bluuebunny/crossref_metadata_2025 huggingface dataset:
P0706THE EFFECT OF NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS ON RENAL OUTCOMES IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION
Authors: Deeprom Siwaporn , Chirananthavat Thanit
Published: June 2020

Background and Aims

Lifelong oral anticoagulation (either with warfarin or a non–vitamin K antagonist oral anticoagulant (NOACs)) is indicated for stroke prevention in most patients with atrial fibrillation (AF). NOACs has been recommended for thromboembolism prophylaxis of nonvalvular AF. However, studies on the impact of NOACs on renal outcomes has been inconclusive.

Method

This retrospective cohort study compared 3 NOACs: apixaban, dabigatran and rivaroxaban to warfarin for their effects on renal outcomes in patients with nonvalvular AF who had been using these medications for at least 2 years as of 2017-2018. The primary outcome was either the incidence of > 30% decline in estimated glomerular filtration rate (eGFR) or doubling of the serum creatinine levels compare to baseline values at 24 months, and the secondary outcome was the incident of primary outcomes in different baseline eGFR subgroups (> 60 vs < 60 ml/min/1.73 m2) and major bleeding as an adverse event.

Results

90 patients were enrolled in each group, totaling to 360 patients. The incidence of > 30% decline in eGFR is significantly higher in rivaroxaban compared to warfarin (hazard ratio: 2.09; 95% confidence interval: 1.35 to 3.24; p = 0.001). After multivariate analysis (using age, stage of chronic kidney disease, eGFR, CHAD2VAS and HASBLED score), dabigatran was also shown to significantly increase the incidence of > 30% decline in eGFR. In subgroup analysis, rivaroxaban resulted in higher incidence of > 30% decline in eGFR, in eGFR < 60 ml/min/1.73 m2 subgroup and higher incidence of doubling of the serum creatinine level in eGFR > 60 ml/min/1.73 m2 subgroup. There was no occurrence of major bleeding.

Conclusion

NOACs, especially rivaroxaban, may increase adverse renal outcomes in patients with nonvalvular AF.
P0708ASSOCIATION OF OBESITY WITH KIDNEY CYST GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE; RESULTS FROM KNOW-CKD COHORT DATA
Authors: Kim Chang Seong , Choi Hong Sang , Bae Eun hui , Ma Seong Kwon , Kim Soo Wan
Published: June 2020

Background and Aims

Overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD) are associated with the decline of glomerular filtration rate. However, little is known about the annual rate of change in total kidney volume (TKV) in patients with ADPKD according to the body mass index (BMI) corrected by TKV and total liver volume (TLV).

Method

We analyzed 364 patients with ADPKD from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease. We compared the changes in TKV in less than 1-year, 2-years and 4-year follow-up from patients by dividing baseline body mass index (BMI) by 18.5 to 22.9 (normal), 23 to 24.9 (overweight), and > 25 kg/m2 (obesity).

Results

During the 4-year follow-up period, TKV tended to increase statistically with increasing BMI (P = 0.032). Similarly, higher BMI group showed higher TKV than lower BMI group (P = 0.016). Conventional BMI is affected by TKV and TLV in advanced ADPKD patients. Therefore, we reclassified patients by corrected BMI using the adjusted body weight (body weight – TKV – TLV). Although the statistical significances between absolute value of TKV and corrected BMI groups were disappeared during the follow-up, TKV% change/year showed significantly higher in ADPKD patients with obesity among corrected BMI groups (normal; 20.2%, overweight; 17.6% and obesity; 30.6%, P for trend = 0.022)

Conclusion

Even after correcting the TKV and TVL, obese patients showed a high of TKV% change/year compared to non-obese patients with ADPKD.
P0710DUAL GPR40/GPR84 FATTY ACID RECEPTOR DELETION IMPROVES ADENINE-INDUCED RENAL INJURY IN MICE
Authors: Cheff Véronique , Blais Amelie , Holterman Chet , Hébert Richard , Kennedy Chris , Thibodeau Jean-Francois
Published: June 2020

Background and Aims

Fatty acid receptors have recently been implicated in the progression of fibrotic disorders. GPR40 deletion predisposes to AKI and CKD-induced fibrosis, while deletion of the pro-inflammatory GPR84 receptor was beneficial in this context. PBI-4050, a novel therapeutic compound with excellent safety and efficacy profiles in both experimental and clinical settings, is a dual GPR40 agonist and GPR84 antagonist. In this study, we sought to determine which of these receptors had a predominant effect in adenine-induced CKD.

Method

Ten-week-old male GPR40/84 double knockout mice (40/84ko) and age/strain matched WT C57BL/6 mice were subjected to a regular or adenine-supplemented diet (0.25%) for 4 weeks (n=10 per group). Plasma samples were collected on a weekly basis for hematocrit assessment. At endpoint, mice were placed in metabolic cages for 24 hours for urine collection. Plasma minerals and electrolytes, urinalysis and a comprehensive blood count were performed at endpoint.

Results

Adenine feeding led to early and sustained weight-loss, which was significantly worse in WT mice compared to 40/84ko mice. At day 14, Hct was significantly decreased in adenine-fed WT mice, while unaffected in the 40/84ko group. Adenine-induced reductions in hemoglobin and red blood cells counts were also greatly improved in 40/84ko mice. Adenine-feeding led to increased circulating neutrophils and decreased lymphocyte in WT mice, which was not seen in 40/84ko mice. Importantly, renal function assessed by plasma creatinine, urea and creatinine-clearance and renal hypertrophy were significantly improved in Ad-fed 40/84ko mice. Moreover, fractional excretion for sodium, potassium and calcium were increased by adenine-feeding in WT, but not in 40/84ko mice.

