scholarly journals Lipidomics Reveals Serum Specific Lipid Alterations in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Xu ◽  
Xiaoyan Xu ◽  
Lu Zhang ◽  
Ke Zhang ◽  
Qiong Wei ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Operating Characteristic ◽  
Early Stage ◽  
Liquid Chromatography Mass Spectrometry ◽  
Characteristic Analysis ◽  
Serum Samples ◽  
Biomarker Panel ◽  
Glucose And Lipid Metabolism ◽  
Specific Lipid

In diabetes mellitus (DM), disorders of glucose and lipid metabolism are significant causes of the onset and progression of diabetic nephropathy (DN). However, the exact roles of specific lipid molecules in the pathogenesis of DN remain unclear. This study recruited 577 participants, including healthy controls (HCs), type-2 DM (2-DM) patients, and DN patients, from the clinic. Serum samples were collected under fasting conditions. Liquid chromatography-mass spectrometry-based lipidomics methods were used to explore the lipid changes in the serum and identify potential lipid biomarkers for the diagnosis of DN. Lipidomics revealed that the combination of lysophosphatidylethanolamine (LPE) (16:0) and triacylglycerol (TAG) 54:2-FA18:1 was a biomarker panel for predicting DN. The receiver operating characteristic analysis showed that the panel had a sensitivity of 89.1% and 73.4% with a specificity of 88.1% and 76.7% for discriminating patients with DN from HCs and 2-DM patients. Then, we divided the DN patients in the validation cohort into microalbuminuria (diabetic nephropathy at an early stage, DNE) and macroalbuminuria (diabetic nephropathy at an advanced stage, DNA) groups and found that LPE(16:0), phosphatidylethanolamine (PE) (16:0/20:2), and TAG54:2-FA18:1 were tightly associated with the stages of DN. The sensitivity of the biomarker panel to distinguish between patients with DNE and 2-DM, DNA, and DNE patients was 65.6% and 85.9%, and the specificity was 76.7% and 75.0%, respectively. Our experiment showed that the combination of LPE(16:0), PE(16:0/20:2), and TAG54:2-FA18:1 exhibits excellent performance in the diagnosis of DN.

scholarly journals Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Christopher Walker ◽  
Tuan-Minh Nguyen ◽  
Shlomit Jessel ◽  
Ayesha B. Alvero ◽  
Dan-Arin Silasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Early Stage ◽  
Ca 125 ◽  
Healthy Controls ◽  
Classification Models ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

Evaluation of urinary TNF-α and KIM-1 biomarkers in T2DM in Upper Egypt

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy EL Sharkawy ◽  
Samir K Abdul-Hamid ◽  
Tarek T Elmelegy ◽  
Mohammed F Adawy
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Clinical Syndrome ◽  
Diabetic Patients ◽  
University Hospitals ◽  
Type 2 Diabetic Patients ◽  
Cross Sectional ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background Diabetes mellitus (DM) is the most frequent cause of chronic kidney failure in both developed and developing countries. Diabetic nephropathy, is a clinical syndrome characterized by albuminuria (>300 mg/day) with permanent and irreversible decrease in glomerular filtration rate (GFR). Aim of the Work To study the role of urinary TNF-α and urine KIM-1 in type 2 diabetic patients as predictors of DN comparative with albuminuria. Patients and Methods This is a cross-sectional study which include 90 type-2 diabetic patients and 30 controls selected from the outpatient clinic of Assiut University hospitals. All patients gave an informed consent and approval for the study was obtained from the IRB committee of the Assiut Medical Faculty. The recruited patients were divided into three groups: Normo-albuminuria Group (A) (n = 30): UACR less than 30 mg/gm, Microalbuminuria Group (B) (n = 30): UACR between 30-299 mg/gm and Macro-albuminuria Group (C) (n = 30): UACR equal or more than 300 mg/gm. Assess Urinary TNF-α and urine KIM-1 in comparision with albuminuria. Results Urinary KIM-1 and urinary TNF-α are statically significant with albuminuria in patients in the early stage of diabetic nephropathy (eGFR _60 mL/min/1.73 m2).Also there are statically significance between patients with macroalbuminuria than microalbuminuria. Conclusion The results of this study recommend the use of KIM-1 and TNF-α as good predictors of early detection of development of diabetic nephropathy.

Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes

2018 ◽  
Vol 6 (01) ◽  
pp. 50-55 ◽  
Author(s):  
Xin Zhao ◽  
Xiao-Mei Zhang ◽  
Ning Yuan ◽  
Xiao-Feng Yu ◽  
Li-Nong Ji
Keyword(s):  
Bone Mineral Density ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Bone Metabolism ◽  
Early Stage ◽  
Chinese Patients ◽  
Creatinine Ratio ◽  
Mineral Density ◽  
Urine Albumin

Abstract Objective To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). Methods In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients’ data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. Results BMD at every location tested (femoral neck, trochanter, inside hip, Ward’s triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (β-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or β-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and β-CTX (p<0.05). Conclusion In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

scholarly journals BAFF Predicts Immunogenicity in Older Patients With Rheumatoid Arthritis Treated With TNF Inhibitors

2020 ◽  
Author(s):  
Borja Hernández-Breijo ◽  
Victoria Navarro-Compán ◽  
Chamaida Plasencia-Rodríguez ◽  
Ioannis Parodis ◽  
Johanna E. Gehin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Older Patients ◽  
Operating Characteristic ◽  
Certolizumab Pegol ◽  
Positive Likelihood Ratio ◽  
Characteristic Analysis ◽  
Serum Samples ◽  
Chi Square ◽  
Baseline Serum ◽  
Logistic Regression Models

Abstract Background: Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum BAFF with immunogenicity after 6 months of TNFi treatment.Methods: A total of 139 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association.Results: At 6 months, 39 patients (28%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value=5.30; p=0.02); therefore, subsequent results were stratified according to mean age (≤/>55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR=1.55; 95% CI: 1.03-2.12). Baseline serum BAFF≥1034pg/mL predicted the presence of ADA at 6 months (positive likelihood ratio=3.7).Conclusions: Our results suggest that the association of BAFF concentration and immunogenicity depends on the patient’s age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.

Effect of pioglitazone on the early stage of type 2 diabetic nephropathy in KK/Ta mice

Metabolism ◽  
2004 ◽  
Vol 53 (11) ◽  
pp. 1473-1479 ◽  
Author(s):  
Mitsuo Tanimoto ◽  
Qiuling Fan ◽  
Tomohito Gohda ◽  
Toshihide Shike ◽  
Yuichiro Makita ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Type 2 Diabetic

Biomarker panels may be superior over single molecules in prediction of renal flares in systemic lupus erythematosus: an exploratory study

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3193-3200
Author(s):  
Serena Fasano ◽  
Luciana Pierro ◽  
Alessia Borgia ◽  
Melania Alessia Coscia ◽  
Ranieri Formica ◽  
...  
Keyword(s):  
Receiver Operating Characteristic ◽  
Adhesion Molecule ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Receiver Operating Characteristic Analysis ◽  
Characteristic Analysis ◽  
Factors Associated ◽  
Biomarker Panel ◽  
Renal Flare ◽  
Receiver Operating

Abstract Objective Recent evidence suggests that some urinary biomarkers, namely Vascular Cell Adhesion Molecule-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), Monocyte Chemoattractant Protein 1 (MCP-1), Neutrophil Gelatinase Associated Lipocalcin and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS), might discriminate SLE patients with ongoing renal activity from those with stable disease. The objective of this study was to assess the role of these markers in predicting renal flares in comparison with conventional biomarkers and to derive a biomarker panel which may improve diagnostic accuracy. Methods Eligible participants were SLE patients prospectively followed at our clinic. Urinary biomarker levels were measured in urinary sample by ELISA assay and were compared by the unpaired Student’s t test or the Mann–Whitney U test as appropriate. Receiver operating characteristic analysis was used to calculate the area under the curve. Cox regression was used to identify independent factors associated with disease flares. Results Urine was collected from 61 patients. During 8 months’ follow-up, eight patients experienced a renal flare. Urinary L-PGDS, ICAM-1 and VCAM-1 levels were significantly increased in the patients who subsequently experienced a renal flare with respect to the remaining 53. At Cox regression analysis, L-PGDS, ICAM-1, VCAM-1, hypocomplementemia and anti-dsDNA antibodies were factors associated with renal flares. Based on receiver operating characteristic analysis, a combination of novel and conventional biomarkers demonstrated an excellent ability for accurately identifying a flare. Conclusion This study might suggest the usefulness of a novel biomarker panel in predicting a renal flare in SLE.

