bluuebunny/crossref_metadata_2025 huggingface dataset:
P0566INCIDENCE AND IMPACT OF ACUTE KIDNEY INJURY (AKI) IN ANDALUSIA
Authors: Aguilera Morales Wenceslao , Lara Ruiz Alfonso , Díaz Díez Irene , Salgueira Lazo Mercedes
Published: June 2020

Background and Aims

Acute Kidney Injury (AKI) is an insufficiently reported clinical entity with significant impact on overall mortality, hospital stay and associated costs, increasing the risk of progression to Chronic Kidney Disease. It is especially relevant in hospitalized patients, where the incidence has doubled in the last decade, reaching 22-25%. Aims: Know the reported incidence of AKI in the Andalusian Autonomous Community, and its impact on mortality, average stay and associated costs.

Method

Cross-sectional descriptive study that analyzes data from all Andalusian hospitals, extracted from CMBDA corresponding to 2017. Hospitalization episodes, reference units, episodes with AKI at discharge, exitus and average stays were collected. An associated cost estimate analysis was also carried out using as reference the costs/day hospitalization in each SAS Assistance Unit according to BOJA Number 218 (14nov2016). The groups were compared according to the presence of the diagnosis of AKI.

Results

There were 525,757 hospital admissions in Andalusia; 25,727 reported the diagnosis of AKI at discharge, assuming an incidence of 4.89%. Patients with AKI total 316,938 stays, with an average stay of 15.5 + 13.8 days, compared to 6.5 + 6 days in which they have no associated diagnosis (p <0.01). The estimated costs associated with the diagnosis of AKI were 168,922,706 euros, with a cost / episode of 24,693 euros vs 3796 in the rest (p <0.01) (AKI/noAKI cost ratio: 6.5), and a cost / day / patient of 823 + 437 euros for AKI compared to 571 euros in the rest. The overall mortality associated with AKI was 26.8% (median 16.6%) vs. 4.76% (median 0.7%) in the rest (p <0.01). AKI/noAKI mortality ratio: 16.

These data may be underestimated since the completion of the CMBDA is not complete in all hospitals and also the diagnosis of AKI may have been present and not reported upon discharge. Estimated costs did not include dialysis sessions.

Conclusion

The incidence of hospital AKI in our Autonomous Community is lower than that reported in the literature, probably due to inadequate reporting to CMBD. In spite of the limitations, our data show the impact of the diagnosis of AKI in hospitalized patients, multiplying by 2.5 the average stay, by 6.5 the associated costs and by 16 mortality, assuming a big problem Public Health that makes it imperative to develop measures to reduce the impact it entails.
P0572ABSENCE OF RENAL FUNCTION RECOVERY AFTER AN ACUTE KIDNEY INJURY PREDICTS SHORT-TERM MORTALITY
Authors: Quiroga Borja , Sanz Sainz Marta , Santos Sánchez-Rey Begoña , Muñoz Ramos Patricia , Ruano Pablo
Published: June 2020

Background and Aims

The incidence of acute kidney injury (AKI) during a hospitalization is frequent and worsen the prognosis. Recovery of renal function after AKI has been lightly studied and cut-off for establishing full recovery has not been determined. The aim of the present study is to evaluate the association between different degrees of renal function recovery after AKI and short-term mortality post-discharge.

Method

This is a retrospective study that included all the AKI codified in the electronic records of our center in 2013 and 2014. We collect epidemiological data and comorbidities at baseline and laboratory values at admission and discharge. To analyze the impact of recovery of renal function after AKI we performed a univariate logistic regression with different cutoff of creatinine after 7 days of the AKI in comparison to baseline. We used the most sensitive cutoff to define recovery and evaluated associated factors (figure 1). Patients were followed during 30 days to assess associated factors to prognosis after AKI.

