Coupling capillary electrophoresis with mass spectrometry for the analysis of oxidized phospholipids in human high-density lipoproteins.

The oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products in human high-density lipoproteins (HDLs) were investigated by low-flow capillary electrophoresis-mass spectrometry (low-flow CE-MS). To accelerate the optimization, native PAPC (n-PAPC) standard was first analyzed by a commercial CE instrument with a photodiode array detector. The optimal separation buffer contained 60% (v/v) acetonitrile, 40% (v/v) methanol, 20 mM ammonium acetate, 0.5% (v/v) formic acid, and 0.1% (v/v) water. The selected separation voltage and capillary temperature were 20 kV and 23°C. The optimal CE separation buffer was then used for the low-flow CE-MS analysis. The selected MS conditions contained heated capillary temperature (250°C), capillary voltage (10 V), and injection time (1 s). No sheath gas was used for MS. The linear range for n-PAPC was 2.5-100.0 µg/mL. The coefficient of determination (R2 ) was 0.9918. The concentration limit of detection was 1.52 µg/mL, and the concentration limit of quantitation was 4.60 µg/mL. The optimal low-flow CE-MS method showed good repeatability and sensitivity. The ox-PAPC products in human HDLs were determined based on the in vitro ox-PAPC products of n-PAPC standard. Twenty-one ox-PAPC products have been analyzed in human HDLs. Uremic patients showed significantly higher levels of 15 ox-PAPC products than healthy subjects.

Association of diabetes, education level, and care dependency with use of temporary vascular access in patients with chronic kidney disease.

OBJECTIVE: Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored. METHODS: This study included patients in a single-center CKD care program who initiated long-term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression. RESULTS: Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28-1.81, p < 0.001), lower albumin (HR 0.82, 95% CI 0.75-0.91, p < 0.001), lower education level (HR 0.75, 95% CI 0.56-1.00, p = 0.055), and total care dependency (HR 1.92, CI 1.44-3.43, p = 0.003). CONCLUSION: Diabetes, education level, and care dependency are associated with TVA at dialysis initiation in patients with CKD.

Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis.

Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Coincidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phosphorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.

Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1- and SIRT3-mediated autophagy induction.

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B-cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)-mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with (Clin J Am Soc Nephrol. 2011, 6, 1301-1307) reduced mitochondrial ROS generation; (Am J Physiol-Renal Physiol. 2011. 301, F1218-F1230) differentially regulated autophagy and NLRP3 inflammasome; (Clin J Am Soc Nephrol. 2012, 7, 427-436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and (Free Radic Biol Med. 2013, 61, 285-297) blunted NLRP3 inflammasome activation through SIRT1- and SIRT3-mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs-mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.

Repeated centrifuging and washing concentrates bacterial samples in peritoneal dialysis for optimal culture: an original article.

BACKGROUND: Bacterial cultures allow the identification of infectious disease pathogens. However, obtaining the results of conventional culture methods is time-consuming, taking at least two days. A more efficient alternative is the use of concentrated bacterial samples to accelerate culture growth. Our study focuses on the development of a high-yield sample concentrating technique. RESULTS: A total of 71 paired samples were obtained from patients on peritoneal dialysis (PD). The peritoneal dialysates were repeat-centrifuged and then washed with saline, namely the centrifuging and washing method (C&W method). The concentrated samples were Gram-stained and inoculated into culture plates. The equivalent unprocessed dialysates were cultured as the reference method. The times until culture results for the two methods were compared. The reference method yielded no positive Gram stain results, but the C&W method immediately gave positive Gram stain results for 28 samples (p < 0.001). The culture-negative rate was lower in the C&W method (5/71) than in the reference method (13/71) (p = 0.044). The average time for bacterial identification achieved with the C&W method (22.0 h) was shorter compared to using the reference method (72.5 h) (p < 0.001). CONCLUSIONS: The C&W method successfully concentrated bacterial samples and superseded blood culture bottles for developing adequate bacterial cultures. The C&W method may decrease the culture report time, thus improving the treatment of infectious diseases.

