Advanced Stages Of Chronic Kidney Disease Research Articles

Kronik böbrek hastalarında anormal kalp geometrisi ve sol ventrikül hipertrofisi

Purpose: The aim of this study was to investigate the incidence of left ventricular geometric patterns in patients with chronic kidney disease (CKD).Materials and Methods: A total of 162 patients (100 males) with stage 2–5 CKD were included in the study. Patient age was between 17 and 79 years. Left ventricular geometry (LVG) patterns were calculated as left ventricular normal geometry (LVNG), left ventricular concentric remodeling (LVCR), concentric left ventricular hypertrophy (cLVH) and eccentric left ventricular hypertrophy (eLVH) by echocardiographic parameters.Results: The incidence of LVH was 45.1%. LVG patterns were found as follows: eLVH in patients 18(11.1%), cLVH in 42(25.9%), LVCR in 51(31.5%), and LVNG 51(31.5%). LVNG was found 10.38% and 34.27% in CKD stage 2 and dialysis, respectively. LVCR was as high as 62.3% in CKD stage2. cLVH and eLVH were found as 35.92% and 29.13% in stage 5 non-dialysis and dialysis, respectively. There was a relationship between clinical characteristics and LVG as follows age and GFR with LVCR, HbA1C and serum levels of albumin and sodium with cLVH, and age and serum albumin with eLVHConclusions: In our CKD patients, abnormal LVG was found as earlier as CKD stage 2. The incidence of cLVH and eLVH was higher in advanced stages of CKD. Nontraditional factors such as volume status and nutrition were also crucial for left ventricular remodeling.

Relationship between GFR, intact PTH, oxidized PTH, non‐oxidized PTH as well as FGF23 in patients with CKD

Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism. In chronic kidney disease (CKD), circulating FGF23 and PTH concentrations progressively increase as renal function declines. Oxidation of PTH at two methionine residues (positions 8 and 18) causes a loss of function. The impact of n-oxPTH and oxPTH on FGF23 synthesis, however, and how n-oxPTH and oxPTH concentrations are affected by CKD, is yet unknown. The effects of oxidized and non-oxidized PTH 1-34 on Fgf23 gene expression were analyzed in UMR106 osteoblast-like cells. Furthermore, we investigated the relationship between n-oxPTH and oxPTH, respectively, with FGF23 in two independent patients' cohorts (620 children with CKD and 600 kidney transplant recipients). While n-oxPTH stimulated Fgf23 mRNA synthesis in vitro, oxidation of PTH in particular at Met8 led to a markedly weaker stimulation of Fgf23. The effect was even stronger when both Met8 and Met18 were oxidized. In both clinical cohorts, n-oxPTH-but not oxPTH-was significantly associated with FGF23 concentrations, independent of known confounding factors. Moreover, with progressive deterioration of kidney function, intact PTH (iPTH) and oxPTH increased substantially, whereas n-oxPTH increased only moderately. In conclusion, n-oxPTH, but not oxPTH, stimulates Fgf23 gene expression. The increase in PTH with decreasing GFR is mainly due to an increase in oxPTH in more advanced stages of CKD.

Depression among Chronic Kidney Diseases Patients Receiving Hemodialysis

Background: Chronic Kidney Disease (CKD) is a progressive irreversible loss of renal function over a period of months or years. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintains life. Hemodialysis is used for patients who require short term dialysis (days to weeks) and for patients with advanced CKD and End Stage renal Disease (ESRD) who require long term or permanent renal replacement therapy. Hemodialysis significantly and adversely affects the lives of patients, both physically and psychologically. Depression is the most common psychological condition among patients with ESRD. Depression in dialysis patients not only effect mortality, but increased rate of hospitalizations and dialysis withdrawal is also very common.
 Methods: A descriptive cross sectional research design was carried out to identify the depression level of chronic kidney disease patients receiving Hemodialysis in Western Regional Hospital, Pokhara using Beck Depression Inventory among forty six patients.
 Results: The study findings revealed that majority of the patients (84.8%) has various degree of depression i.e. mild (21.7%), moderate (30.8%) and severe (32.6%). Only fifteen percent of patient has no depression. There was no statistical association between the level of depression and socio-demographic variables. It can be concluded that the prevalence of depression is high among patients receiving Hemodialysis.
 Conclusion: The prevalence of depression is high among patients receiving Hemodialysis. It is effective to provide mental health services to the CKD patients receiving Hemodialysis which help them better psychologically adaptation to their disease and improve their quality of life.

Chronic kidney disease impacts health-related quality of life of children in Uganda, East Africa.

