CRISP: a deep learning architecture for GC × GC-TOFMS contour ROI identification, simulation and analysis in imaging metabolomics.

Two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) provides a large amount of molecular information from biological samples. However, the lack of a comprehensive compound library or customizable bioinformatics tool is currently a challenge in GC × GC-TOFMS data analysis. We present an open-source deep learning (DL) software called contour regions of interest (ROI) identification, simulation and untargeted metabolomics profiler (CRISP). CRISP integrates multiple customizable deep neural network architectures for assisting the semi-automated identification of ROIs, contour synthesis, resolution enhancement and classification of GC × GC-TOFMS-based contour images. The approach includes the novel aggregate feature representative contour (AFRC) construction and stacked ROIs. This generates an unbiased contour image dataset that enhances the contrasting characteristics between different test groups and can be suitable for small sample sizes. The utility of the generative models and the accuracy and efficacy of the platform were demonstrated using a dataset of GC × GC-TOFMS contour images from patients with late-stage diabetic nephropathy and healthy control groups. CRISP successfully constructed AFRC images and identified over five ROIs to create a deepstacked dataset. The high fidelity, 512 × 512-pixels generative model was trained as a generator with a Fréchet inception distance of <47.00. The trained classifier achieved an AUROC of >0.96 and a classification accuracy of >95.00% for datasets with and without column bleed. Overall, CRISP demonstrates good potential as a DL-based approach for the rapid analysis of 4-D GC × GC-TOFMS untargeted metabolite profiles by directly implementing contour images. CRISP is available at https://github.com/vivekmathema/GCxGC-CRISP.

Incidence of De Novo Post-Transplant Malignancies in Thai Adult Kidney Transplant Recipients: A Single-Center, Population-Controlled, Retrospective Cohort Study at the Highest Volume Kidney Transplant Center in Thailand.

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.

GC × GC-TOFMS metabolomics analysis identifies elevated levels of plasma sugars and sugar alcohols in diabetic mellitus patients with kidney failure.

Two dimensional GC (GC × GC)-time-of-flight mass spectrometry (TOFMS) has been used to improve accurate metabolite identification in the chemical industry, but this method has not been applied as readily in biomedical research. Here, we evaluated and validated the performance of high resolution GC × GC-TOFMS against that of GC-TOFMS for metabolomics analysis of two different plasma matrices, from healthy controls (CON) and diabetes mellitus (DM) patients with kidney failure (DM with KF). We found GC × GC-TOFMS outperformed traditional GC-TOFMS in terms of separation performance and metabolite coverage. Several metabolites from both the CON and DM with KF matrices, such as carbohydrates and carbohydrate-conjugate metabolites, were exclusively detected using GC × GC-TOFMS. Additionally, we applied this method to characterize significant metabolites in the DM with KF group, with focused analysis of four metabolite groups: sugars, sugar alcohols, amino acids, and free fatty acids. Our plasma metabolomics results revealed 35 significant metabolites (12 unique and 23 concentration-dependent metabolites) in the DM with KF group, as compared with those in the CON and DM groups (N = 20 for each group). Interestingly, we determined 17 of the 35 (14/17 verified with reference standards) significant metabolites identified from both the analyses were metabolites from the sugar and sugar alcohol groups, with significantly higher concentrations in the DM with KF group than in the CON and DM groups. Enrichment analysis of these 14 metabolites also revealed that alterations in galactose metabolism and the polyol pathway are related to DM with KF. Overall, our application of GC × GC-TOFMS identified key metabolites in complex plasma matrices.

Considerable international variation exists in blood pressure control and antihypertensive prescription patterns in chronic kidney disease.

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes.

Periodontitis as the risk factor of chronic kidney disease: Mediation analysis.

