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Background/Aims Obesity has known to be a modifiable risk factor associated with worse outcomes in chronic kidney disease (CKD), but few studies have examined the impact of obesity on CKD incidence in the general population. The purpose of this study was to investigate the role of body mass index (BMI) and waist-to-hip ratio (WHR) as predictors of incident CKD and to evaluate the impact of weight reduction on CKD prevention. Methods A total of 2,711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. Results During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00–1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07–1.66; p = 0.009). In the Kaplan–Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). Conclusions Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

Abstract While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan–Meier curve analysis (P

Introduction: Despite the pivotal role of hepcidin in the development of anemia among the patients with chronic kidney disease (CKD), the association between serum hepcidin levels and CKD progression has been never investigated. We here hypothesized that elevation in serum hepcidin levels might be associated with the risk of incident end-stage kidney disease (ESKD) among the patients with pre-dialysis CKD. Methods: A total of 2,109 patients with pre-dialysis CKD at stages 1 to pre-dialysis 5 were categorized into the quartiles by serum hepcidin levels. The study outcome was incident ESKD. The median duration of follow-up was 7.9 years. Results: The analysis of the baseline characteristics revealed that unfavorable clinical features were in general associated with higher serum hepcidin levels. The cumulative incidence of ESKD was significantly differed by serum hepcidin levels, with the highest incidence in the 4th quartile (p < 0.001, by log-rank test). Cox regression analysis demonstrated that, compared to the 1st quartile, the risk of incident ESKD is significantly increased in the 4th quartile (adjusted hazard ratio 1.372, 95% confidence interval 1.070–1.759). Penalized spline curve analysis illustrated a linear, positive correlation between serum hepcidin levels and the risk of incident ESKD. Subgroup analyses revealed that the association is significantly more prominent in the patients with advanced CKD (i.e., estimated glomerular filtration rate

Abstract Background Underweight status increases the risk of cardiovascular disease and mortality in the general population. However, whether underweight status is associated with an increased risk of developing end‐stage kidney disease is unknown. Methods A total of 9 845 420 participants aged ≥20 years who underwent health checkups were identified from the Korean National Health Insurance Service database and analysed. Individuals with underweight (body mass index [BMI]

Dyslipidemia is a potentially modifiable cardiovascular risk factor. Whereas the recommendations for the treatment target of dyslipidemia in the general population are being more and more rigorous, the 2013 Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease (CKD) presented a relatively conservative approach with respect to the indication of lipid lowering therapy and therapeutic monitoring among the patients with CKD. This may be largely attributed to the lack of high-quality evidence derived from CKD population, among whom the overall feature of dyslipidemia is considerably distinctive to that of general population. In this review article, we cover the characteristic features of dyslipidemia and impact of dyslipidemia on cardiovascular outcomes in patients with CKD. We also review the current evidence on lipid lowering therapy to modify the risk of cardiovascular events in this population. We finally discuss the association between dyslipidemia and CKD progression and the potential strategy to delay the progression of CKD in relation to lipid lowering therapy.

Background/Aims The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression. Methods This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period. Results The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43–7.76). Conclusions A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.

Background Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). Methods A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. Results Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190–0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. Conclusion High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Background Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD). Methods From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥–10%,

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

BackgroudHypertension is highly prevalent in patients with kidney transplantation caused by transplantation-related immunologic or non-immunologic risk factors. However, whether a strict definition of hypertension (≥130/80 mmHg) and subdivided blood pressure (BP) groups are associated with an increased risk of graft failure after kidney transplantation using a nationwide large cohort study are still unknown.MethodsUsing Korean National Health Insurance Service data, we included 14,249 patients who underwent kidney transplantation from 2002 to 2016. Patients were categorized into five BP groups according to the 2021 Kidney Disease: Improving Global Outcomes practice guidelines for BP management: normal BP (

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists’ support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient’s condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There are also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

