Biomarkers Of Chronic Kidney Disease Research Articles

Comprehensive analysis of the relationship between xanthine oxidoreductase activity and chronic kidney disease

Chronic kidney disease (CKD) is a common disease that seriously endangers human health. However, the potential relationship between xanthine oxidoreductase (XOR) activity and CKD remains unclear. In this study, we used clinical data, CKD datasets from the Gene Expression Omnibus database, and untargeted metabolomics to explain the relationship between XOR activity and CKD. First, XOR activity showed high correlation with the biomarkers of CKD, such as serum creatinine, blood urea nitrogen, uric acid, and estimated glomerular filtration rate. Then, we used least absolute shrinkage and selection operator logical regression algorithm and random forest algorithm to screen CKD molecular markers from differentially expressed genes, and the results of qRT-PCR of XDH, KOX-1, and ROMO1 were in accordance with the results of bioinformatics analyses. In addition, untargeted metabolomics analysis revealed that the purine metabolism pathway was significantly enriched in CKD patients in the simulated models of kidney fibrosis.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

423-P: Urinary Extracellular Vesicles in African Americans with Chronic Kidney Disease With and Without Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes (T2D) is the leading cause for chronic kidney disease (CKD). Novel biomarkers are critical in early detection of CKD. Methods: Healthy Eatonville Project (HEP) was a prospective study (n=300, females (F)=71%, T2D 32%, CKD 25%) in historically black community of Eatonville, FL. We characterized EVtrap®-isolated urinary extracellular vesicles (uEV) proteins from a balanced HEP cohort of 48 African Americans (mean age 62y, F=73%, BMI 32.2 kg/m2, T2D 46%) with CKD risk ranging from low, intermediate, to high-very high (H-VH), with and without T2D. Differential expression and coexpression network analyses were implemented. Results: We detected 5265 uEV proteins, 46 of which were significantly (fold change&amp;gt;1.5, P&amp;lt;0.05, FDR&amp;lt;0.1) differentially expressed (DE) in CKD risk groups. Of those, 24 were significantly upregulated in H-VH risk CKD (Figure Module Pr.1). A set of 15 DE proteins appeared to represent a protective pathway against CKD (Figure Module Pr.2). Key biomarkers of acute kidney injury IGFBP7, TIMP2, and IL18 had significant negative correlations with CKD risk (-0.59 ≤ r ≤ -0.44, P&amp;lt;0.002). Supporting our findings, several of these biomarkers had been previously reported in kidney disease studies. Conclusion: The uEV proteomic landscape is representative of kidney pathophysiology and suggests potential biomarkers of CKD in Africans Americans. Disclosure T.K.Thethi: Other Relationship; Bayer Inc., Novo Nordisk. A.Bilal: None. M.S.Zaino: None. A.Iliuk: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp &amp; Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. Y.O.Nunez lopez: None.

#5590 PRE-DIALYSIS TRAJECTORIES OF ESTIMATED GFR AND CONCURRENT TRENDS OF CKD-RELEVANT BIOMARKERS

Abstract Background and Aims The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear. Method We adopted a group-based trajectory model to categorize CKD patients by their pre-dialysis eGFR trajectory and then analyzed the concurrent changing trends of CKD-relevant biomarkers, including urine protein-creatinine ratio (UPCR), albumin, and uric acid. Results Using longitudinal data from two years before dialysis initiation, 1,758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared to the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the serum urea level and UPCR, especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. Rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of MCHC and WBC. The albumin level in the group with an accelerated loss of eGFR was below the normal range. Overall, there was a total of 691 (39.3%) deaths observed during the follow-up period. In the 2-year and 5-year follow-up, 302 (17.2%) and 549 (31.2%) deaths were observed, respectively. The corresponding median follow-up times were 2 years (IQR:1.6 – 2.0) and 3.3 years (IQR:1.6 –5.0). Kaplan–Meier survival plots showed that the eGFR trajectory was significantly associated with the risk of mortality two years and five years after dialysis, with the log-rank test P = .0057 and P = .0001, respectively Conclusion The changes in CKD biomarkers were delineated with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.