AIM: To determine sequences and magnitude of causality among periodontitis, diabetes and chronic kidney disease (CKD) by mediation analysis. METHODS: Ten-year-data were retrieved from the Electric Generation Authority of Thailand (EGAT) study. A cohort of 2,635 subjects was identified with no CKD at baseline. The interested outcome was CKD incidence defined as glomerular filtration rate <60 ml/min/1.73 m2 . The percentage of proximal sites with clinical attachment loss ≥5 mm was used to represent periodontitis. Mediation analysis with 1,000-replication bootstrapping was applied to two causal diagrams, diagram A (Periodontitis â†’ Diabetes → CKD) and diagram B (Diabetes â†’ Periodontitis → CKD). RESULTS: The cumulative incidence of CKD was 10.3 cases per 100 persons during 10-year period. In diagram A, each increasing percentage of proximal sites with severe periodontitis increased the adjusted odds ratio of CKD 1.010 (95% CI: 1.005, 1.015) and 1.007 (95% CI: 1.004, 1.013), by direct and indirect effect through diabetes, respectively. In diagram B, diabetes increased the odds of CKD twofold, with 6.5% of this effect mediated via periodontitis. CONCLUSIONS: Periodontitis had significant direct effect, and indirect effect through diabetes, on the incidence of CKD. Awareness about systemic morbidities from periodontitis should be emphasized.

Effect of bioelectrical impedance analysis-guided dry weight adjustment, in comparison to standard clinical-guided, on the sleep quality of chronic haemodialysis patients (BEDTIME study): a randomised controlled trial.

BACKGROUND: Sleep disturbance is common among chronic haemodialysis patients, which leads to poor quality of life, in addition to increased instances of morbidity and mortality. Hypervolemia has been linked to sleep problems observed in chronic haemodialysis patients, which suggests that optimising one's fluid status could improve the sleep quality of this patient group. In our study, we subjectively examined and objectively measured sleep parameters, using actigraphy recordings, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and Epworth Sleepiness Scale (ESS), in order to compare bioelectrical impedance analysis (BIA)-guided and standard clinical-guided dry weight adjustment. METHODS: We randomly selected 19 chronic haemodialysis patients with subclinical hypervolemia, defined as a clinically euvolemic status, despite the ratio of extracellular water to total body water being more than 0.4 in BIA. Furthermore, these patients, who were poor sleepers (PSQI > 5), were assigned to either a BIA-guided dry weight group (BIA group) or a standard clinical-guided one (clinical group). The primary outcome was changes in sleep actigraphy parameters between the groups at 1, 3, and 6 months. Changes observed in the PSQI and ESS score between the two groups over the same period of time were the secondary endpoints. RESULTS: The mean age of the participants was 63.53 ± 11.12 years, and 42% of them were male. All sleep parameters measured by means of actigraphy were not significantly different between the two groups. Interestingly, at 3 and 6 months, the subjective sleep quality significantly improved in the BIA group, as reflected by a greater decline in the PSQI score, in comparison with the clinical group (3 months: mean difference - 1.82 [- 3.13 to - 0.51], P = 0.006; 6 months: mean difference - 3.16 [- 4.49 to - 1.83], P <  0.001). However, sleepiness assessed by the ESS was not significantly different between the groups throughout the study. CONCLUSIONS: Optimisation of the fluid status by employing BIA did not improves sleep actigraphy parameter, however, it significantly ameliorates the subjective sleep quality of chronic haemodialysis patients. This observation should be further explored in larger samples and longer clinical trials. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT02825589 ) on July 7, 2016.

Herbal or traditional medicine consumption in a Thai worker population: pattern of use and therapeutic control in chronic diseases.

BACKGROUND: Herbal and traditional medicines (HTM) are widely used in Asian countries. Specific data on prevalent of HTM usage and association with chronic diseases in the Thai population is currently lacking. We examined the prevalence and factors associated with HTM use in a Thai worker population. In addition, we explored the relationship between HTM use and therapeutic control of cardiovascular risk factors and documented the most common types of HTM used in various chronic diseases. METHODS: Employees of EGAT (The Electric Generating Authority of Thailand) who had participated in a health examination were studied. Each participant documented their HTM consumption and self-reported chronic diseases in a questionnaire. Clinical disease and therapeutic control were also defined by concomitant laboratory tests. RESULTS: Of a total of 6592 subjects, 32.6% were HTM-users. Age < 50 years, female gender, self-reported history of diabetes, liver disease, cancer, dyslipidemia, and alcohol use were independently associated with HTM use. HTM consumption increased in proportion to the numbers of self-reported chronic diseases. There were no differences in the therapeutic control of cardiovascular risk factors between HTM users and non-users. Liver and kidney function were not different. The most commonly used HTM was turmeric. CONCLUSIONS: HTM consumption is common in community-based Thai subjects, with higher use among those with chronic diseases. Although there were no differences in control of cardiovascular risk factors between HTM users and non-users, many of the commonly used herbs have relevant biological activities for chronic disease prevention or treatment.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis.