Results

We included 1720 patients in this study. After the hospitalization due to AKI, 1194 (69%) entered in the final analysis. Of them 869 (73%) recovered renal function. Factors associated to recovery were age (p=0.01), presence of CKD (p=0.04), basal renal function (p<0.001), history of heart failure (p=0.02), having cognitive impairment (p=0.01), dependence (using Barthel index, p=0.002), renal function at admission (p<0.001), severity of AKI (p<0.001), blood pressure at admission (p=0.02) and hemoglobin at admission (p=0.04). Independent predictors of recovery were basal CKD-EPI (p<0.001), CKD-EPI at admission (p<0.001), severity of AKI (p=0.037), hemoglobin at admission (p=0.016), blood pressure at admission (p<0.001) and history of heart failure (0.001). After discharge, 46 (3%) patients died in the first 30 days. Associated factors to mortality were history of neoplasia (p=0.02), cognitive impairment (p<0.001), Barthel index (p<0.001) and the absence of renal recovery after AKI (defined as reaching a creatinine above 1.2 times of the baseline) (p=0.01). In an adjusted model, renal function recovery independently predicted short term mortality (HR 2.6, 95%CI [1.2-5.4], p=0.01).

Conclusion

The absence of recovery after an AKI is an independent predictor of 30-day mortality.
P0573CLINICAL PRESENTATION AND OUTCOMES OF ACUTE INTERSTITIAL NEPHRITIS: A TEN YEARS' EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN KARACHI, PAKISTAN
Authors: Yaqub Sonia , Aziz Rehman Ayesha , Awan Safia
Published: June 2020

Background and Aims

Acute interstitial nephritis (AIN) is a potentially reversible, but relatively under-diagnosed cause of acute kidney injury. The effectiveness of steroids for treatment of AIN is debated. Data is scarce regarding the clinical presentation, use of steroids and its impacts on outcomes in AIN in our part of the world. The objective of our study was to study the clinical features, causes and outcomes of AIN and to evaluate the role of steroids in the management.

Method

We performed a retrospective study of 48 patients with biopsy proven AIN. Exposure was defined as the use of steroids. The main outcomes were recovery of renal function (Early (≤3 weeks) or Late (>3 weeks)) and hemodialysis dependence at 12 weeks

Results

48 (4.9%) AIN cases were found among 978 renal biopsies performed from 2007-2018. Mean age was 47.6 ± 12.1 years. 56.3% were males. The offending agent was identified in 45.8% cases with NSAIDs (45.4%) being the most common, followed by antibiotics (22.7%), diuretics (9%), and PPI (4.5%). 75% presented with eGFR <15 ml/min/1.73m2 (n=36) out of which 58.3 % (n=21) needed hemodialysis. Mean proteinuria was 2.28 ± 0.99 g/day. 81.3% (n=39) patients received steroids out of which 39.6% were started on steroids after an initial period of observation after stopping the offending agent. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Mean time to steroid commencement was 14 ± 17.39 days.

Early use of steroids (≤11 days after presentation) was significantly associated with earlier recovery (p= 0.009) as compared to late steroids (>11 days). A non-significant trend towards complete recovery (within 25% of baseline Creatinine) was noted in early steroid group (52.9%, n=17) vs “no steroid” (33.3%, n=9) or “late steroids” (10.5%, n=19) groups (p=0.208). 47.4% remained dialysis dependent on follow up with no difference made by steroid use (p=0.971).

Conclusion

Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery. Late steroid use was not associated with any further recovery of renal function at an additional risk of exposing patients to undue adverse effects. This is the first report from Pakistan documenting the tendency of nephrologists towards use of steroids for AIN.
P0576LEFT VENTRICULAR FUNCTION ON TISSUE PERFUSION AND RENAL OUTCOMES IN CRITICALLY ILL PATIENTS WITH SEPSIS
Authors: Shin Jungho , Hwang Jin Ho , Kim Su-Hyun
Published: June 2020

Background and Aims

Left ventricular (LV) dysfunction has been regarded as a predictor of mortality in patients with sepsis. However, it remains uncertain whether LV dysfunction deteriorates multiple organ failure by impairing tissue perfusion or it has an independent impact. In this study, we investigated the association between LV dysfunction and tissue perfusion, and their impacts on renal outcomes in critically ill patients with sepsis.

Method

We retrospectively reviewed a total of 162 adult patients with sepsis who met the Sepsis-3 definition. Subjects included 83 (51.2%) with normal LV function, 39 (24.1%) with diastolic dysfunction defined as the septal E/e’ ratio >15 among patients with ejection fraction ≥50% and 40 (24.7%) with systolic dysfunction defined as an ejection fraction <50%. Tissue perfusion was assessed by the levels of blood lactate.