Conclusion

Overall, the loss of both GPR40 and GPR84 led to major improvements in several key renal functional abnormalities associated with adenine-induced CKD including weight-loss, anemia and renal functional decline. These studies, along with our previous work highlight the potential of targeting fatty-acid GPCR’s, notably GPR84, for the treatment of inflammation/fibrosis related kidney diseases.
P0713DIFFERENTIAL PREDICTION OF DECLINE IN GFR IN PROTEINURIC VS NON-PROTEINURIC DIABETIC PATIENTS
Authors: Tanaka Hiroshi
Published: June 2020

Background and Aims

Diabetes mellitus (DM) is known to cause a progressive loss in renal function in at leaset 2 types of clinical presentation: classical diabetic nephropathy with overt proteinuria and non-proteinuric kidney diseases. The mechanisms of the progression should be multifactorial and are considered different at least in some ways in each patient. Now it is important to predict whether each diabetic patient has progressive renal disease or not, hopefully before overt proteinuria appears.

Method

A hospital-wide study with all the laboratory data for a period of 4 years and 2 months was conducted. A total of 2,804 non-dialysis patients with an age 18 or more in whom the eGFR slope was calculated over 731 days or more with HbA1c measured at least twice were retrieved. Medians were used for each laboratory datum, including dipstick proteinuria and haematuria (both changed to numeric variables, e.g. 1+ into 1.0), blood cell count, serum chemistry, and HbA1c. Medication class counts were defined as a total number of groups (DPP4, SGLT2, SU, .. ) where insulin was classified into 3 groups (rapid, mixed, and basal); the required prescription period was 3 months or more for each class. Statistical analysis was performed with R 3.6.0 on Ubuntu. For prediction, missing values were imputed by an R package {mice}.

Results

A total of 2,804 patients (M:F = 1375:1429, age 66.9+-13.6 (18--101, median 68) years) were analyzed whose median HbA1c was 6.14+-0.79 (3.6-11.6, median 5.95)%.

This population was further divided into a proteinuric group (the median of dipstick proteinuria of 1+ or more, n=296) and a non-proteinuric group (the median of dipstick proteinuria of +- or less, n=2508). In the multivariate analysis, the proteinuric DM patients had the eGFR slope associated with initial eGFR, proteinuria, uric acid, and the number of classes of the anti-diabetic medications; higher uric acid and less number of DM medication were significantly associated with faster decline in eGFR. The non-proteinuric DM patients had eGFR slope associated with age, initial GFR, uric acid, chloride, and haemoglobin, but not with proteinuria; the patients with higher uric acid with lower haemoglobin had significantly faster decline in eGFR (-1.86 vs -1.34, P = 0.013). Prediction of faster eGFR decline was analyzed with machine learning technologies, ie, {ranger} and {randomForest}, where precision was 68.9%/67.9% (proteinuric group, ranger/randomForest) vs 76.8%/75.9% (non-proteinuric group, ranger/randomForest).

Conclusion

Propensity to lose kidney function is different in each diabetic patient, which should to be ideally predicted in individual basis.
P0731LOW BIRTH WEIGHT IS ASSOCIATED WITH LOWER MEASURED GLOMERULAR FILTRATION RATE IN ADULT AGE
Authors: Lillås Bjørn Steinar , Tã¸ndel Camilla , Vikse Bjørn Egil
Published: June 2020

Background and Aims

Low birth weight (LBW) has been shown to increase the risk of severe kidney disease. Studies have also shown that LBW is associated with lower estimated glomerular filtration rate (eGFR) or creatinine clearance in young adults. In the present study we investigated whether LBW associate with measured glomerular filtration rate (mGFR) in 40-50 year old adults.

Method

Retrospective longitudinal cohort study using the Medical Birth Registry of Norway to invite 200 individuals with LBW (birth weight ≤ 2300 gram) and 200 individuals with normal birth weight (NBW, 3500 – 4000 grams). All participants were aged 41 – 52 at time of examination. GFR was measured using plasma clearance of iohexol. Birth weight and gestational age were reported from the Medical Birth Registry. Main outcome was difference in measured GFR.

Results

We included 105 individuals – 57 LBW and 48 NBW – 55% females. Mean GFR was 94.8 ± 14.2 ml/min/1.73m2 in the LBW group and 100.2 ± 12.5 ml/min/1.73m2 in the NBW group (p=0.043). In females the mean GFR was 90.4 ± 12.2 ml/min/1.73m2 in the LBW group and 100.5 ± 14.0 ml/min/1.73m2 in the NBW group (p=0.005). In males the mean GFR was 101.4 ± 14.5 and 100 ± 11.2 ml/min/1.73m2 in the LBW and NBW groups respectively (p=0.7). In a multi-regression model adjusting for age, maternal age and maternal civil status, we found an increase in mGFR of 4.5 ml/min/1.73m2 for an increase of 1 kg in birth weight (p= 0.02) for women. For men there was a non-significant decrease of 1.2 ml/min/1.73m2 for an increase of 1 kg in birth weight (p=0.6).

Conclusion

Women aged 41-52 years with low birth weight had significantly lower measured GFR as compared with participants with normal birth weight, there was no difference for men.
P0734THE DELETION OF AKT1 PROMOTES THE RENAL FIBROSIS IN THE MURINE MODEL OF UNILATERAL URETERAL OBSTRUCTION
Authors: Kim Il Young , Ye Byung Min , Kim Min Jeong , Lee Dong Won , Lee Soo Bong , Song Sang Heon , Seong Eun Young
Published: June 2020

Background and Aims

Previous studies have found the increased Akt activity in experimental renal fibrosis. We investigated the role of Akt1, one of the three Akt isoforms, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO).

Method

In vivo, we subjected the wild type and Akt1−/− mice to UUO. In vitro, gene silencing of Akt1 was achieved using the short hairpin RNA delivered by the lentiviral vector in immortalized human proximal tubular cells (HK2 cells) and rat kidney fibroblasts (NRK-49F cells).

