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Background and Aims: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake.Methods and Results: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality.Conclusions: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable. [ABSTRACT FROM AUTHOR]

The transferrin receptor (CD71) is known as a receptor for IgA1 on mesangial cells, but the role of CD71 in IgA nephropathy (IgAN) is unknown. We studied clinical implication of mesangial CD71 in 282 patients with biopsy-proven IgAN (2005-2018). The transcript and protein expression of glomerular CD71 was determined by real-time polymerase chain reaction and immunohistochemistry. Ten subjects with microscopic hematuria only and no evidence of histologic abnormalities on kidney biopsy were considered as controls. Human mesangial cells (HMCs) were treated with sera from IgAN patients and expression levels of CD71 and inflammatory cytokine markers were compared according to disease status. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate from the baseline value. During a mean follow up of 53.5 (18.3-75.9) months, 80 (28.4%) patients developed disease progression. The mRNA expression of CD71 was significantly higher in progressors than in nonprogressors (P = 0.001). Among the Oxford classification scores, patients with M1 had significantly higher CD71 expression levels than those with M0. In a multivariable Cox model, elevated transcript levels of CD71 were significantly associated with 4.32-fold higher risk of disease progression (P = 0.009). Furthermore, CD71 expression levels independently predicted the increase in proteinuria of ≥50% from the baseline (P = 0.03). Finally, HMCs treated with sera from IgAN patients with the higher Oxford score (M1E1S1T0) more increased the mRNA expression of CD71 and inflammatory markers than those with sera from negative score (M0E0S0T0). However, silencing CD71 significantly reduced expression levels of the inflammatory cytokine genes. Our results show that mesangial CD71 is significantly associated with disease progression and may play a biologic role in IgAN. [ABSTRACT FROM AUTHOR]

Previous studies have shown that dietary zinc intake is closely related to cardiovascular complications and metabolic derangements. However, the effect of dietary zinc intake on renal function is not fully elucidated. Data from the Korean Genome and Epidemiology Study were used. Dietary zinc intake was assessed by a Food Frequency Questionnaire and dietary zinc density was calculated as absolute zinc intake amount per daily energy intake (mg/1000 kcal day). The participants were categorized into quartiles according to dietary zinc density. The primary end point was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. A total of 7735 participants with normal renal function was included in the final analysis. The mean age was 52.0 ± 8.8 years, 47.5% were male, and mean eGFR was 92.1 ± 16.1 ml/min/1.73 m2. The mean daily zinc intake and zinc intake density were 8.6 ± 3.4 mg and 4.4 ± 0.9 mg/1000 kcal, respectively. During a median follow up of 11.5 (1.7–12.5) years and 70,617 person-years of observation, CKD developed in 1409 (18.2%) participants. Multivariable cox hazard analysis revealed that risk for CKD development was significantly higher in the quartile with a mean zinc intake density of 3.6 ± 0.2 mg/1000 kcal compared with the quartile with a mean zinc intake density of 5.6 ± 1.0 mg/1000 kcal (Hazard ratio; 1.36; 95% Confidence Interval 1.18–1.58; P < 0.001). This relationship remained significant even after adjustments for confounding factors. Low dietary zinc intake may increase the risk of CKD development in individuals with normal renal function. [ABSTRACT FROM AUTHOR]

Background Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population. Objective We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population. Design Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration <10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the >95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes. Results The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (β: -0.02; 95% CI: -0.02, -0.01; P < 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P < 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P < 0.001). Conclusions Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population. [ABSTRACT FROM AUTHOR]

