Dataset Information

Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease.

ABSTRACT:

Background

Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD.

Method

We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine ?1-microglobulin (?1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner.

Results

The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 ?mol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine ?1MG (median value, 5.7?mg/gCr).

Conclusion

The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.

SUBMITTER: Onishi A

PROVIDER: S-EPMC6636573 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease.

Onishi Akifumi A Sugiyama Hitoshi H Kitagawa Masashi M Yamanari Toshio T Tanaka Keiko K Ogawa-Akiyama Ayu A Kano Yuzuki Y Mise Koki K Tanabe Katsuyuki K Morinaga Hiroshi H Kinomura Masaru M Uchida Haruhito A HA Wada Jun J

Disease markers 20190701

<h4>Background</h4>Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD.<h4>Method</h4>We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 year ...[more]

PMID: 31354889

Similar Datasets

Project description:IntroductionPrior studies indicate that exposure to metals may alter DNA methylation. Evidence also shows that global DNA methylation is associated with chronic kidney disease (CKD). This study aimed to examine the association between CKD and 5-methyl-2-deoxycytidine (5mdC, %), a marker of global DNA methylation, and to evaluate the interaction between metal exposures and 5mdC (%) on CKD. We also explored the mediation effect of 5mdC (%) on the association between metal exposures and renal function (i.e., estimated glomerular filtration rate, eGFR).MethodsA total of 218 CKD patients and 422 controls were recruited in this case-control study. 5mdC (%), concentrations of blood lead and cadmium, plasma selenium, and total urinary arsenic were measured. CKD cases were clinically defined among patients with eGFR <60 mL/min/1.73 m2 for at least 3 months and without hemodialysis. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to examine the association between metal exposures, 5mdC (%), and CKD, adjusted for confounders. Multivariable linear regression models were used to examine associations between metal exposures, 5mdC (%), and eGFR.Results and discussionCKD cases compared to controls had 6.06-fold (95% CI: 3.11-11.81) higher odds of having high blood cadmium and high 5mdC (%) levels. A positive interaction on an additive scale was identified between blood cadmium and 5mdC (%) on CKD. Cases compared to controls had 4.73-fold (95% CI: 2.65-8.45) higher odds of having low plasma selenium and high 5mdC (%) levels; and a significant multiplicative interaction between plasma selenium and 5mdC (%) on CKD was observed. In addition, we found that blood lead and cadmium concentrations were positively associated, while plasma selenium concentrations were inversely associated, with 5mdC (%). The associations of blood lead and plasma selenium with eGFR were partially mediated by 5mdC (%). Our results suggest that 5mdC (%) may interact with plasma selenium and blood cadmium to influence the risk of CKD. The 5mdC (%) also potentially mediates the associations between exposure to metals and renal function.

Dataset Information

Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease.

Background

Method

Results

Conclusion

Publications

Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease.

Similar Datasets

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