Results

In immunohistochemical stain, the expression of Akt1 was significantly higher in obstructed kidneys of wild type mice compared with control sham kidneys and increased gradually as UUO progressed. The fibronectin, type I collagen, and heat shock protein 47 (HSP47) were markedly more expressed in obstructed kidneys of Akt1−/− mice than in those of the wild type mice. Transforming growth factor β1 (TGFβ1) was highly induced within 1 day of UUO in obstructed kidneys of Akt1−/− mice and the expression of TGFβ1 was significantly higher in the Akt1−/− mice than in the wild type mice as UUO progressed. Western blot showed that silencing of Akt1 increased the expression of TGFβ1, which was enhanced by angiotensin II stimulation in HK2 cells, but not in NRK-49F cells. Immunohistochemical stain demonstrated that the expression of cleaved caspase-3 in renal tubules was significantly higher in the Akt1−/− mice than in the wild type mice. Western blot showed that silencing of Akt1 increased the expression of cleaved caspase-3 in HK2 cells, but not in NRK-49F cells.

Conclusion

Our findings suggest that the deletion of Akt1 might contribute to tubulointerstitial fibrosis and tubular apoptosis via TGFβ1 induction. We also showed that TGFβ1 upregulation by genetic deletion of Akt1 is associated with activation of STAT3 independently of the TGFβ1/Smad signaling pathway.
P0736A NOVEL MODEL OF CHRONIC KIDNEY DISEASE AND HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Chade Alejandro , Williams Maxx , Engel Jason , Hall Michael
Published: June 2020

Background and Aims

Patients with chronic kidney disease (CKD) have a significantly higher cardiovascular risk that non-CKD patients, and over 50% of CKD patients die of cardiovascular events. We recently developed a model of CKD that displays major pathological features of clinical CKD: GFR of about 60 ml/min (stage 2-3a), significant renal inflammation, fibrosis, microvascular dysfunction and remodeling, and hypertension. The current study aims to define the cardiac phenotype of this model and, if cardiac abnormalities are present, the potential pathological traits involved.

Method

CKD was induced in 6 pigs via bilateral renovascular disease and dyslipidemia and observed for 14 weeks. After 14 weeks, renal hemodynamics (RBF, GFR) were quantified using multi-detector CT and echocardiographic assessment (morphology and function) performed using ultrasound-doppler. Mean arterial pressure (MAP) was continuously measured by telemetry. Blood was collected to measure circulating inflammatory cytokines (TNF-α, MCP-1, IL-6) and biomarkers of heart failure (ANP, BNP, NT-proBNP). Animals were then euthanized and kidneys and hearts collected for ex vivo studies. Normal pigs were used as time-matched controls.

Results

Loss of renal function in CKD was accompanied by left ventricular hypertrophy, left atrial dilatation, diastolic dysfunction (E/A ratio) with preserved ejection fraction (pEF), elevated ANP, BNP, and NT-proBNP, and hypertension (average MAP of 131.2 mm/Hg, p<0.05 vs. normal). CKD also increased renal (but not cardiac) mRNA expression of TNF-α, MCP-1, IL-6, accompanied by increased circulating inflammatory cytokines (Figure).

Conclusion

This study shows that CKD in the swine model leads to cardiac hypertrophy and diastolic dysfunction (with pEF) and increased biomarkers of heart failure, meeting the criteria for a potential novel model of heart failure with pEF (HFpEF). Our data also suggest that hypertension and inflammatory mediators (possibly originated in the kidney) target the heart and may contribute to HFpEF pathophysiology. HFpEF is considered the largest unmet need in cardiology with no specific treatments and associates with CKD in about 50% of cases. Thus, our study offers a promising new experimental platform to increase our understanding of CKD-HFpEF and to test new treatments in a translational fashion.
P0737THE ASSOCIATION BETWEEN CYSTATIN C AND ARTERIAL STIFFNESS IN NON-CKD PATIENTS
Authors: Piko Nejc , Petreski Tadej , Ekart Robert , Hojs Radovan , Bevc Sebastjan
Published: June 2020

Background and Aims

Serum cystatin C (cysC) is produced by all nucleated cells at a constant rate, is filtered freely by the glomerulus and metabolized after tubular reabsorption. It is influenced less by age, gender and muscle mass compared to serum creatinine. These properties make it an important marker in detecting renal impairment. Arterial stiffness is a hallmark of atherosclerosis and is connected to cardiovascular events and mortality. In patients with chronic kidney disease (CKD), cysC correlates with increased arterial stiffness, but less is known about the association between cysC and arterial stiffness in non-CKD patients.

Method

The study was performed at the University Medical Centre Maribor between October 1st 2018 and January 1st 2020. Basic demographic and laboratory data were recorded. To estimate glomerular filtration rate (eGFR), Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used. Patients with previously diagnosed CKD and/or eGFR ≤ 60 ml/min/1.73m2 at the time of admission, known malignancy, thyroid disease and/or on steroid therapy were not enrolled in the study. Arterial stiffness was measured with applanation tonometry (Sphygmocor®, Australia), carotid-femoral pulse wave velocity (cfPWV) was used as the gold standard of central arterial stiffness and subendocardial viability ratio (SEVR) was used as the marker of myocardial perfusion. SPSS® version 22 was used for statistical analysis.