Limited data exist about causes of chronic kidney disease (CKD) and impact on health-related quality of life (HRQoL) in African children. We evaluated types of kidney disease in Ugandan children 0-18years and compared HRQoL in children with CKD or with benign or resolving kidney disease (non-CKD) to assess predictors of HRQoL. Demographic, socioeconomic, and clinical data were obtained for this cross-sectional study. Pediatric Quality of Life Core Scale™ (PedsQL) was used to survey 4 domains and overall HRQoL. CKD and non-CKD scores were compared using unpaired t test. HRQoL predictors were evaluated using linear and logistic regression analyses. One hundred forty-nine children (71 CKD, 78 non-CKD; median age 9years; male 63%) had the following primary diseases: nephrotic syndrome (56%), congenital anomalies of the urinary tract (CAKUT) (19%), glomerulonephritis (17%), and other (8%). CAKUT was the predominant etiology (39%) for CKD; 63% had advanced stages 3b-5. Overall HRQoL scores were significantly lower for CKD (57 vs. 86 by child report, p < 0.001; 63 vs. 86 by parent proxy report, p< 0.001). Predictors of lower HRQoL were advanced CKD stages 3b-5, primary caregiver non-parent, vitamin D deficiency, and anemia. Like other parts of the world, CAKUT was the main cause of CKD. Most CKD children presented at late CKD stages 3b-5. Compared with non-CKD, HRQoL in CKD was much lower; only two-thirds attended school. Vitamin D deficiency and anemia were potentially modifiable predictors of low HRQoL. Interventions with vitamin D, iron, and erythropoietin-stimulating agents might lead to improved HRQoL.

Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study.

ObjectiveCompare rates of lactic acidosis (LA) among metformin‐exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD).Research Design and MethodsRetrospective, nested case‐control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003‐13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications.ResultsOverall, 320 882 patients were included, contributing a total of 1 331 784 person‐years of follow‐up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93‐2.08) per 1000 person‐years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69‐2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71‐1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19‐4.35 in CKD 3a, HR 3.34, 95% CI 1.95‐5.72 in CKD 3b, HR 7.87, 95% CI 3.51‐17.61 in CKD stage 4&5.ConclusionMetformin was not associated with an elevated risk of LA in persons with stage 1‐2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.

Effects of hemodialysis on upper airways collapsibility in patients with chronic kidney disease

Introduction: The Chronic Kidney Disease (CKD) is characterized as a clinical condition wherein the progressive loss of renal function for a period longer than months to years will lead to the onset of end-stage renal disease (ESRD). In the advanced stages of CKD, patients can only be treated with replacement therapy, dialysis or transplantation. In this context, hemodialysis (HD) presents as the main treatment option for these patients due to the lack of donors. Patients with ESRD in HD often present signs and symptoms related to pre-existing or acquired comorbidities with worsening of the disease. The most frequent are electrolytic disturbances, anemia, malnutrition, bone disease, Melittus diabetes, systemic arterial hypertension, gastrointestinal disorders, respiratory disorders, cardiovascular diseases, neurological changes and sleep disorders. Obstructive sleep apnea (OSA) presents a tenfold prevalence in patients with ESRD when compared to the general population, worsening the clinical symptoms and cardiovascular complications of this disease. The increase in the number of ESRD patients submitted to HD has assumed epidemic proportions worldwide. The causal association between sleep-disordered breathing, in particular OSA and ESRD, is still not well understood, which expands the possibility of new findings for the prevention, diagnosis and treatment of OSA, improving quality of life and reducing morbimortality. Objective: The present study involving ESRD patients undergone HD was designed with three main objectives: 1) to verify the prevalence and severity of sleep-disordered breathing; 2) to analyze the behavior of sleep apnea / hypopnea index (AHI) during the interdialitic period; 3) to verify weight gain and anthropometric measurements during the interdialitic period. Method: A consecutive single-center cross-sectional clinical study will be performed, double-blind, non-randomized to investigate the behavior of AHI in patients with ESRD undergoing HD in the nephrology unit (UNEFRO) at the Hospital of Santa Casa de Misericordia de Avaré, (SP), Brazil. The design and conduct of this study followed the guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement

Kidney transplantation as a treatment of choice for AA amyloidosis due to periodic fever syndrome.

