt;0.001) and phosphate (1.24 vs 1.12, p&lt;0.001) (Table-1). Comparing outcomes showed rapid progression reached ESRD (172 vs 18, p&lt;0.001) but no significant difference in mortality (93 vs 55, p=0.25). Characteristics that were statistically different for stable CKD patients in this large cohort were identified: age, systolic blood pressure, diastolic blood pressure, diabetes, albumin, UPCR and phosphate. NPV analysis did not identify reveal any clear predictors for progression in stable CKD patients.

Conclusion
Several risk factors were identified to distinguish between stable, rapid and improved group. NPV did not identify any predictors in stable group. Further risk prediction models incorporating biomarkers are warranted to identify factors that can guide prognosis thereby stable CKD patients can be managed in the community.
P0700FLAVONOID FISETIN ALLEVIETES RENAL DYSFUNCTION IN A SEVERE MOUSE MODEL OF HYPERURECEMIC NEPHROPATHY
Authors: Ren Qian , Ma Liang , Fu Ping 
Published: June 2020

Abstract

Background and Aims
Flavonoid Fisetin is a natural product that has a wide distribution in many fruits and vegetables and exerts anti-cancer, anti-oxidant, anti-inflammatory and anti-mitotic effects. The renal protective effects of fisetin have been confirmed in models of diabetic nephropathy, cisplatin-induced AKI, ischemia reperfusion kidney injury and lupus nephritis. The current study instigates the protective effect of fisetin in a severe mouse model of hyperuricemic nephropathy (HN) and explores its underlying mechanisms.

Method
Twenty-four C57BL6 mice were randomly divided into four groups: Control, Model, Allopurinol and fisetin. HN was established by oral administration of mixture of adenine (160 mg/kg/d)/potassium oxonate (2400 mg/kg/d) every other day for 28 days. Fisetin (100 mg/kg/d) and allopurinol (10 mg/kg/d) was given by gavage simultaneously. At the end of the treatment, serum uric acid, kidney functions (serum creatinine and BUN) kidney pathological changes, as well as underlying mechanisms were investigated by biochemical assay, histopathological score, RT-PCR, and western blotting analysis.

Results
Oral administration of fisetin to HN mice lowered serum uric acid and improved renal functions. Renal fibrosis and inflammation in HN mice were attenuated by fisetin treatment. fisetin alleviated extracellular matrix deposition and reduced the release of pro-inflammatory cytokine IL-6, IL-1β, TNF-α and in the kidneys of HN mice. Furthermore, fisetin inhibited the activation of TGF-β and STAT3 signaling pathways in the kidneys of HN mice

Conclusion
These data demonstrated that fiseitn exhibited renoprotective effect in a severe mouse model of hyperuricemic nephropathy (HN). Fisetin exerted anti-inflammatory and antifibrotic effects in HN mice, which might be associated with its inhibition on TGF-β /Smad3 and STAT3 pathways.
P0702IMPAIRED MYOCARDIAL MICROCIRCULATION PERFUSION IN ASYMPTOMATIC STAGE 1-4 CHRONIC KIDNEY DISEASE PATIENTS WITH INTRARENAL ARTERIAL LESIONS
Authors: Dai Huanzi , Xiao Fei , Zhang Weiwei , He Yani 
Published: June 2020

Abstract

Background and Aims
Even mild renal disease is a powerful cardiovascular (CV) risk factor. However, the association between these pathophysiological processes, especially in the early asymptomatic stage, remains unclear. This study aimed to explore the relationship of cardio-renal microvascular disease in asymptomatic stage 1-4 chronic kidney disease (CKD) patients without obstructive coronary artery disease (CAD).

Method
This study consisted of 243 asymptomatic patients with stage 1-4 CKD who had no obstructive CAD. We distinguished different degrees of severity of intrarenal arterial lesions according to Oxford classification. Myocardial microcirculation perfusion was measured using single-photon emission computed tomography (SPECT). The summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Coronary microvascular disease (CMD) was defined as abnormal SPECT MPI (SSS ≥4 or SDS≥2 on SPECT images) in the absence of obstructive CAD.

Results
The study subjects showed a stepwise increase in CMD severity with the aggravation of intrarenal arterial lesions; The SSS of no/mild/moderate/severe arterial lesions were 1.64±1.08, 2.56±1.35, 4.42±2.17, 6.48±3.52, respectively (all P&lt;0.05); The SDS of no/mild/moderate/severe arterial lesions were 1.29±0.49, 1.75±0.56, 3.06±1.12, 4.16±1.85, respectively (all P&lt;0.05). The percentage of subclinical CMD in CKD patients with intrarenal arterial lesions was significantly higher than those without arterial lesions (69.57% vs. 14.71%; P=0.01). Vice versa, the scores of intrarenal arterial lesions were significantly higher in patients who had myocardial perfusion defect (4.79±2.01 vs. 2.22±2.07, P=0.000), myocardial ischemia (3.69±2.16 vs. 2.35±1.69, P=0.001) compared to those without arterial lesions. Multiple regression analysis further supported renal arterioles hyalinization (OR=1.109, P=0.027) were independently associated with subclinical CMD in stage 1-4 CKD patients with no obstructive CAD.

