Cell‐free DNA in the Peritoneal Effluent of Peritoneal Dialysis Solutions

Abstract

The beneficial effects of novel peritoneal dialysis solutions low in glucose degradation products regarding peritoneal cell apoptosis and necrosis are well established in vitro, however in vivo data is lacking. Cell-free DNA quantification is a possible method to determine cell damage through apoptosis and necrosis in vivo. We performed a prospective, cross-over study on 26 stable continuous ambulatory peritoneal dialysis (CAPD) patients, treating each patient for 3 months in a randomized order with a conventional, lactate-buffered, acidic solution (solution D) and a novel, bicarbonate/lactate-buffered neutral solution (solution P). The timed overnight peritoneal effluent was sampled for cell-free DNA quantification using a fluorometric assay. The effluent samples of eighteen patients were finally available for DNA quantification. The concentration range of cell-free DNA in the peritoneal effluents was 1.8-9.5 microg/L. The coefficient of intrapatient variation in overnight effluent cell-free DNA appearance was 15.6 +/- 12.4%. Cell-free DNA peritoneal appearance using solutions D and P was 14.9 +/- 6.8 microg and 11.8 +/- 3.4 microg, respectively (P = 0.02), with the average difference of 3.1 microg (95% CI, 0.7-5.6 microg). Our results show that cell-free DNA is present in the overnight peritoneal effluent of stable CAPD patients. A significant decrease in the cell-free DNA appearance with solution P was found; however, before accepting this as an indicator of a more biocompatible profile causing less peritoneal membrane cell necrosis and apoptosis, confirmatory data on larger patient samples are needed. Our results indicate the potential future role of cell-free DNA in the diagnosis and prognosis of therapy-related peritoneal membrane degeneration.

Peritoneal Cell-free DNA: an innovative method for determining acute cell damage in peritoneal membrane and for monitoring the recovery process after peritonitis

“…We evaluated peritoneal effluent cfDNA and WBC counts in the control group and in patients with peritonitis from the first day of peritonitis until the 120th day. We found, in patients without peritonitis, a peritoneal cfDNA concentration range similar to that in previously reported data [11].…”

“…CfDNA has been found in many pathological settings in which apoptosis and/or necrosis are involved [9,10]. Cellfree DNA quantification is a possible method to evaluate cell damage in vivo [11]. cfDNA has been evaluated primarily as a biomarker so far, whereas potential functional effects of cfDNA have not yet been explored.…”

“…Pajek et al were able to isolate and quantify cfDNA in the peritoneal effluent of stable PD patients [11]. However, to the best of our knowledge, the biological role and the levels of cfDNA in PD-related peritonitis and its association with inflammation have not yet been investigated.…”

“…cfDNA can exist in different forms in circulation and may be transported by vesiclebased particles, nucleosomes and virtosomes [12,13]. Its quantification is a possible method to determine cell damage through apoptosis and necrosis in vivo [11]. Furthermore, cfDNA has been found in many cases in which apoptosis or necrosis are involved, suggesting that such events are the main source for its presence [10,14,15].…”

“…Increasing reports over the years document the presence of cfDNA in blood and urine in various healthy and pathological conditions [9][10][11]. cfDNA can exist in different forms in circulation and may be transported by vesiclebased particles, nucleosomes and virtosomes [12,13].…”