Renal AA amyloidosis is the most serious complication of periodic fever syndrome, which, inadequate suppression, due to persistent inflammation, leads to nephrotic syndrome and renal failure over several years. In most cases, periodic fever syndromes begin to manifest clinically in early childhood. Occurrence in adulthood is considered rare and is associated with a poorer clinical course. Kidney transplantation (KT) is an effective and safe treatment for end-stage chronic kidney disease (CKD) based on AA amyloidosis. In this paper, we present cases of two patients after deceased donor KT, who have been diagnosed with adult periodic fever syndrome. In the first one, diagnosis and treatment began in advanced stage of CKD and therefore underwent KT with compensated disease, while in the second patient, the disease manifested and diagnosed in the post-KT period. Timely initiation of treatment ensured protection of the graft from amyloid deposition.

Current Knowledge of Vaccinations in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients are at high risk for infectious complications. This is partly due to their dysfunctional immune system, especially in advanced CKD stages. Vaccination represents an important prevention strategy in these patients, as several studies have reported lower infection rates and significantly reduced morbidity and mortality in hospitals adopting vaccination protocols. However, vaccination rates are particularly low in these patients, and the diminished immune responsiveness remains the main issue of vaccination in CKD patients. Besides, there are various immunization protocols across the world in the absence of optimal vaccination policies. This paper aims to discuss the current knowledge of vaccination in this immunocompromised group of patients based on recent evidence and recommendations.

P0707UREMIC TOXINS IMPAIR SKELETAL MUSCLE REGENERATION PROCESS INDUCING CELL CYCLE ARREST AND APOPTOSIS IN CULTURED MYOBLASTS

Abstract Background and Aims The loss of muscle mass and function has been related to chronic kidney disease (CKD). About 37% of dialysis patients show symptoms of sarcopenia and this has been related to an increased risk of mortality. Changes in sarcopenic muscle include the loss of its regenerative capacity due to a reduction in the number and function of satellite cells, the muscle stem cells. The concentration of serum uremic toxins (UT) increases in parallel to a decline in the glomerular filtration rate in patients with CKD and this uremia may be involved in the development of sarcopenia. Previous studies showed as serum concentration of UT found in the early stages of CKD inhibits myogenic differentiation of cultured myoblasts. Nevertheless, the effect of those concentrations found in the advanced stages of CKD has not been described. The study aimed to analyse whether UT affect the muscular regeneration process by modifying the proliferation capacity of myoblasts (activated satellite cells). Method Cultured mouse myoblasts C2C12 cells were used for all experiments. Cells were grown with 0% or 10% FBS culture media in the presence or absence of indoxyl sulphate and para-cresol at doses of 100µg/ml each one, which are similar to ones found in the advanced stages of CKD. Proliferation was evaluated by scratch wound healing and cell cycle by flow cytometry with propidium iodide and the fluorescent probe CFSE, an intracellular protein binding dye that is divided equally between daughter cells, allowing the discrimination of successive rounds of cell division. Chromosome condensation was assessed by immunofluorescence staining by confocal microscopy. Apoptosis was analysed by annexin V staining. Results C2C12 cells treated with UT shown a significant decrease in the proliferation rate. A significant delay in wound closure was observed in cells treated with UT compared to control cells. Myoblasts treated with UT suffered a significant decrease in the proliferation rate since the probe remained higher than in the vehicle-treated cells. Proliferating cells treated with UT suffered a dramatic cell cycle arrest between the phases S and G2/M. Chromosome condensation was also analysed, finding that in the presence of colcemid, vehicle-treated cells condensed their chromosomes, as expected, whereas UT-treated cells did not, suggesting that UT stop the cell cycle at any point before the entry of cells in the mitosis phase. Besides, there was strong phosphorylation of cdc2 in the presence of UT indicating that cdc2 and the complex cdc2-cyclin B were inactive. This result explains why cells did not enter in the mitosis phase under UT exposition. Finally, UT induced the death of proliferating C2C12 cells by apoptosis. Conclusion In the advanced stages of CKD, uremic toxins concentration increases, thereby inducing a dramatic arrest in the cell cycle of myoblasts, inactivating the cdc2-cyclin B complex, interrupting their proliferation and leading them towards cell apoptosis. These results point to a role of uremic toxins impairing the skeletal muscle regeneration process, which could be involved in CKD-related sarcopenia and frailty.