Abstract Background The reactive oxygen species (ROS) and inflammation, a critical contributor to tissue damage, is well-known to be associated with various disease. The kidney is susceptible to hypoxia and vulnerable to ROS. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of chronic kidney disease and finally, end-stage renal disease. Thus, delivering therapeutic agents to the ROS-rich inflammation site and releasing the therapeutic agents is a feasible solution. Results We developed a longer-circulating, inflammation-sensing, ROS-scavenging versatile nanoplatform by stably loading catalase-mimicking 1-dodecanethiol stabilized Mn3O4 (dMn3O4) nanoparticles inside ROS-sensitive nanomicelles (PTC), resulting in an ROS-sensitive nanozyme (PTC-M). Hydrophobic dMn3O4 nanoparticles were loaded inside PTC micelles to prevent premature release during circulation and act as a therapeutic agent by ROS-responsive release of loaded dMn3O4 once it reached the inflammation site. Conclusions The findings of our study demonstrated the successful attenuation of inflammation and apoptosis in the IRI mice kidneys, suggesting that PTC-M nanozyme could possess promising potential in AKI therapy. This study paves the way for high-performance ROS depletion in treating various inflammation-related diseases. Graphical Abstract

Background Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. Methods We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. Results The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. Conclusion Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.

IntroductionDespite the risk of incident chronic kidney disease among the patients with rheumatoid arthritis (RA), the association of RA and the risk of end-stage renal disease (ESRD) has not been clearly elucidated. We aimed to investigate the association of RA and the risk of ESRD.Materials and methodsA total of 929,982 subjects with (n = 154,997) or without (n = 774,985) RA from the National Health Insurance Service (NHIS) database in Koreas (corresponding to the period between 2009 and 2017) were retrospectively analyzed. RA was defined by the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), codes plus any dispensing of disease-modifying anti-rheumatic drugs. The primary outcome was incident ESRD, identified by a combination of the ICD-10-CM codes and a special code assigned to patients receiving maintenance dialysis for ≥ 3 months or those with a transplant kidney.ResultsCompared to the subjects without RA, the subjects with RA resulted in an increased incidence of ESRD (incidence rates of 0.374 versus 0.810 cases per 1,000 person-years). Accordingly, compared to the subjects without RA, the risk of ESRD was significantly increased among the subjects with RA (adjusted hazard ratio 2.095, 95% confidence interval 1.902–2.308). Subgroup analyses revealed that the risk of ESRD imposed by RA is relatively higher in relatively young and healthy individuals.ConclusionRheumatoid arthritis (RA) increase the risk of ESRD. As the risk of ESRD imposed by RA is relatively higher in relatively young and healthy individuals, kidney-protective treatment, such as biologic agents, should be preferentially considered among these patients with RA.

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists’ support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient’s condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There is also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan–Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.

Abstract Background Although anastomosing hemangiomas are very rare and benign vascular neoplasms, these tumors are more common among patients with end-stage kidney disease. Incidental finding of these tumors in the kidney or adrenal gland has been reported. Herein, we describe a case in which an anastomosing hemangioma was misdiagnosed as a renal cell carcinoma before kidney transplant. Case presentation A 35-year-old woman with lupus nephritis was admitted to our emergency department for suspected uremic symptoms of nausea and general weakness. She had received hemodialysis due to end-stage kidney disease, and a living-donor kidney transplantation from her father was planned. On pre-operative contrast-enhanced computed tomography and magnetic resonance imaging, a 1.7 cm renal cell carcinoma was observed in the right kidney. On staining after radical nephrectomy, irregularly shaped vascular spaces of various sizes were observed, with these spaces having an anastomosing pattern. As the findings of the anastomosing hemangioma are similar to those of a renal cell carcinoma on imaging, histology examination was necessary to confirm the diagnosis of anastomosing hemangioma and to prevent delay in listing for kidney transplantation. Good kidney function was achieved after transplantation, with no tumor recurrence. Conclusion Our case underlines the importance for prompt surgical resection of an enhancing renal mass to confirm diagnosis in patients scheduled for kidney transplantation to avoid any delay.

In the decades since the discovery of angiotensin-converting enzyme 2 (ACE2), its protective role in terms of antagonizing activation of the classical renin-angiotensin system (RAS) axis has been recognized in clinical and experimental studies on kidney and cardiovascular diseases. The effects of ACE inhibitor/angiotensin type 1 receptor blockers (ACEi/ARBs) on ACE2-angiotensin-(1-7) (Ang-(1-7))-Mas receptor (MasR) axis activation has encouraged the use of such blockers in patients with kidney and cardiovascular diseases, until the emergence of coronavirus disease 2019 (COVID-19). The previously unchallenged functions of the ACE2-Ang-(1-7)-MasR axis and ACEi/ARBs are being re-evaluated in the era of COVID-19; the hypothesis is that ACEi/ARBs may increase the risk of severe acute respiratory syndrome coronavirus 2 infection by upregulating the human ACE2 receptor expression level. In this review, we examine ACE2 molecular structure, function (as an enzyme of the RAS), and distribution. We explore the roles played by ACE2 in kidney, cardiovascular, and pulmonary diseases, highlighting studies that defined the benefits imparted when ACEi/ARBs activated the local ACE2-Ang-(1-7)-MasR axis. Finally, the question of whether ACEi/ARBs therapies should be stopped in COVID-19-infected patients will be reviewed by reference to the available evidence.