Abstract: Background: The insulin-like growth factor (IGF) system is known to be associated with inflammation in various populations. However, the association between the IGF system and inflammation has not previously been investigated in automated peritoneal dialysis (APD) patients. Therefore, the aim of this study was to investigate whether the IGF system correlates with inflammation in APD patients. Methods: We prospectively determined IGF-I activity, the ratio of serum IGF-I concentrations to those of IGF binding protein-3 (IGFBP-3), and inflammatory markers at initiation of APD and after 6months of follow-up in 21 incident APD patients. Results: The mean age was 55.2±13.1years, and 11 patients (52.3%) were male. Continuous cyclic PD (CCPD) was performed in 11 patients, and nocturnal intermittent PD (NIPD) in 10 patients. The mean value of IGF-I/IGFBP-3 was 0.21±0.13. At baseline, IGF-I/IGFBP-3 was negatively correlated with high-sensitivity C-reactive protein (hs-CRP) (r =−0.27, P =0.032) and interleukin-6 (IL-6) (r =−0.19, P =0.046) concentrations. After 6months, IGF-I/IGFBP-3 (P =0.048) had decreased significantly, while the hs-CRP (P =0.036) increased significantly in the CCPD group. However, there were no significant changes in IGF-I/IGFBP-3 (P =0.59) and hs-CRP (P =0.14) during 6months in the NIPD group. Furthermore, compared with the NIPD group, IGF-I/IGFBP-3 (P =0.041) decreased greater, whereas hs-CRP (P =0.048) concentrations increased greater in the CCPD group. Conclusions: The IGF system was significantly associated with inflammatory markers in incident APD patients, and different APD modalities modulate the IGF system and inflammation. [Copyright &y& Elsevier]

Abstract: End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 ± 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients. [ABSTRACT FROM AUTHOR]

Abstract: Fibroblast growth factor–21 (FGF-21) is a new metabolic regulator, which is related to antiobesity and insulin sensitivity in vivo. However, the clinical implication of FGF-21 is poorly understood. To investigate whether FGF-21 may play a role as a metabolic regulator in patients with end-stage renal disease, we measured serum concentrations of FGF-21, inflammatory markers, and metabolic parameters in healthy people (n = 63) and nondiabetic patients receiving peritoneal dialysis (PD, n = 72). The patients were treated with angiotensin receptor blocker for 6 months, and the changes in FGF-21 concentration and metabolic parameters were assessed. Compared with controls, serum FGF-21 concentration was 8 times higher in patients undergoing PD (754.2 ± 463.5 vs 86.9 ± 60.2 pg/mL, P < .001). In controls, only lipid parameters correlated positively with FGF-21 concentration. In contrast, inflammatory markers (interleukin-6, fibrinogen, high-sensitivity C-reactive protein) and homeostasis model assessment of insulin resistance (HOMA-IR) correlated positively and residual renal function correlated inversely with serum FGF-21 concentration in PD patients. In a multivariate analysis adjusting these factors, residual renal function, HOMA-IR, and fibrinogen concentration were independent determinants of serum FGF-21 concentration. After 6-month angiotensin receptor blocker treatment, serum FGF-21 concentration declined significantly by 13% and HOMA-IR and inflammatory markers improved in PD patients. These findings suggest that FGF-21 may play a role in insulin resistance in patients with end-stage renal disease. [ABSTRACT FROM AUTHOR]

Abstract: Metabolic syndrome is associated with an increased risk of diabetes and cardiovascular disease. Although some data suggest that the prevalence of metabolic syndrome is higher in patients undergoing peritoneal dialysis (PD), the factors related to this increased risk are not well elucidated. We therefore examined whether peripheral white blood cell (WBC) count is correlated with the risk of metabolic syndrome in nondiabetic PD patients. We enrolled 104 nondiabetic PD patients without current infections or chronic inflammatory diseases. Complete blood cell count, anthropometry, blood pressure, fasting glucose, insulin, and lipid profiles were measured. Metabolic syndrome was defined in accordance with the National Cholesterol Education Program (Adult Treatment Panel III) criteria. Metabolic syndrome was present in 49 patients (47.1%). Patients with metabolic syndrome had a higher WBC count and high-sensitivity C-reactive protein level. As the number of metabolic syndrome components increased, WBC count increased significantly. White blood cell count was significantly positively correlated with body mass index, insulin, homeostasis model assessment of insulin resistance, and triglyceride and negatively correlated with high-density lipoprotein cholesterol. The risk of metabolic syndrome increased significantly with a higher WBC count, resulting in an adjusted odds ratio of 1.65 (per 103/μL increase, P = .002). These findings demonstrate that metabolic syndrome is prevalent among nondiabetic PD patients and that WBC count is strongly associated with metabolic syndrome and its components. [Copyright &y& Elsevier]

