Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 22, 2023

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, but existing therapeutics are limited. Therefore, novel molecular pathways that contribute to DN therapy and diagnostics urgently needed.

Language: Английский

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Prescription of guideline‐directed medical therapies in patients with diabetes and chronic kidney disease from the CURE‐CKD Registry, 2019‐2020

Diabetes Obesity and Metabolism, Journal Year: 2023, Volume and Issue: 25(10), P. 2970 - 2979

Published: July 3, 2023

Abstract Aim Guideline‐directed medical therapy (GDMT) is designed to improve clinical outcomes. The study aim was assess GDMT prescribing rates and prescribing‐persistence predictors in patients with diabetes chronic kidney disease (CKD) from the Center for Kidney Disease Research, Education, Hope Registry. Materials Methods Data were obtained adults ≥18 years old CKD between 1 January 2019 31 December 2020 (N = 39 158). Baseline persistent (≥90 days) prescriptions GDMT, including angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), sodium‐glucose cotransporter‐2 (SGLT2) inhibitor glucagon‐like peptide (GLP‐1) agonist assessed. Results population age (mean ± SD) 70 14 years, 49.6% (n 19 415) women. estimated glomerular filtration rate (2021 CKD‐Epidemiology Collaboration creatinine equation) 57.5 23.0 ml/min/1.73 m 2 urine albumin/creatinine mg/g (31.7‐158.2; median, interquartile range). ≥90‐day rates, respectively, 70.7% 40.4% ACE inhibitor/ARB, 6.0% 5.0% SGLT2 inhibitors, 6.8% 6.3% GLP‐1 (all p < .001). Patients lacking primary commercial health insurance coverage less likely be prescribed an inhibitor/ARB [odds ratio (OR) 0.89; 95% confidence interval (CI) 0.84‐0.95; .001], (OR 0.72; CI 0.64‐0.81; .001) or 0.80‐0.98; .02). lower at Providence than UCLA Health. Conclusions Prescribing suboptimal waned quickly CKD. Type of system associated prescribing.

Language: Английский

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Osteopontin as a Biomarker in Chronic Kidney Disease

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1356 - 1356

Published: May 4, 2023

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

Language: Английский

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Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 19, 2024

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from Gene Expression Omnibus Database were analyzed assess expression mTOR and VDR in human renal tissues. Clinical samples patients minimal change (MCD) controls examined, animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection employed modulate with its components evaluated immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA). Results: Changes pathway observed both model. Overexpression increased decreased levels mTOR, p70s6k, 4E-BP1. Furthermore, treatment regulated autophagy by upregulating LC3I downregulating LC3II expression. Notably, alleviated oxidative stress reducing lipid peroxidation product MDA, while simultaneously increasing superoxide dismutase (SOD) glutathione (GSH), underscoring pathological process potential as target. Conclusion: Unraveling DDIT4’s involvement provides insights discovery, emphasizing future interventions.

Language: Английский

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Gut microbiota profiling reflects the renal dysfunction and psychological distress in patients with diabetic kidney disease

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 15, 2024

Background The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how intestinal microecological imbalance involved context diabetic disease (DKD), leading cause renal failure. Objectives To elucidate microbial signatures associated with DKD progression towards end-stage (ESRD) explore whether they could reflect dysfunction psychological distress. Methods A cross-sectional study was conducted to 29 non-ESRD patients 19 ESRD compared 20 healthy controls. Differential analysis performed detect distinct alterations diversities taxon abundance without ESRD. Renal estimated by urea, creatinine, glomerular filtration rate. Psychological distress assessed using Self-Rating Anxiety Scale, Depression Hamilton Rating Scale. Results Alpha diversity indexes were reduced patients, particularly those Beta revealed that compositions different individuals whereas similar observed patients. Taxon differential showed when controls, exhibit profiles including abundances butyrate-produced, anti-inflammatory bacteria Faecalibacterium , Lachnospira Roseburia Lachnoclostridium increased pro-inflammatory Collinsella Streptococcus etc. These distinctive genera presented consistent associations dysfunction, as well distress, especially Conclusions who have progressed ESRD, unique characteristics their are both may be significant factor deterioration its eventual

Language: Английский

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Still finding ways to augment the existing management of acute and chronic kidney diseases with targeted gene and cell therapies: Opportunities and hurdles

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 7, 2023

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with limited availability viable kidneys transplantation, propelled search alternative strategies to address growing health economic burdens associated these conditions. In such alternatives, significant efforts have been devised augment current primarily supportive management injury novel regenerative strategies. For example, gene- cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, RNAi technologies shown promising outcomes in experimental models. Supporting research also conducted improve our understanding critical aspects facilitate development efficient techniques complex structure traditionally limited. manuscript is intended communicate driven therapies by identifying vectors delivery routes needed drive exogenous transgene incorporation may support treatment diseases.

