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The effectiveness and safety of herbal medicine on children with simple obesity have yet to be clarified.

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1

Posttransplant diabetes mellitus, presenile deafness, and myopathy are not commonly accompanied symptoms after kidney transplant. We report the case of a 48-year-old woman with diabetes mellitus, sensorineural hearing loss, and severe myopathy without neuropathy after deceased donor kidney transplant. ShehadamitochondrialDNApointmutation at position 3243 (A>G), and mitochondrial diseases such as maternally inherited diabetes deafness or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodeswere suspected.Diabetes andother symptoms following kidney transplant can often be overlooked as complications of immunosuppressants taken after kidney transplant. However, in patients without a known cause of their symptoms, appropriate examinations and consultation for other diseases, including genetic diseases, should be considered.

Procalcitonin (PCT) is a useful marker for the diagnosis of systemic inflammatory response syndrome. In addition, PCT is affected by renal function. However, few studies have investigated the relationship between PCT and the development of acute kidney injury (AKI). Hence, we investigated whether serum PCT levels at the time of admission were associated with the development of AKI and clinical outcomes. A total of 790 patients in whom PCT was measured on admission to the intensive care unit (ICU) were analyzed retrospectively. We attempted to investigate whether serum PCT levels measured at the time of admission could be used as a risk factor for the development of AKI in septic and nonseptic patients or as a risk factor for all-cause mortality, and diagnostic usefulness of PCT was further assessed. Serum PCT levels were significantly higher in patients with AKI than in those without AKI (P P = 0.035). However, PCT was not effective in predicting mortality. The cut-off value of PCT for the prediction of AKI incidence was calculated to be 0.315 ng/ml, with sensitivity and specificity of 60.9% and 56.9%, respectively. The odds ratios (ORs) from an equation adjusted for optimum thresholds of PCT levels for developing AKI with and without sepsis were 2.422 (1.222–4.802, P = 0.011) and 1.798 (1.101–2.937, P = 0.019), respectively. However, there were no absolute differences between the pre- and posttest probabilities after including the PCT value for AKI development. This study suggests that the PCT value was higher in AKI patients than in non-AKI patients, but PCT measurement at the time of admission did not improve the prediction model for AKI.

Background: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. Methods: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. Results: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, β-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. Conclusions: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 &micro, g/kg/day) for 4 weeks. Angiotensin II (3 &micro, M)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.

AIM Hepatitis B virus (HBV) infection is an important risk factor for morbidity and mortality in the general population. However, limited data are available on the progression of HBV infection in patients with end-stage renal disease (ESRD), and available data are controversial. Therefore, we investigated the association between hepatitis B surface antigen (HBsAg) seropositivity and mortality in patients with incident ESRD. METHODS All adult patients (≥18 years of age) starting dialysis for ESRD from January 2000 to December 2011 were included. A total of 1090 patients with ESRD were analyzed. HBsAg-positive patients were paired 1:6 with HBsAg-negative patients using propensity score matching. RESULTS Eighty one (7.4%) patients were HBsAg positive. No differences in the survival rates of the HBsAg-positive and HBsAg-negative patients with ESRD were detected in either the entire cohort or the propensity score matched cohort. No differences in survival were detected between the groups of HBsAg-positive patients based on the hepatitis B envelope antigen, hepatitis B envelope antibody, HBV DNA status, or use of antiviral agents. No difference in mortality was found between the haemodialysis (HD) and peritoneal dialysis (PD) subgroups among HBsAg-positive patients. CONCLUSION Our results suggest that hepatitis B surface antigenaemia is not related to increased mortality in patients with incident ESRD. Survival of HBsAg-positive patients undergoing PD was comparable to that of patients undergoing HD.

Kombucha tea (KT) has emerged as a substance that protects the liver from damage, however, its mechanisms of action on the fatty liver remain unclear. Therefore, we investigated the potential role of KT and its underlying mechanisms on nonalcoholic fatty liver disease (NAFLD). db/db mice that were fed methionine/choline-deficient (MCD) diets for seven weeks were treated for vehicle (M + V) or KT (M + K) and fed with MCD for four additional weeks. Histomorphological injury and increased levels of liver enzymes and lipids were evident in the M + V group, whereas these symptoms were ameliorated in the M + K group. The M + K group had more proliferating and less apoptotic hepatocytic cells than the M + V group. Lipid uptake and lipogenesis significantly decreased, and free fatty acid (FFA) oxidation increased in the M + K, when compared with the M + V group. With the reduction of hedgehog signaling, inflammation and fibrosis also declined in the M + K group. Palmitate (PA) treatment increased the accumulation of lipid droplets and decreased the viability of primary hepatocytes, whereas KT suppressed PA-induced damage in these cells by enhancing intracellular lipid disposal. These results suggest that KT protects hepatocytes from lipid toxicity by influencing the lipid metabolism, and it attenuates inflammation and fibrosis, which contributes to liver restoration in mice with NAFLD.

Background/Aims: Liver cirrhosis (LC) is an important problem in patients withend-stage renal disease (ESRD). Few studies have investigated the inf luence ofLC on mortality in patients with ESRD. This study investigated the associationbetween LC and mortality among patients with ESRD and compare mortality betweentwo dialysis modalities. Methods: Adult patients (≥ 18 years of age) starting dialysis for ESRD were enrolledin the present study from 2000 to 2011. We analyzed 1,069 patients withESRD; of these, 742 patients were undergoing hemodialysis (HD) and 327 patientswere undergoing peritoneal dialysis (PD). Results: The prevalence of LC was 44 of 1,069 patients (4.1%). The cumulative 1-,3-, and 5-year survival rates of noncirrhotic patients were 93%, 83%, and 73%, respectively,whereas the equivalent survival rates of cirrhotic patients were 90%,68%, and 48%, respectively (p = 0.011). After adjustment, LC was an independentrisk factor for death in patients with ESRD. No difference in mortality associatedwith LC was found between the HD and PD subgroups. Conclusions: Of the patients with ESRD, cirrhotic patients had poorer survivalthan noncirrhotic patients. Among patients with ESRD and LC, survival of patientsundergoing PD may be comparable with that of patients undergoing HD.