Results

The initial and 24h levels of lactate, and lactate clearance did not differ regardless of the presence of LV dysfunction (P=0.861, 0.907 and 0.363). The incidence rate of acute kidney injury (AKI) among the patients with initial lactate <2 mmol/L was higher in those with LV dysfunction (P=0.044), conversely, the incidence rate was comparable in the patients with initial lactate ≥2 mmol/L (P=0.797). Risks of AKI and renal replacement therapy implementation increased if subjects had blood lactate levels ≥2 mmol/L (P=0.009 and 0.080), however, the impact of LV dysfunction on these outcomes depended on previous chronic kidney disease and lactate levels (diastolic dysfunction: P=0.449 and 0.663; systolic dysfunction: P=0.062 and 0.161). However, renal replacement therapy-free days were shorter in those with LV dysfunction, independent of previous chronic kidney disease (P=0.003). Renal function at discharge was not related to the lactate levels and LV function in this study (P=0.685 and 0.089)

Conclusion

LV dysfunction might not influence tissue perfusion in patients with sepsis, on the other hand, it could lengthen the duration of renal replacement therapy. Therapeutic options for preserving microcirculation should be warranted in patients with sepsis, in addition to individualized therapies tailored their LV function.
P0579EVALUATION OF BIOMARKERS EFFICIENCY IN PREDICTIVE AND EARLY DIAGNOSTICS OF ACUTE KIDNEY INJURY IN ACUTE CORONARY SYNDROME
Authors: Vorobyev Eugene , Smirnov Alexei , Kucher Anatoly , Galkina Olga , Zubina Irina , Anpilova Anastasia , Bogdanova Evdokia , Levykina Elena
Published: June 2020

Background and Aims

Acute Kidney Injury (AKI) is a common complication of acute coronary syndromes (ACS), and associated with higher mortality and adverse outcomes. Despite advances in research over the past years, effective treatments for current AKI are not available. Prevention and early intervention remain the most effective strategies for AKI of any entity. This study aimed to explore a risk factors and biomarkers for predictive and early diagnostic of AKI in ACS.

Method

Study was prospective and cohort, patients hospitalized with ACS in Pavlov First Saint Petersburg State Medical University were included. In case of exclusion of ACS, patients were determined in the comparison group, in case of confirmation of the diagnosis of ACS - in the study group. Biomaterial (blood and urine) was taken at admission (T1), 1 day after admission (T2) and 2 days after admission (T3). For the diagnosis of AKI, KDIGO 2012 criteria were used for the diagnosis of AKI. The measured biomarkers at each point were NGAL, KIM-1, cystatin C, sST2, troponin I.

Results

The study included 73 patients, the diagnosis of ACS was confirmed in 40 patients and AKI development was in 15 patients, all from the ACS group. The most significant for predictive diagnosis was the assessment of the parameters of systemic hemodynamics and the severity of acute heart failure (AHF): heart rate>90 (AUC=0,798, p=0,001), GRACE Risk Score>133 (AUC=0,926, p=0,005). In evaluation the suitability of biomarkers in terms of prognostic diagnosis of AKI, urine NGAL>32 ng/ml (AUC=0,814 p=0,04) and sST2>23.4 ng/ml (AUC=0,718, p=0,02) showed the best results.

Conclusion

In study of biomarkers efficiency, the use of urine sST2 and NGAL is most promising. Together with hemodynamic parameters, biomarkers have high predictive ability in the diagnosis of AKI in ACS.
P0586ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING CARDIAC SURGERY: A PROSPECTIVE, OBSERVATIONAL STUDY TO ASSESS INCIDENCE, SEVERITY, RISK FACTORS AND MORTALITY IN TERTIARY CARE HOSPITAL IN INDIA
Authors: Sharma Reetesh , Jain Salil , Trehan Naresh
Published: June 2020

Background and Aims

Acute kidney injury (AKI) occurs in up to 30% of patients undergoing cardiac surgeries and is associated with increased morbidity and mortality. There is paucity of such data in our country. Hence this study was done to assess the incidence of AKI following cardiac surgery and its associated risk factors along with outcomes, in the Indian context.

