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Background: Low bone mass is common in malnourished patients with chronic kidney disease (CKD) and can lead to a higher risk of fractures. Elderly and CKD patients have the same risk factors for protein-energy wasting, sarcopenia, and osteoporosis. Here, we investigated the association between phase angle (PhA) and bone mineral density (BMD) in dialysis-naïve patients with CKD stage 5 (CKD5) and identified a statistical relationship between PhA and age, which affects bone density. Methods: Bio-impedance spectroscopy for evaluating body composition and PhA and dual-energy X-ray absorptiometry for determining the BMD were simultaneously performed in 167 consecutive patients (mean age, 59.65 ± 13.98 years; women, 40.1%). Two-way analysis of variance (ANOVA) was conducted to assess the potential interaction effect of PhA and age on femoral neck BMD (FN-BMD). Results: Our results showed that PhA and age were independently associated with FN-BMD and T-score in multiple linear regressions analyses. A significant interaction effect of PhA and age on FN-BMD was found on two-way ANOVA (p = 0.028). The average BMD values for the first and second tertiles of the PhA were higher in the young versus elderly group, whereas patients in the elderly group had higher BMD in the third tertiles. Conclusions: A relationship was noted between PhA and BMD in patients with advanced-stage CKD. The effect of PhA level on FN-BMD differed between elderly and young patients. Our study suggested that higher PhA levels could be a marker explaining the maintenance of good bone health in elderly patients with CKD5. Further longitudinal analyses are needed to determine whether PhA predicts the risk of CKD-MBD-related fractures during CKD progression.

BackgroundThe prevalence of atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) is high and increasing; however, current evidence is insufficient and conflicting regarding oral anticoagulant (OAC) use in patients with ESKD and AF.MethodsA retrospective cohort study of patients diagnosed with AF after ESKD from January 2007 to December 2017 was conducted using the Korea National Health Insurance System Database. The primary outcome was all-cause death. Secondary outcomes were ischemic stroke, severe bleeding, and major adverse cardiovascular event (MACE). Outcomes were compared between OAC user and nonuser groups using landmark analysis (6 months after AF diagnosis) and 1:3 propensity score matching.ResultsAmong patients diagnosed with AF after ESKD, the number of patients prescribed any OAC increased 2.3-fold from 2012 (n=3,579) to 2018 (n=8,341), and the proportion prescribed direct OACs (among those prescribed any OAC) increased steadily from 0% in 2012 to 51.4% in 2018. Matched cohort analysis showed that compared with OAC nonusers, OAC users had a lower risk of all-cause death (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.58–86), ischemic stroke (HR 0.63; 95% CI 0.43–92), and MACE (HR 0.76; 95% CI 0.59–0.98) but no increased risk of severe bleeding (HR 1.58; 95% CI 0.99–2.52). Subgroup analysis according to type of OAC revealed that patients receiving direct OACs had a significantly lower risk of all-cause death (HR 0.44; 95% CI 0.28–0.69), ischemic stroke (HR 0.36; 95% CI 0.13–0.99), and MACE (HR 0.42; 95% CI 0.22–0.79) than OAC nonusers but no increased risk of severe bleeding (HR 0.26; 95% CI 0.04–1.90). Conversely, warfarin use was not associated with all-cause death (HR 0.98; 95% CI 0.79–1.21), ischemic stroke (HR 0.78; 95% CI 0.51–1.19), or MACE (HR 1.03; 95% CI 0.79–1.36) but was associated with a higher risk of severe bleeding (HR 2.43; 95% CI 1.50–3.93).ConclusionsIn patients with ESKD and AF, OACs were associated with reduced all-cause death, ischemic stroke, and MACE risks but no increased risk of severe bleeding. Direct OACs were preferable to warfarin with regard to efficacy and safety.Clinical PerspectiveWhat is new?Outcomes of oral anticoagulation in patients with end-stage kidney disease and atrial fibrillation are currently unknown.In this nationwide cohort study of patients with end-stage kidney disease and atrial fibrillation who had a CHA2DS2-VASc score of ≥ 1 (men) or ≥ 2 (women), oral anticoagulant therapy was associated with lower risks of all-cause death, stroke, and major adverse cardiovascular event but was no difference in severe bleeding, compared with no anticoagulation.When analyzing types of anticoagulants, these reduced risks were found in patients receiving direct oral anticoagulants but not warfarin.What are the clinical implications?Anticoagulation therapy may be superior to no anticoagulation in patients with end-stage kidney disease and atrial fibrillation.These findings require confirmation in randomized trials.

