Delafontaine, Phebe

Schepers, Eva

Van Biesen, Wim

Vanholder, Raymond

Verbeke, Francis

Ghent University Academic Bibliography

mass index (BMI) and the rate of progression of CKD has been less well studied.Thisstudy aims to determine the relationship between BMI and progression of CKDadjusted for major confounding factors.METHODS: Retrospective, observational study in a cohort of adult patients with CKDstage 4-5 not yet on dialysis. Patients with recent acute kidney injury or those with glo-merular diseases or vasculitis under immunosuppressive therapy were excluded.Theslope of the regression line of eGFR (MDRD) over time (ml/min/1.73m2/year) wasused to assess the rate of renal failure progression.Patients were divided into 3 sub-groups according to BMI:<25, 25-30, and>30 kg/m2.RESULTS: The study group consisted of 915 patients (mean age 65614 years, 48%women) with a median follow-up time of 23months. Mean eGFR slope was -3.3564.44 ml/min/1.73m2/year.A BMI of 25 kg/m2 represented the cut-off point belowwhich the progression of CKD turn out to be faster. Themean decline of renal functionin this subgroup was significantly faster than the rest of the patients: -4.4164.77 vs. -3.0664.31 ml/min/1.73m2/year (p<0.0001). These 196 patients with a BMI<25 kg/m2were significantly younger, with less comorbidity, well controlled blood pressure withless medication, lower markers of malnutrition and inflammation, and similar protei-nuria, although the number of current smokers was significantly greater.Both BMI as acontinuous and as a dummy variable (BMI below 25 kg/m2) were significant and inde-pendently associated with the rate of progression of CKD (ß¼ 0.103; p¼0.001, and ß¼ -0.121; p<0.0001, respectively) in multivariate linear regression analysis adjustedfor age, sex, comorbidity, CKD etiology, blood pressure, proteinuria, and prescribedmedication.CONCLUSIONS:While obesity is a risk factor for developing CKD, being thin is inde-pendent and significantly associated with a faster progression of CKD at later stages.This association cannot be explained by age, sex, comorbidity, malnutrition-inflamma-tion, and it is independent of CKD etiology, blood pressure or proteinuria.FP317 PROTEINURIA DECREASES IN THE ACTIVITY OF FIBROBLASTGROWTH FACTOR 23 AND REDUCED FGF23 ACTIVITY ISASSOCIATED WITH RENAL PROGRESSION IN PATIENTS WITHCHRONIC KIDNEY DISEASE: RESULT FROM KNOW-CKDSTUDYJee young Lee1, Hae-Ryong Yun1, Jung Tak Park11Department of Internal Medicine, College of Medicine, Institute of Kidney DiseaseResearch, Yonsei University, Seoul, Korea, Republic ofINTRODUCTIONANDAIMS: Both of proteinuria and hyperphosphatemia are wellknown risk factors of CKD progression. Recent experimental study reported that pro-teinuria increases serum phosphate by decreasing biologic activity of fibroblast growthfactor 23 (FGF-23). We examined this relationship in a large chronic kidney disease(CKD) cohort and evaluated combined effect of proteinuria and serum phosphate onCKD progression.METHODS: This prospective longitudinal study was conducted with 1909 patientswho were measured 24 hour urine protein (24h UP) and serum phosphate from theKoreaN cohort study for Outcome in patients with CKD (KNOW-CKD). The activityof FGF-23, measured by fractional excretion of phosphate (FEP)/FGF23 ratio, wascompared according to the degree of proteinuria. Primary outcome was CKD progres-sion defined as50% decline of estimated glomerular filtration rate (eGFR), doublingof serum creatinine, or start of dialysis.RESULTS: Themean age was 53.96 12.1 years, and 60.8% of patients were male. Themean eGFR was 50.66 30.4 mL/min/1.73m2. There was a significantly negative rela-tionship between 24h UP and FEP/FGF-23 ratio after adjustment of multiple con-founders (b, -0.06; P¼ 0.028). In addition, patients with more proteinuria hadsignificantly higher serum phosphate levels from CKD stage 2 to 5 than those with lessproteinuria. After matching variables associated with serum phosphate, patients withmore proteinuria had higher serum phosphate (P< 0.001) and FGF-23 (P¼ 0.045),and lower FEP/FGF-23 ratio (P¼ 0.001) compared to those with less proteinuria. Inthe propensity matched-cohort, 185 (21.7%) events of CKD progression were occurredduring the median follow-up of 33.2 months. Inmultivariable stratified Cox regressionmodel, low FEP/FGF-23 ratio was a significant risk factor of composite renal outcome(hazard ratio, 0.90 per 1 log increase; 95% confidence interval, 0.82-0.99; P¼ 0.03).Furthermore, there was a significant interaction between 24h UP and serum phosphateon CKD progression (P< 0.001).CONCLUSIONS: Proteinuria is associated with hyperphosphatemia and reduced bio-logic activity of FGF-23. Furthermore, diminished activity of FGF23 is an independentrisk factor for renal progression in proteinuric CKD patients.FP318 IMPACT OF THE METRIC USED TO DEFINE PROGRESSION OFKIDNEY FAILURE ON THE CONCLUSIONS OF STUDIESPhebe Delafontaine1, Eva Schepers1, Raymond Vanholder1, Francis Verbeke1,Wim Van Biesen11Renal Division, Ghent University Hospital, Ghent, BelgiumINTRODUCTIONANDAIMS: Chronic kidney disease (CKD) is a common non-communicable disease. Some but not all patients will progress to end stage renal disease(ESRD), and this at different speeds. Accurate estimation of rate of progression is ofimportance for individual prognostication, and in studies evaluating interventions toslow down progression. Especially for this indication, high accuracy is essential. AsESRD (the hard clinical endpoint) occurs only after a long period, there is a need forsurrogate