Cyclodextrin-micellar electrokinetic chromatography of apolipoproteins on human very low-density lipoprotein.

The apolipoproteins (APOs) of human very low-density lipoprotein (VLDL) were investigated by an optimized cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method. The separation buffer consisted of 20 mM sodium phosphate, 40 mM bile salts (50% sodium cholate and 50% sodium deoxycholate), 25 mM carboxymethyl-ß-cyclodextrin (CM-ß-CD) (pH 7.0). For CD-MEKC separation, a sample injection time of 12 s, a separation voltage of 15 KV, and a capillary temperature of 15°C were chosen. The optimal CD-MEKC method showed good resolution and repeatability for VLDL APOs. Identification and quantitation of VLDL APOs CI, CIII, and E were based on comparison with human APO standards. Good linear relationships with correlation coefficient (R2 ) 0.99 were obtained for APOs CI, CIII, and E standards. For these three APOs, the linear ranges were within 0.01-0.54 mg/mL, and the concentration limits of detection (LODs) were lower than 0.02 mg/mL. Moreover, VLDL APOs from four uremic patients and four healthy subjects were compared. The uremic and healthy CD-MEKC profiles showed dramatic difference. The levels of APO CIII were significantly higher for two patients, and the level of APO E was significantly higher for one patient. This study might be helpful for following the disease development of uremia and cardiovascular disease (CVD) in the future.

Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry.

RATIONALE: Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis and pancreatic cancer (PC) is one of the most lethal types of cancer that is symptomless in the early stage. Because the clinical and image findings of CP can overlap that of pancreatic cancer (PC) which leads to confusion in the diagnosis and treatment of PC, discovery/verification/validation of more accurate protein biomarkers to diagnose CP and PC is in urgent need. METHODS: The PubMed, Web of Science, and Google Scholar were searched using the keywords: 'biomarker', 'marker', 'chronic pancreatitis', "pancreatic cancer" or "proteomics" for highly related researches. We focused on the articles published after the year 2005 in this review. RESULTS: We introduce the background to CP and PC and summarize the diagnosis of CP and PC, analytically validated protein biomarkers, and proteomic approaches for discovery/verification/validation. The potential use of mass spectrometry (MS) in clinical diagnosis is also discussed. CONCLUSIONS: Continuously improving sensitivity of MS can provide deeper proteome for new marker discovery and high reliability for protein marker verification, validation, and clinical diagnosis. The analytically validated protein markers could be considered as targeted protein biomarkers for developing a MS platform in the clinical validation process or clinical diagnosis of CP and PC.

Maximum Glomerular Filtration Decline Rate is Associated with Mortality and Poor Renal Outcome in Chronic Kidney Disease Patients.

BACKGROUND: Glomerular filtrate rate (GFR) decline is associated with increased risk of dialysis in patients with chronic kidney disease (CKD). It is unclear whether the maximum, the minimum, or the average of GFR decline rate is associated with the risk of mortality and the initiation of renal replacement therapy (RRT). We investigated prognostic role of the maximum, the minimum, and the average of GFR decline rate in patients with CKD not yet on dialysis. METHODS: Patients, enrolled in the CKD program of China Medical University Hospital between July 2004 and Aug 2013, with CKD stages 3-5 (estimated GFR [eGFR] < 60 mL/min/1.73 m2) not yet on dialysis were analyzed. Primary outcome was a composite of mortality and RRT. The association between 3 readings of GFR decline rate and primary outcome was analyzed using Cox proportional hazard regression. RESULTS: We analyzed 815 patients aged 75 (interquartile range [IQR] 65-82) years with a median follow-up of 5.2 years (IQR 3.9-6.9). The maximum of eGFR decline rate was associated with the primary outcome (hazard ratio 2.19, 95% CI 1.16-4.12, p = 0.015), independent of age, gender, diabetes, cerebrovascular accident, smoking, baseline eGFR, serum albumin, calcium, urine protein/creatinine ratio, usage of renin-angiotensin system blockade. The minimum and the average of eGFR decline rate were not associated with the primary outcome. CONCLUSIONS: The maximum of GFR decline rate was associated with mortality and poor renal outcome in CKD patients, independent of other contributive confounders.