Background and Objectives: Although the need for anticoagulation to prevent thromboembolism is increasing and non-vitamin K antagonist oral anticoagulants (NOACs) have been tried, there is still controversy about the efficacy of anticoagulation in patients with dialysis. Materials and Methods: We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with atrial fibrillation (AF). We retrospectively analyzed all data of 89 patients who received dialysis therapy and were diagnosed with AF. Among them, 27 received anticoagulation (11 warfarin and 16 apixaban 2.5 mg twice a day), while 62 received no anticoagulation. Results: In multivariate Cox regression analysis, compared to no anticoagulation treatment, anticoagulation treatment was associated with a low incidence of all-cause mortality (hazard ratios (HR) 0.36; 95% confidence interval (CI) 0.15–0.88). Compared to no anticoagulation treatment, more anticoagulation treatment patients experienced severe bleeding (HR 4.67; 95% CI 1.26–17.25) and any bleeding (HR 2.79; 95% CI 1.01–7.74). Compared to no anticoagulation, warfarin treatment patients were associated with a low incidence of all-cause mortality (HR 0.26; 95% CI 0.09–0.81) and a high incidence of severe bleeding (HR 4.85; 95% CI 1.12–21.10). All-cause mortality and bleeding were not significantly different between no anticoagulation and apixaban treatment patients. Conclusions: In dialysis patients with AF, anticoagulation therapy is associated with an increased incidence of severe bleeding, but anticoagulation therapy is associated with a low incidence of all-cause mortality. Individualized anticoagulation therapy with careful bleeding monitoring is needed in dialysis patients with AF.

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were -23.58, -33.06, -35.00, and -38.13 in the fimasartan group vs. -8.74, -10.17, -14.91, and -19.71 in the losartan group, p 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

Background and Aims Atrial fibrillation (AF) is common arrhythmia in end stage renal disease patients. Although, the need of anticoagulation to prevent stroke and thromboembolism is increasing, the efficacy of anticoagulation is not proven in most of study. We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with AF. Method By using medical record, we retrospectively analyzed all data of 99 patients who received dialysis therapy and diagnosed AF. Results Among 99 patients who diagnosed AF with dialysis 36 patients received anticoagulation (17 coumadin, 19 apixaban 2.5mg bid), 63 patients received no anticoagulation. There was no significant difference of baseline characteristics between anticoagulation, and no anticoagulation patients. Although no anticoagulation group experienced more all-cause (39.7% vs 32.4%, p=0.572) and cardiovascular mortality (17.6% vs 10.8%, p=0.197) than anticoagulation group it was not statistically significant. Compared to apixaban 2.5mg bid patients, coumadin anticoagulation patients experienced more frequent mfig ajor adverse cardiovascular events (35.3% vs 15.8%, p=0.109) but it was not statistically significant in multi variate Cox regression analysis (Hazard ratio 1.143, 95% Confidence Interval 0.503-2.597). Conclusion Apixaban 2.5mg bid was not inferior than coumadin considering risk and benefit of anticoagulation in dialysis patients.

Osteopenia, sarcopenia, and increased vascular stiffness are common in patients with chronic kidney disease-mineral bone disorder (CKD-MBD) with protein energy wasting and can lead to worse clinical outcomes. We investigated the potential moderating role of the lean tissue index (LTI) in the relationship between bone microarchitecture and vascular stiffness in dialysis naïve patients with stage 5 CKD. Bioimpedance spectroscopy for evaluating LTI, lumbar spine dual energy X-ray absorptiometry for determining the trabecular bone score (TBS), and arterial applanation tonometry measurements for the central augmentation index, at a heart rate of 75 beats/minute (cAIx75), were simultaneously performed in 117 consecutive patients. A hierarchical regression analysis was conducted to assess the moderating effect of LTI on the relationship between TBS and cAIx75 after adjusting for age and sex. The effect of the interaction between LTI and TBS on cAIx75 was statistically significant (p = 0.030), demonstrating that the cAIx75 tends to decrease more, with the joint effect of LTI and TBS. In the separate analyses, the interaction effect was significant only in women (p = 0.048) and the group of diabetes (p = 0.042). Our study suggests that the evaluation of changes in body composition, bone health, and vascular stiffness needs to be performed simultaneously in patients with advanced-stage CKD. Further research in patients with different stages of CKD warranted to generalize and apply our results to patients in other stages.

BACKGROUND The usual calculation of body mass index (BMI) can be misleading in patients with advanced chronic kidney disease (CKD) because their altered fluid balances may not be reflected. We obtained corrected BMI (cBMI) and corrected Geriatric Nutritional Risk Index (cGNRI) values and investigated whether the impedance ratio (IR) of 200/5 kHz, measured using bioimpedance spectroscopy, was associated with cGNRI in older patients with nondialysis CKD stage 5 (CKD5-ND). METHODS Patients over 65 years old (n = 118) were divided into groups by cGNRI tertiles. The differences between the correlations were tested using Steiger's z-test. The IR and cBMI were used as both continuous and categorical variables in the regression analyses to determine the factors that were independently associated with the cGNRI. RESULTS Patients in the third cGNRI tertile had a significantly lower mean IR than those in the other 2 tertiles (P < .001). Across the 3 cGNRI tertile groups, the IR was incrementally lower in the higher cGNRI tertiles (P for trend < .001). The Steiger's z-test showed that the IR had a significantly stronger correlation with cGNRI than cBMI had with cGNRI. In the multivariable linear regression analyses, the IR was independently associated with the cGNRI, after adjusting for various confounders. CONCLUSION The current results revealed that the IR was a more sensitive indicator of nutrition risk than BMI and was independently associated with cGNRI in older patients with CKD5-ND. Our study suggests that the IR is an appropriate tool for nutrition risk screening.