Acute kidney injury (AKI) is a major clinical problem and a predictor of outcomes in critically ill patients who frequently required treatments in the intensive care unit (ICU). Renin-angiotensin-aldosterone system (RAAS) blockers are commonly used for treating hypertension but demands caution because of accompanying illnesses including AKI. The aim of this study was to evaluate whether the use of RAAS blockers affected the incidence of AKI in ICU patients. From a total of 26,287 patients who were admitted to the ICU from January 2003 to December 2013 were included in the final analyses. The primary outcome was the incidence of AKI based on the prescription of RAAS blockers. The secondary outcomes were all-cause mortality. RAAS blocker users were more likely to develop AKI (P < 0.001) and remained an independent risk factor for AKI (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.37-1.79; P < 0.001) after adjusting confounding factors. There was no significant difference in the cumulative 90-day survival rate between the RAAS blocker users and non-users (P = 0.381). However, the adjusted mortality risk associated with AKI was 1.38 (95% CI, 1.22 to 1.56; P < 0.001) and increased as the severity of AKI stage increased from 1 to 3: 1.17 (1.02 to 1.36), 1.77 (1.45 to 2.16), and 1.93 (1.55 to 2.41; P < 0.01 for the trend). RAAS blockers may have a harmful influence to increase the incidence of AKI and temporary withholding of these medications may deserve careful consideration in ICU patients.

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.

Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures. Here, we describe the case of a patient with GLUT-1 deficiency who developed infantile spasms and showed delayed development at 6 months of age. She had intractable epilepsy despite receiving aggressive antiepileptic drug therapy, and underwent a metabolic workup. Cerebrospinal fluid (CSF) examination showed CSF-glucose-to-blood-glucose ratio of 0.38, with a normal lactate level. Bidirectional sequencing of SLC2A1 identified a missense mutation (c.1198C>T) at codon 400 (p.Arg400Cys) of exon 9.

Background Asbestos exposure causes asbestos-related diseases (ARDs) including asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer. Although Korea used substantial amounts of asbestos in the past, no study has focused on its occupational burden of disease (OBD). Therefore, this study aimed to determine the OBDs of ARDs in Korea. Methods The CARcinogen Exposure (CAREX) database was used to determine the proportion of exposed population. Relative risks for lung cancer, laryngeal cancer, and ovarian cancer were used to determine the population-attributable fraction. Data for deaths caused by ARDs during 1998–2013 were obtained from the World Health Organization mortality database. The potential years of life lost (PYLL) and annual average PYLL (APYLL) indicated OBDs. Results In Korea, the number of ARD-attributable deaths and PYLL due to all ARDs during 1998–2013 were 4,492 and 71,763.7, respectively. The number of attributable deaths and PYLL due to asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer were 37 and 554.2, 808 and 15,877.0, 3,256 and 47,375.9, 120 and 1,605.5, and 271 and 6,331.1, respectively; additionally, the APYLL were 15.0, 19.7, 14.6, 13.4, and 23.4, respectively, and the average age at death was 70.4, 62.6, 69.1, 69.9, and 61.8, respectively. Our study showed that although the use of asbestos has ceased in Korea, the incidence of ARDs tends to increase. Conclusion Therefore, efforts to reduce future OBDs of ARDs, including early detection and proper management of ARDs, are needed in Korea., Graphical Abstract

Chronic kidney disease (CKD) represents a major medical challenge and frequently coexists with cardiovascular disease (CVD), which can be treated by statin trerapy. However, whether statin treatment affects renal progression and outcomes in CKD patients remains unclear. We retrospectively reviewed CKD patients at Gachon University Gil Medical Center from 2003-2013. From a total of 14,497 CKD patients, 858 statin users were paired with non-users and analyze with propensity score matching was performed. The outcomes of this study were creatinine doubling, renal death, all-cause mortality, and interactive factors for composite outcomes. Statins were prescribed to 13.5% of the study subjects. Hazard ratios (HRs) [95% confidence intervals (CIs)] for statin treatment for the doubling of serum creatinine levels were significant only in CKD patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and were 0.744 (0.635-0.873) in the unmatched cohort and 0.767 (0.596-0.986) in the matched cohort. In analyses of secondary outcomes, the HRs (95% CIs) for all-cause mortality were 0.655 (0.502-0.855) in the unmatched cohort and 0.537 (0.297-0.973) in the matched cohort. The HRs (95% CIs) for statin therapy for composite outcomes among patients with and without an eGFR ≥30 mL/min/1.73 m2 were 0.764 (0.613-0.952) and 1.232 (0.894-1.697), respectively (P for interaction, 0.017). Thus, statin treatment may have beneficial effects on renal progression and all-cause mortality only for the patients with early- stage CKD.