Abdominal aortic calcification score predicts the occurrence of coronary artery disease in middle-aged peritoneal dialysis patients.

AIM: Abdominal aortic calcification (AAC) score in dialysis patients was associated with coronary artery disease (CAD) in cross-sectional study, but the use of AAC score in the CAD prediction was not clear. We aimed to use AAC score in the estimation of CAD occurrence in middle-aged peritoneal dialysis (PD) patients. METHODS: Middle-aged (45-65 years old) PD patients were recruited and followed up until CAD occurrence, patient mortality, or PD failure. We quantified AAC score by lateral lumbar radiography, and used receiver operation curve (ROC) analysis to find the cut-off value for CAD prediction. RESULTS: There were 187 patients recruited for study with a mean follow-up of 1027 ± 427 days. AAC score in patients with CAD during follow-up period (9.7 ± 7.6, n = 41) was higher than in patients without CAD occurrence (5.5 ± 6.1, n = 146) (P < 0.001). Multivariate hazard ratio of AAC score for CAD was 1.07 (P = 0.044). ROC showed that AAC score of 5.5 had a sensitivity of 0.667 and a specificity of 0.581 in the prediction of CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5 (Log-rank test, P = 0.003). Age (P = 0.002), diabetes (P = 0.002), hypertension (P = 0.032), longer dialysis vintage (P < 0.001) and lower serum potassium (P = 0.012) were parameters significantly associated with higher AAC score. CONCLUSION: AAC score can predict CAD occurrence in PD patients. Age, diabetes, hypertension, dialysis vintage and serum potassium level are factors associated with higher AAC score.

Spironolactone ameliorates endothelial dysfunction through inhibition of the AGE/RAGE axis in a chronic renal failure rat model.

BACKGROUND: Spironolactone can improve endothelial dysfunction in the setting of heart failure and diabetes models. However, its beneficial effect in the cardiovascular system is not clear in the setting of non-diabetic renal failure. We conducted this study to investigate whether spironolactone can ameliorate endothelial dysfunction in a 5/6 nephrectomy model, and to determine the underlying mechanism. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. A renal failure model was created using the 5/6 nephrectomy method. The four groups included: Sham-operation group (Group1), chronic kidney disease (CKD; Group2), CKD + ALT-711 (advanced glycation end products [AGEs] breaker; Group 3), and CKD + spironolactone group (Group4). Acetylcholine (Ach)-mediated vasodilatation responses were compared between the four groups. To investigate the underlying mechanism, we cultured human aortic endothelial cells (HAECs) for in-vitro assays. Differences between two groups were determined with the paired student's t test. Differences between three or more groups were determined through one-way analysis of variance (ANOVA) with post-hoc analysis with LSD method. RESULTS: Compared with Group 1, Group 2 has a significantly impaired Ach-mediated vasodilatation response. Group 3 and 4 exhibited improved vasoreactivity responses. To determine the underlying mechanism, we performed an in-vitro study using cultured HAECs. We noted significant sirtuin-3 (SIRT3) protein downregulation, reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 (p-eNOS), and increased intracellular oxidative stress in cultured HAECs treated with AGEs (200 µg/mL). These effects were counter-regulated when cultured HAECs were pretreated with spironolactone (10 µM). Furthermore, the increased p-eNOS production by spironolactone was abrogated when the HAECs were pretreated with tenolvin (1 µM), a SIRT3 inhibitor. CONCLUSIONS: Spironolactone could ameliorate endothelial dysfunction in a 5/6 nephrectomy renal failure model through AGEs/Receptor for AGEs (RAGEs) axis inhibition, SIRT3 upregulation, and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) and its associated intracellular oxidative stress attenuation.

