Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression. Methods: A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α), and eGFR decline (mGFR-α) were compared between groups. Results: A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23–13.54; p = 0.02). The mGFR-α was greater in rapid progressors (–3.58 mL/min per year in 1C, –3.7 in 1D, and –4.52 in 1E) compared with that in slow progressors (–1.54 in 1A and –2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B). Conclusion: MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients.

BACKGROUND: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. METHODS: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. RESULTS: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total CO2 content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. CONCLUSION: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01630486
Albuminuria ; Alkaline Phosphatase ; Ankle ; Blood Pressure ; Calcium ; Cohort Studies ; Diabetes Mellitus ; Humans ; Korea ; Linear Models ; Osteoprotegerin* ; Plasma ; Prospective Studies ; Pulse Wave Analysis ; Renal Insufficiency, Chronic* ; Risk Factors* ; Vascular Calcification ; Vascular Stiffness*

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m². The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.
Blood Pressure ; Cohort Studies* ; Comorbidity ; Creatinine ; Diabetic Nephropathies ; Diet ; Education ; Epidemiology ; Glomerular Filtration Rate ; Glomerulonephritis ; Health Behavior ; Humans ; Hypertension ; Korea ; Male ; Mass Spectrometry ; Polycystic Kidney Diseases ; Quality of Life ; Renal Insufficiency, Chronic* ; Risk Factors

PURPOSE: Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. MATERIALS AND METHODS: This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). RESULTS: The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97–0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). CONCLUSION: Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.
Area Under Curve ; Bone Diseases ; Bone Diseases, Metabolic* ; Confounding Factors (Epidemiology) ; Cooperative Behavior ; Creatinine* ; Cross-Sectional Studies ; Cystatin C* ; Diet ; Female ; Femur Neck ; Glomerular Filtration Rate* ; Hip ; Humans ; Logistic Models ; Odds Ratio ; Renal Insufficiency ; Renal Insufficiency, Chronic* ; ROC Curve

We report herein a case successful endovascular treatment with a stent-graft of a rare case of rapidly growing mycotic aneurysm of the left common carotid artery due to acute bacterial endocarditis after eradication of the infection. Infected mycotic aneurysms of the peripheral vasculature have been considered as a contraindication for stent-graft implantation because of the possibility of microorganism spreading to the stent-graft; however, if there is evidence of complete eradication of microorganism and surgery is not an option, stent-graft implantation can be an effective and safe treatment modality for exclusion of the mycotic aneurysm.
Acute Disease ; Aged, 80 and over ; Aneurysm, Infected/etiology/radiography/*therapy ; Angioplasty/*methods ; Carotid Artery Diseases/etiology/radiography/*therapy ; Endocarditis, Bacterial/*complications/radiography ; Female ; Humans ; *Stents ; Treatment Outcome

PURPOSE: The renin-angiotensin-aldosterone system activation has been suggested as a potential risk factor for renal progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to evaluate urinary angiotensinogen as a biomarker of renal progression in ADPKD. METHODS: Patients with estimated glomerular filtration rate (eGFR) > or =30 mL/min/1.73m2 were enrolled in the study. Specimens (blood and urine) and computed tomography (CT) were taken from each subject. The eGFR was calculated by 4-variable MDRD equation and total kidney volume (TKV) was measured from CT images by modified ellipsoid method. Urinary angiotensinogen (AGT) and neutrophil gelatinaseassociated lipocalin (NGAL) were measured by ELISA. The concentration of AGT was adjusted with random urine creatinine (Cr). The association between urinary biomarkers, TKV and eGFR were evaluated. RESULTS: A total of 59 (M:F=31:28) subjects were enrolled in the study and their mean age was 46 years. The eGFR and TKV at the enrollment were 77.3+/-15.6 mL/min/1.73m2 and 1389.8+/-925.1 mL, respectively. Log AGT/Cr was associated with TKV (r2=0.117, p=0.01) in the earlier stage of disease (TKV<3,000 mL). However, it did not show significant correlation with eGFR. Log NGAL was not associated with either TKV or eGFR. Urinary AGT/Cr was closely related to the number of anti-hypertensive medication, TKV, and the presence of albuminuria, although there was no correlation with plasma renin activity or aldosterone level. CONCLUSION: Urinary angiotensinogen may be a useful biomarker of disease progression in ADPKD patients.
Albuminuria ; Aldosterone ; Angiotensinogen ; Biomarkers ; Creatinine ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Glomerular Filtration Rate ; Humans ; Kidney ; Lipocalins ; Neutrophils ; Organ Size ; Plasma ; Polycystic Kidney Diseases ; Polycystic Kidney, Autosomal Dominant ; Renin ; Renin-Angiotensin System