P0805SURPRISE QUESTION IN ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Nowadays, patients with end-stage chronic renal disease (ESRD) are initiating dialysis at more advanced ages and having multiple comorbidities. Since the initiation of dialysis in the elderly may not result in increased survival or quality of life, it would be useful to define prognostic criteria for those patients. We aim to evaluate the utility of the surprise question (“Would I be surprised if this patient died in the next 12 months?”) as a predictor of survival in elderly patients in advanced stages of chronic kidney disease (CKD). Method Retrospective cohort study of patients elder than 70 years with CKD stages 4 to 5 according to the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) who attended the CKD information consultation between March 2017 and November 2018. The answer to the surprise question was registered during that office visit. Demographic, clinical and laboratory data (including serum albumin) were analyzed and Charlson Comorbidity Index (CCI) was calculated. Continuous variables are presented as means (±SD) or medians (IQ range), according to normality, and categorical variables as frequencies. Comparisons between groups were made using Student’s T-test and Pearson Chi-squared test. Survival analysis was conducted using Kaplan-Meier test and Cox proportional hazard model. STATA software was used and a p&amp;lt;0.05 was considered significant. Results Of the 60 patients selected, 22 (36.7%) were female, 59 (98%) were white and the median age was 78.6±6.3 years. Half of these patients had diabetes mellitus with end-organ damage and 57% suffered from congestive heart failure. The response to the surprise question was “yes” in 31 (51.7%) patients and “no” in 29 (48.3%) patients. We did not find clinical or demographic differences among these groups. The patients were followed for 26 (20-31) months, during which 19 deaths occurred, 4 (21%) in the SQ-yes group and 15 (79%) in the SQ-no group. The response to the surprise question was associated with patients’ survival (KM – p=0.0009), with a positive and negative predictive values of 79% and 66%, respectively. The multivariate analysis (age, sex, race, serum albumin and CCI) showed that the answer to the SQ is an independent predictor of mortality (HR 0.27 [IC 0.08-0.86]). Conclusion The SQ seems to be a good predictor of survival in elderly patients in advanced stages of CKD and can be used to assess their prognosis in order to help deciding whether the patient is a good candidate to initiate dialysis or not.

MO036SINGLE NUCLEOTIDE POLYMORPHISMS OF THE CYP24A1 AND KL GENES ARE ASSOCIATED WITH THE EXTENT OF ARTERIAL CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Individuals with chronic kidney disease (CKD) constitute a population with an exceptionally high cardiovascular risk. Vascular calcification, a common finding in these patients, is a known contributor to cardiovascular disease and several studies suggest it has a certain genetic component. Single nucleotide polymorphisms (SNPs) associated with the extent of calcification in CKD patients could therefore be used to predict individual susceptibility to calcification and subsequent increased cardiovascular risk. We consequently searched for associations of SNPs from candidate genes of known implication in the pathogenesis of vascular calcification (encoding cytokines, extracellular matrix proteins, members of the RANK/RANKL/OPG axis and vitamin D metabolism proteins) with the extent of arterial calcium deposits in order to improve the risk prediction of cardiovascular events in CKD patients. Method The study was performed in 1439 individuals from the NEFRONA population, which include CKD patients (stages 2-3, 4-5, and dialysis) as well as healthy controls recruited from 81 Spanish hospitals. Individuals were genotyped with the iPLEXGOLD MassARRAY technology and Assay Design v4 software for 61 SNPs from 22 genes. A continuous vascular calcification score was calculated from the echogenicity of atherosclerotic plaques detected by ultrasonography in the carotid and femoral arteries. Among several other clinical variables, the presence of cardiovascular events during a 4-year follow up was collected. Association of SNPs with calcification extent was identified by univariate linear regression models. Multiple linear regression with backward elimination was used for the selection of an appropriate SNP-based model adjusted by age, sex and CKD stages. Finally, a Cox proportional hazard regression model was applied for the prediction of cardiovascular risk. Results Arterial calcification scores were higher with increasing age, male sex, and advanced CKD stages (all p&amp;lt;0.001), as expected. Univariate linear regression analyses of all SNPs with the arterial calcification score as dependent variable retrieved p-values &amp;lt;0.05 for 6 six of them (rs11568820, rs2248359, rs2296241, rs3102735, rs385564 and rs495392), which were selected for subsequent analyses. These polymorphisms were next included in a multivariate linear regression model with CKD stage, age and sex as additional independent variables. Only rs2296241 of CYP24A1 (estimate 0.36, 95% CI 0.14 to 0.58, p=0.001 for homocygous GG) and rs495392 of KL (estimate -0.39, 95% CI -0.69 to -0.09, p=0.011 for homocygous TT) remained independently associated with the extent of calcium deposits. Finally, using Cox regression models, it was determined that both the CKD stage (HR [for dialysis stage]=8.34, 95% CI 4.59 to 15.15, p&amp;lt;0.001) and the calcification score (HR=2.05, 95% CI 1.67 to 2.54, p&amp;lt;0.001) predicted the development of cardiovascular events. Considering all possible risk factors, no differences were found in the rate of development of cardiovascular events according to the genotype for the two associated polymorphisms: rs2296241 HR=1.13, 95% CI 0.87 to 1.48, p=0.36; rs495392 HR=0.80 95% CI 0.63 to 1.03, p=0.08. Conclusions Polymorphisms of KL and CYP24A1 genes are associated with the extent of calcification in CKD individuals although they lack the capacity to predict cardiovascular events. However, the echogenic determination of the extent of arterial calcium deposits in CKD patients seems a promising non-invasive, non-irradiating method for the scoring of calcification and even the prediction of cardiovascular events. Further genetic association studies using this technique could therefore yield valuable results.