The incidence and severity of AKI in patients with normal renal parameters vs those with underlying CKD was studied. We also compared incidence and severity of AKI in patients undergoing surgery off pump vs on pump.

Method

All patients age>25yrs of either gender undergoing cardiac surgeries were enrolled prospectively from July to October 2018. Patients undergoing aortic surgeries or on dialysis, renal transplants or with pre-existing AKI were excluded. Incidence and severity of AKI was defined by the AKIN criteria. NKF/DOQI definition was used to define CKD. Prevalence of risk factors such as age, sex, BMI, diabetes mellitus, hypertension, dyslipidemia, CKD, CVA, peripheral vascular disease (PVD), prior myocardial infarction (MI), peri-operative acute myocardial infarction (AMI), use of cardiopulmonary bypass (CPB) and prolonged ventilation were assessed.

Results

1,040 patients were enrolled with these baseline characteristics: 83.5% were males, mean age 58.2±10.4 years, mean BMI 25.6±4.3, diabetes in 48.2%, hypertension in 57.5%,dyslipidemia in 70%,CVA in 36%,CKD in 6.3%,PVD in 0.9%,peri-operative AMI in 0.6%,use of CPB in 24%. Overall incidence of AKI was 23.3% and was 71.2% in patients with underlying CKD. AKI was more severe in patients with higher CKD stages. Stage3 AKI occurred only in patients with CKD stage 3 and 4. Overall the need for dialysis was 1.1% and it was 4.9% in AKI group. 8.5% of patients with CKD needed dialysis as compared to 4.1% without CKD.In multivariate risk factor analysis hypertension (p=0.01),peri-operative AMI (p=0.03), prolonged ventilation (p=0.01), CVA (p=0.01) and CKD (p<0.001) were found to be significantly associated with AKI whereas diabetes (p =0.12), PVD (p=0.13), use of CPB (p=0.4), prior AMI (p=0.07) were not significant. Mean hospital stay was prolonged in those with AKI (8.33±4.06 vs 7.16±3.01 days (p<0.001)). Overall the mortality was 0.67% and it was 2.9% in AKI group. All mortalities were associated with AKI.

Conclusion

Incidence of AKI (23.3%) and mortality (0.67%) in cardiac surgery patients at our centre in India is similar to other reported studies. We found that underlying CKD is the most significant risk factor for AKI in these patients in addition to hypertension, CVA, prolonged ventilation and pre-operative AMI. Use of CPB did not increase the incidence of AKI. AKI significantly increases mean hospital stay and is also associated with increased in-hospital mortality.
P0604IDENTIFICATION OF NOVEL ENDOTHELIAL ACTIVATION BIOMARKERS IN PATIENTS WITH LEPTOSPIROSIS AND ITS ASSOCIATION WITH ACUTE KIDNEY INJURY
Authors: De Francesco Daher Elizabeth , Andrade de Carvalho Gomes Pedro Eduardo , Studart Galdino Gabriela , Cavalcante Meneses Gdayllon , Costa Martins Alice Maria , Bezerra da Silva Junior Geraldo
Published: June 2020

Background and Aims

Leptospirosis has a broad clinical spectrum. Many patients present a severe disease, with potentially fatal outcomes. Novel biomarkers of endothelial activation are being studied in order to predict the severity of disease and to establish early assistance to the patients.

Method

For the analysis of biomarkers, blood samples were collected at hospital admission, in proper material for serum isolation. Aliquots were frozen at -80 ºC until the analysis was done. To quantify the biomarkers, ELISA kits were used: Syndecan-1 (Abcam–ab47352), ICAM-1 (Abcam–ab47349) e VCAM-1 (Abcam–ab47355), Angiopoietin-2 (R&D Systems–Duoset DY623) e FGF-23 (R&D Systems–Duoset DY2604).