Background: In patients with type 1 diabetes, some consider microalbuminuria to be a predictor of diabetic nephropathy while others believe it is an early feature of diabetic nephropathy.Methods: Levels of mRNAs that are of pathogenetic relevance in diabetic nephropathy were compared in glomeruli isolated from microalbuminuric and overtly proteinuric subjects and in control normoalbuminuric diabetic subjects and living renal transplant donors.Results: In subjects with microalbuminuria and overt proteinuria, glomerular mRNAs were virtually identical and approximately twofold higher for connective tissue growth factor (CTGF; P < 0.01) and collagen alpha2(IV) (P < 0.03) compared to living renal donors and normoalbuminuric patients. Glomerular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) levels were not significantly different among the groups (P = 0.4). Weak but statistically significant correlations were noted between CTGF mRNA and albuminuria (assessed by rank), fractional mesangial surface area, and a composite renal biopsy index. Glomerular CTGF mRNA correlated inversely with creatinine clearance. Glomerular collagen alpha2(IV) mRNA levels correlated with albuminuria (by rank) and less strongly with fractional mesangial area.Conclusion: To our knowledge, these data provide the first biochemical evidence demonstrating that the glomeruli of microalbuminuric patients and those with overt proteinuria do not differ significantly. The data support the concept that microalbuminuria is not "predictive" of diabetic nephropathy, but rather is an earlier point in the spectrum of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

p38 MAPK and MAPK kinase 3/6 mRNA and activities are increased in early diabetic glomeruli. Background. The p38 mitogen-activated protein kinase (MAPK) pathway is activated by several stress factors, potentially leading to cellular apoptosis and growth. Little is known about the pattern of glomerular p38 MAPK pathway activation during the course of diabetic nephropathy (DN). We examined the activity and expression of the p38 MAPK pathway members, p38 MAPK, MKK3/6, cAMP-responsive element binding protein (CREB), and MAPK phosphatase-1 (MKP-1), in experimental DN in rats over the course of four months. Methods. Control (C; N = 16) and diabetic (DM; N = 16) rats were studied. Four rats from each group were sacrificed monthly, and competitive reverse transcription-polymerase chain reaction and Western blot were performed with microdissected and sieved glomeruli, respectively. Results. Glomerular p38 MAPK mRNA expression was significantly higher in DM than C (P < 0.01) throughout the four-month period. Western blot revealed an average 3.1-fold increase in p38 MAPK protein throughout the study period (P < 0.05). However, p38 MAPK activity was significantly increased only in one- and two-month diabetic glomeruli. Glomerular MKK3/6 and CREB mRNA as well as activity were significantly increased only in one- and two-month DM compared with C. MKP-1 mRNA showed a similar pattern. Conclusions. Glomerular p38 MAPK activity was increased in early DN. Parallel to this, we also showed, to our knowledge for the first time, that there were increased MKK3/6 and CREB activities and mRNA expression. This activated p38 MAPK pathway in diabetic glomeruli may, in part, play a role in the pathogenesis of early hypertrophy and extracellular matrix accumulation. [ABSTRACT FROM AUTHOR]