Identification of Urinary Metabolite Biomarkers of Type 2 Diabetes Nephropathy Using an Untargeted Metabolomic Approach.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). To discover early stage biomarkers of DN, untargeted liquid chromatography-mass spectrometry-based metabolomic analysis was performed in urine samples from healthy subjects and patients with micro- or macroalbuminuria due to nondiabetic disease (macro), type 2 DM without microalbuminuria (T2DM), and type 2 DM with microalbuminuria (T2DM+micro). Levels of four metabolites were significantly different among groups, and they were quantified in a larger group of 267 urine samples. Two metabolites were also discovered and validated in targeted metabolic study of amino acids. For diagnosis of nephropathy, N1-methylguanosine had the highest area-under-the-curve (AUC) value of 0.75 when compared to those of valine (0.68), xanthosine (0.67), and 7-methyluric acid (0.69). After combining fasting blood glucose and diastolic blood pressure (DBP) with N1-methylguanosine, the AUC increased to 0.987. To distinguish between T2DM and T2DM+micro conditions, xanthosine and N1-methylguanosine have AUC value of 0.612 and 0.624, respectively. After adjustment of HbA1c and DBP, AUC values of xanthosine and N1-methylguanosine increased to 0.716 and 0.723, respectively, and could be used to predict the development of nephropathy in T2DM patients.

Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation.

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid ß (Aß) stimulates platelet aggregation, we studied whether L5 and Aß function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aß, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aß release via IκB kinase 2 (IKK2). Furthermore, L5+Aß synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aß shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aß-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

Risk of new-onset diabetes in end-stage renal disease patients undergoing dialysis: analysis from registry data of Taiwan.

Background: This study compared the risk of developing new-onset diabetes between hemodialysis (HD) and peritoneal dialysis (PD) patients. We further investigated the effectiveness of icodextrin in reducing the risk of new-onset diabetes in PD patients. Methods: From the Taiwan health insurance database, 36 879 incident HD patients and 6382 incident PD patients from 2000 to 2010 were identified as study cohorts. We further selected an additional HD cohort matched by propensity scores (PSs) of PD patients. Incidence rates and hazard ratios (HRs) of new-onset diabetes were assessed among cohorts and between icodextrin users and nonusers by the end of 2011. Results: For the unmatched cohorts, the incidence of new-onset diabetes was higher in PD patients than in HD patients (9.16 versus 8.18 per 1000 person-years), with an adjusted HR of 1.51 (95% CI 1.30-1.75) for PD patients. For the PS-matched cohorts, the corresponding incidence rates were 9.43 and 5.90 per 1000 person-years, respectively, with an adjusted HR of 1.61 (95% CI 1.32-1.97). Among PD patients, the incidence was lower in icodextrin users than in nonusers (6.22 versus 12.1 per 1000 person-years), with an adjusted HR of 0.66 (95% CI 0.50-0.88) for users. Conclusions: Our study suggests that PD patients are at a higher risk of developing new-onset diabetes than HD patients. Icodextrin is recommended for PD patients to reduce the risk of new-onset diabetes.

Hypothyroidism is associated with all-cause mortality in a national cohort of chronic haemodialysis patients.

AIM: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients. METHOD: Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression. RESULT: Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer. CONCLUSION: Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks.

Comparison of the risk of non-traumatic lower extremity amputation between haemodialysis and peritoneal dialysis patients with end-stage renal disease.