P0857BURDEN OF ANEMIA ASSOCIATED WITH CHRONIC KIDNEY DISEASE IN DIALYSIS AND NON-DIALYSIS-DEPENDENT PATIENTS IN EUROPE: A REVIEW OF PUBLISHED EVIDENCE

Abstract Background and Aims Anaemia is a frequent complication in patients with chronic kidney disease (CKD). The aim of this literature review was to understand the prevalence and burden of anaemia associated with CKD, with a further focus on Europe. Method A targeted literature review was conducted to identify publications on prevalence estimates (search: January 2015 to August 2018), and a systematic literature review was performed to identify publications on humanistic and healthcare resource use (HRU) burden (search: from database inception to July 2018) using MEDLINE®, Embase®, Cochrane Library, and conference proceedings. These were complemented by grey literature searches. Citations were screened per predefined criteria to include observational studies and reviews. Case series/reports and conceptual model studies were excluded. The study population included patients with anaemia associated with CKD, irrespective of CKD stage, dialysis status, or modality. All searches were funded by GSK. Results After applying all inclusion and exclusion criteria, 18 publications were retained that contained prevalence data, of which 9 provided European data. Based on 9 publications, the prevalence of anaemia associated with CKD in European adults was reported to range from 12.8% to 61.5% (Figure). Prevalence was higher in older individuals (aged &amp;gt;60 years) and increased with more advanced CKD stages. However, the methodology used to identify anaemia was not consistent across studies. Anaemia was identified based on varying thresholds of haemoglobin (Hgb) levels per different clinical guidelines (Kidney Disease Improving Global Outcomes [KDIGO], N=4; World Health Organization [WHO], N=2; European Best Practice Guidelines [EBPG], N=3), use of anaemia treatment, or Hgb thresholds without a reference to a specified guideline. Most studies focused on later-stage CKD patients (3 − 5), with only 2 studies reporting rates for stage 1 and 2 patients. A total of 50 publications provided data on humanistic and HRU burden, 6 of which provided European data. The literature on humanistic and HRU burden showed adults with anaemia associated with CKD had significantly poorer health-related quality of life (HRQoL) compared with those without anaemia, with significantly lower Kidney Disease Quality of Life (KDQoL) scores reflecting poorer HRQoL observed in the following domains: symptoms/problems, effect of kidney disease, and burden of kidney disease. This finding was consistent irrespective of instrument used for HRQoL assessment. However, tools used were not specific to anaemia or anaemia associated with CKD, and publications did not mention whether thresholds for clinical meaningfulness had been identified and/or met. Publications on HRU in anaemia associated with CKD in Europe were sparse (N=1): this single published study reported increased HRU in CKD patients with anaemia compared with CKD patients without anaemia. Conclusion Prevalence rates of anaemia associated with CKD reported in Europe vary, with increased prevalence in later stages of CKD. Anaemia negatively impacts patient QoL and leads to increased HRU in patients with CKD. More data are needed to characterise anaemia in earlier stages of CKD and across different populations (e.g. patients with particular comorbidities or undergoing different types of dialysis) in European countries. Due to varied definitions of anaemia, it would be of interest to evaluate the extent of underdiagnosis and its impact on prevalence rates.