12-Lipoxygenase is increased in glucose-stimulated mesangial cells and in experimental diabetic nephropathy. Background. Arachidonic acid-derived 12-lipoxygenase (12-LO) products have potent growth and chemotactic properties. The present studies examined whether 12-LO and fibronectin are induced in cultured rat mesangial cells (MCs) exposed to high glucose and whether they are expressed in experimental diabetic nephropathy. Methods. To determine the effect of high glucose on MC 12-LO mRNA and protein expression, rat MCs were incubated with RPMI medium containing 100 (NG) or 450 mg/dL glucose (HG). For animal studies, rats were injected with diluent (control) or streptozotocin. The latter were left untreated (DM) or treated with insulin (DM + I). At sacrifice after four months, GAPDH, 12-LO, and fibronectin mRNA were measured by competitive reverse transcription-polymerase chain reaction (RT-PCR) in microdissected glomeruli (G). Renal sections were semiquantitatively scored (0 to 4+) for diabetic changes and for 12-LO and fibronectin by immunohistochemistry. Results. 12-LO mRNA expression in MC exposed to HG (12.71 ± 1.17 attm/μL) and DM G (1.78 ± 0.65 × 10-3 attm/glomerulus) was significantly higher than those of MCs in NG media (6.71 ± 0.78 attm/μL) and control G (0.34 ± 0.12 × 10-3 attm/glomerulus, P < 0.005), respectively. Western blot revealed a 1.7- and a 2.8-fold increase in MC and G 12-LO protein expression, respectively (P < 0.05). The immunohistochemistry score for G 12-LO and diabetic nephropathy score was significantly greater in DM and DM + I than controls. MC and G GAPDH mRNA remained unchanged. Conclusions. In MCs exposed to HG and in diabetic rat glomeruli, increments in 12-LO mRNA and protein are associated with changes modeling diabetic nephropathy. These findings suggest a role for the 12-LO pathway in the pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background The association of dyslipidemia with mortality has not been fully evaluated in patients on peritoneal dialysis (PD). Moreover, changes in lipids levels over time and associated death risk have not yet been studied in this population. Objective We studied the association of time-updated serum lipid concentrations with all-cause and cardiovascular (CV) mortalities in a 10-year cohort of 749 incident PD patients. Methods Association was assessed using time-varying Cox proportional hazard regression models with adjustment for multiple variables including statin therapy. Results During a median follow-up of 36 (interquartile range, 21–61) months, 273 all-cause and 107 CV deaths occurred. Compared with those with total cholesterol (TC) of 180 to <210 or low-density lipoprotein cholesterol (LDL-C) of 100 to <130 mg/dL, hazard ratios (95% confidence interval) of the lowest TC (<150 mg/dL) and LDL-C (<70 mg/dL) were 2.32 (1.61–3.35) and 2.02 (1.45–2.83) for all-cause mortality and 1.87 (1.04–3.37) and 1.92 (1.13–3.26) for CV mortality, respectively. Lower triglyceride (<100 mg/dL) and high-density lipoprotein cholesterol (<30 mg/dL) levels were associated with higher all-cause mortality (1.66 [1.11–2.47] and 1.57 [1.08–2.29]) but not with CV mortality. Conclusions Contrary to the general population, lower TC and LDL-C levels over time were significantly associated with both worse survival and increased CV mortality in incident PD patients. Although lower triglyceride and high-density lipoprotein cholesterol concentrations were associated with significantly higher all-cause mortality, they failed to show any clear association with CV mortality. The underlying mechanisms responsible for this apparent paradox await further investigations. [ABSTRACT FROM AUTHOR]

CD99 is a 32kDa surface glycoprotein, which is involved in the migration of leukocytes and the transport of ganglioside GM1 and transmembrane proteins. To identify signaling mechanisms triggered by CD99 engagement, a LexA-based yeast two-hybrid system was utilized to identify proteins interacting with the cytoplasmic domains of CD99. In seven positive clones, we attempted to ascertain whether cyclophilin A (CypA) was involved in CD99-mediated signaling, since CypA had been implicated as a signaling regulator for kinases and phosphatases. The interaction between CD99 and CypA was confirmed by co-immunoprecipitation and confocal immunofluorescence studies. Interestingly, the amounts of CypA associated with CD99 increased upon CD99 engagement. We prepared an expression plasmid by inserting CypA cDNA into pEGFP, in order to visualize cellular CypA. In HeLa or HEK 293T cells transfected with the pEGFP-CypA plasmid, GFP-tagged CypA was diffusely present in the cytoplasm of untreated cells. However, CypA-GFP moved to the cell periphery and membrane blebbing, and became colocalized with CD99 upon CD99 engagement. These results suggest that CypA may be either a signaling mediator or a signaling regulator for CD99. [Copyright &y& Elsevier]

