Aim:To investigate the possible effect of haemodialysis (HD) on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.Methods: A single-dose, open-label, parallel-group study of eight end-stage renal disease (ESRD) patients and eight matched healthy subjects was conducted. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with a 2-week washout between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood, dialysate, and urine samples were collected to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. Results:The GMRs for the maximum concentration and area under the concentration-time curve from time 0 to the last measurable timepoint (AUC last ) of evogliptin when administered before HD compared with after HD were 0.7293 (90% CI 0.6171-0.8620) and 0.9480 (90% CI 0.8162-1.1010), respectively. The maximum DPP-4 inhibitory effect, area under the DPP-4 inhibitory effect-time curve, and time duration of more than 80% DPP-4 inhibition were comparable when evogliptin was administered before and after HD. Compared with healthy subjects, the mean AUC last of evogliptin was approximately 1.4-fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy of evogliptin. Conclusion:The effect of HD on the PK and PD characteristics of evogliptin was not clinically significant; therefore, dose adjustment according to HD status is not necessary.

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Background and Aims This study analysed the association between body mass index (BMI) and waist circumference (WC) with all-cause death, 3-point major cardiovascular event (MACE), end-stage kidney disease (ESKD) and total composite events in nation-wide cohort of Korean advanced chronic kidney disease (CKD) patients. Method This nationwide cohort study, using the National Health Insurance Database, included adult health examinees who received two or more check-ups from 2009 to 2012. Among them, CKD patients (N = 325,657, stage G3a, G3b and 4) were identified. Patients were classified into three groups for BMI (<18.5, 18.5-25 [reference] and ≥25) and four groups for WC (female; <75 cm or male; <85 cm [WC1], female; 75 cm≤WC<85 cm or male; 85 cm≤WC<95 cm [reference], female; 85 cm≤WC<95 cm, male; 95 cm≤WC<105 cm [WC2] and female; ≥95 cm, male; ≥105 cm [WC3]). Risks were evaluated using Cox proportional hazard analysis. Results Patients (58.6±7.7 years) had mean eGFR of 54.32±5.83ml/min/1.73 m2. The underweight (BMI<18.5) group had increased risks of death [HR 1.757, 95% CI (1.573-1.964)] and total events [HR 1.244, (1.144-1.353)]. Overweight (BMI≥25) group showed lower risks of death [HR 0.888, (0.86-0.917)], ESKD [HR 0.855, (0.788-0.927)] and total events [HR 0.975, (0.956-0.995)]. However, the risk was increased for 3-point MACE [HR 1.056, (1.031-1.081)]. For the association between WC and clinical outcomes, the low WC group (WC1) had increased risk of death [HR 1.129, (1.089-1.17)] and reduced risk for 3-point MACE [HR 0.92, (0.894-0.947)]. In higher WC groups, increased risks were observed for death [WC2: HR 1.052, (1.008-1.098), WC3: HR 1.32, (1.213-1.437)], 3-point MACE [WC2: HR 1.071, (1.038-1.104), WC3: HR 1.104, (1.036-1.176)] and total events [WC2: HR 1.049, (1.022-1.077), WC3: HR 1.12, (1.062-1.181)]. Conclusion In CKD patients, both lower BMI and WC were risk factors for mortality and ESKD. However, compared to the reference group, higher BMI group exhibited better outcomes while higher WC groups exhibited poorer outcomes. As increased WC is more specifically related to central obesity, we need different approaches to interpreting clinical risks associated with different BMI and WC criteria.

IntroductionPatients with acute kidney injury (AKI) receiving renal replacement therapy constitute the subgroup of AKI with the highest risk of mortality. Despite recent promising findings on the neutrophil-to-lymphocyte ratio (NLR) in AKI, studies have not yet addressed the clinical implication of the NLR in this population. Therefore, we aimed to examine the prognostic value of NLR in critically ill patients requiring continuous renal replacement therapy (CRRT), especially focusing on temporal changes in NLR.MethodsWe enrolled 1,494 patients with AKI who received CRRT in five university hospitals in Korea between 2006 and 2021. NLR fold changes were calculated as the NLR on each day divided by the NLR value on the first day. We performed a multivariable Cox proportional hazard analysis to assess the association between the NLR fold change and 30-day mortality.ResultsThe NLR on day 1 did not differ between survivors and non-survivors; however, the NLR fold change on day 5 was significantly different. The highest quartile of NLR fold change during the first 5 days after CRRT initiation showed a significantly increased risk of death (hazard ratio [HR], 1.65; 95% confidence intervals (CI), 1.27–2.15) compared to the lowest quartile. NLR fold change as a continuous variable was an independent predictor of 30-day mortality (HR, 1.14; 95% CI, 1.05–1.23).ConclusionIn this study, we demonstrated an independent association between changes in NLR and mortality during the initial phase of CRRT in AKI patients receiving CRRT. Our findings provide evidence for the predictive role of changes in the NLR in this high-risk subgroup of AKI.

A prognostic model to determine an association between survival outcomes and clinical risk factors, such as the Cox model, has been developed over the past decades in the medical field. Although the data size containing subjects’ information gradually increases, the number of events is often relatively low as medical technology develops. Accordingly, poor discrimination and low predicted ability may occur between low- and high-risk groups. The main goal of this study was to evaluate the predicted probabilities with three existing competing risks models in variation with censoring rates. Three methods were illustrated and compared in a longitudinal study of a nationwide prospective cohort of patients with chronic kidney disease in Korea. The prediction accuracy and discrimination ability of the three methods were compared in terms of the Concordance index (C-index), Integrated Brier Score (IBS), and Calibration slope. In addition, we find that these methods have different performances when the effects are linear or nonlinear under various censoring rates.