scholarly journals P302 Diagnostic accuracy of a serum-based biomarker panel for endoscopic activity in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
H Le ◽  
J Neill ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Mucosal Inflammation ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Biomarker Panel ◽  
Endoscopic Remission

Abstract Background The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored. Results A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had &gt; 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1) Conclusion EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted. Reference

scholarly journals Improving the Detection of Hepatocellular Carcinoma using serum AFP expression in combination with GPC3 and micro-RNA miR-122 expression

2019 ◽  
Vol 14 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Jian Li ◽  
Sun Qiyu ◽  
Tiezheng Wang ◽  
Boxun Jin ◽  
Ning Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Operating Characteristic ◽  
Early Stage ◽  
Roc Curves ◽  
Micro Rna ◽  
Serum Samples ◽  
Serum Alpha Fetoprotein ◽  
Laboratory Investigations ◽  
Chronic Hcv ◽  
Positive Controls

AbstractEarly diagnosis of hepatocellular carcinoma (HCC) greatly improves the survival and prognosisfor patients. In this study weevaluate the diagnostic promise of combining serum alpha-fetoprotein (AFP) expression with two potential biomarkers, serum glypican-3 (GPC3) and expression of the micro-RNA miR-122 for hepatitis C virus (HCV) related early-stage HCC. For this study serum samples from 47 patients with early-stage HCC, 54 chronic HCV (CH) carriers, 35 patients with liver cirrhosis (LC) and 54 health controls (HC) were collected. In addition to routine laboratory investigations, serum AFP, GPC3 and miR-122 were measured in all patients and healthy controls. Receiver operating characteristic (ROC) curves were used to present sensitivity and specificity for the biomarkers. The three markers were all significantly elevated in the serum samples from HCC patients. ROC curves showed the three markers had similar diagnostic capacities for distinguishing early-stage HCC from HCV-positive controls (LC + CH). In order to distinguish early-stage HCC from high-risk LC patients, the expression of miR-122 was superior to GPC3. Combination of the three markers as a panel showed a better diagnostic performance than any of the single markers (P <0.05). Overall, this study revealed that serum expression of GPC3 and miR-122 may be useful biomarkers to combine with serum AFP expression for the diagnosis of HCV related early-stage HCC.

Nonalbumin proteinuria is a simple and practical predictor of the progression of early-stage type 2 diabetic nephropathy

2017 ◽  
Vol 31 (2) ◽  
pp. 395-399 ◽  
Author(s):  
Jong Ho Kim ◽  
Sang Soo Kim ◽  
In Joo Kim ◽  
Min Jin Lee ◽  
Yun Kyung Jeon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Type 2 Diabetic

scholarly journals Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan

2014 ◽  
Vol 222 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Tetsuhiro Kakimoto ◽  
Kinya Okada ◽  
Yoshihiro Hirohashi ◽  
Raissa Relator ◽  
Mizue Kawai ◽  
...  
Keyword(s):  
Image Analysis ◽  
Diabetic Nephropathy ◽  
Early Stage ◽  
Automated Image Analysis ◽  
Angiotensin Ii Receptor Blocker ◽  
Analysis Method ◽  
Glomerular Injury ◽  
Image Analysis Method ◽  
Podocyte Injury

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.

Sign in / Sign up

Export Citation Format

Share Document