Graphical abstract Abstract The mesoporous hematite cubic frameworks (α-Fe 2 O 3 microcube) with 2–3 μm sizes were prepared using a simple thermal treatment of the iron oxalate hydrate cubes (4 μm). The α-Fe 2 O 3 microcube structure with a high surface area (36 m2 g−1) had three-dimensionally connected small grain sizes (˜18 nm). In formaldehyde (HCHO) gas sensing, the fabricated device by α-Fe 2 O 3 microcubes shows excellent detection ability even at low HCHO concentration (˜50 ppb) and high response reaching to R gas /R air = 5.2 at 1 ppm as well as long-term stability, compared with conventional Fe 2 O 3 nanoparticles. [ABSTRACT FROM AUTHOR]

Improvement of activity, selectivity, and stability of the catalyst used in Fischer-Tropsch synthesis (FTS) to produce targeted hydrocarbon products has been a major challenge. In this work, the potassium-doped iron-carbide/alumina (K-Fe 5 C 2 /Al 2 O 3 ), as a durable nanocatalyst containing small iron-carbide particles (∼ 10 nm), was applied to high-temperature Fischer-Tropsch synthesis (HT-FTS) to optimize the production of linear alpha olefins. The catalyst, suitable under high space velocity reaction conditions (14–36 N L g cat −1  h −1 ) based on the well-dispersed potassium as an efficient base promoter on the active iron-carbide surface, shows very high CO conversion (up to ∼90%) with extremely high activity (1.41 mmol CO  g Fe −1  s −1 ) and selectivity for C 5 –C 13 linear alpha olefins. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (MN) is the most common glomerulonephritis in elderly patients showing nephrotic syndrome. However, little is known about its treatment options and outcomes in elderly MN patients at long term follow-up. We retrospectively enrolled patients with biopsy-proven MN between April 1990 and December 2015 from eight tertiary hospitals in Korea. Among them, we excluded patients who had secondary causes of MN and subnephrotic-range proteinuria. We evaluated the presenting features and clinical outcomes and analyzed the all-cause mortality, renal outcomes, infection, and remission with respect to age. During the median follow-up at 77.2 months, 198 younger patients (<65 years) and 133 elderly patients (≥65 years) were enrolled. Age was an independent risk factor for all-cause mortality, renal outcome, and infection (for all P <  0.05) except remission. In elderly patients, there was no significant factor associated with mortality rate. The use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) was significantly associated with renal outcome and infection (renal outcome, hazard ration [HR] 0.06, 95% confidence intervals [CI] 0.01–0.36, P  = 0.003; infection, HR 0.20, 95% CI 0.04–0.94, P  = 0.041). Immunosuppressant therapy significantly increased renal outcome ( P  = 0.045) and infection ( P  = 0.029) compared with conservative therapy. In conclusion, old age is one of the clinically important predictors for MN patients. Among the treatment of elderly MN patients, only ACEI or ARB was associated with beneficial effects on renal outcome and infection. Elderly MN patients need a more tailored regimen considering their comorbidities and condition. [ABSTRACT FROM AUTHOR]

