bluuebunny/crossref_metadata_2025 huggingface dataset:
P0709RENAL OUTCOMES AND MORTALITY FOLLOWING TRANSCATHETER AORTIC VALVE IMPLANTATION IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Shabaka Amir , Lucena Valverde Rafael , Escudero Andres , Tirado-Conte Gabriela , Nombela Franco Luis
Published: June 2020

Background and Aims

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

Method

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

Results

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

Conclusion

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

Background and Aims

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

Method

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

Results

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

Conclusion

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

Background and Aims

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

Method

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

Results

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

Conclusion

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

Background and Aims

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

Method

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

Results

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

Conclusion

Plasma adiponectin concentration is only slightly affected by kidney function in elderly Caucasians from the PolSenior study.
P0733PULSE MASS PRESSURE PRODUCT AND GLOMERULAR HEMODYNAMIC FUNCTION IN HEALTHY ADULTS
Authors: Oba Rina , Kanzaki Go , Haruhara Kotaro , Sasaki Takaya , Okabayashi Yusuke , Yamamoto Izumi , Tsuboi Nobuo , Yokoo Takashi
Published: June 2020

Background and Aims

Recent studies have conflicting findings on the association between obesity and the risk of chronic kidney disease (CKD). BMI by itself is an imperfect marker of metabolically unhealthy obesity. The Pulse Mass Index (PMI) and the Pulse Mass Pressure Product (PMPP) show strong correlation with the risk of cardiovascular disease and may reflect an individual's metabolic energy state. However, it is still unknown whether the PMI and PMPP can be helpful to evaluate glomerular hyperfiltration or hypertrophy, which may exacerbate the progression of CKD. In this study, we measured mean glomerular volume (GV) and single nephron glomerular filtration rate (SNGFR) by estimating the number of nephrons from living kidney donors and we evaluated the effects of PMI and PMPP on glomerular hemodynamic function.

Method

We identified 43 living kidney donors at the Jikei University School of Medicine Hospital from 2007 to 2017 who underwent an enhanced CT scan and a kidney biopsy at donation. The GV was determined by Weibel-Gomez methods and the SNGFR was calculated as eGFR divided by the total number of non-sclerosed glomeruli. The PMI is equal to BMI by resting heart rate (RHR) divided by 1730 and The PMPP is equal to BMI by RHR by systolic blood pressure.

Results

Of 43 subjects, 34.9% were males and with a mean age of 56.1 ± 9.9 years old. Mean Arterial Pressure (MAP) was 86.3±9.9 mmHg, eGFR was 77.4±12.4 ml/min/1.73m2, and urinalysis was normal. The estimated total nephron numbers were 743,204±242,020 /kidney, and SNGFR was 61.7±20.5 nl/min/1.73m2. The GV was strongly associated with both of PMI and PMPP (P=0.0291 and 0.0326, respectively). Interestingly, SNGFR was only associated with PMPP (P=0.0443) but whereas not associated with either age, BMI, or MAP.

Conclusion

In healthy adults, we observed a strong positive correlation between PMPP and both GV and SNGFR. This study indicates that PMPP is a more suitable physical measurement for glomerular hyperfiltration or hypertrophy, and a possible maker of the relative risk of CKD at the long term.
P0749THE ASSOCIATION OF VISCERAL ADIPOSITY INDEX WITH PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Adibelli Zelal , Mizrak Soycan , Duran Cevdet
Published: June 2020

Background and Aims

Obesity is becoming an important health problem as its prevalence is increasing. Obesity is also a factor that causes an increase in chronic kidney disease (CKD) cases by facilitating the development of diabetes and hypertension, which leads to CKD, and by a direct effect on the kidney and endocrine mechanism. Obesity is generally defined by body mass index (BMI), which is not a good indicator for visceral adipose tissue (VAT), as visceral fat has been shown to be more metabolically active. A new method called the visceral adiposity index (VAI) has been developed, which is considered to be an indicator for the metabolic function of VAT. Previous studies have confirmed the association between the VAI and CKD prevalence. In this study, we attempted to investigate the association between estimated glomerular filtration rate (eGFR) decline and visceral adiposity.

Method

Data were collected from 129 patients aged 18-80 years with stage 2-5 CKD and not on dialysis; these patients were followed up in the Nephrology Department of Usak University Hospital between December 2017 and November 2018.

Results

Of 129 patients with stage 2-5 CKD enrolled in this study, 64 (40.6%) were females and 66 (59.4%) were males. The mean age was 66.8 (35-80 years). The mean VAI values of patients were 2.86±1.63, and the mean eGFR decline was -12.8±19.0 ml/min/1.73m2. No correlation was observed between the VAI values and decline in eGFR in 1 year. Patients with DM had statistically significant higher eGFR decline (p=0.04) and higher VAI values (p=0.03).