Results

111 patients (65.8% male, average age 64.3±9.4 years) were included in our study. Most common comorbidities were arterial hypertension (n=86, 77.5%), hyperlipidaemia (n=64, 57.7%) and diabetes mellitus (n=22, 19.8%). Mean creatinine value was 77.7±13.8 μmol/L (range 49-108 μmol/L), mean eGFR was 81.3±9.4 ml/min/1.73m2 (range 62-90 ml/min/1.73m2) and mean value of cysC was 0.94±0.18 mg/L (range 0.67-1.63 mg/L). Mean SEVR value was 165.7±36.1% (range 92-299%) and mean cfPWV value was 10.1±2.4 m/s (range 6.2-16.8 m/s). Significant correlation was found between cysC and SEVR (r=-0.316, p<0.001) and between cysC and cfPWV (r=0.472, p<0.001). Multiple regression analysis of arterial stiffness indices and cysC, age, gender, diabetes mellitus, arterial hypertension, eGFR and hyperlipidemia, showed statistically significant association between cysC and cfPWV (ß=0.220, p=0.038) and cysC and SEVR (ß=-0.278, p=0.017).

Conclusion

Serum cysC is independently associated with increased arterial stiffness, reduced myocardial perfusion and increased cardiovascular risk in non-CKD patients.
P0741CHRONIC KIDNEY DISEASE PROGRESSION IN A LARGE PREVENTION COHORT IN COLOMBIA
Authors: Rivera Angela , Bernardo Angelito , Vesga Jasmin , Ronderos Izcay , Sanabria Mauricio
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) is a syndrome that today has important implications for the health of populations and the economic sustainability of health systems around the world, therefore strategies to slow disease progression are necessary.

Aims: To estimate the incidence of renal replacement therapy (RRT) in a cohort of patients included in a CKD secondary prevention program and to describe the decrease of the estimated glomerular filtration rate (eGFR).

Method

This is a historical, multicenter, observational cohort study in a prevention program between January 1, 2010, and December 31, 2017, with follow-up until December 31, 2018, at the Renal Care Services (RCS) network. Socio-demographic and clinical characteristics of all patients were summarized descriptively. We estimated the incidence of RRT rate with Kaplan Meier analysis. Progression rate to RRT was analyzed by mixed-effects model adjusted for the eGFR reduction rate at 180 days; the model considered the diagnosis of diabetes.

Results

7131 patients met the inclusion criteria for data analysis. The mean age was 65 years, 50.5% were female, (Table 1). There were 577 events of RRT with a rate of 2.02 events of RRT per 100 patients-year [95% CI,1.86 to 2.19], characteristics at the RRT initiation are presented in Table 2. At the beginning of the program the eGFR was 45.3 ml / min / 1.73m2 in non-diabetics, and 40.9 3 ml / min / 1.73m2 in diabetics. The CKD progression was - 0.48 ml / min / 1.73m2 per 180 days in diabetics and - 0.20 ml / min / 1.73m2 per 180 days in non-diabetics. The final events of the cohort are presented in Figure 1; the mortality rate was 0.89 events per 100 patients-year [95% CI, 0,79 to 1,01].

Conclusion

This population of patients in a CKD prevention program presented a low rate of initiation of dialysis therapy and a slight decrease of eGFR; the diabetic status influences the CKD progression.
P0743COMPARISON OF PROTEINURIA LEVELS BETWEEN PROFESSIONAL AND RECREATIONAL CROSSFIT ATHLETES
Authors: Diniz Renan , De Francesco Daher Elizabeth , Bezerra da Silva Junior Geraldo , Nunes Filho Julio Cesar Chaves , Nunes Marilia Porto Oliveira
Published: June 2020

Background and Aims

High intensive sports athletes are under risk of muscular injuries and likely renal damage secondary to it. As CrossFit is becoming more popular in last years, few consistent studies are available evaluating renal damage associated to this sport. The purpose of this study was to compare proteinuria levels between recreational and professional CrossFit athletes who were under training for a local competition.

Method

These athletes were invited to answer a survey. After this step, they were submitted to proteinuria analysis through urine dipstick reading. They also were divided into two groups (professional X recreational athletes) and the results were compared using chi-square test.

Results

A total of 99 athletes have concluded all the steps of the study. Among professional athletes, age average was 34.1 +3.9 year old, body mass index (BMI) 27.14 + 3.14 kg/m2 while in the recreational group the age average was 28.7 + 5.9 and BMI 26.49 + 4.56 kg/m2. Comparing proteinuria analysis, 44.4% of professional group have shown levels between 300 and 1000mg/dL and 14.8% have reached levels above 1000mg/dL, while only 2.8% among recreational ones have reached levels above 300mg/dL (p=0.001) with no one in this groups showing levels > 1000mg/dL.

Conclusion

This study has shown high proteinuria levels among professional CrossFit athletes comparing to recreational ones. As the literature is scarce in showing long-term kidney damage among CrossFit athletes, epidemiological studies warn about likely kidney damage related to this practice, a fact that can suggest better medical follow-up for CrossFit athletes.
P0744CLINICAL IMPACT OF SERUM INDOXYL SULPHATE MEASURED BY NEW ENZYMATIC METHOD IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Yasuda Yoshinari , Kikuchi Ryosuke , Goto Kazunori , Kaihan Ahmad Baseer , Kato Sawako , Maruyama Shoichi
Published: June 2020

Background and Aims

Uremic toxins have been highlighted as serious risk factors for deterioration of renal function and onset/progression of cardiovascular diseases (CVD). Serum level of indoxyl sulphate (IS), a major uremic toxin, was demonstrated its significant association with vascular disease and mortality in a cohort of chronic kidney disease (CKD) patients, however, IS has not been available in clinical setting due to time consuming and expensive measurement cost. Recently epoch-making IS measurement method applicable for general auto analyzer has been developed, which could explore new therapeutic avenue in CKD from the view point of uremic toxin management.

In this study, clinical utility of new enzymatic IS measurement method was analyzed in association with renal function and CVD among CKD patients.

Method

Subjects were consecutive 150 CKD patients in Nagoya University Hospital whose serum samples were collected between 2009 and 2014. Serum IS levels were measured by “NIPRO” reagent and analyzed with eGFR, CVD events and renal outcomes defined by 30% decrease in eGFR.