Patients with chronic kidney disease (CKD) have a high prevalence of left ventricular hypertrophy (LVH), which increases as kidney function decreases. LVH pathophysiology is complex, making it difficult to generalise its evolution in CKD. Therefore, early detection and prevention of risk factors are critical. Assessment and management of volume status can minimise cardiovascular complications including LVH. We retrospectively investigated the associations between fluid overload and LVH in patients with stage 5 CKD not undergoing dialysis in prospective cohort of 205 patients (age: 59.34 ± 13.51 years; women: 43.4%). All patients, free of intrinsic heart disease, were assessed for relative overhydration/extracellular water (OH/ECW) by bioimpedance spectroscopy. Our results show that markers reflecting fluid balance were significantly higher in the LVH group and as OH/ECW increased, the left ventricular mass index (LVMI) trended higher. Furthermore, our results show that systolic blood pressure, serum phosphorus levels, and OH/ECW were independently associated with LVMI and that OH/ECW was independently associated with LVH. Structural and functional evaluation of the heart using echocardiography and volume status assessment using bioimpedance should be performed simultaneously in patients with early-stage CKD, even in those without evident cardiovascular disease.

Background:Regular monitoring of vascular access in patients on maintenance hemodialysis is important to detect early vascular access complications. We compared vascular access blood flow determined by blood temperature monitor and Doppler ultrasonography to evaluate the usefulness of blood temperature monitor.Methods:In total, 70 patients on maintenance hemodialysis were enrolled from three dialysis centers. Vascular access blood flow was measured thrice at 6-month intervals using Doppler ultrasonography to determine arterial inflow (Q-DUa), venous outflow (Q-DUv), and flow between punctures (Q-DUb) using BTM® (Q-BTM). Twister® was placed between the hemodialysis needle and blood lines, allowing simple reversal of flow without stopping the hemodialysis pump.Results:In total, 203 measurements were recorded, with median values (interquartile range) for Q-BTM, Q-DUa, Q-DUv, and Q-DUb of 1139.0 (868.0–1588.0) mL/min, 960.3 (658.7–1380.4) mL/min, 946.0 (552.0–1515.0) mL/min, and 1067.7 (544.8–1635.0) mL/min, respectively. For all measurements, the mean intraclass correlation coefficients were 0.52 (95% confidence interval, 0.36–0.64) for Q-DUa; 0.37 (95% confidence interval, 0.15–0.53) for Q-DUv; and 0.45 (95% confidence interval, 0.26–0.59) for Q-DUb. Analysis of a receiver operating characteristics curve yielded a cut-off of 627 mL/min for Q-BTM to predict stenosis.Conclusion:In patients on maintenance hemodialysis, blood flow measured by blood temperature monitor moderately correlated with Doppler blood flow. It was more related to arterial inflow than venous outflow or flow between punctures. The blood temperature monitor method was not inferior to Doppler ultrasonography. Therefore, blood temperature monitor could be recommended for routine vascular access monitoring because it can be done quickly without interrupting dialysis.

Background and Aims American College of Cardiology/American Heart Association (ACC/AHA) guidelines and cardiovascular disease (CVD) and chronic kidney disease (CKD) in diabetes patients remain unclear. We aimed to examine the effects of BP categories defined by the 2017 ACC/AHA guidelines in diabetes patients on the risk of CVD and CKD. Method In this population-based cohort study we analyzed data from the National Health Information Database in Korea during 2009-2017. The BP categories were defined as per the 2017 ACC/AHA guidelines: level 1 (systolic Results Overall, 490,352 diabetes patients (men 313,752 [64·0%], women 176,599 [36·0%]) were included in the analysis. Over a mean follow-up of 5 years, 6,508 CVD events occurred. Compared to people with BP levels 1, the adjusted hazard ratios (HRs) for CVD in people with BP levels 2, 3, and 4 were 1·07 (95% confidence interval [CI], 0·98-1·16), 1·12 (95% CI, 1·04-1·20) and 1·17 (95% CI, 1·08-1·26), respectively. There were also increased risks of CKD [1·18 (95% CI, 1·12-1·24) and 1·22 (95% CI, 1·15-1·29)], cerebrovascular disease [1·21 (95% CI, 1·14-1·29) and 1·52 (95% CI, 1·42-1·63)], and CVD mortality [1·31 (95% CI, 1·09-1·56) and 1·91 (95% CI, 1·58-2·32)] among subjects with BP levels 3 and 4 compared with those with BP level 1. Moreover, among people not taking antihypertensive medications, there were higher risks of CVD, CKD, cerebrovascular disease, and CVD mortality in those with BP levels 3 and 4 than in those with BP level 1. The risks of CVD, CKD, cerebrovascular disease, and CVD mortality significantly increased in patients with a systolic BP of 130 mmHg and diastolic BP of 80 mmHg. These findings provide evidence supporting the 2017 ACC/AHA guidelines for BP targets in diabetes patients. Conclusion The risks of CVD, CKD, cerebrovascular disease, and CVD mortality significantly increased in patients with a systolic BP of 130 mmHg and diastolic BP of 80 mmHg. These findings provide evidence supporting the 2017 ACC/AHA guidelines for BP targets in diabetes patients.