P0809LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PATIENTS WITH DIABETIC CHRONIC KIDNEY DISEASE

Abstract Background and Aims Left ventricle diastolic dysfunction (LVDD) is common cardiac changes in diabetic patients without renal insufficiency. LVDD is also frequently occurs in chronic kidney disease (CKD). Diabetic patients with CKD are at increased risk of developing cardiovascular diseases. Therefore, early detection and prevention of risk factors are critical. The aim of this study was to evaluate the impact of type 2 diabetes on left ventricular (LV) diastolic function among CKD stage 3 and 5 patients, and whether markers of fluid balance can predict LVDD. Method A total of 409 patients (age and sex matched non-diabetic CKD stage 3 [nDMCKD3], n = 106; diabetic CKD stage 3 [DMCKD3], n = 106; non-diabetic CKD stage 5 [nDMCKD5], n = 73; diabetic CKD stage 5 [DMCKD5], n = 124) were analyzed. The stage 3 CKD patients were retrospectively reviewed, and stage 5 CKD patients were prospectively analyzed. All cohort patients with stage 5 CKD were hospitalized to plan their first dialysis treatment. The following exclusion criteria were applied: ejection fraction less than 45%, history of coronary artery disease and/or intervention treatment, history of angina or myocardial infarction, abnormalities of cardiac rhythm, moderate or severe valvular heart diseases, systemic immunologic diseases, liver cirrhosis, malignancy, infection, and previous renal transplantation. Coronary artery disease having regional wall motion abnormalities on echocardiographic examination was also ruled out. Clinical and echocardiographic parameters were compared among groups. Echocardiography, bioimpedance spectroscopy, and serum NT-proBNP were analyzed in patients with stage 5 CKD. The LVDD was defined as E/é ratio greater than 15. Extracellular water/total body water (ECW/TBW) and NT-proBNP were used as markers of fluid balance. Results Patients with E/é ratio &amp;gt; 15 presented with more advanced stages of CKD. Prevalence of LVDD in patients with diabetes was higher compared to those without diabetes. Patients in DMCKD5 group demonstrated higher E/é ratios compared to those with nDMCKD5, DMCKD3, and nDMCKD3 (16.63±5.04 vs. 14.12±4.60 vs. 14.69±4.65 vs. 13.07±3.76, p &amp;lt; 0.001). The E/é ratio in patients with DMCKD5 were significantly higher than those with DMCKD3 (16.63±5.04 vs. 14.69±4.65, p = 0.003). In contrast, the E/é ratio was not significantly different between nDMCKD3 and nDMCKD5 patients (13.07±3.76 vs. 14.12±4.60, p = 0.099). The ECW/TBW in patients with DMCKD5 were significantly higher than nDMCKD5 patients (0.51±0.04 vs. 0.48±0.05, p &amp;lt;0.001). In a multiple regression analysis, the presence of diabetes, serum albumin level, NT-proBNP, and ECW/TBW were significantly associated with LVDD in CKD5 patients. Conclusion Our results suggest that an echocardiographic examination and assessment of volume status should routinely be performed in patients with type 2 DMCKD. Early detection of LVDD before clinical symptoms are apparent is important, regardless of the stage of DMCKD. Fluid overload could be one of the aggravating factors of LVDD in DMCKD patients. Early evaluation of volume status and control of fluid overload should be considered important therapeutic approaches for LVDD in DMCKD patients, especially for those in advanced stages.

P0784RAPID WEIGHT CHANGE OVER TIME IS A RISK FACTOR FOR ADVERSE OUTCOMES IN PREDIALYSIS CHRONIC KIDNEY DISEASE: RESULTS FORM KNOW-CKD STUDY

Abstract 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&amp;lt; to ≤-2.5 %/year (122 subjects), group 3; -2.5&amp;lt; to &amp;lt;2.5%/year (1642 subjects), group 4; 2.5≤ &amp;lt;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 &amp;lt;0.001, &amp;lt;0.001, =0.001 and &amp;lt;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 &amp;lt;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 &amp;lt;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.

P0037POPULATION CHARACTERISTICS ACROSS AN EXPANDED POOLED DATABASE OF MULTIPLE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE CLINICAL STUDIES

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and the fourth-leading cause of kidney failure. Over the past two decades, various studies have been conducted to characterize the natural history of ADPKD and investigate impacts of potential treatments on disease progression. Previously, we created a pooled longitudinal database of unique subjects from nine studies to evaluate and analyze outcomes. The database was expanded to include data from two recent tolvaptan (TOL) trials (156-13-210 and 156-13-211). Here, we describe the baseline characteristics of the expanded pooled population. Method Data from 11 ADPKD studies (from 2001 to 2018, sponsored by Otsuka or National Institutes of Health) were combined and divided into two groups: TOL and standard of care (SOC). TOL consisted of trial subjects initiating treatment in one of seven trials (156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271, and 156-13-210); SOC included subjects from placebo arms of two TOL randomized trials (156-04-251 and 156-09-290), all standard blood pressure control arms in the HALT-PKD trials, and subjects from two observational studies (156-10-291 and CRISP). Subjects in the placebo arm of study 156-13-210 received TOL for 5 weeks before randomization and were therefore included in the TOL group. Eligible subjects who completed an early TOL study continued TOL treatment in the extension study 156-08-271 and/or in a second extension study 156-13-211. Estimated glomerular filtration rate (eGFR) was calculated in all studies using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Total kidney volume (TKV) was measured by magnetic resonance imaging and available in all studies except 156-13-210, 156-13-211, and HALT-PKD study B. Results The pooled analysis included 7,117 eligible subjects (TOL: 2,928; SOC: 4,189) from the United States (47.5%) and other countries. The two cohorts had similar age (mean age, 43.6 vs. 44.1 years) and sex distribution (50.5% male vs. 45.2% male). The TOL group had more white subjects (90.5% vs. 80.7%) and fewer Hispanic subjects (4.0% vs. 12.6%), a lower baseline mean eGFR (60 vs. 70 mL/min/1.73 m2), more in chronic kidney disease (CKD) stage 3 or above (58.1% vs. 41.0%), and more frequent history of signs of rapid disease progression (e.g., nephrolithiasis, hematuria, urinary tract infection). Among 4,917 subjects with TKV assessments, mean baseline TKV was higher in the TOL group (1,817 mL) compared with SOC (1,627 mL). Conclusion In this large, longitudinal database of unique subjects with ADPKD, distinct differences exist in some baseline characteristics of the TOL and SOC groups. Compared with the previous database, the expanded database doubled the size of the TOL group and included more subjects who were older and with advanced chronic kidney disease stage. This database provides a diverse ADPKD population to assess outcomes.