Results

Characteristics of patients were 69 ± 10 years old, 29% female, eGFR: 44 ± 20 mL/min/1.73m2 (∼G3a: 43％, G3b: 29％, G4: 24％, ï¼§5: 4％), proteinuria 2.8 ± 3. 5ï½‡/ï½‡Cr (A1: 29％, A2: 29％, A3: 42％), HTN: 83％, and DM: 39％. Serum IS levels (μmol/L) were 10.5 ± 7.5 (∼G3a: 1.8 ± 0.6, G3b: 2.1 ± 0.6, G4: 15.8 ± 8.1, ï¼§5: 22.9 ± 13.5), and strongly correlated with eGFR (r =0.518, P<0.001). Among IS low (<6), middle and high (≥12) tertiles, significantly different factors were age, eGFR, Hb, iPTH and LDL-C. In multiple logistic regression analysis, only eGFR was significant associating factor with IS tertiles. IS levels in 2 patients prescribed AST-120 (Kremezin) were 8.1 and 10.3, which seems to be very low in comparison to their eGFR of 13.8 and 13.7. During observation period of 5.1 ± 1.0 years, 59 renal outcomes and 9 CVD events were observed. Kaplan-Meier survival curve analysis free from renal outcomes revealed better tendency in IS low group (p= 0.0617 in log-rank test). According to IS levels adjusted by eGFR, only 1 out of 9 CVD events occurred in low IS/eGFR tertile group.

Conclusion

Serum IS levels could be measured in new enzymatic method. Strong correlation between IS and eGFR was demonstrated, and AST-120 might be effective to improve IS. In renal and CVD outcome analysis, more sample size is needed for further study.
P0756THE RELATIONSHIP BETWEEN ABDOMINAL AORTIC CALCIFICATION AND PROGRESSION OF RENAL INSUFFICIENCY IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: KIM SO MI , Cho Jong Tae , Jeon Ji Hyun , Lee Yong-Moon , Lee Eun Kyoung , Lee Hwa Young
Published: June 2020

Background and Aims

Although abdominal aortic calcification (AAC) is known to be associated with cardiovascular mortality in patients with chronic kidney disease (CKD), there are little information about the impact of AAC on progression of CKD. Therefore, we investigated the relationship between the AAC and progression of renal insufficiency in CKD patients with early stage.

Method

A total of 183 patients with CKD, stage 3 was included. The degree of AAC was evaluated by computed tomography and the score was calculated as follows: abdominal calcification index (ACI)= (total score of calcification on all slices)/12 × 1/(number of slices) × 100%. Based on tertile of ACI, the patients were divided into three groups: low-, intermediate-, and high-groups. The annual decline of glomerular filtration rate (GFR) and time to dialysis were assessed.

Results

The AAC was found (ACI > 0) in 129 patients (70.4%), and the mean ACI was 21.3 %. The average duration of follow-up was 46.9 months. The high ACI group showed higher annual decline in GFR compared to other groups (27.8 vs 14.5 vs 11.3 mL/min, p=0.042). During the follow-up, 68.8% (42/61) of high ACI group received dialysis and the time to dialysis was significantly shorter than other groups (14.8 vs. 25.8 vs.29.1 months, p=0.038)

Conclusion

In this study, we showed the AAC was associated with rapid progression of CKD. Evaluation of the AAC in CKD with early stage provides useful information for predicting the progression of CKD.
P0757THO ROLE OF MARKERS TO ASSESS RISK FOR DEVELOPING CARDIORENAL SYNDROME
Authors: Tasic Danijela , Radenkovic Sonja , Kocic Gordana , Poskurica Mileta , Stojanovic Dijana
Published: June 2020

Background and Aims

Biomarkers are circulating proteins and metabolites, which are released in the body fluids from the damaged organ or tissue is detected specific essays and plays a role in the diagnosis, evaluation and monitoring of patients. Today there is a large number of markers that assess the intensity of pro-inflammatory and oxidative processes in the cardio-renal syndrome, whose determination would have great diagnostic and prognostic significance. The aim of our investigation was to identifying which of the examined parameters stand out as independent risk factors for the development of the cardiorenal syndrome (CRS).

Method

The study included 114 subjects older than 18 years, of both sexes, divided into clinical and control group. The control group was consisted of 35 healthy males and females with similar characteristics as well as clinical groups. The clinical group was consisted of 79 patients: 40 (50.63%) male and 39 (49.37%) female, mean age of 70.72 ± 9.26 years, diagnosed on the basis of the current classification of cardiorenal syndrome. The respondents were familiar with the case studies and signed informative consent. The study was approved by the Ethics Committee and conducted in compliance with the Helsinki Declaration on Medical standards of Good Clinical Practice.

Results

With correlation analysis of examined biomarkers in respondents of the clinical group was established positive correlation between plasma BNP and IL-8 (r = 0.383, p = 0.006), BNP and cTnhsT (r = 0.518, p = 0.001) BNP and cystatin C (r = 0.447, p = 0.001) and BNP and CRP (r = 0.306, p = 0.046), while a negative correlation was observed between the BNP and the activities of MDA (r = - 383, p = 0.007). Negative correlations were also between the activity of the MDA and the IL-8 concentration (r = -0.237, p = 0.038), and MDA cTnhsT (r = -0.321, p = 0.009) and MDA and cystatin C (r = -0.315, p = 0.005 ). XOD activity cost was positively correlated with the XD (r = 0.942, p <0.001), and the activity of XO was positively associated with TnI (r = 0.522, p = 0.009) and negatively correlated with the XD (r = -0.423, p <0.001 ). The concentration of IL-8 was positively associated with cTnhsT concentrations (r = 0.427, p <0.001) and with concentrations of CRP (r = 0.411, p = 0.001), the concentration of PAI-1 with cTnhsT concentration (r = 0.558, p <0.001), with TnI concentration cTnhsT (r = 0.852, p <0.001), and cTnhsT with cystatin C (r = 0.338, p = 0.006) and CRP (r = 0.358, p = 0.011). Cystatin C stood positively related to the concentration of CRP (r = 0.510, p <0.001).