Abstract Identification of individuals at risk of hypertension development based on socio-economic status have been inconclusive, due to variable definitions of low socio-economic status. We investigated whether educational status of individuals or their parents predicts prevalent hypertension in young adult population, by analyzing data of more than 37,000 non-institutionalized subjects from Korea National Health and Nutrition Examination Survey 2008 to 2017. Although low educational status of individual subjects was robustly associated with elevation of systolic blood pressure and increased prevalence of hypertension in general population, its impact on prevalent hypertension differed across age subgroups, and was remarkably attenuated in young adults. Parental educational status was significantly associated with prevalent hypertension in young adults, but not or only marginally in elderly population. Low parental educational status was also associated with high sodium intake in young adults, irrespective of subject’s own educational status. These collectively indicate that parental educational status, rather than individual’s own educational status, better and independently predicts prevalent hypertension in young adults, and that young adults with low parental educational status are prone to intake more sodium, possibly contributing to the increased risk of hypertension development. We expect that our findings could help define young individuals at risk of high sodium intake and hypertension.

BackgroundThe impact of left ventricular (LV) geometry on the renal outcomes in patients with chronic kidney disease (CKD) has not been established yet. We aimed to investigate the association of LV geometry with renal outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,144 subjects from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) were categorized by LV geometry, which was defined by LV mass index and relative wall thickness [normal geometry, concentric remodeling, eccentric hypertrophy (eLVH), and concentric hypertrophy (cLVH)]. Study outcomes were composite renal events [decline of kidney function (the first occurrence of > 50% decline of eGFR or doubling of serum creatinine from the baseline) and onset of ESRD (initiation of dialysis or kidney transplantation) during follow-up periods)] and all-cause mortality.ResultsCox regression analysis revealed that eLVH [adjusted hazard ratio (HR) 1.498, 95% confidence interval (CI) 1.197–1.873] and cLVH (adjusted HR 1.289, 95% CI 1.011–1.643) were associated with increased risk of composite renal events, whereas concentric remodeling (adjusted HR 1.881, 95% CI 1.135–3.118) and cLVH (adjusted HR 2.216, 95% CI 1.341–3.664) were associated with increased risk of all-cause mortality. Sensitivity analyses confirmed that concentric remodeling (adjusted HR 1.993, 95% CI 1.197–3.368) and eLVH (adjusted HR 1.588, 95% CI 1.261–2.001) are independently associated with all-cause mortality and composite renal events, respectively.ConclusionIn conclusion, we report that LV geometry is significantly associated with adverse renal outcomes and all-cause mortality in patients with pre-dialysis CKD. Echocardiographic determination of LV geometry may help the early identification for the patients with high risk of CKD progression.

Intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. Here the authors show that VEGF-C expression in specialized IntSCs is regulated by YAP/TAZ, and VEGF-C is responsible for maintaining lacteal integrity, thus influencing dietary fat drainage into lacteals.

Fibroblastic reticular cells (FRC) are important for lymph node (LN) structure and function. Here the authors show that the YAP/TAZ complex downstream of Hippo signalling regulates FRC commitment and maturation, with YAP/TAZ deficiency impairing FRC differentiation, while hyperactivation of YAZ/TAZ inducing myofibroblastic FRCs and LN fibrosis.