Language: Английский

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TGF-β: elusive target in diabetic kidney disease

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: April 3, 2025

Transforming growth factor-beta (TGF-β), a cytokine with near omnipresence, is an integral part of many vital cellular processes across the human body. The family includes three isoforms: 1, 2, and 3. These cytokines play significant role in fibrosis cascade. Diabetic kidney disease (DKD), major complication diabetes, increasing prevalence daily, classical diagnosis diabetes based on presence albuminuria. occurrence nonalbuminuric DKD has provided new insight into pathogenesis this disease. emphasis multifactorial pathways involved developing highlighted some markers associated tissue fibrosis. In diabetic nephropathy, TGF-β significantly its pathology. Its serum urine means that it could be diagnostic tool while regulation provides potential therapeutic targets. Completely blocking signaling reach untargeted regions cause unanticipated effects. This paper reviews basic details as cytokine, DKD, updates research carried out to validate candidacy.

Language: Английский

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The Effect of Autologous Dendritic Cell Therapy on Renal Perfusion in Diabetic Kidney Disease: Analysis of Doppler Ultrasound and Angiogenesis Biomarkers

Diseases, Journal Year: 2025, Volume and Issue: 13(4), P. 116 - 116

Published: April 16, 2025

Background: Diabetes mellitus (DM) is a global health challenge with severe burden. Approximately 40% of diabetic patients develop kidney disease (DKD), leading to failure. Autologous dendritic cell therapy may enhance renal function by modulating vascular markers. Methods: Involving 35 patients, this quasi-experimental study assessed the pulsatility index (PI), resistive (RI), endothelial growth factor (VEGF), and endothelin levels before four weeks following autologous administration. Results: A significant reduction in median PI was found from 1.61 ± 0.63 1.21 0.26 (p < 0.001). The increase mean RI insignificant 0.74 0.07 0.75 0.06 = 0.17). VEGF showed slight 522.10 608.6 473.70 550 0.589) 1.74 0.71 1.63 0.76 0.554). Conclusions: This shows that improve perfusion DKD indicated PI. These findings suggest potential therapeutic benefits for DKD.

Language: Английский

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Trends and Disparities in the Burden of Chronic Kidney Disease due to Type 2 Diabetes in China From 1990 to 2021: A Population‐Based Study

Journal of Diabetes, Journal Year: 2025, Volume and Issue: 17(4)

Published: April 1, 2025

ABSTRACT Background This study analyzes the trends in burden of chronic kidney disease due to type 2 diabetes (CKD‐T2D) China from 1990 2021, evaluates variations risk factors, and projects through 2036. Method Estimates prevalence, incidence, mortality, disability‐adjusted life years (DALYs) for CKD‐T2D were retrieved along with their 95% uncertainty intervals (UIs). Age‐period‐cohort analysis was used assess identify factor population attributable fractions (PAFs), project Results In there 20 911 520 cases China, an age‐standardized prevalence rate (ASPR) 1053.92 per 100 000, incidence (ASIR) 23.07, mortality (ASMR) 5.72, DALY (ASDR) 122.15. Although overall showed a slow decline continued rise. The 2021 data revealed marked age effect, rising age. Period effects also contributed increased risk, metabolic factors such as high fasting plasma glucose BMI contributing most. Projections suggest DALYs by 2036, while will keep increasing. Conclusion Despite declines ASMR ASDR, continue rise, especially among males elderly. increasing is driven aging factors. Early screening, education, management are essential addressing China.

Language: Английский

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Association of different domains of physical activity with diabetic kidney disease: a population-based study

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 28, 2024

Background The aim of this cross-sectional study was to elucidate the associations between various domains physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall activity (PA), diabetic kidney disease. Methods Our encompassed 2,633 participants, drawn from surveys National Health Nutrition Examination Survey (NHANES) 2007 2018, employed survey-weighted logistic regression, generalized linear restricted cubic spline (RCS) analyses ascertain relationship different Results After controlling for all confounders, multivariate regression revealed a lack correlation prevalence Multiple showed that durations PA (β = 0.05, 95% CI, 0.01–0.09, P 0.012) TPA 0.32, 0.10–0.55, 0.006) were positively associated with eGFR levels; LTPA inversely UACR levels -5.97, -10.50 - -1.44, 0.011). RCS curves demonstrated nonlinear PA, OPA, eGFR, well ACR. Subgroup sensitivity largely aligned outcomes underscoring robustness our findings. Conclusion population-based explored association Contrary expectations, we found no significant duration across nephropathy. Nonetheless, renal function markers, including UACR, exhibited correlations total (TPA) (LTPA), respectively, among patients. Interestingly, findings suggest patients engage in preserve function, ensuring moderate exercise not exceeding 35 hours per week.

Language: Английский

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