P1457COMPARISON OF PEPTIDOMES BETWEEN URINE, PLASMA, AND HEMODIALYSIS FLUID INDICATES SELECTIVITY IN RENAL PEPTIDE PROCESSING

Abstract Background and Aims The physiological and related body fluids, urine, plasma and hemodialysis (HD) fluid spent dialysate (a mixture of technical HD fluid and patient´s ultrafiltrate) are rich biological sources of information especially in the context of kidney diseases. Of particular relevance are proteins and peptides, as they reflect essentially every biological process. Urine is produced as a result of glomerular plasma filtration and subsequent tubular reabsorption in the kidney. In analogy, HD spent dialysate is a result of ultrafiltration by an artificial kidney (dialysis membrane), but lacking tubular reabsorption and thereby accumulating in huge amounts of &amp;gt; 100 L per session comparable to primary urine. A recent study suggested that tubular reabsorption may be selective for specific proteins, and this process may represent a major difference between “natural” and artificial kidney. In this study, we aim at gaining insight into the composition of the peptidome/proteome in these body fluids of renal significance in a comprehensive analysis, in order to shed light on the relevant pathophysiological processes that take place in kidney, which may help developing better strategy in advanced-stage chronic kidney disease and detoxification in renal replacement therapies (RRT). Method We collected 15 plasma, 15 urine and 13 HD filtrate (spent dialysate during the first 30min of RRT) from age and sex matched subjects with stage 4 or above chronic kidney disease. Peptide identification and quantification were performed with capillary-electrophoresis coupled mass spectrometry and tandem mass spectrometry (CE-MS). The abundance, overlap and differences of the peptidome/proteome of the three body fluids were evaluated. Results We were able to detect 6281 urinary peptides, 1750 plasma peptides and 1728 peptides from spent dialysate. Of these we could identify 1764, 452 and 374 sequenced peptides, respectively Among them, there are 318 peptides detectable in both urine and spent dialysate, 307 detectable in both plasma and urine and only 191 detectable in both plasma and spent dialysate. Among the most abundant peptides in plasma were Thymosine-ß4 and fragments from hemoglobin, fibrinogen and collagen. In dialysate, the most abundant proteins detected in these patients were ß-2-microglobuline, Thymosine-ß4, and fragments from fibrinogen, while in urine fragments derived from collagen, albumin, and from alpha-1-antitrypsin were of the highest abundance. When investigating proteins/peptides found in at least 2 body fluids, a strong correlation in peptide abundance between urine and spent dialysate (P=4.2e-27, Rho=0.56), and a moderately strong correlation between HD fluid and plasma (P=3.7e-5, Rho=0.29) were detected. However, there is no significant correlation between peptide abundance in urine and plasma (P=0.22, Rho=0.07). Collagen peptides are the most abundant peptides in all three body fluids. Conclusion This dataset will serve as a valid basis to define the protein and peptide contents in blood, urine, and spent dialysate. The data show, as expected, substantial similarity between plasma and spent dialysate, but, surprisingly, very little similarity between urine and plasma. This further supports the hypothesis that tubular reabsorption may be selective for specific proteins and peptides, possibly excluding collagen-derived peptides. A more detailed investigation into the process and relevance of tubular reabsorption appears warranted in the light of the data. The fact that the samples investigated in this study are derived from advanced stage CKD patients must be taken into account, significant differences exist in comparison to urine produced by healthy kidney. The identification of molecular differences between urine and dialysate spent may present an opportunity to design future “biologically adapted” removal devices.