#3115 THE ASSOCIATION OF FIBROBLAST GROWTH FACTOR-23 AND CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS

Abstract Background and Aims Previous studies suggest that interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing diabetes mellitus rate. It is known that fibroblast growth factor-23 (FGF-23) has been found to be related to kidney metabolism especially as a biomarker and a key factor to be used in the kidney field. The aim of our study was to assess potential therapeutic approaches of the use of FGF-23 in clinical settings as a potential circulating biomarker for CVD and CKD. Method A total of 155 patients with DT2, aged 34 to 84 years (60 [60;72]), were examined. Control group included 94 healthy people the same age. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of FGF-23 in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Results The levels of FGF-23 were significantly higher in DT2 patients with CKD 5 in comparison with stages 1–4. There were positive strong significant association between FGF-23 and creatinine (r = 0.71, p&amp;lt;0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR; 95% CI 1.890; 1.362-2.622, p&amp;lt;0,001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 was 0,9 pmol/l. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively (AUC 0.832±0.035 with 95% CI: 0.764-0.901, p&amp;lt;0.001). DT2 patients with left ventricular hypertrophy (LVH) were characterized by higher levels of FGF-23 (2,45 [0,65;7,43] vs 0,57 [0,19;2,19] pmol/l in control group). DT2 patients with LVH and natriuretic peptides levels ≥ 35 pg/ml for BNP and/or ≥125 ng/ml for NT-proBNP had significantly high concentrations of FGF-23 than patients with normal levels of natriuretic peptides (3,22 [1,09;9,55] vs. 0,52 [0,27;1,08] pmol/l, p&amp;lt;0,0001). In order to assess the diagnostic significance of the FGF-23 for predicting left ventricular mass index (LVMI) thickening and increasing the proBNP concentration, a ROC analysis was performed. Thus, at the level of FGF-23 (AUC-0.702) = 0.9 pmol/l, the sensitivity and specificity for LVMI thickening were 66.9% and 67.3%. Conclusion Our study identifies FGF-23 as a promising target of novel therapeutic interventions in cardiorenal syndrome, which should be investigated in future clinical studies.

Protein Biomarkers in Chronic Kidney Disease in Children-What Do We Know So Far?

Chronic kidney disease (CKD) in children is a major concern of medical care and public health as it is related to high morbidity and mortality due to progression to end-stage kidney disease (ESKD). It is essential to identify patients with a risk of developing CKD to implement therapeutic interventions. Unfortunately, conventional markers of CKD, such as serum creatinine, glomerular filtration rate (GFR) and proteinuria, have many limitations in serving as an early and specific diagnostic tool for this condition. Despite the above, they are still the most frequently utilized as we do not have better. Studies from the last decade identified multiple CKD blood and urine protein biomarkers but mostly assessed the adult population. This article outlines some recent achievements and new perspectives in finding a set of protein biomarkers that might improve our ability to prognose CKD progression in children, monitor the response to treatment, or even become a potential therapeutic target.

Molecularly imprinted polymer dual electrochemical sensor for the one-step determination of albuminuria to creatinine ratio (ACR)

The urinary albumin to creatinine ratio (ACR) is a convenient and accurate biomarker of chronic kidney disease (CKD). An electrochemical sensor for the quantification of ACR was developed based on a dual screen-printed carbon electrode (SPdCE). The SPdCE was modified with carboxylated multiwalled carbon nanotubes (f-MWCNTs) and redox probes of polymethylene blue (PMB) for creatinine and ferrocene (Fc) for albumin. The modified working electrodes were then molecularly imprinted with coated with polymerized poly-o-phenylenediamine (PoPD) to form surfaces that could be separately imprinted with creatinine and albumin template molecules. The seeded polymer layers were polymerized with a second coating of PoPD and the templates were removed to form two different molecularly imprinted polymer (MIP) layers. The dual sensor presented recognition sites for creatinine and albumin on different working electrodes, enabling the measurement of each analyte in one potential scan of square wave voltammetry (SWV). The proposed sensor produced linear ranges of 5.0–100 ng mL−1 and 100–2500 ng mL−1 for creatinine, and 5.0–100 ng mL−1 for albumin. LODs were 1.5 ± 0.2 ng mL−1 and 1.5 ± 0.3 ng mL−1, respectively. The dual MIP sensor was highly selective and stable for seven weeks at room temperature. The ACRs obtained using the proposed sensor compared well (P > 0.05) with the results from immunoturbidimetric and enzymatic methods.