Background and Aims The demand for Kidney transplantation (KT) is increasing and the number of patients who are waiting for KT is steadily increasing. Therefore, there is an increasing prevalence of KT done by cadaver donor especially, expanded criteria donor. We used Kidney Donor Profile Index (KDPI) to predict the renal prognosis of expanded criteria donor (ECD) KT recipient. Method We investigated patients undergo KT by ECD from March 2013 to June 2018 respectively. Through the donor’s last creatinine level, KDPI score, and Kidney Donor Risk Index (KDRI) score the renal survival rate was compared with ROC curve analysis. Results The mean age of a total 59 ECD KT recipient is 53.85 ± 9.9 years old. Mean follow up duration after KT was 35.0 ± 18.5 months. 10 patients had KDPI score above 85 (KDPI ≥ 85). Five cases undergo dialysis after KT. Nine cases expired during follow up (four sepsis, three sudden cardiac arrest, one hyperkalemia). Glomerular filtration rate one year after KT was significantly associated with KDPI (r=-0.772, p Conclusion Our results show that KDPI could be used as an indicator for predicting the prognosis of the Korean ECD KT.

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 > 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 < 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 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.

Kidney transplantations using expanded criteria donors (ECD) are being increasingly adopted, but no consensus tools are available to evaluate donor kidney status. Beta-2 microglobulin (B2MG) is a marker of kidney function, and herein, we evaluate the usefulness of assessing B2MG to evaluate donor kidney status. Fifty-seven kidney transplantations were performed from March 2017 to April 2019. Medical records were retrospectively reviewed, and relationships between clinical and laboratory variables and transplant outcomes were investigated. Thirty-eight patients received a standard criteria donor kidney and 19 patients an ECD kidney. Ten patients experienced delayed graft function (DGF), but no patient experienced primary nonfunction. Of the parameters studied, only donor renal replacement therapy (RRT) [odds ratio (OR) 24.162; p = 0.018] and donor serum B2MG (OR 22.685; p = 0.022) significantly predicted DGF. The presence of either of these two risk factors can better reflect the condition of the donor than previous classification. However, on their last follow-up creatinine and estimated glomerular filtration rate values in those with or without these risk factors were not significantly different. For an ECD with a B2MG level of

Objectives Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the down-regulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE-5 inhibitor could preserve epithelial mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Materials and methods 10 weeks SD rats (N=24, 200 g, male) were divided (N=6) into four groups, which received: A LSD, L-NAME 1 mg/mL in drinking water, udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase-associated lipocalin), and cGMP were measured using ELISA. Kidney was subjected to evaluate PCNA (proliferative cell nuclear antigen), α-SMA (smooth muscle cell antigen), E-cadherin, and klotho expression. Results Urine cGMP decreased after treatment of PDE-5 inhibitor compared with control due to blocking degradation of cGMP (p

Aims The present extension study evaluated the long-term safety and efficacy of gemigliptin during a 40-week follow-up period after a 12-week study. Methods The main study was a randomized, placebo-controlled, double-blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) with moderate or severe renal impairment over a 12-week period. Patients with a glycated haemoglobin (HbA1c) level of 7-11% and an estimated glomerular filtration rate (eGFR) of 15–59 mL/min/1.73 m2 were enrolled in the main study. After 12 weeks, the patients in the gemigliptin group continued to receive gemigliptin (N = 50), whereas the patients in the placebo group were transitioned from placebo to linagliptin (N = 52). Each group received the indicated treatment over the subsequent 40-week period. A total of 102 patients consented to participate in the extension study, and 79 patients ultimately completed the study. Results The HbA1c levels of both groups were significantly reduced at week 52 compared with baseline. Specifically, the adjusted mean change ± standard error in the HbA1c level in the gemigliptin and placebo/linagliptin groups was 1.00 ± 0.21% and 0.65 ± 0.22% lower at week 52 than at baseline (P

Background Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. Methods Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection. We performed serum and urinary assays of creatinine and neutrophil gelatinase-associated lipocalin (NGAL) to estimate renal injury and performed Western blotting for endothelial nitric oxide synthase and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) to document the underlying mechanism. Results The CsA-treated group showed increased urinary creatinine excretion, polyuria, and renal glycosuria without GFR reduction, suggesting adequate CsA-induced renal tubular injury. Urinary NGAL excretion also increased significantly in the CsA group. Conversely, apelin attenuated CsA-induced tubular injury and had no effect on urinary NGAL excretion. In histopathologic examination, the apelin-treated group had lower tubulo-interstitial injury scores compared with those in the CsA group. Regarding the effects of apelin, our results indicate that apelin provides protection against CsA-induced tubular injury by activating nitric oxide and/or the NFATc1 pathway. Notably, we also found that CsA inhibits renal glucose reabsorption by reducing Na+-K+ ATPase expression and that apelin reverses reduced renal glucose reabsorption by CsA in tubular cells. Conclusions Our study demonstrates the renoprotective effect of apelin against CsA-induced renal tubular toxicity and provides novel insights into the effects of CsA and apelin on renal tubular cells.

BackgroundFluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease.MethodsBioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy.ResultsFluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors.ConclusionsFluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.

Early detection and regular monitoring of the nutritional status of patients with diabetic chronic kidney disease (DMCKD) with reliable tools are necessary. We aimed to determine the clinical significance of the phase angle (PhA) in patients with DMCKD stage 5 not undergoing dialysis. A total of 219 patients (non-diabetic CKD stage 5 [nDMCKD5], n = 84, diabetic CKD stage 5 [DMCKD5], n = 135) were analyzed. The nDMCKD5 group had a significantly higher PhA (p = 0.001), intracellular water/body weight (p = 0.001), and albumin level (p = 0.010) than the DMCKD5 group. The DMCKD5 group experienced significantly more overhydration (p &lt, 0.001). The PhA was positively associated with the lean tissue index (LTI) (r = 0.332, p &lt, 0.001), hemoglobin level (r = 0.223, p = 0.010), albumin level (r = 0.524, 0.001), and estimated glomerular filtration rate (eGFR, r = 0.204, p = 0.018) in the DMCKD5 group. Multivariate logistic regression analysis showed the eGFR (odds ratio [OR]: 0.824, 95% confidence interval [CI]: 0.698&ndash, 0.974), p = 0.023), LTI (OR: 0.771, 95% CI: 0.642&ndash, 0.926, p = 0.005), and albumin level (OR: 0.131, 95% CI: 0.051&ndash, 0.338, 0.001) were significantly associated with undernutrition (PhA &lt, 4.17&deg, ) in the DMCKD5 group. Our observations suggest that the PhA could be used as a marker to reflect the nutritional status in patients with DMCKD5.

The metabolic burden caused by hyperglycemia can result in direct and immediate metabolic injuries, such as oxidative stress and tissue inflammation, in the kidney. Furthermore, chronic hyperglycemia can lead to substantial structural changes such as formation of advanced glycation end-products, glomerular and tubular hypertrophy, and tissue fibrosis. Glomerular hypertrophy renders podocytes vulnerable to increased glomerular filtration, leading to podocyte instability and loss. Thus, prevention of glomerular hypertrophy and attenuation of glomerular hyperfiltration may have therapeutic potential for diabetic nephropathy (DN). Adiponectin is an adipokine that improves insulin sensitivity in obesity-related metabolic disorders, including diabetes, but its efficacy is unknown. Moreover, the recently developed adiponectin receptor agonist, AdipoRon, shows therapeutic potential for DN. In this review, we focus on the role of glomerular hypertrophy in the pathogenesis of DN and discuss the role of adiponectin in its prevention.

Introduction In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients. Subjects and methods This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262). Non-anuric (urine volume > 500 mL/day) subjects on PD were enrolled. Subjects in the control group received fluid management based on the clinical information alone. Those in the BIS group received BIS-guided fluid management along with clinical information. Results The subjects ( N = 137, mean age 51.3 ± 12.8 years, 54% male) were randomly assigned to the BIS group ( n = 67) or to the control group ( n = 70). There were no significant differences between the 2 groups with regard to age, sex ratio, cause of kidney failure, duration of PD, baseline comorbidity, RRF, PD method, or peritoneal transport type. At baseline, the 2 groups were not different in terms of RRF (glomerular filtration rate [GFR], 5.1 ± 2.9 vs 5.5 ± 3.7 mL/min/1.73 m2). After follow-up, changes in the GFR between the 2 groups were not different (-1.5 ± 2.4 vs -1.3 ± 2.6 mL/min/1.73 m2, p = 0.593). Over the 1-year study period, both groups maintained stability of various fluid status parameters. Between the 2 groups, there were no differences in the net change of various fluid status parameters such as overhydration (OH) and extracellular water/total body water (ECW/TBW). A net change in ECW over 1 year was slightly but significantly higher in the control group (net increase, 0.57 ± 1.27 vs 0.05 ± 1.63 L, p = 0.047). However, this difference was not translated into an improvement in RRF in the BIS group. There were no differences in echocardiographic parameters or arterial stiffness at the end of follow-up. Conclusion Routine BIS-guided fluid management in non-anuric PD patients did not provide additional benefit in volume control, RRF preservation, or cardiovascular (CV) parameters. However, our study cannot be generalized to the whole PD population. Further research is warranted in order to investigate the subpopulation of PD patients who may benefit from routine BIS-guided fluid management.