AIM: We used insurance claims data of Taiwan to compare the risk of non-traumatic lower extremity amputation between haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: We identified 77 669 HD patients and 10 035 PD patients without prior amputation from 2000 to 2010. Incidence rates and hazard ratios (HRs) of lower extremity amputation, and subsequent 30-day mortality after amputation were evaluated up to 31 December 2011. RESULTS: There were 2427 and 216 patients undergoing lower extremity amputation during follow-up in the HD and PD groups with incidence rates of 8.35 and 5.79 per 1000 person-years, respectively. Compared with the HD group, the overall adjusted HR of lower extremity amputation for the PD group was 1.27 (95% CI = 1.10-1.46). The impact of diabetes status on the risk of lower extremity amputation interacted with dialysis modality significantly (P < 0.001). Compared with the corresponding HD patients, the PD patients with diabetes had an adjusted HR of 1.44 (95% CI = 1.24-1.67) for amputation, whereas those without diabetes had an adjusted HR of 0.58 (95% CI = 0.36-0.95). The subsequent 30-day mortality rates after amputation were not significantly different between the HD and PD groups (8.45% vs. 9.72%) with an adjusted odds ratio of 1.41 (95% CI = 0.87-2.28, PD versus HD). CONCLUSION: Compared with corresponding HD patients, the amputation risk is higher for PD patients with diabetes, while the risk is lower for PD patients without diabetes. Dialysis patients have a high 30-day mortality risk after amputation.

Abdominal aortic calcification score can predict future coronary artery disease in hemodialysis patients: a 5-year prospective cohort study.

BACKGROUND: Abdominal aortic calcification (AAC) has been known to be associated with cardiovascular mortality in hemodialysis. However, the association between AAC and future coronary artery disease (CAD) occurrence is not clear. We aimed to clarify the association of AAC severity and the occurrence of future CAD events in hemodialysis patients. METHODS: Hemodialysis (HD) patients were recruited in this prospective cohort study. AAC severity was quantified by AAC score, which was measured by lateral lumbar radiography. We used receiver operation curve (ROC) analysis to find the cutoff AAC value for CAD prediction. CAD-free survival was analyzed by Kaplan-Meier study. RESULTS: There were 303 patients recruited for study with a median (interquartile range) follow-up of 95 (65-146) months. The AAC score in patients with occurrence of new CAD [9 (3-15.25), n = 114] was higher than in patients without new CAD occurrence [5 (1-9) n = 189], p < 0.001. Multivariate hazard ratio of AAC score for CAD was 1.039 (p = 0.016). ROC study showed that an AAC score of 5.5 had a sensitivity of 0.658 and a specificity of 0.587 in the prediction of new CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5. Age, diabetes, prior history of CAD, and longer dialysis vintage were major factors associated with higher AAC score. CONCLUSIONS: AAC score can predict the occurrence of future CAD events in HD patients. The best cut-off value of AAC score is 5.5. AAC score greater than 5.5 is a reliable abdominal aortic calcification marker, and can predict future CAD in ESRD patients. Major contributive factors for higher AAC score were age, presence of diabetes, prior history of CAD, and longer dialysis vintage.

Vegetarian diet may ameliorate uremic pruritus in hemodialysis patients.

OBJECTIVES: Systemic inflammation has been reported to be associated with uremic pruritus (UP). Although a vegetarian diet can reduce systemic inflammation in hemodialysis patients, the effect of vegetarian diet on UP is not clear. The purpose of the study was to know the possible effects of vegetarian diet on UP. METHODS: A cross-sectional study was done to compare the severity of UP and blood levels of systemic inflammatory markers between vegetarian and non-vegetarian hemodialysis patients. Six non-vegetarian patients with uremic pruritus changed their non-vegetarian diet to vegetarian diet for 2 months. Visual Analogue Scale (VAS) and pruritus score (PS) were used to measure the UP severity. The serum high-sensitivity C-reactive protein (hs-CRP), and interleukin-2 (IL-2) were used as markers of inflammation. RESULTS: Both the median VAS scores (p = .043) and the median PS scores (p < .001) were lower in the Vegetarian than in the non-vegetarian group. The median values of hs-CRP in Vegetarian were lower than that for the non-vegetarian (p = .020). The median value of IL-2 was also lower in Vegetarian than that of the non-vegetarian (p = .016). There were 6 non-vegetarian patients shift to vegetarian for 2 months. The pruritus score improved and IL-2 level decreased after change to vegetarian diet. CONCLUSION: We concluded that vegetarian diet might be associated with the amelioration of the uremic pruritus severity in hemodialysis patients.