Osteopontin as a Biomarker in Chronic Kidney Disease.

Osteopontin (OPN) is a ubiquitously expressed protein with a wide range of physiological functions, including roles in bone mineralization, immune regulation, and wound healing. OPN has been implicated in the pathogenesis of several forms of chronic kidney disease (CKD) where it promotes inflammation and fibrosis and regulates calcium and phosphate metabolism. OPN expression is increased in the kidneys, blood, and urine of patients with CKD, particularly in those with diabetic kidney disease and glomerulonephritis. The full-length OPN protein is cleaved by various proteases, including thrombin, matrix metalloproteinase (MMP)-3, MMP-7, cathepsin-D, and plasmin, producing N-terminal OPN (ntOPN), which may have more detrimental effects in CKD. Studies suggest that OPN may serve as a biomarker in CKD, and while more research is needed to fully evaluate and validate OPN and ntOPN as CKD biomarkers, the available evidence suggests that they are promising candidates for further investigation. Targeting OPN may be a potential treatment strategy. Several studies show that inhibition of OPN expression or activity can attenuate kidney injury and improve kidney function. In addition to its effects on kidney function, OPN has been linked to cardiovascular disease, which is a major cause of morbidity and mortality in patients with CKD.

Chronic kidney disease awareness and updates on the management of diabetic kidney disease

AbstractThe prevalence of chronic kidney disease (CKD) is rising worldwide and is a major contributor to morbidity and mortality. It is estimated to affect over 800 million people globally.CKD and its complications carry a substantial financial burden to the NHS in both primary and secondary care. The lack of public awareness of CKD and its complications leads to a reduction in planned follow‐up attendance; clinician awareness of the biomarkers of CKD and progression is still lacking. Measures to improve awareness are needed.Diabetes mellitus remains the single most common cause of progressive renal impairment and over 40% of patients with diabetes will develop diabetic kidney disease in their lifetime. A multidisciplinary approach to management and early intervention are therefore key to halt the progress of diabetic kidney disease. The National Institute for Health and Care Excellence has set clear guidelines for the management of diabetic kidney disease, highlighting newer therapeutic agents like SGLT2 inhibitors. New guidelines are also in place for referral to secondary care involving the Kidney Failure Risk Equation, as it identifies patients at increased risk of progressing to end stage kidney disease.Without robust measures for early detection and management of CKD, progression to kidney failure may occur, exacerbating the increase in cardiovascular disease, premature deaths and poor quality of life. This article is a call to action for the optimal and timely management of CKD. Copyright © 2023 John Wiley &amp; Sons.

Cardiac Imaging Biomarkers in Chronic Kidney Disease.

Uremic cardiomyopathy (UC), the peculiar cardiac remodeling secondary to the systemic effects of renal dysfunction, is characterized by left ventricular (LV) diffuse fibrosis with hypertrophy (LVH) and stiffness and the development of heart failure and increased rates of cardiovascular mortality. Several imaging modalities can be used to obtain a non-invasive assessment of UC by different imaging biomarkers, which is the focus of the present review. Echocardiography has been largely employed in recent decades, especially for the determination of LVH by 2-dimensional imaging and diastolic dysfunction by pulsed-wave and tissue Doppler, where it retains a robust prognostic value; more recent techniques include parametric assessment of cardiac deformation by speckle tracking echocardiography and the use of 3D-imaging. Cardiac magnetic resonance (CMR) imaging allows a more accurate assessment of cardiac dimensions, including the right heart, and deformation by feature-tracking imaging; however, the most evident added value of CMR remains tissue characterization. T1 mapping demonstrated diffuse fibrosis in CKD patients, increasing with the worsening of renal disease and evident even in early stages of the disease, with few, but emerging, prognostic data. Some studies using T2 mapping highlighted the presence of subtle, diffuse myocardial edema. Finally, computed tomography, though rarely used to specifically assess UC, might provide incidental findings carrying prognostic relevance, including information on cardiac and vascular calcification. In summary, non-invasive cardiovascular imaging provides a wealth of imaging biomarkers for the characterization and risk-stratification of UC; integrating results from different imaging techniques can aid a better understanding of the physiopathology of UC and improve the clinical management of patients with CKD.