BackgroundThe impact of left ventricular diastolic dysfunction (LVDD) on cardiovascular (CV) outcomes in patients with pre-dialysis chronic kidney disease (CKD) has been rarely unveiled. We here investigated the association of LVDD with CV outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,135 patients with pre-dialysis CKD from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) cohort were dichotomized by the absence or presence of LVDD, which was defined as the ratio of the early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e′) > 14.ResultsCox regression analysis revealed that LVDD was significantly associated with increased risk of composite CV events [adjusted hazard ratio (HR) 2.194, 95% confidence interval (CI) 1.486–3.240] and all-cause mortality (adjusted HR 1.830, 95% CI 1.168–2.869). Restricted cubic splines visualized stringent linear correlations of E/e′ with both composite CV events and all-cause mortality. In the sensitivity analysis only including the subjects with left ventricular ejection fraction ≥ 50%, LVDD was still significantly associated with adverse CV outcomes (adjusted HR 1.984, 95% CI 1.325–3.000) and all-cause mortality (adjusted HR 1.727, 95% CI 1.083–2.754), suggesting that the impact of LVDD on the outcomes in patients with CKD is independent of LV systolic function. Subgroup analyses revealed that the associations were not modified by various clinical contexts, such as age, sex, burden of comorbid conditions, body mass index, estimated glomerular filtration rate, and albuminuria.ConclusionLVDD is independently associated with adverse CV outcomes and all-cause mortality in patients with pre-dialysis CKD.

Gemifloxacin, a broad-spectrum antibacterial agent of the fluoroquinolone class, is used to treat bacterial infections, including acute bacterial exacerbation of chronic bronchitis and community-acquired pneumonia. This study aimed to develop a simple and robust analysis of gemifloxacin in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The sample was prepared using simple protein precipitation procedures with acetonitrile and separated using the Gemini C18 column with a mobile phase (0.1% formic acid: 0.1% formic acid in acetonitrile = 78: 22 (V/V)). Moxifloxacin was used as an internal standard. The mass spectrometer was operated in the positive ion mode using multiple reaction monitoring. Each precursor ion of gemifloxacin and moxifloxacin was monitored at m/z 390.1/402.1, and their product ions were monitored at m/z 372.3/384.4. The calibration curve showed linearity in 0.005–5 μg/mL with an appropriate correlation coefficient (≥0.99). The variation coefficient of intra- and interprecision values of gemifloxacin was

Background: Serum adiponectin level predicts cardiovascular (CV) outcomes and progression of coronary artery calcification (CAC) in the general population, although the association has not been validated in patients with chronic kidney disease (CKD). In this study, we investigated the association of high serum adiponectin level with the risk of adverse CV outcomes and progression of CAC in patients with pre-dialysis CKD.Methods: A total of 1,127 patients with pre-dialysis CKD from a nationwide prospective cohort of patients with pre-dialysis CKD in Korea were divided into the tertile by serum adiponectin level at the baseline. CV outcome of interest was fatal and non-fatal CV events and all-cause mortality. Progression of CAC was defined as coronary artery calcium score (CACS) change more than 200 during a 4-year follow-up.Results: Cox regression analysis revealed that high serum adiponectin is associated with increased risk of fatal and non-fatal CV events (adjusted hazard ratio 2.799, 95% CI 1.348–5.811). In contrast, high serum adiponectin level was not significantly associated with all-cause mortality (adjusted hazard ratio 0.655, 95% CI 0.203–2.113). Binary logistic regression analysis revealed that high serum adiponectin level is also associated with increased risk of progression of CAC (adjusted odds ratio [OR] 2.078, 95% CI 1.014–4.260). Subgroup analyses demonstrated that the association of high serum adiponectin with increased risk of fatal and non-fatal CV events is not modified by age, gender, history of diabetes, estimated glomerular filtration rate (eGFR), or spot urine albumin-to-creatinine ratio (ACR).Conclusions: High serum adiponectin level is associated with adverse CV outcomes and progression of CAC in patients with pre-dialysis CKD.

BackgroundWe investigated whether high body weight variability (BWV) is associated with a higher prevalence of coronary artery calcification (CAC) or more rapid progression of CAC in patients with predialysis chronic kidney disease (CKD).MethodsA total of 1,162 subjects from a nationwide prospective cohort of predialysis CKD were analyzed. The subjects were divided into the tertile (T1, T2, and T3) by BWV. CAC was assessed at the baseline and a 4-year follow-up by CT scan. Rapid progression of coronary artery calcification was defined as an increase in coronary artery calcium score (CACS) more than 200 Agatston units during a 4-year follow-up.ResultsOne-way ANOVA revealed that CACS change during the follow-up period is significantly higher in the subjects with high BWV, although CACS at the baseline and 4-year follow-up was not different among the tertile groups by BWV. Logistic regression analysis revealed that compared to low BWV (T1), both moderate (T2, adjusted odds ratio (OR) 2.118, 95% CI 1.075–4.175) and high (T3, adjusted OR 2.602, 95% CI 1.304–5.191) BWV was associated with significantly increased risk of rapid progression of CAC. Importantly, the association between BWV and progression of CAC remained robust even among the subjects without significant BW gain or loss during follow-up periods (T2, adjusted OR 2.007, 95% CI 1.011–3.984; T3, adjusted OR 2.054, 95% CI 1.003–4.207).ConclusionHigh BWV is independently associated with rapid progression of CAC in patients with predialysis CKD.