Conclusion

The VAI, which is used to assess the metabolic function of VAT, was not associated with the eGFR decline in 1 year for patients with stage 2-5 CKD.
P0752THE EXPRESSION AND DIAGNOSTIC VALUE OF URINE ANGIOTENSINOGEN IN CHRONIC KIDNEY DISEASE
Authors: Huang Qiuyan , Chen Junzhe , Tang Ying , Xu Yanchun , Xu Anping
Published: June 2020

Background and Aims

This article aims to detect the expression of urine angiotensinogen (uAGT) in patients with chronic kidney disease (CKD) and its correlation with clinical and renal pathology.

Method

Patients who diagnosed with CKD and undergoing renal biopsy for the first visit to Sun Yat-sen Memorial Hospital from March 1st ,2018 to October 1st, 2019 were enrolled. First morning urine samples from CKD patients before renal biopsy and healthy volunteers as controls were collected during the same period. These samples were tested for uAGT by ELISA. Linear regression analysis was used to explore the correlation between uAGT and clinical indicators as well as renal pathology in CKD patients. The receiver operating curve (ROC curve) was used to explore the diagnostic value of uAGT for CKD stage 3 or above and glomerular sclerosis ratio>50%.

Results

A total of 133 CKD patients with 59 (44.4%) in stage 1, 31 (23.3%) in CKD stage 2, 17 (12.8%) in stage 3, 17 (12.8%) in stage 4 and 9 (6.7%) in stage 5 were included in our study. At the same time, 20 healthy volunteers were included as control. uAGT levels of CKD patients were significantly higher than healthy controls(275.0 vs 774.2,P<0.001). Compared with CKD stage 1-2 patients, uAGT levels in patients with stage CKD 3 or above were significantly increased, and the difference was statistically significant (P<0.001) (Table 1). The result of multivariate linear regression analysis showed that uAGT levels in CKD patients were positively correlated with 24h urine protein (beta = 0.193, P = 0.012) and negatively correlated with eGFR (beta = -0.489, P<0.001) (Table 2). We also demonstrated that uAGT was positively correlated with the ratio of glomerular sclerosis(P = 0.003) (Table 3). Our results showed that the area under the curve (AUC)of uAGT for the diagnosis of renal function with CKD stage 3 or above was 0.789 (Figure 1) with the cut-off value was1959.9pg/ml. The sensitivity and specificity were 51.2% and 97.3% respectively, Furthermore, the positive predictive value (PPV) was 88.0% and negative predictive value (NPV) was 82.95%.The AUC of uAGT for the diagnosis of renal pathological glomerular sclerosis ratio>50% was 0.677 (Figure 2).The cut-off value of uAGT was 2131.8pg/ml.The sensitivity and specificity were 50% and 89.5% respectively. Meanwhile, the PPV was 41.67% and the NPV was 92.25%.

Conclusion

uAGT was significantly increased in CKD patients, which is closely related with the urinary protein, eGFR, and renal pathology.The specific cut-off value of uAGT can be used as a predictive indicator of advanced CKD stage and severe glomerular sclerosis.
P0754FGF23 AND URINARY PHOSPHATE EXCRETION FOR ESTIMATION OF NEPHRON NUMBER: DIFFERENCES BETWEEN CHRONIC KIDNEY FAILURE AND KIDNEY TRANSPLANTATION
Authors: Pasquali Marzia , De Martini Natalia , Tartaglione Lida , Rotondi Silverio , Catalfamo Marta , Ceravolo Maria Josè , Bagordo Domenico , Mazzaferro Sandro
Published: June 2020

Background and Aims

Assuming that FGF23 levels correlate with phosphate excretion per nephron, nephron number can be estimated by measuring FGF23 levels and urinary phosphate excretion (FEP). Kuro-O proposed that the ratio of FEP to serum FGF23 levels should correlate with nephron number and is defined as the Nephron Index (NI).

The aim of the study is calculating NI as nephron number estimation in patients affected by various degree of chronic kidney disease, both transplanted and not.

Method

In 147 CRF patients kidney function, mineral metabolism biomarkers and NI were evaluated. Nephron Index was calculated following Kuro-o’s equation (kuro-o 2019): NI=FEP·Ps·eGFRFGF23

Observed patients were divided into two groups: patients with CKD (noTX) and transplanted ones (TX).

Results

noTX group was made up of 67 patients (40 males and 27 females) affected by CKD stages from G1 to G5. TX group was composed by 80 patient (49 males and 31 females) with various degree of CKD (G1T-G4T) showing mean graft age of 83,2 ± 54,8 months (range: 10,3-268,0). The two groups differed for age (mean age 59 ± 15,6 years in CKD, 55± 10,3years in TX). Mean eGFR did not differ between TX and noTX but NI was higher in TX since FEP was higher despite lower FGF23 levels in TX. The difference in FGF23 levels does not appear to depend on Klotho and PTH whose serum levels were no different between Tx and noTx. (Table1). As far as correlations are concerned, NI correlated with eGFR, FGF23, PTH and 1,25D in both group, while NI correlated with FEP only in the TX group. It's interesting that no correlation existed between FGF23 and sP, FEP, eGFR and sKlotho in TX differently from noTX (Table2).