BACKGROUND: The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. OBJECTIVES: To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis. METHODS: This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr. RESULTS: Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months. CONCLUSION: High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN.

Impact of POR and CYP3A5 Polymorphisms on Trough Concentration to Dose Ratio of Tacrolimus in the Early Post-operative Period Following Kidney Transplantation.

BACKGROUND: Tacrolimus, a critical dose drug, is widely used in transplantation. Knowing the contribution of genetic factors, which significantly influence tacrolimus variability, is beneficial in the personalization of its starting dose. The significant impact of CYP3A5*3 polymorphisms on tacrolimus exposure has been reported. Conflicting results of the additional influence of POR*28 polymorphisms on tacrolimus pharmacokinetic interindividual variability have been observed among different populations. The objective of this study was to explore the interaction between POR*28 and CYP3A5*3 polymorphisms and their main effects on tacrolimus trough concentration to dose ratios on day 7 after kidney transplantation. METHODS: Two hundred sixteen adult kidney transplant recipients participated in this retrospective study. All participants received a twice daily tacrolimus regimen. Blood samples and data were collected on day 7 after transplantation. A 2-way analysis of covariance was performed. Tested covariates were age, hemoglobin, serum albumin, and prednisolone dose. RESULTS: A 2 × 2 analysis of covariance revealed that the interaction between CYP3A5 polymorphisms (CYP3A5 expresser and CYP3A5 nonexpresser) and POR polymorphisms (POR*28 carrier and POR*28 noncarrier) was not significant (F(1, 209) = 2.473, P = 0.117, (Equation is included in full-text article.)= 0.012). The predicted main effect of CYP3A5 and POR polymorphisms was significant (F(1, 209) = 105.565, P < 0.001, (Equation is included in full-text article.)= 0.336 and F(1, 209) = 4.007, P = 0.047, (Equation is included in full-text article.)= 0.019, respectively). Hemoglobin, age, and steroid dose influenced log C0/dose of tacrolimus (F(1, 209) = 20.612, P < 0.001, (Equation is included in full-text article.)= 0.090; F(1, 209) = 14.360, P < 0.001, (Equation is included in full-text article.)= 0.064; and F(1, 209) = 5.512, P = 0.020, (Equation is included in full-text article.)= 0.026, respectively). CONCLUSIONS: After adjusting for the influences of hemoglobin, age, and prednisolone dose, significant impacts of the CYP3A5 and POR polymorphisms on tacrolimus exposure were found. The effect of POR*28 and CYP3A5*3 polymorphisms during the very early period after kidney transplantation is independent of each other.

Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors for rapid loss of renal function in type 2 diabetic patients with diabetic kidney disease.

BACKGROUND: Increased monocyte chemoattractant protein-1 (MCP-1) and decreased epidermal growth factor (EGF) are promising biomarkers to predict progressive decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney disease (DKD). METHODS: T2DM patients (n = 83) with DKD at high risk for renal progression were followed up prospectively. The baseline urine values of MCP-1 to creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary outcome was a decline in estimated glomerular filtration rate (GFR) of ≥25% yearly from baseline. RESULTS: During follow-up time of 23 months, patients with rapid decline in estimated GFR of ≥25% yearly from baseline had significantly higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio. All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73 (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84 (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis, UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently associated with rapid GFR decline. CONCLUSIONS: UMCP-1 or UEGF/MCP-1 ratio were associated with rapid renal progression independent from conventional risk factors in DKD.

Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis.