Diagnosis of Bacterial Pathogens in the Urine of Urinary-Tract-Infection Patients Using Surface-Enhanced Raman Spectroscopy.

(1) Background: surface-enhanced Raman spectroscopy (SERS) is a novel method for bacteria identification. However, reported applications of SERS in clinical diagnosis are limited. In this study, we used cylindrical SERS chips to detect urine pathogens in urinary tract infection (UTI) patients. (2) Methods: Urine samples were retrieved from 108 UTI patients. A 10 mL urine sample was sent to conventional bacterial culture as a reference. Another 10 mL urine sample was loaded on a SERS chip for bacteria identification and antibiotic susceptibility. We concentrated the urine specimen if the intensity of the Raman spectrum required enhancement. The resulting Raman spectrum was analyzed by a recognition software to compare with spectrum-form reference bacteria and was further confirmed by principal component analysis (PCA). (3) Results: There were 97 samples with single bacteria species identified by conventional urine culture and, among them, 93 can be successfully identified by using SERS without sample concentration. There were four samples that needed concentration for bacteria identification. Antibiotic susceptibility can also be found by SERS. There were seven mixed flora infections found by conventional culture, which can only be identified by the PCA method. (4) Conclusions: SERS can be used in the diagnosis of urinary tract infection with the aid of the recognition software and PCA.

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease.

BACKGROUND: Enhanced advanced glycation end products deposition within myocardial tissue may cause diastolic dysfunction. However, whether this is related to left ventricular hypertrophy or inappropriate left ventricular mass remains unclear. METHODS: We prospectively enrolled 139 subjects at risk for cardiovascular diseases. We used echocardiography for measurements of left ventricular mass and cardiac systolic and diastolic functional parameters. An advanced glycation end product reader was applied for measurements of skin autofluorescence values. Comparisons of left ventricular mass and echocardiographic parameters between the higher and lower skin autofluorescence groups were analyzed. RESULTS: Compared with the lower skin autofluorescence group, left ventricular mass index and the ratio of observed left ventricular mass/predicted left ventricular mass (oLVM/pLVM) was significantly higher in the higher skin autofluorescence group (61.22 ± 17.76 vs. 47.72 ± 11.62, P < 0.01, 1.62 ± 0.38 vs. 1.21 ± 0.21, P < 0.01). After adjustment for potential confounding factors, skin autofluorescence was an independent factor for left ventricular mass index (ß = 0.32, P < 0.01) and the ratio of oLVM/pLVM (ß = 0.41, P < 0.01). Skin autofluorescence ≥2.35 arbitrary unit predicted left ventricular hypertrophy at a sensitivity of 58.8%, and a specificity of 73.0% (P < 0.01). Skin autofluorescence ≥2.25 arbitrary unit predicted inappropriate left ventricular mass at a sensitivity of 71.1%, and a specificity of 83.9% (P < 0.01). Skin autofluorescence was positively correlated with E/E', an indicator for diastolic dysfunction (r = 0.21, P = 0.01). CONCLUSIONS: Skin autofluorescence is a useful tool for detecting left ventricular hypertrophy, inappropriate left ventricular mass and diastolic dysfunction.

Prolonged QT interval is linked to all-cause and cardiac mortality in chronic peritoneal dialysis patients.

AIM: Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS: The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS: Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (P = 0.03, log-rank test) and cardiac mortality free survival (P = 0.05, log-rank test). CONCLUSIONS: Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.