Discussion. NI could not be properly defined as nephron number estimation in TX pts. However it may represent higher function of residual nephrons, since higher FEP did not correlate to FGF23 and could be determined by compensatory hyperfiltration (increased single nephron GFR) in transplanted patients.

Conclusion

After kidney transplantation, high NI value could have a functional meaning rather than represent residual number of nephrons.
P0755CALCIUM/MAGNESIUM RATIO: NEW PREDICTOR OF INCREASED PULSE PRESSURE IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Carias Eduarda , Mendes Filipa , Fragoso André , Leão Neves Pedro , Silva Ana
Published: June 2020

Background and Aims

Cardiovascular disease (CVD) is the main cause of death in chronic kidney patient. Increase pulse pressure (PP) is associated with adverse cardiovascular outcomes and is an independent risk factor of progression of chronic kidney disease.

In this study we aim to identify the risk factors associated with increased PP in a population with severely decreased glomerular filtration rate.

Method

This was a prospective analysis conducted in an outpatient nephropathy clinic between 2005-2018, enrolling 692 patients with stage 4 CKD.

Patients were divided into two groups according to their pulse pressure. Group 1 mean PP< 50 mmHg, Group2 mean PP >50 mmHg.

Based on the calcium/magnesium ratio (rCaMg), the subjects were also divided into 4 risk groups according to the following criteria: <25th percentile (rCaMg < 3.8mg/dl; n=168) – G1; 25-50th percentile (rCaMg: 3.8-4.7; n=171) – G2; 50-75th percentile (rCaMg: 4.7-8.6; n=188) – G3; and >75th percentile (rCaMg: > 8.6; n=165) - G4.

We used descriptive analysis, Student's t test, Univariate logistics regression analysis and CHAID analysis to determine the relationship between variables and PP.

Results

Total of 682 patients, with mean age 70 (SD 12.5), female 54%.

An independent t-test was conducted to compare groups. There was a significant difference in mean hemoglobin level (p=0.005), calcium (p=0.029), phosphorus (p=0.017), magnesium (p<0.001), Ca/Mg ratio (p<0.001) and eGFR (p=0.034).

Phosphorus OR 1.906 (CI 1.338-2.715) p<0.001, eGFR OR 1.440 (CI 1.023-2.027) p=0.037 were all associated with increased PP. We also compared PP with the subjects of the 4 groups based on calcium/magnesium ratio. Results: G2= OR 7.003 (CI 4.162-11.783) p<0.001; G3= OR 5.136 (CI 3.205-8.230) p<0.001; G4= OR 6.695 (CI 3.999-11.208) p<0.001.

After adjusting for confounding variables only sex OR 0.613 (CI 0.420-0.896) p=0.012 and rCa/Mg groups: G1 OR 7.392 (CI 4.362-12.527) p<0.001, G2 OR 6.436 (CI 3.361-12.323) p<0.001 and G3 OR 8.485 (CI 4.009-17.957) p<0.001, showed significant differences.

CHAID analysis identified rCa/Mg G2, G3, G4 (82.4%) as the more likely significant predictor to PP> 50 mmHg (p<0.001) in association with male gener (86.2%) (p=0.037). The model correctly classified 76.2% of patients and the estimate of the risk misclassification of events was 0.238±0.016.

Conclusion

These results suggest increased calcium/magnesium rate and male gender were associated with increased pulse pressure in a population with stage 4 CKD.

Further studies are needed to understand this relationship.
P0760THE INFLUENCE OF MICROBIOME COMPOSITION ON THE DEVELOPMENT OF IGA NEPHROPATHY
Authors: Nakhoul Farid , Nakhoul Nakhoul , Nakhoul Rula , Farber Evgeny
Published: June 2020

Background and Aims

Overall, human microbiota contains 1014 bacterial cells. The human intestine is particularly dense of microbes, 1012 bacteria per g (dry weight), especially at colon level. Under healthy conditions, the human microbiota provides trophic and protective functions. Bacteroidaceae, and Prevotellaceae differed among IgA and Healthy Control subjects (HC). Enterobacteriaceae species were almost the highest in the fecal samples of patients.

Bifidobacterium species decreased in the fecal samples of Patients compared to HC subjects. Increasing evidence indicates that changes in the microbiota composition known as Dysbiosis, can affect human health and disease. Altering the balance of the gut microbiota can also affect kidney physiology and pathology, such as IgAN. we hypothesize that the aberrantly IgA1 that produced in IgAN in response to a mucosal infection may be influenced by the composition of the patient microbiome by inducing excessive abnormal mucosal IgA responses.