Fluid overload is linked to hypertension and cardiovascular diseases in patients on peritoneal dialysis (PD). It is important to monitor the residual urinary volume in patients with end-stage renal disease (ESRD). In fact, fluid overload and residual urinary volume have been considered the risk factors of mortality in ESRD patients on PD. However, the relationship between residual urinary volume and fluid overload was still controversial. Therefore, the objective of this cross-sectional study was to evaluate the association between residual urinary volume and the volume status of PD patients. Body composition was measured using a portable multifrequency whole-body bioimpedance assessment. Relative overhydration was defined when the ratio of overhydration to extracellular water was > 0.15. We examined 75 patients, with a mean age of 50.7 years and mean body mass index of 23.5 kg/m(2). Dialysis vintage was 46.5 months. The patients were divided into the anuric group (n = 30; urine output ≤ 100 mL/day) and the group of urine output > 100 mL/day (n = 45). The anuric group showed higher degree of relative overhydration compared to the patients with the urine output of > 100 mL/day (p = 0.020). In a multivariable linear regression analysis, anuria, diabetes, and serum albumin level were independently associated with relative overhydration. In conclusion, volume status should be closely monitored in anuric patients, and the preservation of residual urinary volume is one of important goals to maintain volume status in PD patients.

In 2009, Korea banned the import, transport, and use of asbestos, and the Asbestos Injury Relief Act (AIRA) was promulgated in 2011. Two environmental health centers for asbestos (EHCA), including Pusan National University Yangsan Hospital (PNUYH) and SoonChunHyang University Cheonan Hospital (SCHUCH), were adapted to find environmental asbestos-related diseases (ARDs) and to support the purposes of AIRA. EHCA conducted a health impact survey (HIS) on persons who resided or reside near asbestos factories or mines. A total of 13,433 persons have taken screening examinations in PNUYH EHCA, and 623 persons (4.6%) have had secondary examinations. Of the 21,014 persons who had screening examinations in SCHUCH EHCA, 2490 persons (11.8%) had secondary examinations. Some of those who tested positive for ARDs through HISs filed applications for the asbestos victims’ medical pocketbook (AVMP). Approximately 116 and 612 persons received AVMPs as a result of PNUYH and SCHUCH examinees, respectively. EHCAs have conducted HISs, public relations, and education for asbestos victims, ordinary citizens, and physicians. As HISs are based on voluntary participation, they does not monitor high-risk groups. Active surveillance focusing on high-risk groups has been blocked by the personal information protection act. Although important work has been performed in finding environmental asbestos victims and increasing public awareness on asbestos, it is necessary to improve the current system and registration.

Aim The receptor for advanced glycation end products (RAGE) has emerged as a central regulator of vascular inflammation and atherosclerosis. Soluble RAGE (sRAGE) has an anti-inflammatory effect by quenching ligands for RAGE. On the other hand, extracellular RAGE-binding protein S100A12 (EN-RAGE) shows a pro-inflammatory effect in a way, but may play pleiotropic roles related to inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in haemodialysis (HD) patients and evaluated their relationship with vascular calcification. Methods We performed a cross-sectional study with 199 HD patients. Plain X-ray images of the lateral lumbar spine from all subjects were studied to calculate semiquantitative vascular calcification scores (VCS), as described by Kauppila. Commercially available enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentration of sRAGE and S100A12. Results The patients were 57.1 ± 13.7 years of age; 54.3% were male, 49.2% were diabetic, and 36.2% had a history of cardiovascular disease. In a univariate analysis, serum sRAGE was negatively associated with VCS (log sRAGE, r = –0.208, P = 0.003), whereas S100A12 showed a positive tendency (log S100A12, r = 0.235, P = 0.085). Even after adjustments for confounding risk factors, sRAGE was independently associated with VCS (β = –1.679, P = 0.002). Conclusion This study demonstrated that the circulating sRAGE level was inversely associated with VCS in HD patients independent of the S100A12 level and the severity of systemic inflammation.

Peritoneal dialysis (PD) has some advantages, such as hemodynamic stability and volume regulation, compared with hemodialysis (HD). However, the influence of the dialysis modality on survival is still controversial. This study assessed the mortality of incident patients undergoing HD versus PD using a propensity score approach. This study enrolled 873 subjects who began dialysis therapy at Gachon University Gil Hospital in Korea between January 2000 and June 2009. A propensity score comprising demographic, clinical, and laboratory variables was used to select a 1:1 matched cohort. The overall 1-, 2-, 3-, and 5-year survival rates for the HD patients (n = 212) were 95.1, 89.6, 82.5, and 65.3%, respectively, whereas the equivalent survival rates for the PD patients (n = 212) were 93.6, 83.1, 73.9, and 48.4%, respectively (P = 0.002 by log rank test). In patients without diabetes or patients with a low modified Charlson comorbidity index (MCCI), including hypertension, cardiovascular disease, liver disease, etc., there was no difference in mortality between PD and HD. However, PD was associated with a higher mortality for diabetic patients (HR, 2.86; 95% CI, 1.73-4.74) and for patients with a high MCCI (HR, 2.54; 95% CI 1.57-4.10). These data suggest that survival for PD may be comparable with that for HD in incident dialysis patients without diabetes or high MCCI and that HD could be more beneficial in patients with diabetes or high MCCI in this propensity score-matched cohort.