BACKGROUND: Tubulointerstitial injury is important to predict the progression of lupus nephritis (LN). Urine neutrophil gelatinase-associated lipocalin (NGAL) has been reported to detect worsening LN disease activity. Thus, urine NGAL may predict renal outcomes among lupus patients. METHODS: We conducted a prospective multi-center study among active LN patients with biopsy-proven. All patients provided urine samples for NGAL measurement by ELISA collected from all patients at baseline and at 6-month follow-up after induction therapy. RESULTS: In all, 68 active LN patients were enrolled (mean age 31.7 ± 10.0 years, median UPCR 4.8 g/g creatinine level with interquartile range (IQR) 2.5 to 6.9 and mean estimated glomerular filtration rate (GFR) 89.6 ± 33.7 mL/min/1.73 m2). At baseline measurement, median urinary NGAL in complete response, partial response and nonresponse groups was 10.86 (IQR; 6.16, 22.4), 19.91 (IQR; 9.05, 41.91) and 65.5 (IQR; 18.3, 103) ng/mL, respectively (p = 0.006). Urinary NGAL (ng/mL) correlated positively with proteinuria and blood pressure, and correlated negatively with serum complement C3 level and estimated GFR. Based on ROC analysis, urinary NGAL (AUC; 0.724, 95%CI 0.491-0.957) outperformed conventional biomarkers (serum creatinine, urine protein, and GFR) in differentiating complete and partial response groups from the nonresponse group. The urine NGAL cut-off value in the ROC curve, 28.08 ng/mL, discriminated nonresponse with 72.7% sensitivity and 68.4% specificity. CONCLUSION: Urine NGAL at baseline performed better than conventional markers in predicting a clinical response to treatment of active LN except serum complement C3 level. It may have the potential to predict poor response after induction therapy.

Risk scores to predict decreased glomerular filtration rate at 10 years in an Asian general population.

BACKGROUND: Asians have among the highest prevalence of chronic kidney disease (CKD) or end-stage renal disease in the world. A risk score capable of identifying high risk individuals at the primary care level could allow targeted therapy to prevent future development of CKD. Risk scores for new CKD have been developed in US general populations, but the impact of various risks factors for development of CKD may differ in Asian subjects. In this study, we aimed to develop risk models and simplified risk scores to predict the development of decreased glomerular filtration rate (GFR) at 10 years in an Asian general population using readily obtainable clinical and laboratory parameters. METHODS: Employees of EGAT (The Electric Generating Authority of Thailand) were studied prospectively. Multivariable logistic regression models were used to assess risk factors and used to derive risk models and risk scores for developing decreased GFR at 10 years: Model 1 (Clinical only), Model 2 (Clinical + Limited laboratory tests), and Model 3 (Clinical + Full laboratory tests). The performance of the risk models or risk scores to predict incident cases with decreased GFR were evaluated by tests of calibration and discrimination. RESULTS: Of 3186 subjects with preserved GFR (eGFR ≥60) at baseline, 271 (8.5%) developed decreased GFR (eGFR < 60) at 10 years. Model 1 (Age, sex, systolic blood pressure, history of diabetes, and waist circumference) had good performance (χ2 = 9.02; AUC = 0.72). Model 2 (Age, Sex, systolic blood pressure, diabetes, glomerular filtration rate) had better discrimination (χ2 = 10.87, AUC = 0.79) than Model 1. Model 3 (Model 2+ Uric acid, Hemoglobin) did not provide significant improvement over Model 2. Based on these findings, simplified categorical risk scores were developed for Models 1 and 2. CONCLUSIONS: Clinical or combined clinical and laboratory risk models or risk scores using tests readily available in a resource-limited setting had good accuracy and discrimination power to estimate the 10-year probability of developing decreased GFR in a Thai general population. The benefits of the risk scores in identifying high risk individuals in the Thai or other Asian communities for special intervention requires further studies.

Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation.

PURPOSE: The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized tacrolimus regimen. METHODS: A total of 164 patients participated in the study. All received oral tacrolimus twice daily starting on the day of surgery with the target pre-dose (trough) concentration of 4-8 ng/ml for prevention of allograft rejection. Cytochrome P450 (CYP) 3A5 genotypes were determined. The patients were divided into CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (homozygous CYP3A5*3). Whole blood tacrolimus concentrations on days 3 and 7 posttransplantation and the incidence of biopsy-proven acute rejection (BPAR) at 3-month posttransplantation were compared between groups. RESULTS: On day 3, the median (IQR) dose-and-weight-normalized trough concentration in expressers and nonexpressers were 54.61 (31.98, 78.87) and 91.80 (57.60, 130.20) ng/ml per mg/kg/day, respectively (p < 0.001). Although only 47 and 42% of expressers and nonexpressers were within the target range on day 3, approximately 60% of both groups were within the target range on day 7. Proportions of BPAR among expressers and nonexpressers were 6.0 and 7.4 %, respectively (p = 0.723). The median (IQR) times to the first rejection in CYP3A5 expressers and nonexpressers were 32 (12, 68) and 15 (12, 37) days, respectively (p = 0.410). CONCLUSIONS: Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis.

