Plasma Cell-Free DNA Levels in Children on Peritoneal Dialysis

Abstract

Background/Aims: Plasma levels of cell-free DNA (cfDNA) are elevated in various clinical conditions including cancer, stroke, trauma, myocardial infarction, autoimmune disorders, and pregnancy-associated complications. Previously, increased cfDNA levels were reported during hemodialysis. However, there is limited data regarding cfDNA levels in peritoneal dialysis (PD) patients. The aim of this study was to investigate the levels of cfDNA in children on PD. Methods: Twenty-one children on PD (median age: 12; range: 4–18 years) and 21 healthy children (median age: 10; range: 6–16 years) were enrolled into the study. Plasma cfDNA was measured using a real-time quantitative PCR for the beta-globin gene. Results: The median concentrations of cfDNA in the plasma of PD patients and healthy controls were 2,205 genome-equivalents/ml of plasma (range: 39–5,845) and 1,033 genome-equivalents/ml of plasma (range: 254–5,116), respectively (p = 0.026). A significant positive correlation was observed between C-reactive protein levels and plasma cfDNA levels (r: 0.52, p < 0.0001). Conclusion: Our data have demonstrated for the first time that cfDNA is increased in children on PD treatment. However, the mechanism by which the levels of cfDNA is increased and the clinical significance of this finding in PD patients is unclear. Further studies are warranted to clarify the precise mechanism and clinical significance of elevated cfDNA in children on PD.

Plasma Cell-free DNA levels in children with Henoch Schönlein purpura

“…However there is still a long way to go for widespread routine clinical application. [2,[4][5][6][7][8][9][10] The exact mechanism of cfDNA presence in circulation is not clear. Release from apoptotic or necrotic cells are reported to be among the main sources [1,2].…”

“…The origin is reported to be the apoptosis of lymphocytes and other nucleated cells or an active physiological secretion by lymphocytes [1][2][3] Elevated levels of cell-free nucleic acids have been reported in various clinical conditions such as cancer, stroke, trauma, myocardial infarction, autoimmune disorders, pregnancy complications and peritoneal dialysis. This fact has stimulated researchers to investigate the possibility to use circulating nucleic acids as a potential marker for early detection or follow-up of some diseases [2,[4][5][6][7][8][9][10]. Henoch-Schönlein purpura (HSP) is the most common vasculitic disease of childhood with potentially serious systemic involvement.…”

Extracellular Nucleic Acids and Cancer

“…In the late 1990s (after the landmark papers by Chen et al [12] and Nawroz et al [13] were published) this observation initiated a surge of papers confirming and extending the results described by Leon et al Unfortunately, it became clear very soon that the increase in cfDNA in tumor patients is not specific and that many factors/diseases lead to the higher quantity of cfDNA (see chapter "The Biology of CNAPS"). When cfDNA had been quantified it was shown that the amount is increased in a variety of different conditions such as myocardial infarction [14], cardiac arrest [15], exhaustive exercise [16][17][18], in patients with systemic lupus erythematosis [19], in older humans [20], in febrile patients [21], in children on peritoneal dialysis [22], in patients with obstructive sleep apnea [23], patients with chronic kidney disease [24], patients with severe sepsis or septic shock [25], in trauma [26] and burn patients [27] (chapter "CNAPS and General Medicine"). In an attempt to differentiate lung cancer patients from a control population according to their sputum cfDNA it was demonstrated that the amount of cfDNA was related to the severity of the inflammatory processes but not the presence of lung cancer [28].…”

Mass spectrometric based analysis, characterization and applications of circulating cell free DNA isolated from human body fluids

“…However, the signal contamination from single-stranded nucleic acids, proteins and RNA contributes to the poor specificity and decreased sensitivity for the quantitative analysis of low concentration CCFDNA. The development of DNA specific reagents such as Invitrogen’s PicoGreen ® dsDNA quantitation reagent assays [90], real-time quantitative PCR assay (RT-qPCR) [9, 55, 91–97], digital PCR approach [98], and fluorometric PCR assay [99, 100] have decreased the sample size requirement and increased the reliability of CCFDNA identification and quantitation.…”