Background/Aims: Hyperuricemia has been considered a risk factor for renal disease and cardiovascular disease. However, the potential contribution of hyperuricemia to mortality remains uncertain, and the results in the available literature vary according to kidney function. The aim of this study was to determine the association between hyperuricemia and mortality in patients undergoing percutaneous coronary intervention (PCI) across the interaction of kidney function. Method: We retrospectively reviewed patients who underwent PCI from 2003 to 2009. Propensity scores for hyperuricemia (>7 mg/dl for males and >6 mg/dl for females) were used to assemble a matched cohort of 693 pairs of patients with and without hyperuricemia for analysis from the 3,201 patients who fulfilled the inclusion criteria among the 4,842 patients who underwent PCI. Results: Of the 3,201 patients who underwent PCI and for whom data were available regarding their baseline serum uric acid level, 763 (23.8%) had hyperuricemia. The hyperuricemia-associated hazard ratios (HRs) [95% confidence intervals (CIs)] for all-cause mortality were 1.780 (1.270-2.495) in the unmatched cohort and 1.655 (1.109-2.468) in the matched cohort. The HRs (95% CI) for all-cause mortality among those with and without chronic kidney disease (CKD) were 2.080 (1.318-3.283) and 1.592 (0.778-3.256), respectively (p for interaction, 0.001). Conclusions: Hyperuricemia is an independent risk factor for all-cause mortality in those patients with CKD but not in those without CKD.

Vascular calcification is an important factor associated with mortality in dialysis patients. Recently, soluble receptor for advanced glycation end product (sRAGE) and extracellular RAGE binding protein S100A12 (EN-RAGE) have been reported to be involved in the process of vascular calcification. Therefore, we investigated whether sRAGE and S100A12 are useful indicators of progression of abdominal aortic calcification in hemodialysis (HD) patients. We analyzed annual changes in vascular calcification score (VCS) for up to 4 years, compared to clinical and biological parameters in 149 HD patients. VCS was assessed annually using plain X-ray images of the lateral lumbar spine. The progression group was defined as patients with an increase in VCS more than 1 point each year on average during the observation period. Time-averaged concentrations were also evaluated to examine the association between biological parameters and changes in VCS. The patients had a mean age of 58.59 ± 12.93 years; 53.7% were male, and 45% were diabetic. The VCS increased in 55 patients; the mean increase was 1.60 ± 2.91 points. In a stepwise multivariate logistic analysis, we found that higher levels of S100A12 were significantly associated with progression of VCS (odds ratio [OR], 2.622; 95% confidence interval [CI], 1.371-5.016; P = 0.004). The relationship between sRAGE and VCS was not statistically significant (OR, 0.644; 95% CI, 0.302-1.374; P = 0.255). Our findings suggest that serum levels of S100A12 are associated with progression of abdominal aortic calcification in HD patients, independent of sRAGE level.

Sarcomatoid carcinoma is a rare tumor with rapid growth and a poor prognosis. A 60-year-old man underwent kidney transplantation. Three months after transplantation, multiple tumors were found in the liver and bone, and the patient died several days later. Pathological examination of liver and bone marrow biopsies revealed metastatic sarcomatoid carcinoma. Pretransplantation, the patient's workup was positive only for mild thrombocytopenia and a complicated cyst with peripheral rim calcification (Bosniak IIF) in the right kidney. Retrospectively, we found the abdominal computed tomography film, which had been examined at another hospital 6 years previously. The calcified complicated cyst was a 3-cm enhancing solid mass in the right kidney, suggesting renal cell cancer. It is possible that the cancer developed from the calcified complicated cyst. In this case, immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis.

Higher levels of coronary artery calcification score (CACS) are associated not only with an increased risk for cardiovascular death, but also with lower glomerular filtration rates (GFRs). However, its role in renal disease progression in patients has not been elucidated.We evaluated the change of estimated GFR in 279 nondialytic outpatients, who had undergone computed tomographic coronary angiography and follow-up over a period of 3 months.The mean age of the participants was 57.7 ± 10.5 years, and the mean GFR was 88.2 ± 15.7 mL/min/1.73 m(2). Although there was no difference in baseline GFR between the CACS ≤ 200 AU group (n = 240) and the CACS200 AU group (n = 39), the latter group had a lower level of final GFR and higher annual reduction rate of GFR than the former group after an observation period of 13.1 ± 5.97 months. After adjusting for confounding variables, including age, gender, baseline GFR, albumin, and proteinuria, high levels of CACS showed an independent association with an annual reduction rate of GFR (r = -0.142, P = .048).The results suggest that CACS was related to an annual decrease in GFR and may predict the faster decline in GFR in patients with symptoms requiring computed tomographic coronary angiography.

Coronary artery plaque is related to development of coronary artery disease (CAD), and chronic kidney disease is associated with CAD. However, the association of renal dysfunction (RD) with coronary artery plaque characteristics has not been fully elucidated. We evaluated the association between RD and coronary artery plaque characteristics in patients with suspected CAD, who underwent multislice computed tomographic angiography (CTA). A total of 918 patients were classified into 4 groups: group with no plaque (NP) (48.9%), group with calcified plaque (CP) (16.0%), group with noncalcified plaque (NCP) (22.4%), and group with mixed plaque (MP) (12.7%). NCP is considered as rupture-prone soft plaque, and CP as more stable lesion. The mean of estimated glomerular filtration rate (eGFR) was 82.5 ± 15.4 mL/min/1.73m2, and the prevalence of RD (defined as eGFR < 60 mL/min/1.73m2) was 6.3%. The prevalence of RD was 3.3% in the NP group, 10.2% in the CP group, 5.3% in the NCP group, and 14.5% in the MP group (P < 0.001 by ANOVA tests). The adjusted odds ratio for RD was 3.38 (95% confidence interval, 1.27 - 9.04) for the MP group, compared with the NP group. The presence of RD showed an independent association with the MP counts (r = 0.155, P < 0.001); however, there was no association between RD and other plaque characteristics. In conclusion, RD is associated with MP rather than CP or NCP, compared with NP, which may reflect one of the developmental processes of CAD in patients with RD.