Since beginning with the first organ transplantation from brain-dead donor in 1979, organ transplantation has been developing continuously in Korea. However, organ shortage still is a serious problem in the field of solid organ transplantation. For this reason, it is necessary to promote deceased donor organ transplantation and achieve self sufficiency. There are two system requirements managing deceased donor organ transplantation; operational and regulatory systems. In operational system, mutual and balanced cooperation between transplantation centers, organ procurement organism (OPO), registration/allocation system and NGOs is one of most important determinants to maximize brain dead donor. Especially, transplantation center and OPO need to improve in their organ donation process through evaluating donation practices and developing critical pathway for each step. In addition, public education program focusing on the hospital staff, the family of deceased donors and students should be enhanced to increase public awareness for organ donation. In regulatory system, national transplantation authority for the transplant coordination among various structures and policy-making on the issue of organ donation is necessary. For this purpose, Korean Network for Organ Sharing (KONOS) has to be improved into professional and authoritative body and establish more expanded national database network system. Further improvement in operational and regulatory systems to activate organ donation could enable to achieve the Asian leadership in the field of transplantation as well as self sufficiency for organ transplantation.
Asian Continental Ancestry Group ; Brain Death ; Critical Pathways ; Humans ; Korea ; Organ Transplantation ; Tissue and Organ Procurement ; Tissue Donors ; Transplants

BACKGROUND AND OBJECTIVES: Patients with isolated vertigo could have central or peripheral vestibular disorders. Although some differential points exist between the two conditions, sometimes it is not easy to differentiate central vertigo from that of peripheral vestibular origin, especially in patients with isolated vertigo. We performed this study to determine the frequency of acute infarction and predictors of vertigo associated with stroke in isolated spontaneous vertigo. MATERIALS AND METHODS: We prospectively evaluated 185 consecutive patients who were admitted to neurology department with acute isolated vertigo, after excluding the patients with benign paroxysmal positioning vertigo. Diffusion-weighted MRI (DWI) was obtained in 161 (87.0%) patients. Demographics, stroke risk factors, associated symptoms and signs were reviewed. Also, the locations and vascular territories of the lesions on DWI were investigated. RESULTS: Twenty three (14.3%) patients had acute infarction on DWI. Old age and male sex were the predictors of stroke using multivariate analysis (p=0.03 and 0.02). The lesions were located in the cerebellum in 17 patients, medulla in four, and pons in another four. Cerebellar lesions were in the territory of the posterior inferior cerebellar artery in all patients. CONCLUSION: Isolated spontaneous vertigo may develop in posterior circulation stroke, especially in men of old age. The possibility of central origin should be considered in patients with isolated vertigo and DWI might be a good diagnostic tool.
Arteries ; Cerebellum ; Cerebral Infarction ; Demography ; Diffusion Magnetic Resonance Imaging ; Humans ; Infarction ; Male ; Multivariate Analysis ; Neurology ; Pons ; Prospective Studies ; Risk Factors ; Stroke ; Vertigo

Porcine to rat corneal xenotransplantation resulted in severe inflammation and rejection of the corneal stroma, whereas an allograft showed mainly endothelial cell-associated rejection. We, therefore, investigated and compared the gene expression between porcine keratocytes and corneal endothelial cells. RNA was isolated from primary cultured porcine or human keratocytes and porcine corneal endothelial cells. Gene expression was comparatively analyzed after normalization with microarray method using Platinum pig 13 K oligo chip (GenoCheck Co., Ltd., Ansan, Korea). Real-time polymerase chain reaction (PCR) was performed for C1R, CCL2, CXCL6, and HLA-A in porcine keratocytes and corneal endothelial cells. As a result, upregulated expression more than 2 folds was observed in 1,162 genes of porcine keratocytes versus porcine endothelial cells. Among the immune-regulatory genes, SEMA3C, CCL2, CXCL6, F3, HLA-A, CD97, IFI30, C1R, and G1P3 were highly expressed in porcine keratocytes, compared to porcine corneal endothelial cells or human keratocytes. When measured by real-time PCR, the expression of C1R, CCL2, and HLA-A was higher in porcine keratocytes compared to that in porcine corneal endothelial cells. In conclusion, the increased expression of C1R, CCL2, and HLA-A genes in porcine keratocytes might be responsible for the stromal rejection observed in a porcine to rat corneal xenotransplantation.
Animals ; Cells, Cultured ; Chemokine CCL2/metabolism ; Complement C1r/metabolism ; Corneal Transplantation/*immunology/pathology ; Endothelium, Corneal/*metabolism/pathology ; *Gene Expression Profiling ; Graft Rejection/*immunology/pathology ; HLA-A Antigens/metabolism ; Humans ; Keratinocytes/*metabolism ; Oligonucleotide Array Sequence Analysis ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Swine ; Transplantation, Heterologous ; Up-Regulation