Background Dialysis patients are at high risk for cardiovascular diseases, but until now there have been no detailed analyses of the incidences among Asian patients initiating dialysis. The aims of this study were to determine the incidence rates of major adverse cardiac and cerebrovascular events (MACCE) and to compare them between incident HD patients and PD patients. Methods We included all patients who had started dialysis between January 1, 2005 and December 31, 2008 in Korea, and analyzed 30,279 eligible patients [22,892 hemodialysis (HD) patients and 7387 peritoneal dialysis (PD) patients] by intention-to-treat. Median follow-up was 21.5 months. Results The crude incidence rates were as follows: MACCE, 182 per 1000 patient-years (PY); major adverse cardiac events (MACE), 138/1000 PY; all-cause mortality, 116/1000 PY; non-fatal acute myocardial infarction (AMI), 18/1000 PY; target vessel revascularization (TVR), 17/1000 PY; and non-fatal stroke, 60/1000 PY. When comparing all baseline covariate-adjusted relative risks between HD and PD patients, HD is overall superior to PD in terms of MACCE. Further examined by each endpoint, all-cause mortality, non-fatal AMI, and TVR occurred significantly more frequently in patients on PD than in those on HD, whereas non-fatal hemorrhagic stroke occurred significantly more frequently in patients on HD than in those on PD. Conclusions The incidence of MACCE may be different from Western dialysis patients. HD is overall superior to PD in terms of MACCE as an initial dialysis modality. Underlying mechanisms differentially affecting cardiovascular outcomes by dialysis modality remain to be further elucidated. [ABSTRACT FROM AUTHOR]

Abstracts Objective In end-stage renal disease, deleterious effect of sarcopenia on cardiovascular disease has been explained mainly by chronic inflammation. However, evidence emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we sought to investigate the effect of irisin, a recently introduced myokine, on the association between sarcopenia and cardiovascular disease in peritoneal dialysis (PD) patients. Methods Serum irisin concentrations were assessed by enzyme-linked immunosorbent assay in 102 prevalent PD patients and 35 age- and sex-matched controls. To determine sarcopenia and cardiovascular disease, anthropometric indices including mid-arm muscle circumference (MAMC) and carotid intima-media thickness (cIMT) were measured. Results Serum irisin concentrations were significantly lower in PD patients than in controls (184.2 ± 88.0 vs. 457.2 ± 105.5 ng/mL, P < 0.001). In PD patients, univariate linear regression analysis showed that serum irisin was positively correlated with MAMC and thigh circumference, but negatively correlated with residual renal function and cIMT. Multivariate analysis revealed that MAMC (per 1 cm increase, B = 8.78, 95% confidence interval [CI] = 0.77–16.79, P = 0.03) had an independent association with serum irisin. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in PD patients (per 1 g/mL increase, odds ratio = 0.990, 95% CI = 0.982–0.997, P = 0.007). Conclusion This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in PD patients. Additional studies to provide a confirmation and examine possible mechanisms are warranted. [ABSTRACT FROM AUTHOR]

To date, only a few large-scale studies have measured the effect of dialysis modality on mortality in Asian populations. Here, we sought to compare survival between incident hemodialysis (HD) and peritoneal dialysis (PD) patients using the Korean Health Insurance Review & Assessment Service database. This enabled us to perform a population-based complete survey that included 32,280 incident dialysis patients and followed them for a median of 26.5 months. To reduce biases due to nonrandomization, we first matched 7049 patient pairs with similar propensity scores. Using the log-rank test, we found the mortality rate in PD patients was significantly higher than that in HD patients. Subsequent subgroup analyses indicated that in older patients (55 years and older), with the exception of the subgroup of patients with no comorbidities and the subgroup of patients with malignancy, PD was consistently associated with a higher mortality rate. In younger patients (under 55 years), regardless of the covariates, the survival rate of PD patients was comparable to that of HD patients. Thus, while the overall mortality rate was higher in incident PD patients, mortality rates of some incident PD and HD patients were comparable in Korea. [ABSTRACT FROM AUTHOR]