Results

A group of 27 patients was evaluated. 24 (88.9%) were males and 3 (11.1%) were females. Mean age was 39.1 ± 17.6 years. 14 (53.8%) required dialysis. Patients who required dialysis presented higher levels of syndecan-1 (572 [300-811] vs. 263 [106-421] ng/mL; p = 0.03), angiopoietin-2 (1.52 [0.72-2.72] vs. 0.63 [0.4-1.38] ng/mL; p = 0.01), and FGF-23 (291 [56-2,031] vs. 10 [10-806] pg/mL; p = 0.021). There were no significant differences in the levels of VCAM-1 and ICAM-1 between the two groups. Syndecan-1 showed significant correlation with the levels of creatinine at hospital admission (r = 0.546; p = 0.05) and total bilirubin at hospital admission (r = 0.534; p = 0.013). Angiopoietin-2 showed significant correlation with the levels of creatinine at hospital admission (r = 0.513; p = 0.009) and the number of hemodialysis sessions (r = 0.406; p = 0.049). No correlation was shown concerning FGF-23.

Conclusion

Novel biomarkers revealed leptospirosis-associated endothelial activation and were significantly increased in patients with renal involvement. Therefore, they may be useful for establishing early identification and assistance in those patients.
P0607CLINICAL SIGNIFICANCE OF HYPOALBUMINEMIA FOR ACUTE KIDNEY INJURY IN PATIENTS WITH SCRUB TYPHUS
Authors: Lee Kwang Young , Sun In O
Published: June 2020

Background and Aims

The aim of this study is to investigate the clinical significance of hypoalbuminemia (HA) for acute kidney injury (AKI) in patients with scrub typhus.

Method

From 2010 to 2017, 449 patients were diagnosed with scrub typhus. We divided the patients into two groups [normoalbuminemia (NA) vs. hypoalbuminemia (HA)] based on the serum albumin level of 3.5 g/dL, and compared the incidence, clinical characteristics, and severity of AKI based on RIFLE classification between two groups.

Results

Of the total 449 patients, 52 (11.6%) were categrized as HA group. Compared with patients in NA group, patients in HA group were older (74 ± 8 vs. 63 ± 13, P<0.01) and had higher total leukocyte counts (10.4 × 103/ mL vs. 6.9 × 103/mL, P<0.01). HA group showed significantly longer hospital stay (10.1 ± 4.7 vs 8.8 ± 4.5, p<0.01) and higher incidence of acute kidney injury (56% vs. 19%, p<0.01). The overall incidence of AKI was 22.9%; of which, 12.2%, 10.0% and 0.7% were classified as Risk, Injury and Failure, respectively. In a multivariate logistic regression analysis for predciting AKI, age, presence of chronic kidney disease, leukocytosis and hypoalbuminemia were significant predictors of AKI. Most patients recovered baseline renal function without renal replacement therapy following antibiotics therapy and supportive care.

Conclusion

Hypoabluminemia was closely associated with scrub typhus associated with AKI.
P0629ESTABLISHING MORTALITY ASSOCIATED WITH AKI IN A DGH AND THEN TRYING TO DO SOMETHING ABOUT IT- INTRODUCTION AND AUDIT OF THE AKI7 CARE BUNDLE
Authors: Paisey Christopher , Chapman David , Achilleos Kat , Yiu Vivian
Published: June 2020

Background and Aims

Acute kidney injury (AKI) is a prevalent and treatable contributor to inpatient mortality. Simple management steps for AKI are frequently omitted or delayed in patient care due to its insidious onset and lack of symptoms. The NCEPOD report in 2009 found that only 50% of patients with AKI received good care. One response to this has been increased use across trusts of the electronic medical record for recognition and monitoring of AKI. Such systems also enable collection of reproducible datasets for audit as well as a platform for prompting the use of best practice guidelines.

We sought to establish mortality for patients with AKI and to audit the introduction of an electronic alert system and order set proforma for AKI: the AKI7 care bundle.

Method

We collated data from all inpatients in West Suffolk Hospital (WSH) flagged as developing AKI by the recording system ‘eCare’ over a 2-year period and present a mortality analysis for this cohort. Data was collected retrospectively from eCare and statistical analysis conducted in ‘R’.

Results

Of 3527 individuals who developed AKI over a 2 year period in WSH; 79% did not progress beyond AKI stage 1, 13% stage 2 and 8% stage 3, the mean age was 74 years and mean length of stay 13 days. Across all stages of AKI, 75% were investigated with urinalysis, 94% received fluid balance monitoring, 5% were investigated with renal tract US and 58% were referred to a nephrologist for specialist input. Mortality analysis for this same cohort revealed an association between survival at 60 days and use of urinalysis p=<0.001, fluid balance monitoring p=<0.001 and investigation with renal tract US p=<0.001. The 1 year mortality associated with AKI increased significantly with severity; 29% for AKI stage 1, 51% for AKI stage 2 and 65% for AKI stage 3 (Figure.1). The all cause 1 year mortality for all stages of AKI combined was 39.1%. Following launch of the AKI7 care bundle we found that use of the document template promoted requests for renal tract US (20% versus 5%), urinalysis (83% versus 75%) and requests for input by renal physicians (75% versus 65%).