BACKGROUND/AIMS: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). METHODS: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. RESULTS: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. CONCLUSION: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

Simple and fast analysis of iohexol in human serums using micro-hydrophilic interaction liquid chromatography with monolithic column.

A simple and rapid method based on micro-liquid chromatography using a synthetic monolithic capillary column was developed for determination of iohexol in human serums, a marker to evaluate the glomerular filtration rate. A hydrophilic methacrylic acid-ethylene dimethacrylate monolith provided excellent selectivity and efficiency for iohexol with separation time of 3 min using a mobile phase of 40:60 v/v 50 mM phosphate buffer pH 5/methanol. Four serum protein removal, methods using perchloric acid, 50% acetonitrile, 0.1 M zinc sulfate, and centrifuge membrane filter were examined. The method of zinc sulfate was chosen due to its simplicity, compatibility with the mobile phase system, nontoxicity, and low cost. Interday calibration curves were conducted over iohexol concentrations range of 2-500 mg/L (R(2) = 0.9997 ± 0.0001) with detection limit of 0.44 mg/L. Intra- and interday precisions for peak area and retention time were less than 2.8 and 1.4%, respectively. The method was successfully applied to serum samples with percent recoveries from 102 to 104. The method was applied to monitor released iohexol from healthy subject. Compared with the commercially available reversed-phase high-performance liquid chromatography method, the presented method provided simpler chromatogram, faster separation with higher separation efficiency and much lower sample and solvent consumption.

Effects of glomerular filtration rate estimating equations derived from different reference methods on staging and long term mortality risks of chronic kidney disease in a Southeast Asian cohort.

AIM: There are limited data on the risks of chronic kidney disease (CKD) in Southeast Asian populations. Several GFR estimating equations have been developed in diverse Asian populations, but they produce markedly discrepant results. We investigated the impact of Asian equations on the mortality risk of CKD in a Thai cohort during long term follow-up, and explored the differences between equations grouped according to the reference GFR methods used to develop them. METHODS: Employees of the Electricity Generating Authority of Thailand (n = 3430) were enrolled in a health survey and followed up for 22 years. The risks for all-cause mortality for each GFR stage classified by CKD-EPI or different Asian equations were assessed by using Cox proportional hazard models. RESULTS: Equations derived from DTPA clearance (Chinese MDRD, Thai GFR, Singapore CKD-EPI) produced higher GFR, whereas equations from inulin clearance (Japanese CKD-EPI, Taiwan MDRD or Taiwan CKD-EPI) produced lower GFR compared to CKD-EPI. (Average ΔGFR: inulin, -14.9 vs. DTPA +5.80 mL/min per 1.73 m(2) , P < 0.001). CKD prevalence varied widely (0.7 to 24 %) with inulin-based equations being higher than DTPA-based. GFR stage concordance was over 80% for equations using similar reference method compared to less than 40% between inulin and DTPA-based equations. Low GFR (<45) was an independent mortality risk factor when DTPA-based equations were used, but not when inulin-based equations were used. CONCLUSION: Chronic kidney disease prevalence and prognosis in Thais varied widely depending on the equation used. Differences in the reference GFR methods could be an important cause for the discrepancies between Asian equations.

Low hip bone mineral density predicts mortality in maintenance hemodialysis patients: a five-year follow-up study.

BACKGROUND: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.

Vascular calcification in long-term kidney transplantation.

AIM: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS: The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS: The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS: Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.

An Increase in Vascular Stiffness Is Positively Associated With Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Older Adults.

The cardio-ankle vascular index (CAVI) is a noninvasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a noninvasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the older adults.. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand between 2017 and 2018. A total of 1 640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into 3 groups based on their CAVI values as high (CAVI ≥ 9), moderate (9 > CAVI ≥ 8), and low (CAVI < 8), in which each group comprised 702, 507, and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.