Introduction Patients with chronic kidney disease have an extremely high risk of developing cardiovascular disease (CVD). In patients with end-stage renal disease (ESRD), coronary artery calcification (CAC) is associated with increased mortality from CVD. Methods The present study aimed to investigate the risk factors for CAC in Korean patients with incident dialysis. Data on 423 patients with ESRD who started dialysis therapy between December 2012 and March 2014 were obtained from 10 university-affiliated hospitals. CAC was identified by using noncontrast-enhanced cardiac multidetector computed tomography. The CAC score was calculated according to the Agatston score, with CAC-positive subjects defined by an Agatston score >0. Findings Patients' mean age was 55.6 ± 14.6 years, and 64.1% were men. The CAC-positive rate was 63.8% (270 of 423). Results of univariate analyses showed significant differences in age, sex, etiology of ESRD and comorbid conditions according to the CAC score. However, results of multiple regression analysis showed that only a higher age was significantly associated with the CAC score. Receiver operating characteristic curves showed that the sensitivity and specificity of L-spine radiography for diagnosing CAC were 56% and 91%, respectively, for diagnosing CAC (area under the curve, 0.735). Discussion CAC was frequent in patients with incident dialysis, and multiple regression analysis showed that only age was significantly associated with the CAC score. In addition, L-spine radiography could be a helpful modality for diagnosing CAC in patients with incident dialysis.

Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients. Methods: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months

Background The utilization of expanded-criteria donors (ECDs) has increased to overcome donor shortages. Unfortunately, the discard rate has also increased, especially in ECDs with acute kidney injury (AKI). We evaluated the outcomes of kidney transplantation in ECDs and standard-criteria donors (SCDs) with and without AKI. Methods We reviewed the medical records of patients who underwent kidney transplantation. We used the AKI definition published by the Kidney Disease: Improving Global Outcomes group and reviewed the demographic characteristics of donors and recipients. We analyzed transplantation outcomes. Results Twenty-seven patients underwent kidney transplantation from ECDs with AKI ( n = 6) or without AKI ( n = 5) and SCDs with AKI ( n = 6) or without AKI ( n = 10). Initial creatinine and estimated glomerular filtration rate (eGFR) were not significantly different between the groups. The incidence of delayed graft function was highest in ECDs with AKI ( n = 3; 36.4%), but this was not a significantly difference. There was no difference in the last creatinine and eGFR in ECDs with AKI (1.32 mg/dL, 58.7 mL/min/1.73 m 2 ), ECDs without AKI (1.67 mg/dL, 44.2 mL/min/1.73 m 2 ), SCDs with AKI (0.94 mg/dL, 81.5 mL/min/1.73 m 2 ) and SCDs without AKI (0.97 mg/dL, 81.8 mL/min/1.73 m 2 ). Conclusions As the donor pool is extended to ECDs, young transplant surgeons may increasingly face decisions regarding ECDs with AKI or allocation failure. There is no consensus regarding discard criteria. However, if the donor showed initially normal creatinine levels or if dual-kidney transplantation can be performed, young transplant surgeons should not hesitate to use ECDs with AKI or allocation failure.

Delta neutrophil index (DNI), representing an elevated fraction of circulating immature granulocyte in acute infection, has been reported as a useful, predictable marker for mortality in patients with sepsis. We have hypothesized that an increased recipient DNI is associated with poor prognosis in cadaver donor kidney transplantation.We investigated patients undergoing kidney transplantation from cadaver donors from March 2013 to January 2018. Rejection was diagnosed by kidney biopsy with Banff classification and excluded subclinical rejection.In a total of 73 patients undergoing cadaver kidney transplantation, 25 (34.2%) patients were diagnosed with rejection based on the Banff classification. Among them, 11 patients were diagnosed with early rejection. The recipients' postoperative DNI (%) was different between patients with early rejection and patients without rejection (0.18 vs 1.21, P .001). In the univariate logistic regression analysis, cold ischemic time, donor preoperative last creatinine level, postoperative DNI level, and perioperative infection were predictive of early rejection. However, in a multivariate adjusted logistic regression test, only a high level of DNI (odds ratio 12.307, 95% confidence interval [CI] 1.22-129.82) was associated with early rejection. The C-statistic was 0.777 (95% CI 0.604-0.951, P = .004) for DNI. In multivariate Cox regression analysis, the donor's last creatinine level (hazard ratio 2.25, 95% CI 1.26-4.13) and preoperative DNI (hazard ratio 14.02 95% CI 2.62-75.26) were predictors of renal survival.Increased DNI in cadaver donor kidney transplantation recipients might be one of the predictive values of early kidney rejection and prognosis.