Elevated Levels of Plasma Collagen Triple Helix Repeat Containing 1 (CTHRC1) Are Strongly Associated with eGFR and Albuminuria in Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) has various etiologies, making it impossible to fully understand its complex pathophysiology. Elevated levels of plasma creatinine, proteinuria, and albuminuria and declined eGFR are traits observed in CKD patients. The current study attempts to highlight the collagen triple helix repeat containing 1 (CTHRC1) protein as a putative blood biomarker for CKD in addition to existing recognized indicators of CKD progression. Methods: A total of 26 CKD patients and 18 healthy controls were enrolled in this study. Clinical characteristics and complete blood and biochemical analyses were collected, and human ELISA kits were used to detect possible CKD biomarkers. Results: The study's findings showed that CTHRC1 correlates with key clinical markers of kidney function such as 24 h urine total protein, creatinine, urea, and uric acid. In addition, CTHRC1 demonstrated a strong significant difference (p ≤ 0.0001) between the CKD and control group. Conclusions: Our research demonstrates that the plasma level of CTHRC1 can distinguish between those with CKD and healthy patients. Plasma CTHRC1 levels may aid in the diagnosis of CKD given the current state of knowledge, and these results call for further investigation in a wider, more diverse patient group.

Identification of common molecular signatures of SARS-CoV-2 infection and its influence on acute kidney injury and chronic kidney disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of COVID-19, causing hundreds of millions of confirmed cases and more than 18.2 million deaths worldwide. Acute kidney injury (AKI) is a common complication of COVID-19 that leads to an increase in mortality, especially in intensive care unit (ICU) settings, and chronic kidney disease (CKD) is a high risk factor for COVID-19 and its related mortality. However, the underlying molecular mechanisms among AKI, CKD, and COVID-19 are unclear. Therefore, transcriptome analysis was performed to examine common pathways and molecular biomarkers for AKI, CKD, and COVID-19 in an attempt to understand the association of SARS-CoV-2 infection with AKI and CKD. Three RNA-seq datasets (GSE147507, GSE1563, and GSE66494) from the GEO database were used to detect differentially expressed genes (DEGs) for COVID-19 with AKI and CKD to search for shared pathways and candidate targets. A total of 17 common DEGs were confirmed, and their biological functions and signaling pathways were characterized by enrichment analysis. MAPK signaling, the structural pathway of interleukin 1 (IL-1), and the Toll-like receptor pathway appear to be involved in the occurrence of these diseases. Hub genes identified from the protein-protein interaction (PPI) network, including DUSP6, BHLHE40, RASGRP1, and TAB2, are potential therapeutic targets in COVID-19 with AKI and CKD. Common genes and pathways may play pathogenic roles in these three diseases mainly through the activation of immune inflammation. Networks of transcription factor (TF)-gene, miRNA-gene, and gene-disease interactions from the datasets were also constructed, and key gene regulators influencing the progression of these three diseases were further identified among the DEGs. Moreover, new drug targets were predicted based on these common DEGs, and molecular docking and molecular dynamics (MD) simulations were performed. Finally, a diagnostic model of COVID-19 was established based on these common DEGs. Taken together, the molecular and signaling pathways identified in this study may be related to the mechanisms by which SARS-CoV-2 infection affects renal function. These findings are significant for the effective treatment of COVID-19 in patients with kidney diseases.