Henöch-Schönlein purpura nephritis (HSPN) is considered a systemic form of immunoglobulin A nephropathy (IgAN). Although these are different pictures of a single disease, there are no studies directly comparing long-term outcomes of these two clinical entities. To clarify this, we studied 120 patients with biopsy-proven HSPN and 1070 patients with IgAN. The primary outcome was the composite of a doubling of baseline serum creatinine, end-stage renal disease, or death. Secondary outcomes included the individual renal outcomes or the rate of decline in estimated glomerular filtration rate. In the unmatched cohort, patients with HSPN had more vasculitic symptoms, more favorable histologic features, and were more commonly treated with steroids than patients with IgAN. The risk of reaching the primary outcome was significantly lower in HSPN patients than patients with IgAN (hazard ratio, 0.67). The 1:2 propensity score matching gave matched pairs of 89 patients with HSPN and 178 patients with IgAN, resulting in no differences in baseline conditions. In this matched cohort, there were no significant differences in reaching the primary and secondary outcomes between the two groups. Thus, after adjustment by propensity score matching, clinical outcomes did not differ between HSPN and IgAN, suggesting the two forms of the same disease have a similar prognosis. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a chronic, multisystemic vasculitis that theoretically affects all sizes and types of blood vessels. Although pathogenesis remains enigmatic, endothelial cells are believed to be the primary target in this disease. We detected the target protein using western blotting and immunoprecipitation and determined the amino-acid sequence of the peptide by liquid chromatography-matrix assisted laser desorption/ionization-tandem time-of-flight analysis (LC-MALDI-TOF/TOF). Serum reactivity against the recombinant target protein was analyzed by immunoblotting. Serum reactivity against streptococcal 65-kD heat shock protein (hsp-65) and the recombinant target protein was investigated by ELISA. The 36-40-kD protein band that was obtained from immunoprecipitation, which was analyzed by LC-MALDI-TOF/TOF, exhibited the amino-acid sequences of heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP-A2/B1). Reactivity of serum IgA against human recombinant hnRNP-A2/B1 was detected in 25 of 30 BD patients (83.3%), 4 of 30 systemic lupus erythematosus patients (13.3%), 8 of 30 rheumatoid arthritis patients (26.7%), 9 of 30 Takayasu's arteritis patients (30%), 6 of 30 healthy controls (20%), and none of 30 IgA nephropathy patients. Optical densities obtained from ELISAs against the recombinant human hnRNP-A2/B1 were correlated with those against the recombinant streptococcal hsp-65.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis. Methods: A cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen. Results: Plasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p =0.007) and IL-6 (p =0.002), whereas sRAGE was negatively associated with those inflammatory markers (p =0.001, p =0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β =−0.230, p =0.037, β =0.155, p =0.045) and VCS (β =−0.205, p =0.049, β =0.197, p =0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03–1.25, p =0.009), presence of diabetes (OR 13.4, 95% CI: 1.20–150.18, p =0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05–5.11, p =0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT>1.0mm and/or plaque formation). Conclusions: Our findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients. [Copyright &y& Elsevier]

Abstract: Backgrounds: Osteoprotegerin (OPG) is known to regulate bone mineral metabolism and to be also associated with inflammation, cardiovascular disease (CVD) and mortality. Malnutrition-inflammation-atherosclerosis (MIA) syndrome is commonly found and closely linked to mortality in dialysis patients. The aim of this study was to investigate the associations between OPG and MIA syndrome in prevalent peritoneal dialysis (PD) patients. Methods: Prevalent PD patients for more than 6 months were prospectively followed up from March 2005 to May 2010. At baseline, OPG, hs-CRP, albumin, and %lean body mass (LBM) by creatinine kinetics were checked, and subjective global assessment (SGA) was performed. New-onset cardiovascular events were evaluated during the study period. Based on the median level of OPG, patients were classified as lower OPG (LO) group (n =88) and higher OPG (HO) group (n =88). Results: A total of 176 patients (age 52.0±11.8 years, male 50.6%, duration of PD 105.3±67.2 months) were recruited and followed. In HO group, age, hs-CRP level and Charlson''s comorbidity indices were higher, whereas serum albumin level, %LBM and SGA score were significantly lower than LO group. OPG levels were positively correlated with inflammatory markers, whereas negatively correlated with nutritional status. Cardiovascular events occurred in 51 patients during the study period. Newly developed cardiovascular events were significantly common in HO group (n =36, 40.9%) than LO group (n =15, 17%, p =0.002). Cox regression analysis revealed that higher OPG level (per 1-SD increase in OPG, HR: 1.44; 95% CI: 1.03–2.00; p =0.034) was a significant risk factor for cardiovascular events even after adjustments for demographic and biochemical parameters. Conclusion: OPG was significantly correlated with markers of systemic inflammation and malnutrition and was a significant predictor of CVD in PD patients. These findings suggest OPG might be a prognostic indicator of MIA syndrome in prevalent PD patients. [Copyright &y& Elsevier]