Background: Fluid overload and protein-energy wasting (PEW) are common in patients with end-stage renal disease (ESRD) and lead to a poor prognosis. We aimed to evaluate the volume and nutritional status of ESRD patients and to determine the clinical significance of phase angle (PhA). Methods: This study was a cross-sectional comparison of bioimpedance spectroscopy (BIS) findings in patients with non-dialysis chronic kidney disease (CKD) stage 5 (CKD5-ND, N = 80) and age/sex-matched peritoneal dialysis patients (PD, N = 80). PEW was defined as a PhA less than 4.5&deg, Results: The PhA was found to be positively associated with a geriatric nutritional risk index (GNRI, r = 0.561, p &lt, 0.001), lean tissue index (LTI, r = 0.473, p &lt, 0.001), and albumin (r = 0.565, p &lt, 0.001) while OH/ECW (r = &minus, 0.824, p &lt, 0.001) showed an inverse correlation. The CKD5-ND group had more overhydration (p = 0.027). The PD group had significantly higher PhA (p = 0.023), GNRI (p = 0.005), hemoglobin (p &lt, 0.001), and albumin (p = 0.003) than the CKD5-ND group. The cut-off values predicting PEW were found to be 3.55 g/dL for albumin, 94.9 for GNRI, and 12.95 kg/m2 for LTI in PD patients. Conclusions: This study demonstrated that PhA could be used as a marker to reflect nutritional status in patients with ESRD. Since BIS can inform both volume and nutritional status, regular monitoring will provide the basis for active correction of fluid overload and nutritional supplementation, which may improve outcomes in patients with ESRD.

Objective Malnutrition is very complex in patients with end-stage renal disease (ESRD) and is associated with poor prognosis. This is because hemodynamic changes, hormonal changes, persistent inflammatory reactions, and fluid overloads are more complicated as uremia is worsening. Bio-impedance spectroscopy (BIS) is a useful method to estimate fluid balance (Overhydration/ extracellular water, OH/ECW) and nutritional status (Phase angle, PhA). We aimed to evaluate the volume and nutritional status by BIS and to investigate the relationship between the appetite regulating hormones and the parameters of BIS in patients with stage 5 chronic kidney disease not undergoing dialysis (CKD5-ND). Methods We enrolled a total of 91 CKD5-ND patients. We measured routine serum markers including albumin and NT-proBNP and the appetite regulating hormones, leptin and ghrelin. We defined poor nutritional status as a PhA < 4.5°, and proper nutritional status as a PhA ≥ 4.5°. We also evaluated each patient’s nutritional status by assessing their geriatric nutritional risk index (GNRI) and their volume status by measuring NT-proBNP. Results Forty-one patients (45%) had poor nutritional status. Patients with a poor nutritional status had significantly higher OH/ECW (29.6 ± 12.7% vs. 6.2 ± 10.3%, p

Kidney transplantation is the preferred treatment in end stage renal disease for autosomal dominant polycystic kidney disease (ADPKD) patients. Removal of the native kidney is not usually recommended for ADPKD patients during a transplantation proce- dure because the operation time may be prolonged or the risk of bleeding may be higher. Therefore, native kidney removal is indicated for patients with chronic pain by enlarged kidney, frequent complications from cysts, such as infection or bleeding, and renal tumor development. Here, we report a case of a patient whose native kidneys were removed during a kidney trans- plantation procedure, and multifocal adenomas were identified in the removed kidneys after the procedure.

AIMS Urinary cystatin C has been suggested as a useful biomarker for diagnosis of acute kidney injury (AKI). Multiple myeloma is often complicated by AKI. Therefore, we investigated whether the urinary cystatin C was available for diagnosis of AKI in multiple myeloma. MATERIALS AND METHODS This study included 39 patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. We reviewed the medical records retrospectively and investigated whether urinary γ-globulin and myeloma progression had effects on urinary cystatin C excretion. RESULTS Spearman's correlation analysis showed that serum β2-microglobulin and serum cystatin C had a significant positive correlation with the urinary cystatin C excretion (r = 0.513, p = 0.001, r = 0.659, p < 0.001) and FEcystatinC (r = 0.585, p = 0.002, r = 0.711, p < 0.001). The GFRcr also had a significant negative correlation with the urinary cystatin C excretion (r = -0.582, p < 0.001) and FEcystatinC (r = -0.474, p = 0.002). In addition, the urinary γ-globulin had a significant positive correlation with the urinary cystatin C excretion (r = 0.678, p < 0.001) and FEcystatinC (r = 0.731, p < 0.001). Urinary γ-globulin was the most significant factor to influence urinary cystatin C excretion in multiple regression test. CONCLUSION These results indicate that urinary γ-globulin and myeloma progression can increase the fractional and total excretion of urinary cystatin C. Therefore, it is believed that the urinary cystatin C can be affected by urinary γ-globulin and myeloma progression in the diagnosis of AKI in multiple myeloma. In addition, urinary γ-globulin is believed to be the most significant factor to influence on urinary cystatin C.