COMPARATIVE EVALUATION OF CREATININE IN SERUM AND SALIVA OF CHRONIC KIDNEY DISEASE PATIENTS

Background &amp; objectives: Chronic kidney disease (CKD) is progressive reduction in renal function. Renal excretory function can be assessed by measurement of creatinine concentrations in plasma which illustrates the ltration capacity of the glomerulus. The increased serum creatinine levels in CKD patients create a concentration gradient that facilitates increased diffusion of creatinine from serum into the saliva. Saliva has many advantages as a diagnostic media over serum, which includes non-invasive collection, good patient compliance, minimal risk of contracting infection, repeated sampling possible and is cost effective. The purpose of this study was to estimate and correlate serum and salivary creatinine in patients with CKD and to evaluate use of salivary creatinine as an alternative biomarker to serum creatinine in CKD patients. A total sample of 40 subjects aged 25 -6 Methods: 5yrs, inclusive of both genders comprising 20 cases of healthy controls (Group I) and 20 diagnosed cases of CKD (Group II) were selected. 2ml of blood and unstimulated whole saliva was collected from both the groups. The blinded samples were processed in autoanalyzer using Jaffe's kinetic reaction. The collected data were subjected to Statistical analysis. In the present Results: study we found signicant correlation of serum creatinine and salivary creatinine in both controls and CKD. Serum creatinine (6.21 ±4.02) and Salivary creatinine (0.70± 0.61) were both increased in CKD cases compared to Controls Serum creatinine (0.83±0.21) and Salivary creatinine (0.11± 0.07). Serum creatinine and salivary creatinine were xii both increased as CKD progressed. A sensitivity of 75% and specicity of 90% of salivary creatinine was found. We therefore recommend Conclusion: salivary creatinine as a biomarker in CKD and also as an alternative biomarker to serum creatinine in detecting and staging CKD, for assessing disease progression, therapeutic modalities and in screening of large population

Comparative Efficacy of Novel Antidiabetic Drugs on Albuminuria Outcomes in Type 2 Diabetes: A Systematic Review.

Albuminuria, or elevated urinary albumin-to-creatine ratio (UACR), is a biomarker for chronic kidney disease that is routinely monitored in patients with type 2 diabetes (T2D). Head-to-head comparisons of novel antidiabetic drugs on albuminuria outcomes remain limited. This systematic review qualitatively compared the efficacy of novel antidiabetic drugs on improving albuminuria outcomes in patients with T2D. We searched the MEDLINE database until December 2022 for Phase 3 or 4 randomized, placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on changes in UACR and albuminuria categories in patients with T2D. Among 211 records identified, 27 were included, which reported on 16 trials. SGLT2 inhibitors and GLP-1 RAs decreased UACR by 19-22% and 17-33%, respectively, versus placebo (P < 0.05 for all studies) over median follow-up of ≥ 2years; DPP-4 inhibitors showed varying effects on UACR. Compared with placebo, SGLT2 inhibitors decreased the risk for albuminuria onset by 16-20% and for albuminuria progression by 27-48% (P < 0.05 for all studies) and promoted albuminuria regression (P < 0.05 for all studies) over median follow-up of ≥ 2years. Evidence on changes in albuminuria categories with GLP-1 RA or DPP-4 inhibitor treatment were limited with varying outcome definitions across studies and potential drug-specific effects within each class. The effect of novel antidiabetic drugs on UACR or albuminuria outcomes at ≤ 1year remains poorly studied. Among the novel antidiabetic drugs, SGLT2 inhibitors consistently improved UACR and albuminuria outcomes in patients with T2D, with continuous treatment showing long-term benefit.

Plasma Galectin-3 Biomarkers in Chronic Kidney Disease

Assessment of renal function is based on determination of serum creatinine and creatinine-based equations to assess GFR. However, this marker is not perfect or accurate, especially for longitudinal monitoring of kidney function in Chronic Kidney Disease (CKD patients). Decreased kidney function can be slowed or even anticipated with early detection, so as to avoid secondary complications. So it is important to find new biomarkers that can identify individuals at risk as early as possible. Plasma galectin-3 is a ?-galactoside-binding lectin expressed in monocytes, which plays an important role in inflammation, immunity, cancer, and is involved in the pathogenesis of atherosclerosis, diabetes, renal fibrosis and asthma. Higher galectin-3 levels were associated with reduced eGFR in a cross-sectional study. Galectin-3 is essential in various biological activities including cell growth, cell proliferation, differentiation, apoptosis, pre-mRNA splicing, transformation, angiogenesis, inflammation, fibrosis, fibrogenesis and host defense. Galectin-3 is a stable biomarker and is not associated with age, body mass index or sex. Galectin-3 is also useful for detecting the early stages of some diseases. Galectin-3 shows no circadian variation and increases slightly after exercise, returning to normal levels after 1-3 hours. Higher concentrations of galectin-3 may be associated with CKD development, indicating the potential for new mechanisms related to galectin-3 expression that may contribute to CKD development. Galectin-3 has also been reported to play an important role in renal interstitial fibrosis. Thus, galectin-3 inhibition may be a promising therapeutic strategy to prevent kidney disease progression.