Background/Aims: The effects of chronic kidney disease (CKD) on the risk of death for patients with malignant disease are uncertain. The aim of this study was to determine the association between the presence of CKD and mortality in cancer patients. Method: We retrospectively reviewed the cases of 8,223 cancer patients with one or more serum creatinine measurements from January 1, 2000 to December 31, 2004. The key outcome was cancer-specific mortality within the follow-up period. The cumulative incidence rate for death from cancer was estimated using methods of competing risks survival analysis. Cox proportional-hazards regression with the use of Fine and Gray’s proportional-hazards model were evaluated in multiple analyses. Results: CKD was associated with an increased risk of death in cancer patients. The adjusted hazard ratios were 1.12 for patients with an estimated glomerular filtration rate (eGFR) of 30–59 ml/min/1.73 m2 (95% confidence interval 1.01–1.26, p = 0.04) and 1.75 for patients with an eGFR 2 (95% confidence interval 1.32–2.32, p < 0.001). Conclusions: CKD should be considered a risk factor for survival among patients with cancer.

Haemodialysis patients are at higher risk of developing active tuberculosis (TB) infection. However, tuberculin skin tests (TST) have limitations and the diagnostic usefulness of interferon-γ-release assays (IG-RAs) remains unclear in immunocompromised hosts including haemodialysis patients. Haemodialysis patients were enrolled from a dialysis centre in Korea, an intermediate TB-burden country with a high bacille Calmette–Guérin (BCG) vaccination rate. The QuantiFERON-Gold TB In tube test® (QFT) and the T-SPOT TB test® (T-SPOT) were performed, along with the TST. We stratified patients to low- and high-risk groups, according to the risk factors for latent TB. Association between each of the three diagnostic tests and the risk of latent TB was analysed. One hundred and sixty-seven patients were enrolled. The positive rates for the TST, the QFT and T-SPOT were 23.5, 45.9 and 60.4%, respectively. Previous BCG vaccination increased the TST-positive rate in the low-risk group (OR 4.438), whereas it affected neither QFT nor T-SPOT. The positive QFT rates were 41.2 and 62.5% in the low- and high-risk groups, respectively. The QFT was associated with the high-risk group (OR 2.578), whereas the TST was not. The positive T-SPOT rates were 58.9 and 65.7% in the low- and high-risk groups, respectively. The frequency of indeterminate results was higher for the QFT (12.6%) compared with the T-SPOT (4.8%). In conclusion, the IG-RAs can be useful for the diagnosis of latent TB infection in haemodialysis patients.

The long-term clinical benefits of vascular access blood flow (VABF) measurements in hemodialysis (HD) patients have been controversial. We evaluated whether early VABF may predict long-term vascular access (VA) patency in incident HD patients. We enrolled 57 patients, of whom 27 were starting HD with arteriovenous fistulas (AVFs) and 30 with arteriovenous grafts (AVGs). The patients' VABF was measured monthly with the ultrasound dilution technique over the course of the first six months after the VA operation. During the 20.4-month observational period, a total of 40 VA events in 23 patients were documented. The new VA events included 13 cases of stenosis and 10 thrombotic events. The lowest quartile of average early VABF was related to the new VA events. After adjusting for covariates such as gender, age, hypertension, diabetes, VA type, hemoglobin levels, body mass index, parathyroid hormone, and calcium-phosphorus product levels, the hazard ratio of VABF (defined as

Hypokalemia occurs frequently in patients undergoing peritoneal dialysis (PD). However, the therapeutic strategy may differ from that of non-PD-related hypokalemia. We investigated clinical features and related factors of de novo hypokalemia in incident PD patients. We retrospectively enrolled 82 normokalemic patients starting PD at Gachon University Gil Hospital, Korea. The patients were divided into hypokalemia (K(+)

Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA stability. Here, we report that TTP suppress the growth of human colon cancer cells both in vivo and in vitro by regulating of the expression of vascular endothelial growth factor (VEGF). TTP protein expression in human colonic tissues was markedly decreased in colonic adenocarcinoma compared with in normal mucosa and adenoma. VEGF expression was higher in colonic adenocarcinoma than in normal mucosa and adenoma. Specific inhibition of TTP expression by RNA-interference increased the expression of VEGF in cultured human colon cancer cells, and TTP overexpression markedly decreased it. In addition, elevated expression of TTP decreased the expression level of luciferase linked to a 3' terminal AU-rich element (ARE) of VEGF mRNA. Colo320/TTP cells overexpressing TTP grew slowly in vitro and became tumors small in size when xenografted s.c into nude mice. These findings demonstrate that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells, suggesting that it can be used as novel therapeutic agent to treat colon cancer.

A Case of Childhood Sleep-Related Rhythmic Movement Disorder Tae Yeon Kim, M.D., Hyun Hee Lee, M.D., Sung Ku Kim, M.D., Kon Hee Lee, M.D. Department of Pediatrics, Kangnam Sacred Heart Hospital, School of Medicine Hallym University Sleep-related rhythmic movement disorder (SRMD) is defined by uniformed, repetitive movements, which occurs from onset of sleep to light sleep and sometimes during deep sleep. We experienced a 21 month-old girl complained of the rhythmic movements during sleep. After controlling her circadian rhythm for 45days, her symptoms dramatically improved; there was no more hitting her head or legs on the floor. We considered that rhythmic movement would be related to circadian rhythm without medication.