Study aim is to explore if IgAN patients have different microbiome composition compared with the healthy control individuals.

Method

Stool sample from 26 IgAN patients & from 26 healthy control individuals subjected to microbiome array and to taxonomic analysis, to characterize their microbiome compositions. Serum Creatinine\ albumin and urine proteinuria levels are used for evaluate the renal function of each IgAN patient. The clinical and laboratory evaluations will be crossed with the taxonomic data using statistical analysis methods.

Results

Based on our preliminary result with 11 IgAN patients and 11 healthy control individuals, there are significant differences in the microbiome composition between the two groups.

IgAN patients have a significant increase in the Bacteroides phylum accompanied with a significant decrease in the amount of both the Actinobacteria and Verrucomicrobia phyla, compared with the healthy individuals.

At the genus level, there is a significant increase in the Prevotella bacteria in the IgAN subjects compared with the healthy individuals.

Conclusion

1. A strong association between specific bacteria population and IgAN disease, we isolate specific population of bacteria that leads to IgAN or even aggravate its manifestation.

2. It may help to predict the tendency of each individual to develop IgAN and even predict the prognosis of each IgAN patient according to their microbiome.

3. it is rational to alter the intestinal barrier, the content of gut microbiota and its metabolites in the realm of CKD using different strategies such Prebiotics and symbiosis.

4. To develop disease-specific therapies based on microbiome modulations and manipulations such as modifying the gut microbiota through diet, antibiotic therapies, probiotic, bariatric surgery, fecal transplants.
P0770IMPAIRED FASTING GLUCOSE AND CHRONIC KIDNEY DISEASE: A MENDELIAN RANDOMIZATION STUDY
Authors: Noh Hyunjin , Kim Hyoungnae , Park Su Yeon , Hwang Dohui , Choi Kyoungin
Published: June 2020

Background and Aims

Diabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population.

Method

This study included 6,354 participants without diabetes and CKD from the KoreanGenome Epidemiology Study. The genetic risk score (GRS9) was calculated using nine genetic variants associated with fasting glucose in previous genome wide association studies. Incident CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+). The causal relationship between fasting glucose and CKD was evaluated using Mendelian randomization (MR) approach.

Results

The GRS9 was strongly associated with fasting glucose (β, 1.01; P < 0.001). During a median follow-up of 11.6 years, 531 (8.4%) CKD events occurred. After adjusting for confounding factors, fasting glucose was not associated with incident CKD (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.980–1.003; P =0.139). In the MR analysis, GRS9 was not associated with CKD development (OR per 1 standard deviation increase, 1.179; 95% CI, 0.819–1.696; P = 0.376). Further evaluation with various other MR methods using inverse-variance weighted, MR-Egger, and weighted median methods for multiple genetic variants and strict CKD criteria (decrease in the eGFR of ≥ 30% to a value of < 60 mL/min/1.73m2) found no significant relationship between GRS9 and incident CKD.

Conclusion

Impaired fasting glucose was not causally associated with CKD development in nondiabetic population.
P0777REPRODUCTIVE HISTORY AND INCIDENT CKD IN MIDDLE-AGED WOMEN
Authors: Kim Kipyo , Ko Gang-Jee , Moon Ju-Young
Published: June 2020

Background and Aims

Previous epidemiologic data showed female has slower renal function decline compared to male and experimental studies showed the renoprotective effects of estrogen. Nevertheless, clinical studies that supports the beneficial effects of female sex hormone on chronic kidney disease (CKD) progression are limited. Middle age in women is the period of experiencing hormonal alteration. Therefore, we investigated that the associations of reproductive history with incident CKD in middle-aged women.

Method

A total of 4481 women aged ≥ 40 years with normal renal function were included in the study from the Korean Genome and Epidemiology Study database. The cohort consisted of community-based general population and were followed up from 2001 to 2016. Primary outcome was the incident occurrence of CKD (eGFR< 60 ml/min/1.73m2 and 25% decline from baseline creatinine). We additionally defined the endogenous estrogen exposure (menopausal age - age at baseline - 0.75 x each childbirth) to examine the effect of estrogen exposure on renal function. Multivariable Cox proportional hazards analysis was performed with time-varying covariates including childbirth, menopausal status, and hormone replacement therapy.