Paraoxonase 1 and Chronic Kidney Disease: A Meta-Analysis.

Oxidative stress is known to be associated with the pathophysiology of chronic kidney disease (CKD). Paraoxonase 1 (PON1) is an antioxidant enzyme that has been proposed as a biomarker for CKD. While several studies have reported an association between serum PON1 activity and CKD, consensus based on systematically analyzed data remains necessary. We set out to conduct a meta-analysis of literature on PON1 in CKD. Electronic databases, such as MEDLINE, Embase and CENTRAL, were searched for available studies on PON1 activity in patients with CKD (without dialysis) as published before December 2022. A random-effects meta-analysis was performed. In total, 24 studies (22 studies on paraoxonase and 11 on arylesterase activity) were eligibly identified. Patients with CKD showed a lower activity of paraoxonase (standard mean difference [SMD], -1.72; 95% confidence interval [CI], -2.15 to -1.29) and arylesterase (SMD, -2.60; 95%CI, -3.96 to -1.24) than healthy controls. In the subgroup analyses, paraoxonase activity was lower in chronic kidney failure (CKF), an advanced stage of CKD, than in non-CKF. In summary, PON1 activity is low in patients with CKD, suggesting that the antioxidant defense by PON1 is impaired in CKD. The decrease in enzyme activity is pronounced in advanced CKD showing some variability depending on the substrate employed to measure PON1 activity. Further studies are warranted.

Pretreated Screen-Printed Carbon Electrode and Cu Nanoparticles for Creatinine Detection in Artificial Saliva

Creatinine is the final metabolic product of creatine in muscles and a widely accepted biomarker for chronic kidney disease. In this work, we present a non-enzymatic sensor based on an electrochemical pretreated screen-printed carbon electrode (PTSPCE) with electrodeposited Cu nanoparticles (CuNPs). To function in a PoC format, the prepared PTSPCE/CuNPs non-enzymatic sensors were used as disposable elements in a portable potentiostat. The pretreatment using mild anodic and cathodic potentials in PBS resulted in an increased electroactive surface area and improved conductivity, confirmed by cyclic voltammetry and electrochemical impedance. Moreover, the detection through the CuNPs–creatinine interaction showed an enhanced performance in the PTSPCE surface compared to the bare electrode. The optimized PTSPCE/CuNPs sensor showed a linear working range from 10 to 160 μM (R2 = 0.995), a sensitivity of 0.2582 μA·μM−1 and an LOD of 0.1 μM. The sensor analytical parameters covered the requirements of creatinine detection in biofluids such as blood and saliva, with a low interference of common biomarkers such as urea, glucose, and uric acid. When evaluated in Fusayama/Meyer artificial saliva, the PTSPCE/CuNPs showed an average recovery rate of 116%. According to the observed results, the non-enzymatic PTSPCE/CuNPs sensor can potentially operate as a creatinine early screening system in PoC format.

Potential biomarkers of chronic kidney disease progression among kidney-derived proteins; a review

The incidence and mortality rate of kidney disease and its progression to end-stage disease have predominantly increased worldwide. Other morbid conditions, such as diabetes and hypertension, are major risk factors for kidney disease. Detection of kidney disease is difficult due to its heterogeneity and complex pathophysiology. Kidney injury and advanced stages of the disease are currently assessed by traditional biomarkers such as serum creatinine, albuminuria, proteinuria and estimated glomerular filtration rate. Numerous biomarkers derived from the kidney involved in endothelial dysfunction, inflammatory processes and tubular cell damage are potential targets for disease progression management. The review summarized potential biomarkers of chronic kidney disease (CKD) to improve patient care in various clinical practices with an increased focus on loss of kidney function.