IL-10, a powerful anti-Th1 cytokine, has shown paradoxical effects against diabetes. The mechanism underlying such variable function remains largely undefined. An approach for controlled mobilization of endogenous IL-10 was applied to the NOD mouse and indicated that IL-10 encounter with diabetogenic T cells within the islets sustains activation, while encounter occurring peripheral to the islets induces tolerance. Insulin β-chain (INSβ) 9-23 peptide was expressed on an Ig, and the aggregated (agg) form of the resulting Ig-INSβ triggered IL-10 production by APCs, and expanded IL-10-producing T regulatory cells. Consequently, agg Ig-INSβ delayed diabetes effectively in young NOD mice whose pathogenic T cells remain peripheral to the islets. However, agg Ig-INSβ was unable to suppress the disease in 10-wk-old insulitis-positive animals whose diabetogenic T cells have populated the islets. This is not due to irreversibility of the disease because soluble Ig-INSβ did delay diabetes in these older mice. Evidence is provided indicating that upon migration to the islet, T cells were activated and up-regulated CTLA-4 expression. IL-10, however, reverses such up-regulation, abolishing CTLA-4-inhibitory functions and sustaining activation of the islet T lymphocytes. Therefore, IL-10 supports T cell tolerance in the periphery, but its interplay with CTLA-4 sustains activation within the islets. As a result, IL-10 displays opposite functions against diabetes in young vs older insulitis-positive mice.

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071–1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123–1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016–1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996–1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612–2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566–1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation., Graphical Abstract

The aim of this study was to determine the ability of the ginsenosides, extracts of Panax ginseng C.A. Meyer, to cause differentiation of F9 teratocarcinoma stem cells as a model system. F9 stem cells cultured in the presence of the ginsenosides together with dibutyryl cyclic AMP (dbcAMP) became parietal endoderm-like cells. Moreover, the expression of differentiation marker genes, such as laminin B1 and type IV collagen, was increased after treatment with the ginsenosides. Among the various purified ginsenosides, Rh1 and Rh2 were the most effective at causing differentiation of F9 cells. Since ginsenosides and glucocorticoid hormone have similar chemical structures, we examined the possibility of the involvement of a glucocorticoid receptor (GR) in the differentiation process induced by the ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarded as a GR was detected in F9 cells cultured in the medium containing the ginsenosides Rh1 or Rh2. In addition, F9 stem cells treated with the ginsenosides Rh1 or Rh2 and with RU486, a glucocorticoid antagonist with a high affinity for the GR, did not differentiate into endoderm cells morphologically, and the expression of laminin B1 gene was not induced in these cells. In a gel mobility shift assay, protein factors capable of binding to the glucocorticoid responsive element (GRE) specifically were detected in nuclear extracts of the ginsenoside-treated F9 cells. Moreover, overexpression of GR by cotransfection of GR expression vector and GRE-luciferase vector enhanced the transactivation activity of GRE promoter in the presence of ginsenosides Rh1 or Rh2 and was further augmented by dbcAMP. In addition, ginsenosides Rh1 and Rh2 bound to a GR assessed by whole-cell binding assay, even though the specific binding affinity was weaker compared to dexamethasone. Based on these data, we suggest that the ginsenosides Rh1 and Rh2 cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a GR or its analogous nuclear receptor.

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21 ± 17.32 vs. 72.97 ± 17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97 ± 598.05 ng/mL vs. 685.09 ± 111.65 ng/mL; P = 0.002 in serum; 3361.11 ± 250.86 ng/mL vs. 741.72 ± 101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI.

TO THE EDITOR: Cytomegalovirus (CMV) is a major cause of morbidity and mortality after transplantation. However, the risk of CMV infection increases with more intense treatment outside transplantation settings. We describe a case of fatal CMV disease in a pediatric patient with standard risk acute lymphoblastic leukemia (ALL). She developed life-threatening toxic megacolon and interstitial pneumonia, complicated with bacterial sepsis, during induction chemotherapy. With a diagnosis of ganciclovir (GCV)-resistant CMV disease, she was successfully treated with foscarnet and has remained in complete remission for >2 years. We discuss the association between CMV and immune suppression, the clinical utility of diagnostic tools, and CMV antiviral resistance.

Fluid overload has been linked to mortality in peritoneal dialysis (PD) patients. Residual renal function is important for patient survival. Therefore, the objective of this study was to analyze volume status in PD patients, and to identify associations between volume status and residual renal volume. We performed a cross-sectional, observational, single-center study. Body composition was measured using a portable multifrequency whole-body bioimpedance assessment, and residual renal volume was measured. We examined 75 patients (66.7% male), with a mean age of 50.7±13.0 years and mean body mass index of 23.5±3.5 kg/m2. Length of time on dialysis was 46.5±37.9 months. Anuria (≤100 mL/day) is associated with relative overhydration (ROH) (p=0.014) and extracellular water volume (p=0.014). In a multivariable linear regression analysis, anuria (coefficient β=0.217, p=0.025), diabetes (coefficient β=0.213, p=0.027), and serum albumin level (coefficient β=−0.533, p

The timing for dialysis initiationis still debated. The aim of this study was to compare mortality rates, using a propensity-score approach, in dialysis patients with early or late starts. From January 2000 to June 2009, incident adult patients (n = 836) starting dialysis for end-stage renal disease (ESRD) were enrolled. The patients were assigned to either an early- or late-start group depending on the initiation time of the dialysis. After propensity-score-basedmatching, 450 patients remained. At the initiation of dialysis, the mean estimated glomerular filtration rate (eGFR) was 11.1 mL/min/1.73 m(2) in the early-start group compared with 6.1 mL/min/1.73 m(2) in the late-start group. There were no significant differences in survival between the patients in the early- and late-start groups (Log rank tests P = 0.172). A higher overall mortality risk was observed in the early-start group than in the late-start group for the patients aged ≥ 70 yr (hazard ratio [HR]: 3.29; P = 0.048) and/or who had albumin levels ≥ 3.5 g/dL (HR: 2.53; P = 0.046). The survival of the ESRD patients was comparable between the patients in the early and late-start groups. The time to initiate dialysis should be determined based on clinical findings as well as the eGFR.