Background The cyclosporin A (CsA) nephrotoxicity limits its usefulness as an immunosuppression. We studied the administration of both nitroprusside and phosphodiesterase-5 inhibitor (udenafil) in order to determine whether these agents could ameliorate the renal injury in CsA nephrotoxicity. Methods 30 8-week-old SD rats were divided into 5 groups: the control (1), SQ with 15 mg/kg CsA (Group 2), CsA along with 5 mg/kg IP nitroprusside (Group 3), CsA with 10 mg/kg PO udenafil (Group 4), and CsA with udenafil and nitroprusside (Group 5). Results Group showed an increase in creatinine compared o the control group. Group 5 showed a decrease in creatinine compared to Group 2. In TUNEL, Group 2 increased apoptosis in proximal tubules compared to control. Group 5 showed a decrease in apoptosis compared to Groups 2, 3, and 4. In IHC, the eNOS in Group 2 was stronger than in the controls. Groups 3, 4, and 5 showed decreased staining intensity compared to Group 2. In IHC, the VEGF in Groups 2, 3, and 4 increased compared to the controls. The eNOS protein expression was increased in both Groups 3 and 5 compared to the controls. The VEGF protein expression was increased in Groups 3 and 5 compared to Group 2. The eNOS mRNA was decreased in Group 2 compared to the control group and tended to increase in Groups 3, 4, and 5 compared to Group 2. The VEGF mRNA was increased in Group 2 and tended to increase more in Groups 3 and 5. Conclusion The udenafil and nitroprusside ameliorated renal injury in rat model of CsA nephrotoxicity. The mechanism appears to be associated with decreasing tubular apoptosis by decreasing eNOS and increasing VEGF.

Background Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to diastolic dysfunction and heart failure. We investigated whether markers of fluid status, such as NT-proBNP and bioimpedance spectroscopy (BIS), can predict echocardiographic findings of diastolic dysfunction in non-dialysis CKD5 patients. Methods BIS, echocardiography, and measurement of serum NT-proBNP were performed in patients with non-dialysis CKD stage 5 at a single study visit. E/e´ ratio reflect mean LV diastolic pressure and a ratio greater than 15 was used as a definition of diastolic dysfunction. Results Eighty-four patients were analyzed. Forty-six patients (54.76%) had E/e´ ratio ≤15 and 38 patients (45.24%) had E/e´ > 15 (diastolic dysfunction). Patients with E/e´>15 had significantly higher serum NT-proBNP (14,650 pg/mL) than patients with to E/e´≤15 (4,271 pg/mL) and had more overhydration (OH), 5.1 liters compared to 2.4 liters. The cut-off values predicting diastolic dysfunction were found to be 2,797 pg/mL for NT-proBNP and 2.45 liters for OH. Conclusions Regular monitoring of fluid status by BIS and NT-proBNP can be used to find patient with risk of developing diastolic dysfunction. Treatments to correct fluid overload may reduce the risk of developing diastolic dysfunction and improve cardiovascular outcome in patients with CKD.

The measurement of glomerular filtration rate (GFR) applying serum creatinine (Cr) does not reflect the GFR of patients accurately, and thus recently, studies on the measurement of GFR applying serum cystatin-C (Cys-C) have been conducted. We investigated the relationship between Cys-C and proteinuria in patients with chronic kidney disease.We compared the biochemical test, including serum Cys-C, the amount of proteinuria and the concentration of Cys-C measured by the 24-h urine test, and the difference of GFR on 105 patients who visited our hospital in 6 months (January to June 2007).Among 105 patients, 58 patients were males, and the mean age was 56.74 ± 16.31 years. With regard to underlying diseases, the group with diabetes had 76 patients and the group showing nephrotic proteinuria [nephrotic syndrome (NS)] had 29 patients. The GFR-Cys-C in the NS group (44.17 ± 26.32 mL/min) was higher than in the non-NS group (33.68 ± 14.29 mL/min; p = 0.041). The fractional excretion (FE) of Cys-C increased according to FE of albumin ( p = 0.000) and GFR-modification of diet in renal disease (MDRD) equation (p = 0.000). Serum Cys-C increased according to corrected urine Cys-C (p = 0.010). The GFR calculated by serum Cys-C decreased according to FE of albumin (p = 0.003). The degree of difference between GFR-Cys-C and GFR-MDRD was negatively correlated according to the FE of albumin (p = 0.001).We confirmed that urinary excretion of Cys-C could be altered by previously known mechanisms such as proteinuria. Difference between GFR-Cys-C and GFR-MDRD was negatively correlated according to FE of albumin.

Background: Alcoholic ketoacidosis (AKA) is known as a benign disease, but the related mortality reported in Korea is high. Acidosis and alcohol change the immunity profile, and these changes can be identified early using the delta neutrophil index (DNI). We aimed to evaluate the use of DNI and other standard laboratory parameters as predictors of prognosis in AKA patients. Methods: One hundred eighteen males with AKA were evaluated at the Wonju Severance Christian hospital between 2009 and 2014. We performed a retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating characteristic curves (ROC) and multivariate Cox regression was used to identify renal survival and mortality. Results: Survival patients had lower initial DNI levels than non-survival patients (4.8±6.4 vs 11.4±12.5, p