Conclusion

Early detection of occurrence of functional and structural damage to the heart and kidneys, highly sensitive and specific markers would enable not only their discovery, but also prevention and treatment.
P0765RHEUMATOID ARTHRITIS AND CHRONIC KIDNEY DISEASE: DOES INFLAMMATION SAY IT ALL?
Authors: Reis Marina Sofia Rodrigues , Salvador Pedro , Gomes Ana Marta , Beça Sara , Fernandes João Carlos
Published: June 2020

Background and Aims

Rheumatoid arthritis (RA) increase risk of developing chronic kidney disease (CKD), but it is unknow which risk factors contributes to CKD in this population. This study aims to determine predictors for the development of CKD in RA patients.

Method

A retrospective study was conducted in 106 patients with RA followed at a sub-specialized internal medicine appointment between January 2007 and December 2017. RA was defined according to the American College of Rheumatology criteria and CKD was defined as an estimated glomerular filtration rate less than 60mL/min/ 1.73m2 or presence of abnormalities of urinary sediment for 3 months.

Results

The mean age was 61 ± 12.83 years, and 67.9% (n=72) were female. The prevalence of CKD was 20.8% (n=22). Renal disease had multifactorial etiology in 20 patients, and one case of ANCA negative glomerulonephritis and other of diabetic nephropathy. Individuals with RA and CKD were older, presented more cardiovascular disease, diabetes and hypertension. There was no statistically significant association between gender and the presence of CKD (p = 0.131). Age (p = 0.031) and diabetes (p = 0.031) were independent risk factors for development of CKD in RA patients. RA duration in patients with CKD (8, 4-13) was not statistically different from RA duration in non-CKD patients (7.50, 4,75 – 12,25), (p=0.890).

Conclusion

Patients with RA and CKD had higher incidence of cardiovascular events, diabetes and hypertension which are a major cause of mortality and morbidity in this group. The presence of diabetes mellitus that often arise as an adverse effect of drugs used in the treatment of RA, significantly increased the risk of developing CKD. Otherwise, RA duration didn’t represent a risk factor for developing CKD. Thus, it is important to control diabetes, particularly glucocorticoid-induced diabetes to prevent development of CKD in AR patients.
P0773ESTIMATING THE BURDEN OF CHRONIC KIDNEY DISEASE (CKD) IN THE UK: COMPARISON OF TWO HEALTH ECONOMIC POLICY ANALYSIS METHODS
Authors: Garcia Sanchez Juan Jose , Xu Michael , Sörstadius Elisabeth , Darlington Oliver , McEwan Phil , Lande Simon , Pearson-Stuttard Jonathan , Webber Laura
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) represents an important health policy concern due to a growing population and its associated morbidity and mortality. Predicting the future burden of CKD overall and in high-risk populations such as patients with elevated albuminuria, type 2 diabetes (T2D) or heart failure (HF) is important if healthcare services are to be resourced properly. Health economic policy models based on epidemiological and clinical outcomes data provide a useful way by which to make such predictions; different methods of varying complexity have been employed to do this. This study aims to compare two different analytical approaches to estimating the burden of CKD in the UK, and to estimate how this is predicted to change in the future.

Method

Analysis 1 and 2 characterised the prevalent and incident CKD population, disease progression, clinical outcomes, costs and quality of life sourced from published data over a 5-year horizon.

Analysis 1 utilised an open cohort analysis based on a Markov framework, with health states defined by CKD stages. Disease progression was modelled through the application of published estimates of the rate of estimated glomerular filtration rate (eGFR) decline, stratified by the presence of T2D, HF and albuminuria.

Results

Conclusion
P0774KIDNEY FUNCTION, KIDNEY FUNCTION DECLINE AND THE RISK OF ALL CAUSE, VASCULAR AND ALZHEIMER'S DEMENTIA: THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT
Authors: Xu Hong , Trevisan Marco , Evans Marie , Lindholm Bengt , Carrero Juan Jesus
Published: June 2020

Background and Aims

Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk are conflicting. In this large Swedish population-based cohort, we explore the links between kidney function, kidney function decline and dementia incidence.

Method

In the Stockholm CREAtinine Measurements (SCREAM) project, we studied the association of baseline eGFR with the risk of incident dementia among 329,822 residents of Stockholm who accessed healthcare, were ≥65 years and had no previous history of dementia. We estimated the rate of eGFR decline among the 205,622 residents with repeated eGFR measurements during the first year and investigated its association with dementia risk. The primary outcome was dementia incidence based on ICD-10 codes or use of anti-dementia drugs. Secondary outcomes were incidence of the dementia subtypes Alzheimer’s and vascular dementia.

Results

18,983 cases of dementia (5.8% of participants) were detected throughout 1,185,304 person-years. Dementia incidence rates (IR) were progressively higher with lower eGFR: from 6.56/1000 person-years in persons with eGFR 90-104 ml/min to 30.28/1000 person-years in those with eGFR<30 ml/min). Compared with eGFR of 90-104 ml/min, lower eGFR was associated with a higher dementia risk [adjusted hazard ratio (HR), 1.69; 95% confidence interval (CI], 1.52-1.89 in eGFR 30-59 ml/min and HR 2.55, 1.86-3.50 in eGFR<30 ml/min). A steeper decline in eGFR within one year was linearly associated with higher dementia risk for declines greater than 2ml/min/1.73 m2/year. Risk magnitudes were stronger for vascular dementia than for Alzheimer. Sensitivity analyses across predefined strata or after excluding early events yielded similar results. As many as 11% (95% CI 7-14%) of dementia cases were attributed to chronic kidney disease (eGFR<60 mL/min/1.73m2), a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.