Conclusion

The AKI7 care bundle improves clinician awareness of AKI and promotes the use of important steps in AKI management. Since mortality increases with AKI stage, management targeted to ameliorate progression of AKI is vital and can be supported by well designed electronic care bundles. The association of improved survival with fluid balance monitoring and investigations for AKI further supports measures to promote the use of these steps. We intend to encourage use of the AKI7 care bundle during induction for junior doctors coupled with distribution of cards as an aide-memoire.
P0648LEVELS OF PHYSICAL ACTIVITY FOLLOWING AN EPISODE OF STAGE 3 AKI ARE ASSOCIATED WITH RENAL RECOVERY
Authors: Asad Anam , Dungey Maurice , Hull Katherine , Burton James , March Daniel
Published: June 2020

Background and Aims

Acute kidney injury (AKI) is a known risk factor for the development of chronic kidney disease (CKD). Animal studies have demonstrated the potentially reno-protective effects of physical activity, both against the development of AKI and in promoting renal recovery. However, this has not been investigated in humans. The aim of the study was to investigate the association between physical activity levels and recovery in kidney function, measured by eGFR and creatinine, following an episode of stage 3 AKI.

Method

Twelve hospitalised participants with non-obstructive stage 3 AKI (as per KDIGO criteria) were asked to complete two questionnaires; the General Practitioner Physical Activity Questionnaire (GPPAQ), a measure of physical activity and; the Duke Activity Status Index, a measure of functional capacity. Baseline questionnaires were completed whilst in hospital (where participants were asked to recall their physical activity and functional capacity levels before hospitalisation) and again at 6-months post discharge. In addition, participants wore a pedometer for 7 consecutive days following discharge to ascertain their daily step count. Baseline renal function was collected using eGFR and creatinine measurements within the 12-months prior to admission; further readings were collected 25 ± 46 days after discharge as a measure of renal recovery (referred to as recovered creatinine).

Results

Data from the 12 participants who provided step count information were analysed. At diagnosis of stage 3 AKI, participants had a mean creatinine of 547 ± 280 with their mean baseline and recovered creatinine as follows; 95 ± 35 and 172 ± 83. A higher daily step count after discharge was associated with both a higher baseline eGFR (r=0.73, p<0.01) and significant improvements to their renal recovery (r=0.69, p=0.01). There were positive associations between renal recovery and physical activity levels measured using the GPPAQ (r=0.55, p=0.06) and functional capacity (0.17, p=0.6), although not to statistical significance. The participants were divided into two groups based on their recovered creatinine levels. Those who recovered renal function back to within 25% of baseline (n=5) had a higher mean step count compared to those whose renal recovery was less pronounced (n=7); (3712 ±3960 vs 3334 ± 2254, respectively).

Conclusion

These results show a positive association between physical activity levels and renal recovery following an episode of AKI. This suggests that higher levels of physical activity may be protective and promote recovery of renal function following an episode of AKI. Physical activity and exercise interventions should be tested in the setting of AKI to see whether they are efficacious in promoting renal recovery.
P0672CALPAINS 1 AND 2 ARE INCREASED DURING THE DEVELOPMENT OF CHRONIC KIDNEY DAMAGE IN MICE FED WITH AN ADENINE RICH DIET
Authors: Gutiérrez-Calabrés Elena , Campillo de Blas Sofía , Bohorquez Magro Lourdes , Griera-Merino Mercedes , García Ayuso Diego , Vaillo David , De Frutos García Sergio , Rodríguez-Puyol Manuel , Calleros Laura , Rodríguez-Puyol Diego
Published: June 2020

Background and Aims

Calpains are intracellular cysteine proteases that play a critical role in cell remodeling, being involved in multiple biological processes linked to tissue damage and repair mechanisms. In addition, they are released into the circulation, being able to carry out systemic actions with pathological consequences. The aim of this study was to investigate the role of calpains in the progression of chronic kidney disease (CKD) in an experimental model of chronic renal damage induced by adenine.