The prognostic value of urinary angiotensinogen (UAGT) in patients with chronic kidney disease (CKD) has not been completely evaluated, although the association of UAGT with renal outcomes has been suggested in specific subsets of CKD. In the present study, to investigate the association of UAGT with renal outcomes in patients with non-dialysis CKD irrespective of the primary cause, a total of 1688 subjects from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into the quintile by UAGT to urine creatinine ratio (UAGT/Cr) level. The primary outcomes of interest were composite renal event, which included decline in kidney function and onset of end-stage renal disease during follow-up periods. The median follow-up duration was 6.257 years. Cox regression model analysis unveiled that the risk of composite renal event was significantly higher in the fifth quintile (adjusted hazard ratio 1.528, 95% confidence interval 1.156 to 2.021) compared to that of the first quartile. The association between high UAGT/Cr level and adverse renal outcome remained consistent in sensitivity analyses, including the analysis of the cause-specific hazard model. Subgroup analyses revealed that the association of UAGT level with renal outcomes is modified by certain clinical contexts, such as BMI and albuminuria. In conclusion, high UAGT level is associated with adverse renal outcomes in patients with non-dialysis CKD. Further studies are warranted to elaborate and expand the predictive role of UAGT as a biomarker for renal outcomes in CKD.

CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in ccn1-knockdown zebrafish embryos. CCN1 activated VEGFR2 and downstream MAPK/PI3K signalling pathways, YAP/TAZ, as well as Rho effector mDia1 to enhance tip cell activity and CCN1 itself. VEGFR2 interacted with integrin αvβ3 through CCN1. Integrin αvβ3 inhibitor repressed tip cell number and sprouting in postnatal retinas from endothelial cell-specific Ccn1 transgenic mice, and allograft tumours in Ccn1 transgenic mice showed hyperactive vascular sprouting. Cancer patients with high CCN1 expression have poor survival outcomes and positive correlation with ITGAV and ITGB3 and high YAP/WWTR1. Thus, our data underscore the positive feedback regulation of tip cells by CCN1 through integrin αvβ3/VEGFR2 and increased YAP/TAZ activity, suggesting a promising therapeutic intervention for pathological angiogenesis.

Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P

Background: Inhibition of histone deacetylase (HDAC) was reported to suppress cardiac hypertrophy and fibrosis in various hypertrophic animal models. However, the HDAC expression profile and HDAC enzyme activity have not yet been investigated in DOCA-salt hypertensive rats. Methods: Unilaterally nephrectomized rats were implanted with DOCA strips. DOCA-salt rats then received a control diet with vehicle or valproate. We measured the expression of cardiac hypertrophic markers, class I HDACs, class II HDACs, fibrosis, and HDAC enzyme activity. Results: Here we report that sodium valproate inhibits the cardiac hypertrophy accompanied by fibrosis in the heart of chronic hypertensive rats. We show that expression of GATA6 and HDAC6 is upregulated in DOCA-salt hypertension. In addition, HDAC6 and HDAC8 enzyme activity is attenuated by sodium valproate. Conclusion: These results suggest that a novel HDAC6- and HDAC8-selective inhibitor is needed to treat or prevent pathological cardiac hypertrophy.

We report an unusual case of probable Creutzfeldt–Jakob disease (CJD) in hemodialysis patient. A woman 59 years of age with a past history of hypertension and end-stage renal disease presented with a stuporous state preceded by rapidly progressive cognitive dysfunction, myoclonus, and akinetic mutism. At first, the cause of the altered mental status was assumed to be uremic or hypertensive encephalopathy combined with fever. Proper managements, however, did not improve the neurologic symptoms. Diffusion-weighted magnetic resonance imaging revealed bilaterally asymmetric high signal intensity in both basal ganglia and cerebral cortices. Electroencephalography showed diffuse generalized theta-to-delta range slow wave and intermittent medium-to-high voltage complexes with a characteristic triphasic pattern on both hemispheres. Cerebrospinal fluid assay for the 14-3-3 protein was positive and diagnostic of CJD.