Molecular profiling of urinary extracellular vesicles in chronic kidney disease and renal fibrosis.

Chronic kidney disease (CKD) is a long-term kidney damage caused by gradual loss of essential kidney functions. A global health issue, CKD affects up to 16% of the population worldwide. Symptoms are often not apparent in the early stages, and if left untreated, CKD can progress to end-stage kidney disease (ESKD), also known as kidney failure, when the only possible treatments are dialysis and kidney transplantation. The end point of nearly all forms of CKD is kidney fibrosis, a process of unsuccessful wound-healing of kidney tissue. Detection of kidney fibrosis, therefore, often means detection of CKD. Renal biopsy remains the best test for renal scarring, despite being intrinsically limited by its invasiveness and sampling bias. Urine is a desirable source of fibrosis biomarkers as it can be easily obtained in a non-invasive way and in large volumes. Besides, urine contains biomolecules filtered through the glomeruli, mirroring the pathological state. There is, however, a problem of highly abundant urinary proteins that can mask rare disease biomarkers. Urinary extracellular vesicles (uEVs), which originate from renal cells and carry proteins, nucleic acids, and lipids, are an attractive source of potential rare CKD biomarkers. Their cargo consists of low-abundant proteins but highly concentrated in a nanosize-volume, as well as molecules too large to be filtered from plasma. Combining molecular profiling data (protein and miRNAs) of uEVs, isolated from patients affected by various forms of CKD, this review considers the possible diagnostic and prognostic value of uEVs biomarkers and their potential application in the translation of new experimental antifibrotic therapeutics.

Predictive Modeling of Metabolomics data for the Identification of Biomarkers in Chronic Kidney Disease

Chronic kidney disease is a specific type of Kidney Disease in which, a gradual loss of Kidney Function over a period of 3-30 months is noticeable. Early detection is imperative to prevent this catastrophic event and initiate treatment that may mitigate renal injury. Metabolomics data in Chronic Kidney Disease carries a lot of information about biomarkers. However, it is not clear which of these biomarkers are significant, biostatistical analysis of metabolomics data might provide the clues. In this work, an attempt has been made to find novel biomarkers that may be responsible for causing Chronic Kidney Disease by employing bioinformatics and advanced computational tools. The Chronic Kidney Disease data of the patients (in stages 3 and 4) was selected and data was segregated based on renal and cardiovascular parameters. The study consisted 441 patients and 293 metabolites. Subsequently the identification of top metabolites (as biomarkers) was carried out using statistical methods like t-test, Principal component analysis and partial least square analysis. Nine biomarkers were identified from these statistical analyses i.e Galacturonic acid, p-cresol, L-serine, L-glutamine, Lactose, 2-O-Glycerol-.alpha.-d-galactopyranoside, hexa-TMS, Butanoic acid, 2,4-bis[(trimethylsilyl)oxy]-, trimethylsilyl ester, Pseudo uridine penta-tms and Myo-inositol. The Reactivity of identified metabolites was confirmed by using quantum chemistry calculations in Gaussian software. Heat Map was constructed to find out the variations in concentrations of biomarkers in healthy and CKD patients and the showed the higher concentrations of L-serine, Galacturonic acid , L-glutamine and lower concentrations of Pseudo uridine penta-tms, Butanoic acid, 2,4-bis[(trimethylsilyl)oxy]-, trimethylsilyl ester , 2-O-Glycerol-.alpha.-d-galactopyranoside, hexa-TMS , Myo-inositol , p-cresol , Lactose in Death Patients. The biological significance of identified top metabolites has been evaluated by identifying the metabolic pathways in which the metabolites are involved. The metabolites which were found to be toxic are pseudouridine, L-glutamine, and galactouronic acid as per the previous reported literature. The Variations in concentration of these metabolites are responsible for the Death of patient with Chronic Kidney Disease.