Conclusion
This study demonstrated for the first time impaired myocardial microcirculation perfusion in asymptomatic stage 1-4 CKD patients with intrarenal arterial lesions. Renal arteriolar hyalinization may be a useful marker of the presence of CMD in CKD.
P0709RENAL OUTCOMES AND MORTALITY FOLLOWING TRANSCATHETER AORTIC VALVE IMPLANTATION IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Shabaka Amir , Lucena Valverde Rafael , Escudero Andres , Tirado-Conte Gabriela , Nombela Franco Luis 
Published: June 2020

Abstract

Background and Aims
Transcatheter aortic valve implantation (TAVI) is indicated for the treatment of patients with severe aortic stenosis with a high surgical risk that are rejected for surgical valve placement. The aim of this study is to evaluate the effect of TAVI on long-term kidney function in stage 3-4 chronic kidney disease (CKD) patients.

Method
We performed a single-center retrospective observational study of 529 consecutive patients that underwent TAVI between August 2007 and January 2018. We included patients with stage 3 or 4 CKD, with at least two stable measurements of glomerular filtration rate during the three months before TAVI. We excluded patients that presented with an acute kidney injury during the three months that preceded TAVI.

Results
165 patients (31.3%) of the patients who underwent TAVI had a stable stage 3 or 4 CKD before implantation. Their mean age was 83.61 ±5.08 years, BMI of 27.79 ± 4.54 kg/m2, baseline serum creatinine of 1.62 ± 0.49 mg/dl for an eGFR measured by MDRD-4 of 40.19 ± 10.79 ml/min, EuroScore-II of 6 (IQR 4-8). 42 patients (28.6%) had a post-procedural acute kidney injury (AKI), 2 of them required temporary renal replacement therapy and 30 patients (71.4%) recovered to their baseline kidney function. Mean contrast media administered was 162.0 ±77.8 ml. Mean serum creatinine decreased from 1.64 ± 0.51 mg/dl to 1.46 ± 0.52 ml/min after 1 year of follow-up (p=0.032). Only 2.4% of patients showed a &gt;50% increase in serum creatinine after 1 year. Median follow-up was 3.8 years (IQR 2.3-5.7 years) during which time no patient progressed to end-stage kidney disease. 33.3 % of patients died during follow-up, with a one-year survival rate of 87% and two-year survival of 82%. Post-interventional major bleeding (14.6 vs 5.8%, p&lt;0.001) and the need for post-interventional pacemaker implantation (25 vs 13.3%, p&lt;0,001)were the only risk factors associated with the development of AKI. Contrast volume was not associated with the development of AKI. AKI was associated with an increased in-hospital stay (13.2 vs 7.4 days, p&lt;0.001), but was not associated with either a reduced kidney function at end of follow-up or an increased mortality (Log-rank X2=1.72, p=0,578).

Conclusion
Despite the high incidence of post-interventional AKI after TAVI, our study did not show an association between AKI and increased mortality or reduced renal survival. In most cases after AKI patients recovered to their baseline kidney function. There is an improvement in kidney function after one year of treatment of severe aortic stenosis with TAVI in patients with CKD Stage 3-4.
P0710ADOJUKSAN AMELIORATES OBSTRUCTIVE KIDNEY INJURY IN MICE
Authors: Jiang Songling , Ha Hunjoo 
Published: June 2020

Abstract

Background and Aims
Sarcopenia and physical inactivity synergistically progress in patients with chronic kidney disease (CKD). Sarcopenia is also strongly associated with the risk of mortality in the end-stage kidney disease. Exercise improves skeletal muscle mass and strength, and PGC-1α is significantly upregulated in muscle after exercise. Since patients with CKD have physical limitation to exercise, the present study aimed to find natural compounds that mimic exercise. Dojuksan, a traditional decoction was confirmed to increase PGC-1α expression in c2c12 muscle cells.

Method
Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal tubulointerstitial fibrosis, a key feature of CKD. Either Dojuksan (50, 100, and 200 mg/kg/day) or losartan (1.5 mg/kg/day), a standard clinical treatment for CKD, was administered orally for 7 days, started one day prior to surgery. Phytochemicals of Dojuksan were identified by LC-MS analysis.