Method

We induced an experimental model of CKD, in mice fed for 2 weeks with an adenine-supplemented diet (0.2% adenine) (A). Animals receiving this diet develop a tubulointerstitial damage resembling that is observed in human CKD. Mice with standard diet were used as controls (C). Renal function was assessed by measuring serum blood urea nitrogen (BUN) and creatinine (mg/dl). Fibrosis markers (collagen type I and fibronectin) were determined by RT-qPCR. Changes in the renal content of calpains 1 and 2 were analyzed by western blot (protein content), and RT-qPCR (mRNA expression).

Results

Our results show functional and structural changes at renal level in the adenine-fed mice, with increased BUN (A: 72 mg/dl, C: 28 mg/dl, p < 0.05), creatinine (A: 0.58 mg/dl, C: 0.25 mg/dl, p < 0.05), collagen type I mRNA expression (A: 12.9 units, C: 1.2 units, p < 0.05) and fibronectin mRNA expression (A: 3.46 units, C: 1.3 units, p < 0.05). Furthermore, protein content of calpains 1 (A: 1.27 units, C: 0.78 units, p < 0.05) and 2 (A: 1.30 units, C: 0.66 units, p < 0.05) was significantly higher in adenine-fed mice when compared to control. At the same time, we observed a significant increase in gene expression of both calpain 1 (A: 4.21 units, C: 0.51 units, p < 0.05) and 2 (A: 4.93 units, C: 0.56 units, p < 0.05) in the adenine model regarding to mice with standard diet. Our results demonstrate that calpain 1 and 2 expression in renal tissue increases as CKD progresses. Interestingly, we found statistically significant correlations between renal calpains 1 and 2 protein and mRNA content and plasma BUN and creatinine (p < 0.05, r between 0.79 and 0.92), as well as protein expression of calpain 2 and mRNA expression of collagen type I (p < 0.05, r = 0.76). These data suggest a potential direct relationship between renal calpain 1 and 2 content and loss of renal function, in part due probably to the modulation of the fibrotic changes, in adenine fed mice.

Conclusion

We suggest an implication of calpains 1 and 2 in the development of CKD. Thus, effective calpain blockade or downregulation could be useful as a therapeutic strategy to prevent CKD. Further experiments will be necessary to establish the relationship between these factors.
P0673INVERSE ASSOCIATION OF TRANSFERRIN SATURATION WITH MORTALITY RISK IN CHRONIC KIDNEY DISEASE
Authors: Li Xin , Danielson Kristin , Forsal Innas , Iseri Ken , Dai Lu , Heimbürger Olof , Barany Franz Peter , Stenvinkel Peter , Qureshi Abdul Rashid Tony , Lindholm Bengt
Published: June 2020

Background and Aims

Transferrin saturation (TSAT) is an indicator of iron deficiency or overload, but its relationship with mortality in patients with different stages of chronic kidney disease (CKD) is unclear. We investigated the association of TSAT with mortality in CKD patients.

Method

In 479 CKD patients (97 CKD3-4 patients, 298 CKD5 non-dialysis patients and 84 peritoneal dialysis patients; median age 58 years, 67% males, 33% cardiovascular disease, CVD, and 29% diabetes), biomarkers of iron status (plasma iron, TSAT, transferrin and ferritin), systemic inflammation (high sensitivity C-reactive protein, hsCRP, and interleukin-6, IL-6) and nutritional status were assessed. During median follow-up of 35.6 months, 139 (29%) patients died, and 176 (37%) patients underwent renal transplantation. Patients were stratified into low (n=157) and high (n=322) TSAT tertile groups. All-cause and CVD mortality risk were analyzed with competing risk regression with renal transplantation as competing risk.