Hyperhomocysteinemia induces oxidative stress and endothelial dysfunction, which share the proposed pathophysiologic mechanisms of contrast-induced nephropathy (CIN). However, no study has investigated the relation between hyperhomocysteinemia and CIN. The aim of the present study was to evaluate the effects of hyperhomocysteinemia on CIN in patients undergoing percutaneous coronary intervention. This was an observational cohort study that included 572 patients who underwent percutaneous coronary intervention. CIN was defined as an absolute ≥0.5 mg/dl or a relative ≥25% increase in the serum creatinine level at 48 hours after the procedure. The incidence of CIN was significantly greater in patients in the third homocysteine tertile (from lowest to highest, 4.7%, 7.3%, and 24.2%, p <0.001). Furthermore, the homocysteine levels were significantly greater in patients with CIN than in those without CIN (16.9 ± 4.9 vs 13.5 ± 4.2 μmol/L, p <0.001). In multiple logistic regression models, hyperhomocysteinemia was an independent risk factor for CIN (per the SD change in the plasma homocysteine level [4.44 μmol/L], odds ratio 1.70, 95% confidence interval 1.07 to 2.71, p = 0.025) after adjusting for major risk factors such as age, diabetes, and baseline cardiac and renal function. In subgroup analyses according to diabetes, acute coronary syndrome, or baseline estimated glomerular filtration rate, significant, graded associations were found between the homocysteine level and the incidence of CIN. In conclusion, hyperhomocysteinemia is independently associated with a greater risk of CIN in patients undergoing percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Abstract: Aims: We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally. Methods: The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008. Results: Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD. Conclusions: Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia. [Copyright &y& Elsevier]

Background: Peritoneal fibrosis is a serious complication in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, but the underlying mechanism is not well understood. Since high glucose activates the p38 mitogen-activated protein kinase (MAPK) pathway in various kinds of cells, and because mesothelial cells are always exposed to high glucose dialysate, we examined the activity and expression of p38 MAPK members in cultured human peritoneal mesothelial cells (HPMCs) under high glucose conditions.Methods: HPMCs were isolated from omentum and subcultured. After serum restriction, HPMCs were exposed to 5.6 mmol/L glucose (low glucose), 5.6 mmol/L glucose + 34.5 mmol/L mannitol (low glucose + mannitol), or 40 mmol/L glucose (high glucose) for 3 minutes to 48 hours with or without SB203580. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine mRNA and protein expression, respectively.Results: p38 MAPK and cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB) activities and mRNA expressions were significantly increased in HPMCs exposed to high glucose compared to low glucose or low glucose + mannitol after 10 minutes and remain at higher levels to 48 hours (P < 0.05), but total p38 MAPK and CREB protein expressions did not differ. MAPK kinase 3/6 (MKK3/6) activity and mRNA expression were also higher in high glucose cells after 3 minutes (P < 0.05), and fibronectin mRNA expression was significantly increased in HPMCs exposed to high glucose after 2 hours (P < 0.05). In contrast, high glucose significantly inhibited MAPK phosphatase-1 (MKP-1) protein and mRNA expression after 10 minutes (P < 0.05). SB203580 (1 micromol/L) pretreatment for 1 hour significantly reduced high glucose-induced CREB activity and fibronectin mRNA expression by 89% and 75%, respectively (P < 0.05).Conclusion: p38 MAPK activity was increased in HPMCs exposed to high glucose, in parallel with increased MKK3/6 activity and decreased MKP-1 expression, resulting in CREB activation. This activated p38 MAPK pathway may play a role in the pathogenesis of peritoneal fibrosis. [ABSTRACT FROM AUTHOR]