Results
UUO-induced renal inflammation and fibrosis were decreased by Dojuksan as much as losartan. Interestingly, Dojuksan significantly increased PGC-1α level and AKT phosphorylation in skeletal muscle of UUO mice. Losartan did not increase PGC-1α expression and AKT activation under our experimental condition. LC-MS analysis showed that the main compounds of Dojuksan were chlorogenic acid, liquiritigenin, akeboside, and glycyrrhizic acid.

Conclusion
These data suggest that Dojuksan may inhibit the progression of interstitial fibrosis possibly through mimicking exercise.
P0719SRC KINASES AGGRAVATE DIABETIC KIDNEY INJURY THROUGH ACTIVATION OF ENDOPLASMIC RETICULUM STRESS
Authors: Dorotea Debra , Ha Hunjoo 
Published: June 2020

Abstract

Background and Aims
Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease which is characterized by prominent kidney fibrosis. Src family kinases (SFKs), a family of proto-oncogenes, has been acknowledged to mediate the development of kidney fibrosis. While, several studies in liver and skeletal muscle suggested the role of Src kinases in activating endoplasmic reticulum (ER) stress. The present study aimed to investigate the mechanism of Src kinases-ER stress in mediating the progression of DKD.

Method
Type 1 diabetes was induced by a single 60 mg/kg i.p injection of streptozotocin (STZ) in 7-week-old male, Sprague-Dawley rats. Diabetic rats received 8-week-treatment of either KF-1607 (30 mg/kg/day), a pharmacological inhibitor of SFKs, or losartan (1 mg/kg/day), a standard treatment for patients with DKD.

Results
Among SFKs, Fyn and Lyn kinases were particularly increased in the diabetic kidney. Inhibition of Src kinases by KF-1607 improved kidney function and inhibited tubular injury, presented by decreased serum creatinine, albuminuria, and urinary KIM-1 excretion. Pathological changes in the kidney, such as enhanced glomerular volume, tuft area, and fractional mesangial area, were ameliorated in KF-treated rats. Highly-accumulated collagen network as well as increased TGF-β and α-SMA mRNA levels in the diabetic kidney were also significantly reduced in response to KF treatment. Furthermore, it consistently attenuated kidney inflammation and oxidative stress. The renoprotective effects of KF were interestingly similar to those of losartan. We showed increases in protein levels of phosphorylated IRE-1α, ATF6, GRP78 as well as CHOP indicating an exacerbated ER stress in the diabetic kidney. These ER stress markers were significantly decreased in KF treated mice.

Conclusion
Altogether, Src kinases through activation of ER stress aggravates kidney injury in STZ-induced diabetic rats.
P0732DOES KIDNEY FUNCTION INFLUENCE PLASMA ADIPONECTIN CONCENTRATION IN ELDERLY CAUCASIANS?
Authors: Adamczak Marcin , Dudzicz Sylwia , Chudek Jerzy , Zejda Jan , Zdrojewski Tomasz , Wiecek Andrzej Jan 
Published: June 2020

Abstract

Background and Aims
Adiponectin is a hormone produced almost exclusively by the adipose tissue with vaso-protective activity and mostly metabolized in the kidneys. Glomerular filtration rate (GFR) is declining with age in elderly subjects and therefore it is expected to be followed by accumulation of adiponectin in the circulation. The aim of this study was to assess the plasma concentration of adiponectin in relation to GFR in the older population-based on the PolSenior study cohort.

Method
The PolSenior study was a multicenter cross-sectional study which assessed the health status of older adults in Poland. In 3913 subjects aged 65 years or above (2041 male and 1872 female, BMI 28.1±5.1 kg/m2, mean age 79±9 years) plasma adiponectin concentration (ELISA; B-Bridge International) was measured. GFR was estimated using a short MDRD formula. All results are presented as means with standard deviations.

Results
In studied subjects eGFR was 76 ml/min/1.73 m2. eGFR below 60 ml/min/1.73 m2 was observed in 842 (22%) subjects. Plasma concentration of adiponectin was 11.9±6.4 µg/ml. In subjects with eGFR &lt; 60 ml/min/1.73 m2 significantly higher plasma adiponectin concentrations were observed compared to subjects with eGFR ≥ 60 ml/min/1.73 m2 (12.5±6.7 vs. 11.8±6.3 respectively, p=0.01). Plasma adiponectin concentration depends strongly on BMI (R= -0.28; p&lt;0.001) and marginally on the kidney function (R=-0.05; p=0.005). Multivariate regression analysis including plasma adiponectin concentration, BMI, eGFR, occurrence of diabetes mellitus and hypertension, showed that BMI and prevalence of diabetes (b=-0.24, p&lt;0.001, b=-0.11, p&lt;0.0001, respectively) but not eGFR explain variability of plasma adiponectin concentration.

Conclusion
Plasma adiponectin concentration is only slightly affected by kidney function in elderly Caucasians from the PolSenior study.