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

Abstract

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.

New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

“…Furthermore, in non-dialyzed patients, urinary levels of cfDNA were predictors of unfavorable renal outcomes [133]. These findings were consistent with the results of Li et al (2020), which demonstrated that increased serum cfDNA levels were associated with an increased risk of diabetic nephropathy in a cohort of diabetic patients [134], suggesting the potential of cfDNA as a biomarker of disease progression.…”

Donor-derived Cell-free DNA: Advancing a Novel Assay to New Heights in Renal Transplantation

“… 96 , 97 There is currently a paucity of data on dd-cfDNA levels in this setting; however, host-derived circulating DNA has been reported in systemic lupus erythematous, progressive diabetic kidney disease, and urinary mitochondrial DNA has also been described in IgA nephropathy. 98 - 100 It should be noted that cell-free DNA may be extruded during the inflammatory process of neutrophil extracellular traps formation. 101 NETosis involves the deployment of extracellular chromatin, which is speculated to entangle microbes as host-defense mechanism, and is seen in a number of autoimmune conditions.…”

The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases

“…Finally, although ecDNA was higher in hemodialysis patients compared to CKD or peritoneal dialysis patients, no differences were observed in general between patients and healthy participants [ 209 ]. Despite this, it seems that ecDNA may have a broader potential for disease prediction, since the increase of serum levels was associated with the risk of progression of diabetic kidney disease [ 210 ]. Apart from its potential prognostic features, removal of excess ecDNA by DNase was successful in amelioration of IRI-induced AKI [ 211 ].…”