Conclusion

In the general population, both low kidney function and faster kidney function decline are associated with increased risk of developing dementia, particularly vascular dementia.
P0778INVESTIGATION THE EFFECT OF SERUM URIC ACID ON NEW-ONSET AND PROGRESSION OF CHRONIC KIDNEY DISEASE(CKD) IN JAPANESE GENERAL POPULATION : IKI EPIDEMIOLOGICAL STUDY OF ARTHEROSCLEROSIS AND CHRONIC KIDNEY DISEASE(ISSA-CKD) RETROSPECTIVE PHASE
Authors: Tada Kazuhiro , Maeda Toshiki , Takahashi Koji , Ito Kenji , Yasuno Tetsuhiko , Mukoubara Shigeaki , Masutani Kosuke , Arima Hisatomi , Nakashima Hitoshi
Published: June 2020

Background and Aims

Chronic kidney disease is one of the most urgent public health issue in Japan as well as other countries. Many risk factors for development and progression of CKD have been recognized, such as hypertension, diabetes, obesity. However, it is still unclear whether increase of serum uric acid has negative impact on kidney function. The aim of this study is to investigate how serum uric acid influences the new-onset and progression of CKD in Japanese general population.

Method

The Iki epidemiological Study of atherosclerosis And Chronic Kidney Disease (ISSA-CKD) is a population-based retrospective cohort study using annual health check-up data in the Iki Island (Nagasaki Prefecture, Japan), which has approximately 27,000 residents. A total of 7,645 residents underwent annual health check-ups from fiscal year 2008 to 2016. After excluding residents who visited only 1 health check-up and those with missing information of serum creatinine or serum uric acid, a total of 5507 adults were included in the present analysis. The outcome of the present analysis was new-onset of CKD (reduction in estimated glomerular filtration rate [eGFR] less than 60mL/min/1.73m2 or development of proteinuria among participants without CKD at baseline) and CKD progression (worsening of the stages of eGFR or proteinuria according to the KDIGO guideline among participants with CKD at baseline).

Results

During a mean follow-up of 4.6 years, 757 (16.7%) new-onset CKD and 193 (19.7%) progression of CKD were observed. Serum uric acid had significant relationship with new-onset CKD even after adjustment for sex, age, obese, hypertension, dyslipidemia, and diabetes mellitus: hazard ratio 1.14 per 1 mg/dL increase, 95% confidence interval 1.07-1.21, P<0.001). On the other hand, serum uric acid did not have significant relationship with CKD progression: hazard ratio 1.08 per 1 mg/dL increase, 95% confidence interval 0.96-1.21, P=0.190). Similar results were observed for hyperuricemia defined as serum uric acid level ≥7mg/dl.

Conclusion

The findings of the present analysis show that serum uric acid was significantly associated with increased risks of new onset of CKD, but was not associated with progression of CKD in Japanese general population.
P0779THE POPULATION ATTRIBUTABLE FRACTION OF HYPERURICEMIA FOR ALL-CAUSE AND CARDIOVASCULAR MORTALITY: A NATIONWIDE COMMUNITY-BASED STUDY
Authors: Tanaka Tomomi , Tanaka Tomomi , Miyata Masahiro , Ichikawa Kazunobu , Konta Tsuneo , Fujimoto Shouichi , Iseki Kunitoshi , Moriyama Toshiki , Yamagata Kunihiro , Tsuruya Kazuhiko , Narita Ichiei , Kondo Masahide , Yugo Shibagaki , Kasahara Masato , Asahi Koichi , Watanabe Tsuyoshi
Published: June 2020

Background and Aims

Hyperuricemia is often observed in subjects with chronic kidney disease and is associated with all-cause and cardiovascular mortality. In this study, we evaluated the effect size of hyperuricemia for all-cause and cardiovascular mortality in a community-based population, using the index of population attributable fraction (PAF).

Method

This large-scale cohort study used the nationwide database of 500,511 health check-up participants (215,728 men, 284,783 women, average age 62 years) and calculated the PAF of hyperuricemia (serum uric acid >7 mg/dL) for all-cause and cardiovascular deaths during the 7-year follow-up period.

Results

The frequency of hyperuricemia at baseline was 9.7% in total subjects (men: 22.0%; women: 2.6%). During the follow-up period, 5,578 deaths (1.1%) were noted (men: 3,749 [1.7%], women: 1,829 [0.6%]), including 1,104 cardiovascular deaths (0.2%) (men: 762 [0.4%], women: 342 [0.1%]). In the Cox proportional hazard analysis adjusted for confounding factors including age, gender, body mass index, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia and eGFR, hyperuricemia was an independent risk factor for all-cause and cardiovascular mortality, (adjusted hazard ratios [95% confidence interval]; 1.39 [1.27-1.53] for all-cause mortality, and 1.76 [1.47-2.11] for cardiovascular mortality). The adjusted PAF of hyperuricemia for all-cause and cardiovascular deaths were 3.1% and 4.7% (approximately 1 in 32 all-cause deaths, and 1 in 21 cardiovascular deaths), respectively. In subgroup analyses, the association between hyperuricemia and death was stronger in men and smokers. The adjusted PAF for all-cause and cardiovascular deaths was 5.5% and 8.6% (approximately 1 in 18 all-cause deaths, 1 in 12 cardiovascular deaths) in men, and 6.2% and 8.2% (approximately 1 in 16 all-cause deaths, 1 in 12 cardiovascular deaths) in smokers, respectively.