endpoints. At present, there is no consensus on which surrogate endpoint touse as metric. A variety of metrics is applied, and over different time frames, leading toa lack of comparability between study results. We intended to investigate the agreementamong the most commonly used surrogate endpoints for progression of CKD to ESRDto assess their impact on conclusions of studies.METHODS: All serum creatinine values of a longitudinal cohort of 169 patients withCKD attending the nephrology outpatient clinic of a university hospital were collected.Patients were classified as progressors vs non progressor based on eleven different met-rics within 3major categories: 1/ visual analysis of the data by a panel of 9 nephrologistsusing three differently plotted graphs; 2/ interpretation based on commonly used sur-rogate endpoints in clinical trials 3/ an analysis using composite endpoints. For 2 and 3,a systematic search onmetrics used in RCTs was performed to select potential candi-dates. For all different methods, inter rater reliability (IRR) was assessed based on theCohen’s kappa statistic.RESULTS: All calculated Cohen’s kappa values stayed (far) beneath the required limitfor adequate agreement in healthcare research (for examples, see table). The panel ofnephrologists could not come to a coherent classification of a patient being a progressoror not based on visual interpretation of eGFR graphs. Also, classification of patientsbased on the surrogate endpoints currently used in research and on the assessed com-posite endpoints to evaluate progression to ESRD was not consistent neither amongstthe different surrogate metrics nor with the nephrologists opinion. There was also alack of agreement between the samemetrics when used over 5 or 10 year timeframes.CONCLUSIONS:Our results confirm a lack of agreed definition of progression ofCKD to ESKD using surrogate metrics. This confirmed lack of agreement is an impor-tant issue, as conclusions of studies assessing interventions to slow down progressionapparently will differ based on the selected surrogate marker.Examples of IRRmethod 1 method 2 kappa 95%CIMetric A 5 years Metric 10 10 years 0.59 0.30-0.89Metric A 5 years Nephrologist panel 0.03 -0.13-0.14Metric A 5 years Metric B 5 years 0.16 -0.01-0.30Metric B at 5 years Nephrology panel 0.12 -0.07-0.31FP319 NRF2 ACTIVATOR, RTADH404, ATTENUATES RENALTUBULAR INJURY VIA MITOCHONDRIAL PROTECTION INNEPHROTIC MODEL MICEYuji Sogawa1, Kidokoro, Yoshisuke Haruna, Minoru Satoh Hajime Nagasu,Megumi Kondo, Yoshihisa Wada, Kengo, Tamaki Sasaki, Naoki Kashihara1Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, JapanINTRODUCTIONANDAIMS:Nephrotic syndrome, including diabetic kidney dis-eases (DKD), leads to renal failure due to severe proteinuria. Urinary protein isresorbed in proximal tubular cells, and lipid peroxidation combined with albumininduced reactive oxidative species (ROS) via mitochondrial dysfunction. These factssuggested regulation of ROS is one of the therapeutic strategies for DKDwith proteinu-ria. So, we focus on NF-E2-related factor 2 (Nrf2) which is a master regulator for thecellular defense against oxidative stress. Recently study, tubulointerstitial damage byischemic-reperfusion injury was exacerbated in Nrf2 knockout mice (Nrf2KO). Nrf2activator has a renoprotective effect by eliminating excessive ROS. However, the mech-anisms of renoprotective effect are not fully understood, especially in DKD.We thusinvestigated whether RTAdh404 attenuates proteinuria-induced renal tubular damagevia mitochondrial protection.METHODS: To know the effect of RTAdh404 for proteinuria induced tubular injury,Three-week-old male ICR-derived glomerulonephritis mice (ICGN), which developnephrotic syndrome, and ICRmice were used. Themice were divided into threegroups: ICR, ICGNþVehicle (Vehi), and ICGNþRTAdh404 (dh404). dh404 was dis-solved in sesame oil and administered orally for three weeks (dh404;10mg/kg/day)).Blood, urine and kidney tissue samples were harvested after 3 weeks of treatment.Serum creatinine/urea nitrogen was evaluated as a renal function. Tubular damage wasevaluated by urinary N-GAL and KIM-1 staining. Fibrotic changes were evaluated bymasson staining and collagen IV staining. Mitochondrial function was assessed byCOX staining and transmission electron microscope (TEM). Next, in vitro study,human proximal tubular epithelial cells (hPTECs) were used to determine the mecha-nism of renal protective effect by dh404. hPTECwere stimulated with bovine serumalbumin(BSA) binding to free fatty acid (FFA) and treated with or without dh404 forsix hours.RESULTS: In ICGNþVehi groups, renal function, based on the serum creatinine andurea nitrogen, was significantly exacerbated. dH404 was able to attenuate renal dys-function in ICGNmice. Then Tubulointerstitial injury and fibrotic change were signifi-cantly worsened. Mitochondrial respiratory enzyme and the mitochondrial formationwere injured. These damages were improved in ICGNþdh404 groups. These data sug-gest that RTAdh404 has a renoprotective effect via mitochondrial protection. In vitroAbstracts Nephrology Dialysis Transplantationi138 | AbstractsDownloaded from https://academic.oup.com/ndt/article-abstract/33/suppl_1/i138/4997422by Ghent University useron 20 July 2018

Impact of the metric used to define progression of kidney failure on the conclusions of studies

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Impact of the metric used to define progression of kidney failure on the conclusions of studies

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