Results

TSAT [median 23% (IQR 17-30%)] was negatively associated with presence of DM and CVD, body mass index, hsCRP, IL-6, Framingham´s CVD risk score (FRS), erythropoietin resistance index (ERI) and iron supplementation, and positively associated with hemoglobin, ferritin and s-albumin. In competing risk analysis, low tertile of TSAT was independently associated with increased all-cause mortality risk (sHR=1.50, 95%CI 1.05-2.14) after adjusting for CKD stages, 1-SD of FRS, 1-SD of hemoglobin, 1-SD of hsCRP, 1-SD of ESA dose and iron supplementation (Figure 1).

Conclusion

TSAT was inversely associated with mortality risk in CKD patients. When evaluating clinical outcomes of CKD patients, iron status using TSAT as a predictive marker, should be considered.
P0674DCR2,AS A SENESCENCE MARKER,IS ASSOCIATED WITH DISEASE SEVERITY AND PROGRESSION IN IGA NEPHROPATHY PATIENTS
Authors: Dai Huanzi , Hu Wei , Chen Jia , He Yani
Published: June 2020

Background and Aims

Accelerated senescence of renal tubular epithelial cells (RTECs) may contribute to the progression of IgA Nephropathy (IgAN). Our previous studies demonstrated that DcR2 may reflect senescence of RTECs in experimental models and patients with diabetic nephropathy. The objective of this study was to investigate the association of DCR2 with disease severity and progression in IgAN.

Method

We included a retrospective cohort of 105 patients with biopsy proven IgAN. 15 normal renal tissue specimens displaying insignificant alterations biopsied from patients with renal carcinoma were recruited as controls. Renal biopsies from all patients were scored according to Oxford classification (MEST-C score). We analysed the degree of expression and localization of DCR2 in biopsies from kidneys with IgAN, and correlated their immunostaining levels with various clinical and histological parameters at baseline. Cox regression was performed for the composite renal outcome defined as 30% reduction in initial estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD), and for the individual components during a follow-up for 60 or more months.

Results

DCR2 was overexpressed in the cytoplasm of RTECs obtained from kidneys of patients with IgAN [male: 60.9%, age:39.5±13.0 years, mean arterial pressure (MAP): 95.2±18.0 mmHg, proteinuria: 1.9 (0.7, 3.7)g/day, Initial eGFR:89.8±37.2 ml/min/1.73 m2], and were elevated with the increasing T scores. At baseline, DCR2 protein levels in the RTECs was inversely correlated with eGFR (R=−0.597, P=0.000) and positively associated with 24h-proteinuria (R=0.379, P=0.000) and the T score (R=0.632, P = 0.000). During a median follow-up of 80 (60, 125) months, patients with ≥25% tubular DCR2 positive showed worse eGFR slopes (the rate of eGFR decline) than those<25% DCR2 positive group [4.35 (2.17, 5.53) versus 0.36 (-0.96, 1.19) ml/min per 1.73 m2 per year; P=0.000)]. Kaplan–Meier survival analysis revealed that renal survival for the composite outcome was significantly lower in the ≥25% DCR2 positive group than in the<25% DCR2 positive group (P=0.000). In Cox regression models, ≥25% tubular DCR2 positive expression independently associated with poor renal outcome (HR=2.02, P=0.001) after adjustment for multiple known risk factors for IgAN progression, including baseline proteinuria, hypertension, eGFR, Oxford scores, and steroids/immunosuppressive therapy. Moreover, tubular DCR2 expression showed the highest sensitivity and specificity (80.8% and 87.3%, respectively) at a cut-off value of 25.5% DCR2 positive expression over proteinuria and eGFR for the composite outcome. The area under the receiver operating characteristic curve (AUROC) of tubular DCR2 expression was 0.880.

Conclusion

DCR2 is associated with disease severity and prognosis in IgAN patients and may have additional prognostic value besides established risk markers.
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

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

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

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

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<-3) and 212 patients in the improved group (delta eGFR>0.50).

Negative predictive value analysis was performed on all patients with an outcome of a GFR < 30ml/min/1.73m2.

Results

Stable CKD patients had a significantly higher age compared to RP ( 69 vs 62, p<0.001). Further patients in the stable CKD group had a comparatively lower median blood pressure (141.5 vs 137, p<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<0.001), raised urine protein creatinine ratio (154.6 vs 18.8, p<0.001) and phosphate (1.24 vs 1.12, p<0.001) (Table-1). Comparing outcomes showed rapid progression reached ESRD (172 vs 18, p<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

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

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<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<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.