In paired living kidney exchange donation from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. However, the impact of donors older than recipients on transplant outcomes remains unclear.We retrospectively reviewed the charts of primary living kidney transplantation patients who were divided into two groups based on the age difference between donor and recipient (recipient age subtracted from donor age, donor-recipient20 vs ≥ 20). The donor-recipient age difference20 group comprised 75 and donor-recipient age difference ≥ 20 group, 25 subjects. Outcome measures included serum creatinine, acute rejection episodes as well as graft and patient survivals at 1 and 5 years after transplantation.The mean donor age difference cohorts of20 and ≥ 20 years showed donor ages of 33 ± 8 and 54 ± 8 years, respectively. The mean recipient age in both groups averaged under 40 years. The acute rejection rate within the first year posttransplantation was greater among age difference ≥ 20 years. The mean serum creatinine values of the donor-recipient age difference20 group was lower than the ≥20 years group at 1 and 5 years posttransplant. The 1-year difference was associated with an increased creatinine value at 5 years. However, death-censored graft survival of the age difference of the ≥ 20 years group was not different (hazard ratio [HR] = 0.1, 95% confidence interval [CI] = 0.01-1.37, P = .08). Patient survival of the age difference ≥ 20 years group showed no difference compared with the age difference20 years group (HR = 0.25, 95% CI = 0.01-6.35, P = .4).Although the cohort of a donor-young recipient age difference ≥ 20 years showed a greater risk of an acute rejection episode early posttransplantation, it did not affect graft or patient survivals. When considering paired kidney donation, older age donors should not necessarily be limited.

Patient with end stage renal disease have characteristics in common with heart failure patients, and volume overload in heart failure is associated with poorer outcomes. Fluid removal during the hemodialysis (HD) is the cornerstone of volume management in this population. The objective of this study is to assess the long-term prognostic effect of interdialytic fluid retention (IDFR) and its relationship with cardiovascular (CV) events in incident HD patients who newly started dialysis. IDFR is defined as the difference between the predialysis weight and the weight at the end of the previous dialysis session, and it mainly reflects the consequence of salt and water intake between two consecutive dialysis sessions. We retrospectively reviewed the 172 patients who newly started and maintained HD over 6 months at Gachon University Gil Hospital between 1 January 2003 and 31 December 2008. The average data were collected for 3 months during the beginning period, including total IDFR and IDFR/dry weight (IDFR%), nutritional parameters, blood pressure, and other biochemical parameters. Patients were classified into 3 cohorts according to the tertile of IDFR%; low (T1; ≤ 3.21%), intermediate (T2; 3.21%-4.56%), and high (T3; ≥ 4.56%). The high IDFR% group showed higher prevalence of diabetes and better nutritional status. The adjusted odds ratio for CV events was 1.562 (95% confidence interval, 1.026-2.378) for high IDFR% group, compared with the low IDFR% group. In incident HD patients, greater IDFR% soon after HD initiation showed an independent association with higher risk for CV events.

The role of the angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) in the pathophysiology of contrast-induced acute kidney injury (AKI) is controversial, and the available literature is contradictory.A retrospective propensity score-matched study to analyze the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI.Using propensity score matching, 1,322 ACE-inhibitor/ARB recipients and nonrecipients were paired for analysis from 5,299 patients and fulfilled the inclusion criteria among 11,447 patients receiving coronary angiography (CAG) or percutaneous coronary intervention.ACE-inhibitor/ARB use based on prescription and risk factors for contrast-induced AKI.The incidence of contrast-induced AKI defined by AKI Network (AKIN) criteria: an absolute increase in serum creatinine levels ≥0.3 mg/dL or a relative increase ≥50% from baseline values within 48 hours after exposure to the contrast medium.Baseline serum creatinine, hemoglobin, and albumin levels; volume of contrast agents; preprocedural medication; and post-CAG serum creatinine levels.An ACE inhibitor/ARB was prescribed for 64.0% of patients receiving CAG. ACE-inhibitor/ARB users showed an increased incidence of contrast-induced AKI after propensity score matching (11.4% vs 6.3%; P0.001). In multivariable analysis, use of ACE inhibitors/ARBs remained an independent and significant predictor of contrast-induced AKI in an unmatched cohort (OR, 1.39; 95% CI, 1.10-1.76; P = 0.06). In the matched cohort, use of ACE inhibitors/ARBs also was associated with a higher adjusted OR of contrast-induced AKI (OR, 1.43; 95% CI, 1.06-1.94; P = 0.02).A retrospective study at a single center.Use of ACE inhibitors/ARBs during CAG has a possible influence to increase the incidence of contrast-induced AKI. Further randomized clinical trials are warranted to confirm the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI.

