scholarly journals Serum cell-free DNA and progression of diabetic kidney disease: a prospective study

2020 ◽  
Vol 8 (1) ◽  
pp. e001078 ◽  
Author(s):  
Xuan Li ◽  
RenZhi Hu ◽  
Ting Luo ◽  
Chuan Peng ◽  
Lilin Gong ◽  
...  

AimsCell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD).MethodsIn this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression.ResultsIn total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=−0.219 p=0.009) and 3-year eGFR change (r=−0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89).ConclusionSerum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

2018 ◽  
Vol 72 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Zahra Aryan ◽  
Alireza Ghajar ◽  
Sara Faghihi-Kashani ◽  
Mohsen Afarideh ◽  
Manouchehr Nakhjavani ◽  
...  

Background/Aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024–1.032) for CHD, 1.025 (1.021–1.029) for diabetic neuropathy, 1.037 (1.030–1.043) for diabetic retinopathy, and 1.035 (1.027–1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.


2019 ◽  
Vol 12 (2) ◽  
pp. 169-178
Author(s):  
Lili Liu ◽  
Bixia Gao ◽  
Jinwei Wang ◽  
Chao Yang ◽  
Shouling Wu ◽  
...  

2022 ◽  
Author(s):  
Jin-Lin Chu ◽  
Shu-Hong Bi ◽  
Yao He ◽  
Rui-Yao Ma ◽  
Xing-Yu Wan ◽  
...  

Abstract Background: Complications of diabetes mellitus (DM) are the leading cause of DM-related disability and mortality. Notably, diabetic kidney disease (DKD), one of the main complications of DM, has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions.Methods: We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially modified 5hmC marker genes (DMGs) and differentially expressed genes (DEGs) from the GEO datasets GSE30528 and GSE30529. Cytoscape software was used to construct the protein-protein interaction (PPI) network and identify the hub genes.Results: The final gene panel of 9 hub genes, including (CTNNB1, PTEN, MYD88, ITGAM, CD28, ITGB2, VCAM1, CXCR4, CD44) were confirmed. Further analysis indicated that this 9-gene signature showed a good capacity to distinguish between DKD and DM. Conclusions: The 5hmC-Seal assay was successfully applied to the cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures in plasma cfDNA indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and be a part of diabetic care.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masood Faghih Dinevari ◽  
Mohammad Hossein Somi ◽  
Elham Sadeghi Majd ◽  
Mahdieh Abbasalizad Farhangi ◽  
Zeinab Nikniaz

Abstract Background There are limited number of studies with controversial findings regarding the association between anemia at admission and coronavirus disease 2019 (COVID-19) outcomes. Therefore, in this research, we aimed to investigate the prospective association between anemia and COVID-19 outcomes in hospitalized patients in Iran. Methods In this prospective study, the data of 1274 consecutive patients hospitalized due to COVID-19 were statistically analyzed. All biomarkers, including hemoglobin and high-sensitivity C-reactive protein (hs-CRP) levels were measured using standard methods. Anemia was defined as a hemoglobin (Hb) concentration of less than 13 g/dL and 12 g/dL in males and females, respectively. Assessing the association between anemia and COVID-19 survival in hospitalized patients was our primary endpoint. Results The mean age of the participants was 64.43 ± 17.16 years, out of whom 615 (48.27%) were anemic subjects. Patients with anemia were significantly older (P = 0.02) and had a higher frequency of cardiovascular diseases, hypertension, kidney disease, diabetes, and cancer (P < 0.05). The frequency of death (anemic: 23.9% vs. nonanemic: 13.8%), ICU admission (anemic: 27.8% vs. nonanemic:14.71%), and ventilator requirement (anemic: 35.93% vs. nonanemic: 20.63%) were significantly higher in anemic patients than in nonanemic patients (P < 0.001). According to the results of regression analysis, after adjusting for significant covariate in the univariable model, anemia was independently associated with mortality (OR: 1.68, 95% CI: 1.10, 2.57, P = 0.01), ventilator requirement (OR: 1.74, 95% CI: 1.19, 2.54, P = 0.004), and the risk of ICU admission (OR: 2.06, 95% CI: 1.46, 2.90, P < 0.001). Conclusion The prevalence of anemia in hospitalized patients with COVID-19 was high and was associated with poor outcomes of COVID-19.


2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Wael M. Osman ◽  
Herbert F. Jelinek ◽  
Guan K. Tay ◽  
Mohamed H. Hassan ◽  
Wael Almahmeed ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e033923
Author(s):  
Kieran Mccafferty ◽  
Ben Caplin ◽  
Sinead Knight ◽  
Paul Hockings ◽  
David Wheeler ◽  
...  

IntroductionDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment.Methods and analysisHEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR.Ethics and disseminationEthical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.


BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e036443 ◽  
Author(s):  
Miyang Luo ◽  
Linda Wei Lin Tan ◽  
Xueling Sim ◽  
Milly Khiam Hoon Ng ◽  
Rob Van Dam ◽  
...  

PurposeThe diabetic cohort (DC) was set up to study the determinants of complications in individuals with type 2 diabetes and examine the role of genetic, physiological and lifestyle factors in the development of complications in these individuals.ParticipantsA total of 14 033 adult participants with type 2 diabetes were recruited from multiple public sector polyclinics and hospital outpatient clinics in Singapore between November 2004 and November 2010. The first round of follow-up was conducted for 4131 participants between 2012 and 2016; the second round of follow-up started in 2016 and is expected to end in 2021. A questionnaire survey, physical assessments, blood and urine sample collection were conducted at recruitment and each follow-up visit. The data set also includes genetic data and linkage to medical and administrative records for recruited participants.Findings to dateData from the cohort have been used to identify determinants of diabetes and related complications. The longitudinal data of medical records have been used to analyse diabetes control over time and its related outcomes. The cohort has also contributed to the identification of genetic loci associated with type 2 diabetes and diabetic kidney disease in collaboration with other large cohort studies. About 25 scientific papers based on the DC data have been published up to May 2019.Future plansThe rich data in DC can be used for various types of research to study disease-related complications in patients with type 2 diabetes. We plan to further investigate disease progression and new biomarkers for common diabetic complications, including diabetic kidney disease and diabetic neuropathy.


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