Results

The mean age of participants was 52.3 ± 8.9 years, and 51.5% (n=2306) of patients have reached menopause at baseline. The mean eGFR was 94.1 ± 12.7 mL/min/1.73 m2 and 7.0% (n=315) participants experienced childbirth during follow-up period. Age-adjusted Cox model showed that childbirth (HR 1.58, CI 1.24-2.02) and menopause (HR 1.31, CI 1.04-1.63) were significantly associated with high risk of incidental CKD, but not in hormonal therapy. These associations remained after multivariate adjustment (childbirth, HR 1.55, CI 1.21-1.98; menopause, HR 1.26, CI 1.01-1.57). Endogenous estrogen exposure ranged 0 to 14 years, and was categorized into no exposure (51.5%), moderated exposure (1-6 years), and high exposure (>6 years). High exposure group was associated with the lower risk of CKD compared to no exposure group (HR 0.74, CI 0.58-0.94). Restricted cubic spline analysis also showed the inverse relationship between estrogen exposure and the risk of incident CKD.

Conclusion

In middle-aged women, menopause and childbirth were significantly associated with higher risk of incident CKD. These associations could be attributable to the reduction of endogenous estrogen exposure.
P0785POSITIVE CORRELATION OF SERUM RESISTIN LEVEL WITH PERIPHERAL ARTERY OCCLUSIVE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 TO 5
Authors: Tang Chi-Chong , Hou Jia-Sian , Hsu Bang-Gee
Published: June 2020

Background and Aims

Resistin named for its ability to resist insulin action has an important link between obesity, insulin resistance and diabetes. Moreover, additional reports suggest that resistin has a pathogenic role in the development and progression of atherosclerosis and coronary artery disease. Chronic kidney disease (CKD) accelerates atherosclerosis via augmentation of inflammation and perturbation of lipid metabolism. Peripheral arterial occlusive disease (PAOD) is associated with an increased risk of death in CKD patients. The aim of this study was to evaluate the relationship between serum resistin level and PAOD by ankle-brachial index (ABI) in CKD patients.

Method

Fasting blood samples and baseline characteristics were obtained from 240 patients with CKD (stage 3-5). ABI values were measured using the automated oscillometric method (VaSera VS-1000). ABI values that were < 0.9 were included in the low ABI group. Concentrations of human serum resistin were determined using a commercially available enzyme immunoassay kit.

Results

Among the 240 CKD patients, 30 of them (12.5%) were in the low ABI group. Compared with patients in the control group, the patients in the low ABI group had higher prevalence of diabetes (p = 0.033), hypertension (p = 0.023), current smoking (p = 0.013), older age (p < 0.001), higher systolic blood pressure (p = 0.013), glucose (p = 0.022) level and resistin (p < 0.001) levels. In addition, the multivariable logistic regression analysis showed that serum resistin levels (Odds ratio [OR]: 1.140, 95% confidence interval [CI]: 1.054-1.234, p = 0.001) and age (OR: 1.102, 95% CI: 1.051-1.156, p < 0.001) were the independently associated with PAOD in CKD patients. The area under the receiver-operating characteristic (ROC) curve predicting PAOD by serum resistin level in CKD patients was 0.699 (95% CI: 0.636-0.756, p = 0.0001).

Conclusion

In this study, serum resistin level was found to be associated with PAOD in non-dialysis CKD stage 3-5 patients.
P0791MATRIX GLA PROTEIN AND PREMATURE VASCULAR CALCIFICATION IN PATIENTS WITH END-STAGE RENAL DISEASE
Authors: Dai Lu , Qureshi Abdul Rashid Tony , Ripsweden Jonaz , Brismar Torkel B , Söderberg Magnus , Barany Franz Peter , Schurgers Leon , Lindholm Bengt , Stenvinkel Peter
Published: June 2020

Background and Aims

Vitamin K is a potential protective factor against premature vascular aging and vascular calcification (VC). Whether vitamin K supplement could halt VC progression in patients with end-stage renal disease (ESRD) is not clear, partially due to the heterogeneity of measurements of VC in different vascular sites. Here we investigated the associations between non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP), a circulating marker of vitamin K insufficiency, and premature vascular aging phenotypes evaluated by coronary artery calcium (CAC) scoring, aortic valve calcium (AVC) scoring, and histology scoring of presence of media calcification in vascular biopsies in patients with ESRD.

Method

In this observational cohort study, 223 ESRD patients (median age 54 years, 68% males) comprising non-dialysis patients (n=109), prevalent peritoneal dialysis (PD, n=80, median dialysis vintage 11.6 months) and prevalent hemodialysis patients (HD, n=34, median dialysis vintage 12.0 months) underwent baseline measurements of plasma dp-ucMGP and scoring of CAC and AVC by computed tomography scan. Framingham risk score (FRS), inflammation and other relevant clinical and biochemical data were determined at baseline. In a sub-group of patients (n=94), scoring of media calcification by histology in epigastric artery biopsies was also performed.