P0688GREATER MUSCLE STRENGTH IS ASSOCIATED WITH LOWER RISK OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Frailty is a known risk factor for chronic disease and mortality. However, the association between frailty assessed by hand grip strength (HGS) and chronic kidney disease (CKD) among adults has not been elucidated. This study evaluated the association between muscle strength and the risk of CKD. Method Data were retrieved from a nationwide cohort study (Korean National Health and Nutrition Examination Surveys VI-VII, 2014-2017) and participants aged 40 to 80 years were included in the study analysis (male=6,660, female=8,195). HGS was measured using digital hand dynamometer and normalized to body mass index (BMI). The association between the risk of CKD (estimated glomerular filtration rate [eGFR] &amp;lt;60 mL/min/1.73 m2 or the presence of proteinuria) and quartile of HGS per BMI was evaluated among male and female subjects. Results The mean age was 58.8 ± 11.6 years and mean eGFR level was 88.2 ± 18.7 mL/min/1.73 m2. The mean levels of HGS per BMI were 1.5 ± 0.3 and 0.9 ± 0.2 in male and female subjects, respectively. Those in higher quartile of HGS per BMI showed lower prevalences of advanced CKD stages than lowest quartile among both male and female subjects. When univariable logistic regression analysis for the risk of CKD was performed, higher quartile of HGS per BMI was significantly associated with lower risk of CKD in both male and female subjects. After adjustment for confounding factors including age, systolic blood pressure, smoking and alcohol intake, education and income levels, history of hypertension, diabetes, or arthritis, physical activity, baseline eGFR, total cholesterol, hemoglobin, and daily protein intake, the higher quartile of HGS per BMI were associated with lower risk of CKD in both male and female subjects (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.49-0.88 in Q4; OR, 0.64; 95% CI 0.49-0.83 in Q3 in male; OR, 0.59; 95% CI, 0.43-0.81 in Q4; OR, 0.61; 95% CI, 0.47-0.80 in Q3; OR, 0.70;95% CI, 0.55-0.90 in Q2 in female, Q1 as reference group). These associations were consistent when the HGS per BMI was treated as continuous variable that 34% and 54% of risk was reduced as 1 m2 increase in male and female subjects. Conclusion Greater muscle strength normalized to BMI is associated with lower risk of CKD in adults. These findings suggest that frailty in adults is an important risk factor for CKD development.

P0752THE EXPRESSION AND DIAGNOSTIC VALUE OF URINE ANGIOTENSINOGEN IN CHRONIC KIDNEY DISEASE

Abstract 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&amp;gt;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&amp;lt;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&amp;lt;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&amp;lt;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&amp;gt;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.

P0786CLINICAL SIGNIFICANCE AND RELATED FACTORS OF GFR SLOPE IN A LARGE MULTICENTER OBSERVATIONAL STUDY IN JAPAN

Abstract 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) &amp;lt;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.

Single-Nephron GFR in Patients With Obesity-Related Glomerulopathy

IntroductionObesity-related glomerulopathy (ORG) is a slowly progressive kidney disease occurring in association with obesity. It is characterized histopathologically by glomerulomegaly, likely caused by single-nephron hyperfiltration that has not been demonstrated in humans because of technical difficulty in measuring single-nephron glomerular filtration rate (SNGFR) in the clinical setting.MethodsTotal glomerular number per kidney, with or without global glomerulosclerosis, was estimated by the combination of cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Mean glomerular volume was calculated from the measured area of glomerular tufts. Both SNGFR and single-nephron urinary protein excretion (SNUPE) were estimated by dividing values for estimated glomerular filtration rate and urinary protein excretion by the number of nonsclerotic glomeruli. Living kidney donors were used as healthy controls.ResultsA total of 48 ORG patients with average nonsclerotic glomerular numbers of 456,000 ± 235,000 per kidney were included. The values for SNGFR in ORG patients with chronic kidney disease (CKD) stages 1 and 2 were higher than for nonobese and obese controls (97 ± 43 vs. 59 ± 21 vs. 64 ± 21 nl/min, respectively, P = 0.001). Nonsclerotic glomerular number decreased with advancing stages of renal functional impairment. The presence of ORG with more advanced CKD stages was associated with lower SNGFR and marked elevation in SNUPE levels, with no difference in the mean glomerular volume between the stages.ConclusionsThese results provide functional evidence for single-nephron hyperfiltration in patients with ORG, and identify compensatory failure to maintain effective SNGFR as a feature of advanced-stage ORG.