Conclusion

This study showed that a substantial number of all-cause and cardiovascular deaths, was statistically attributed to hyperuricemia in the community-based population, especially men and smokers.
P0784RAPID WEIGHT CHANGE OVER TIME IS A RISK FACTOR FOR ADVERSE OUTCOMES IN PREDIALYSIS CHRONIC KIDNEY DISEASE: RESULTS FORM KNOW-CKD STUDY
Authors: Ryu Hyunjin , Hong Yeji , Kang Eunjeong , Kang Minjung , Kim Jayoun , Oh Yun Kyu , Yang Soo Jin , Ahn Curie , Oh Kook-Hwan
Published: June 2020

Background and Aims

Both obesity and underweight are related to the adverse outcomes in the chronic kidney disease (CKD). However, the effects of longitudinal weight changes on predialysis CKD population has not been studies so far. In this study, we analysed the effects of longitudinal body weight changes on the adverse outcomes in the predialysis CKD population, using the multicentre prospective cohort study in Korean pre-dialysis CKD cohort, so called KNOW-CKD.

Method

In this longitudinal analysis, total 2,022 patients were included. Longitudinal weight changes of study population were calculated into the percent change per year using regression analysis and classified into five groups: group 1; ≤ -5%/year (74 subjects), group 2; -5< to ≤-2.5 %/year (122 subjects), group 3; -2.5< to <2.5%/year (1642 subjects), group 4; 2.5≤ <5 %/year (123 subjects), and group 5; ≥ 5 %/year (61 subjects). The risk of end-stage renal disease (ESRD) development and composite outcome of cardiovascular disease (CVD) and all-cause death were compared according to the longitudinal weight changes.

Results

During the median 4.4 years of follow-up, total 414 and 188 events of ESRD and composite outcome of CVD and death occurred. When cause-specific regression analysis was conducted before and after adjusting age, sex, body mass index, mean blood pressure, estimated glomerular filtration rate, urine albumin-to-creatinine ratio, diabetics, cardiovascular disease, and modified Charlson Comorbidity Index score, all groups showed significant increased HR compared to group 3 for the ESRD. There was U-shape correlation between the degree of longitudinal body weight changes and the renal outcome (HR 3.89, 2.00, 1.89 and 3.34, P <0.001, <0.001, =0.001 and <0.001 for group 1, 2, 4 and 5, respectively). Also similar U-shape relationship was seen with composite outcome, (HR 3.14, 2.05, 1.65 and 2.68, P <0.001, 0.007, 0.123 and 0.007 for group 1, 2, 4 and 5, respectively) when compared to the reference group 3 When spline curve was drawn between the longitudinal body weight changes and adjusted HR for ESRD and composite of CVD and death, clear U-shape relationship was observed (Figure). The U-shape correlation was highlighted in the subgroup of estimated glomerular filtration rate <45 mL/min/1.73m2.

Conclusion

Both rapid weight reduction and gain are independent risk factor for the ESRD development and composite outcome of CVD and death in predialysis CKD patients, especially in advanced CKD stages. Therefore, monitoring bodyweight changes are important and more studies are needed to give safe guideline to the predialysis CKD for maintaining optimal nutritional status.
P0786CLINICAL SIGNIFICANCE AND RELATED FACTORS OF GFR SLOPE IN A LARGE MULTICENTER OBSERVATIONAL STUDY IN JAPAN
Authors: Kamijo Yuji , Hashimoto Koji , Yamada Yosuke , Harada Makoto , Aida Masatsugu , Yamauchi Shitotomo
Published: June 2020

Background and Aims

Recently, glomerular filtration rate (GFR) slope has attracted attention as an important surrogate marker for the prognosis of chronic kidney disease (CKD), with a reduction in slope of eGFR decline by 0.75 mL/min/1.73 m2 per year reportedly having clinical significance. As few large clinical studies on Japanese CKD patients exist, this investigation addresses the clinical significance of GFR slope and its related factors.

Method

To evaluate the clinical impact of GFR slope, we conducted a prognostic investigation of CKD patients in Japan by means of a large, multicenter, retrospective, observational study. Patients with CKD who were seen at among 15 general hospitals between January and March 2014 were surveyed using medical records. The selection criteria were age ≥20 years, estimated GFR (eGFR) <60 mL/min/1.73 m2, and receiving medical treatment for CKD. Baseline patient characteristics, eGFR changes, and hard endpoints (death or end-stage kidney disease requiring renal replacement therapy) during observation were analysed. We calculated GFR slope using GFR data of 2 years following the observation start point by 2 calculation methods, the linear mixed model and least squares linear regression, and examined the relationship of GFR slope with the hazard ratio of the composite hard endpoints. The factors related to GFR slope were also assessed by multiple regression analysis.

Results

Among a total of 11233 collected patients, we analyzed the data of 7490 CKD G3 and G4 patients whose GFR data during 2 years could be obtained (60% male, mean age: 71 years, CKD G3a: 55%, G3b: 30%, G4: 15%, mean eGFR: 44.1 mL/min/1.73 m2, urine protein positive: 51%, diabetes mellitus: 49%, use of RAS inhibitors: 57%). The mean observation period was 1040 days. Hard endpoints after the GFR slope measurement period occurred in 301 subjects. The GFR slope of the cohort was -0.948 mL/min/1.73 m2 per year (95% confidence interval [CI] -1.016, -0.880) in the linear mixed model and -0.982 mL/min/1.73 m2 per year (95% CI -1.075, -0.889) according to least squares linear regression. Both calculated GFR slopes were significantly related to the hazard ratio of the composite hard endpoints. Hazard ratio decreased by 0.85 (linear mixed model) and 0.9 (least squares linear regression) times in case of a reduction in slope of eGFR decline by 0.75 mL/min/1.73 m2 per year. Multiple regression analysis revealed strongly significant associations for GFR slope with urine protein and CKD stage and undetectable relationships for GFR slope with diabetes and age.

Conclusion

This study demonstrated the clinical significance of GFR slope as a surrogate marker for renal prognosis in Japanese CKD patients. In order to reduce slope of eGFR decline, active intervention for proteinuria before the progression to an advanced CKD stage appears to be effective.