Results

Plasma dp-ucMGP levels (median 1568 pmol/L) significantly correlated with age (rho=0.38), presence of cardiovascular disease (CVD, rho=0.16), triglycerides (rho=0.19), FRS (rho=0.33), high-sensitivity C-reactive protein (hsCRP; rho=0.35), CAC score (rho=0.30) and AVC score (rho=0.24) but did not differ with regards to treatment modality (i.e. non-dialysis, PD and HD). In multivariate regression analyses, with adjustment for presence of CVD, FRS, hsCRP and triglycerides, increased dp-ucMGP levels were independently associated with increased CAC score (coefficients 0.12, p=0.04), but not with AVC score nor presence of media calcification in epigastric arteries.

Conclusion

Our data suggest that vitamin K insufficiency as indicated by increased dp-ucMGP levels associates with premature vascular calcification evaluated by CAC but not with AVC or media calcification assessed by histology. This discrepancy warrants further studies to explore the pathophysiological background between vitamin K metabolism and susceptibility of calcification in different vascular sites as well as the pattern of VC (i.e. intima and media calcification) within sites.
P0798ASSOCIATION BETWEEN RENAL DYSFUNCTION AND GENERAL COGNITIVE FUNCTION IN COMMUNITY DWELLING OLDER ADULTS: KOREAN FRAILTY AND AGING COHORT STUDY
Authors: Kong Jiyoon , Kim Jin Sug , Kang Min Hye , Kang Shin Yeong , Ra Ri , Won Chang Won , Hwang Hyeon Seok , Jeong Kyung Hwan
Published: June 2020

Background and Aims

Cognitive impairment is common in older adults. Similarly, the prevalence of renal dysfunction is also increased in the elderly. We conducted this study to clarify the relationship between the renal function and cognitive impairment in community dwelling older adults in Korea.

Method

A cross-sectional analysis was performed on the data of the Korean Frailty and Aging Cohort Study (KFACS), a nationwide cohort study that began in 2016. Of the 3014 participants assessed in the first and second year, 2847 participants (1333 men, 1514 women) who completed baseline assessments were enrolled. The estimated glomerular filtration rate (eGFR, mL/min/1.73m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function of the participants was classified into four groups by eGFR quartile. General cognitive function was accessed with mini-mental state exam in the Korean version (MMSE-KC). Participants who had MMSE-KC score less than 1.5 standard deviation by age, gender, and education level were regarded as the cognitive impairment. Multivariate logistic regression model was used to examine the relationship between renal function and cognitive impairment. In addition, we investigated to find the point of eGFR interval at which the odds ratio begins to increase.

Results

The mean eGFR in quartile 1 was 91.7 ± 3.22 ml/min/1.73m2, and 84.9 ± 1.81 in quartile 2, 76.1 ± 3.66 in quartile 3, and 57.2 ± 10.75 in quartile 4. In baseline characteristics, participants with lower eGFR had lower MMSE-KC scores. And the prevalence of cognitive impairment was 10.8% in quartile 1, 15.9% in quartile 2, 15.2% in quartile 3, 14.9% in quartile 4. After multivariate adjustment, the odds ratio (OR) of cognitive impairment in quartile 2 [adjusted OR: 1.569, 95% confidence intervals (CI): 1.141 - 2.158, p = 0.006] compared with quartile 1. And the odd ratios of cognitive impairment were 1.539 (95% CI: 1.113 - 2.127, p = 0.009) in quartile 3, 1.475 (95% CI: 1.062 - 2.049, p = 0.020) in quartile 4 compared with quartile 1, respectively. Among the participants with eGFR above 60 ml/min/1.73m2, the renal function was grouped by 5 ml/min/1.73m2 interval. The risk of cognitive impairment started to increase from eGFR between 80 and 85 ml/min/1.73m2 (adjusted OR: 1.667, 95% CI: 1.128 - 2.463, p = 0.010).

Conclusion

Renal dysfunction was associated with lower global cognitive function in older adults. And the risk of cognitive impairment increased from quartile 2, especially, eGFR between 80 and 85 ml/min/1.73m2 in this population. These results suggest that mild decline of kidney function is also a risk factor of cognitive decline in the elderly.
P0802RELATIONSHIP BETWEEN RENAL INSUFFICIENCY AND AIRFLOW LIMITATION AND THEIR IMPACT ON MORTALITY IN A COMMUNITY-BASED POPULATION: THE YAMAGATA (TAKAHATA) STUDY
Authors: Miyata Masahiro , Tanaka Tomomi , Suzuki Natsuko , Kudo Kosuke , Ichikawa Kazunobu , Inoue Sumito , Watanabe Masafumi , Kayama Takamasa , Konta Tsuneo
Published: June 2020

Background and Aims

Chronic kidney disease and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality. In this study, we investigated the association between renal deficiency and airflow limitation that characterizes COPD, and its effect on 10-year mortality in a community-based population.