Background/aims The aim of this study was to determine the prevalence of vitamin D deficiency in hemodialysis (HD) patients and the relationship between seasonal variations in vitamin D levels and vascular calcification. Methods As a prospective observational study, we analyzed 289 HD patients. We have assessed serum 25-hydroxyvitamin D (25D) levels at the end of the summer (September) and winter (March) and analyzed the data to reveal the association of serum 25D level with vascular calcification scores (VCS) at the end of the summer, when vitamin D levels were found to peak. Plan X-ray images of lateral lumbar spine from all subjects were studied for calculation of semiquantitative VCS as described by Kauppila. Results The prevalence of 25D deficiency was 86.2% at the end of the summer and increased to 96.2% at the end of the winter. Female gender and diabetes were associated with vitamin D deficiency. According to univariate analysis, 25D levels were inversely related to vascular calcification. However, after correcting for confounding factors, this relationship lost statistical significance. Multivariate analysis showed that age, systolic blood pressure, and LDL-cholesterol levels were directly associated with a higher VCS. Conclusion Vitamin D deficiency was highly prevalent in HD patients with marked seasonal variation. However, low 25D levels could not be identified as an independent predictor of vascular calcification in these patients.

The use of higher erythropoietin (EPO) doses is associated with an increased risk of an adverse outcome and increased mortality in patients with renal failure. Resistin is related to heart disease, and may contribute to an increased atherosclerotic risk. We hypothesized that a link between resistin and EPO responsiveness may exist. We therefore investigated the relationship between resistin and the EPO resistance index (ERI) in nondiabetic hemodialysis (HD) patients. Fifty-seven patients enrolled in the study underwent HD for ≥ 3 months and intravenous EPO therapy to maintain a target hemoglobin (Hb) level of 11.0 g/dl. The ERI was defined as the weekly EPO dose per unit Hb per body weight. The mean patient age was 52.6 ± 11.9 years and the mean time on dialysis was 4.9 ± 4.4 years. Serum Hb and ERI were 10.4 ± 0.7 g/dl, and 13.3 ± 7.0 (IU/kg/week/g/dl), respectively. Serum resistin levels were 23.6 ± 9.3 μg/L. EPO resistance is associated with low body mass index (BMI) (coefficient β =−0.393, p = 0.002) and with high serum resistin levels (coefficient β = 0.332, p = 0.018). According to a multiple regression analysis, the serum resistin level was a significant independent factor related to EPO resistance (p = 0.017). The results suggest that serum resistin levels reflect EPO responsiveness in nondiabetic HD patients. Resistin may therefore be considered as a new marker of EPO responsiveness in HD patients.

Summary Introduction The performance of serial interferon-γ-release assays (IGRAs) for the diagnosis of latent tuberculosis has not been studied in hemodialysis patients. Method The QuantiFERON-TB-Gold In-Tube test (QFT) and T-SPOT-TB test (TSPOT) were performed 1 year after initial testing at a hemodialysis center. Results Ninety-eight patients were included in the final analysis. Positive rates for the initial tuberculin skin test (TST), QFT and TSPOT were 26.5%, 43.9% and 58.2%, respectively. The follow-up QFT and TSPOT showed positive responses in 52.0% and 53.1%. Conversion rates of the QFT and TSPOT were 20.0% and 26.8%. Reversion rates of the QFT and TSPOT were 16.3% and 29.8%; however, they decreased to 0.0% and 4.8% in patients with a concordantly positive response at the initial TST. A group at high risk for latent tuberculosis increased the risk for the TSPOT conversion [odds ratio (95% confidence interval), 7.76 (1.27–47.40)] and showed a trend of increasing the risk for the QFT conversion [1.97 (0.45–8.71)]. Reversion of both the QFT [18.92 (2.01–178.65)] and TSPOT [6.16 (1.57–24.19)] occurred more frequently in the group at low risk. Conclusions Both conversion and reversion of the IGRAs were associated with the risk for latent tuberculosis in hemodialysis patients. However, serial IGRAs results should be interpreted cautiously due to their high variability.

Background: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1α). Therefore, we investigated the association of HIF-1α polymorphisms with ischemia/hypoxia-related events in hemodialysis patients. Methods: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1α were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed. Results: A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5′ upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03–0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12–0.72). Conclusion: Genetic polymorphisms of HIF-1α were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic syndrome characterized by elevated serum IgG4 concentrations and tumefaction or tissue infiltration by IgG4-positive plasma cells. We experienced a case of IgG4-RD involving multiple organs in a 64-year-old female who was referred for a suspected uroepithelial tumor. A mass biopsy confirmed dense lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. We discuss this case and review the literature to bring IgG4-RD to the attention to clinicians because it responds dramatically well to steroid therapy and should be kept in mind as a differential diagnosis to avoid unnecessary surgery.

Autoimmunity presumably manifests as a consequence of a shortfall in the maintenance of peripheral tolerance by CD4+CD25+ T regulatory cells (Tregs). However, the mechanism underlying the functional impairment of Tregs remains largely undefined. In this study a glutamic acid decarboxylase (GAD) diabetogenic epitope was expressed on an Ig to enhance tolerogenic function, and the resulting Ig-GAD expanded Tregs in both young and older insulitis-positive, nonobese diabetic (NOD) mice, but delayed autoimmune diabetes only in the former. Interestingly, Tregs induced at 4 wk of age had significant active membrane-bound TGF-β (mTGF-β) and sustained protection against diabetes, whereas Tregs expanded during insulitis had minimal mTGF-β and could not protect against diabetes. The Tregs probably operate suppressive function through mTGF-β, because Ab blockade of mTGF-β nullifies protection against diabetes. Surprisingly, young Tregs that modulated pathogenic T cells maintained stable frequency over time in the protected animals, but decreased their mTGF-β at the age of 8 wk. More strikingly, these 8-wk-old mTGF-β-negative Tregs, which were previously protective, became unable to confer resistance against diabetes. Thus, a developmental decline in active mTGF-β nullifies Treg function, leading to a break in tolerance and the onset of diabetes.