Method

The study subjects were 1,233 health check-up participants (mean age 64 years; 46.7% men). We defined renal insufficiency as GFR <60 mL/min/1.73m2 estimated using serum creatinine (Cr) or cystatin C (CysC), and airflow limitation (AFL) as forced expiratory volume in 1 second to forced vital capacity ratio <70% on spirometry.

Results

The prevalence of Cr-based and CysC-based renal insufficiency, and AFL in total subjects was 6.6%, 14.8%, and 11.2%, respectively. Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CysC-based renal insufficiency (24.6% vs. 13.5%, P <0.01), but not of Cr-based renal insufficiency (8.0% vs. 6.4%, P =0.77). The prevalence of CysC-based renal insufficiency was increased, along with the progression of AFL severity (P for trend <0.01). During the follow-up period, there were 154 (12.5%) deaths. Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.76 (1.12-2.71) in subjects with CysC-based renal insufficiency alone, 1.13 (0.62-1.94) in those with AFL alone, and 2.30 (1.20-4.18) in those with both CysC-based renal insufficiency and AFL, with subjects without both CysC-based renal insufficiency and AFL as the reference. In contrast, the adjusted hazard ratios for all-cause mortality did not reach statistical significance in subjects with both Cr-based renal insufficiency and AFL, with subjects without both Cr-based renal insufficiency and AFL as the reference.

Conclusion

This study showed that CysC-based renal insufficiency and AFL are strongly associated and that their overlap is a significant risk for mortality in community-based populations.
P0819THE EFFECT OF SMOKING UPON CKD IN A JAPANESE NATIONWIDE 6-YEARS FOLLOW UP SERVEY
Authors: Nagasawa Yasuyuki , Matsumoto Ayako , Yamamoto Ryohei , Shinzawa Maki , Isaka Yoshitaka , Nanami Yoshimasa , Hasuike Yukiko , Takahiro Kuragano , Iseki Kunitoshi , Yamagata Kunihiro , Tsuruya Kazuhiko , Yoshida Hideaki , Fujimoto Shouichi , Asahi Koichi , Watanabe Tsuyoshi , Moriyama Toshiki
Published: June 2020

Background and Aims

Cigarette Smoking is one of important risks for cardiovascular diseases, and also smoking had been reported to have harmful effect upon Choric kidney Diseases. Our group had reported that smoking canceled the beneficial effect caused by alcohol drinking using Japanese Nationwide Survey cross-sectional data (Matsumoto-A et al Hypertension Res, 2017). In this cohort study, we aimed to reveal the effect of smoking upon incidence of proteinuria and decline of kidney function using longitudinal large cohort of general population in Japan.

Method

The present nationwide longitudial survey included members of the general Japanese population who underwent the Specific Health Check and Guidance in Japan between April 2008 and March 2014. 149,260 who were not lack of essential data without chronic kidney diseases and whose kidney function was 60≦eGFR<120mL/min/1.73m2 were enrolled in this analysis. Demographic, physical, and laboratory data included age, sex, body mass index (BMI; weight [kg]/height2 [m2]), mean arterial pressure (MAP, diastolic blood pressure + [systolic blood pressure - diastolic blood pressure]/3), serum concentration of creatinine (enzymatic method), and levels of hemoglobin A1c, triglycerides, high-density lipoprotein (HDL) cholesterol, uric acid, and urinary protein as detected by a dipstick test. Proteinuria was defined as 1+ or more of urinary protein. We made statistical analysis using Kaplan-Meier analysis, Log-rank test, Cox proportional hazard method using STAT ver15. As outcomes, incidence of proteinuria (more than (1+) by dip stick, decline of eGFR more than 15 mL/min/1.73m2 from baseline kidney function were used.

Results

Smoker had significantly higher incidence rate of proteinuria than non-smoker (p<0.001). Smoker also had significantly higher incidence decline of kidney function more than 15ml/min than non-smoker (p<0.001). Smoking was significantly risk both for proteinuria (Hazard Rate 1.24(95％CI 1.15-1.34, p<0.001)) and for decline of kidney function HR 1.24(95％CI 1.16-1.31, p<0.001) in multivariate analyses. After stratification of four groups using smoking status and incidence of proteinuria during study periods. Smoker with incident proteinuria had significantly higher rate of decline of kidney function than non-smoker without incident proteinuria both in male (figure 1) and in female (Figure 2)

Conclusion

Smoking was risk for proteinuria and decline of kidney function. Moreover, smoker with incident proteinuria had worst kidney prognosis.
P0826OBESITY AND RISK FOR CHRONIC KIDNEY DISEASE IN THE HEALTHY MIDDLE-AGED KOREAN POPULATION
Authors: Cho Minhae , KIM MI JI , CHO WON HEE , Moon Ju-Young , Jeong Kyung Hwan , Lee Sang-Ho , Hwang Hyeon Seok , Kim Jin Sug , Kim Yang-Gyun
Published: June 2020

Background and Aims

Although obesity is a well-known risk factor for chronic kidney disease (CKD), previous epidemiologic studies have produced mixed results. This study was purposed to investigate the relationship between obesity and CKD occurrence in the healthy middle-aged Korean population.

Method

We used a prospective, longitudinal data from the Korean Genome and Epidemiology Study (KoGES), a population-based, epidemiology study in South Korea (2001-2014). A total of 6,678 participants aged 40-69 who were free of diabetes, hypertension, and CKD at baseline were followed-up biennially. CKD was defined as at least two-time occurrence of estimated glomerular filtration rate < 60 mL/min/1.73m2 using CKD-EPI equation during the follow-up period.

Results

A total of 433 participants (6.5%) developed CKD. We divided the participants into 5 groups by BMI: underweight (BMI < 18.5), normal-weight (BMI 18.5-22.0), overweight 1 (BMI 23.0-24.9), overweight 2 (BMD 25-29.9), and obesity (BMI >30). Compared to the normal-weight group, hazard ratio of CKD occurrence was elevated in overweight 2 (HR=1.43, p=0.01) and obesity (HR=1.73, p=0.03) in multivariate-adjusted regression analysis (variates: age, newly developed hypertension, newly developed diabetes, fasting glucose > 126mg/dL, 2hours glucose > 200mg/dL, systolic blood pressure > 140mmHg, physical activity, alcohol consumption, smoking). When dividing the participants into three age groups: the 40s, 50s, and 60s, only the 60s group showed a significant correlation of BMI with CKD occurrence (overweight 2: HR=1.93, p=0.05, obesity: HR=3.94, p=0.03).

Conclusion

The risk of CKD was significantly high for those in their 60s who were overweight or obese despite free of underlying diseases in the Korean population.
P0835IDENTIFYING THE FREQUENCY OF CHRONIC KIDNEY DISEASE OF UNKNOWN ETIOLOGY (CKDU) IN A RURAL POPULATION OF BANGLADESH
Authors: Iqbal Md M , Roy S C , Chowdhury MAA , Banerjee Sajal Krishna , Islam S , Hossain R M , Hassan M S , Hassan M Z , Chaudhury S R , Arslan M I , Islam M N
Published: June 2020

Background and Aims

The common etiologies of CKD are diabetes, hypertension and glomerulonephritis. Prevalence of CKD of unknown (CKDu) etiology is being increasingly considered as an emerging etiology, especially in the developing countries, with environmental predisposition to hot humid climate, dehydration and toxic metal contaminations. The aim was to identify the frequency of CKDu as an etiology in a rural population with environmental exposure.

Method

In this observational study subjects were selected from a geographically defined rural population in Bangladesh. Baseline information was recorded by the translated WHO STEP wise approach surveillance- Instrument v.3.1 (Core and Expanded). Blood Pressure was measured by digital blood pressure monitor. Serum creatinine was measured by enzymatic method using assays traceable to isotope dilution mass spectrometry (IDMS). A fasting blood sample and spot urine was collected. BP ≥140/90mmHg; FBS > 5.6 mmol/l and HbA1c ≥6.5%; and eGFR< 60ml/min (CKD-EPI equation) or urine ACR > 30mg/g was taken as diagnostic cut-offs for hypertension, diabetes and nephropathy respectively. From diagnosed CKD patients CKDu group was further identified by stepwise approach of WHO criteria as suspected and probable stages.

Results

The mean age was 41.3 ± 12.7 years with male/female ratio 37/63 in preliminary 303 study subjects. They were 12.5% diabetic, 21% hypertensive and 75% had some form of dyslipidemia. Among all 51 subjects (16.8%) were diagnosed as CKD based on single measurement of eGFR and ACR. Of these 30 study subjects (58%) met the criteria of suspected CKDu. After repeat measures of eGFR and ACR at 3 months, prevalence of CKD came down to 10.2% persisting in 31 subjects (G1:5.3%, G2:2.3% and G3: 2.6%). Of these 7 study subjects (23%) met the criteria of probable CKDu. The main etiologies of CKD among these subjects were diabetic nephropathy (48%) followed by CKDu. The frequency of CKDu in total study population as a whole was 2.3%.The pattern of environmental exposures like types of farming, use of pesticide-fertilizer, NSAIDs intakes, water sources, amount of drinking water per day, duration of work under direct sun, pattern of fish-meat intakes, etc. were not different between subjects with CKDu versus the others.

Conclusion

The prevalence of chronic kidney disease in a rural area of Bangladesh is one in ten (10.2%). Among these nearly one-fourth (23%) of the subjects belonged to probable CKDu category. This alarmingly high frequency of CKDu needs further extensive evaluation to identify the predisposing factors responsible.