Peritoneal Effluent Cell-Free DNA Sequencing in Peritoneal Dialysis Patients With and Without Peritonitis

Burnham, Philip; Chen, Fanny; Cheng, Alexandre Pellan; Srivatana, Vesh; Zhang, Lisa T.; Edusei, Emmanuel; Albakry, Shady; Botticelli, Brittany; Guo, Xunxi; Renaghan, Amanda D.; Silberzweig, Jeffrey; Dadhania, Darshana; Lenz, Joan Sesing; Heyang, Michael; Iliev, Iliyan D.; Hayden, Joshua; Westblade, Lars F.; Vlaminck, Iwijn De; Lee, John Y.K.

doi:10.1016/j.xkme.2021.08.017

Cited by 3 publications

(8 citation statements)

References 18 publications

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“… 22 Therefore, they concluded that DNase I treatment cannot prevent IRI, which is different from what we observed. We believe that the reason for this is that DNase I was administered by intraperitoneal injection in the study by Albadawi et al Due to a large amount of cell-free DNA (cfDNA) present in the peritoneal fluid, 37 , 38 blood, 32–35 and other body fluids, DNase I was consumed, and the effective concentration eventually distributed in the region of IR was not sufficient to alter the prognosis of IRI. Our experiment also confirmed that local application of DNase I in the ischemic area was more effective than the intravenous injection, as evidenced by better restoration of blood perfusion ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps

Wang¹,

Wang²,

Jiang³

et al. 2023

JIR

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Purpose Neutrophil extracellular traps (NETs) play an important role in ischemia-reperfusion injury (IRI) of the hindlimb. The aim of this study was to investigate the effect of recombinant DNase I and sivelestat in eliminating NETs and their effects on IRI limbs. Patients and Methods An air pump was used to apply a pressure of 300 mmHg to the root of the right hindlimb of the rat for 2 h and then deflated to replicate the IRI model. The formation of NETs was determined by the detection of myeloperoxidase (MPO), neutrophil elastase (NE), and histone H3 in the skeletal muscles of the hindlimbs. Animals were administered 2.5 mg/kg bw/d DNase I, 15 or 60 mg/kg bw/d sivelestat by injection into the tail vein or intramuscularly into the ischemic area for 7d. Elimination of NETs, hindlimb perfusion, muscle fibrosis, angiogenesis and motor function were assessed. Results DNase I reduced NETs, attenuated muscle fibrosis, promoted angiogenesis in IRI area and improved limb motor function. Local administration of DNase I improved hindlimb perfusion more than intravenous administration. Sivelestat at a dose of 15 mg/kg bw/d increased perfusion, counteracted skeletal muscle fibrosis, promoted angiogenesis and enhanced motor function. However, sivelestat at a dosage of 60 mg/kg bw/d had an adverse effect on tissue repair, especially when injected locally. Conclusion Both DNase I and moderate doses of sivelestat can eliminate IRI-derived NETs. They improve hindlimb function by improving perfusion and angiogenesis, preventing muscle fibrosis. Appropriate administration mode and dosage is the key to prevent IRI by elimination of NETs. DNase I is more valid when administered topically and sivelestat is more effective when administered intravenously. These results will provide a better strategy for the treatment of IRI in clinical.

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Section: Discussionmentioning

confidence: 99%

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps

Wang¹,

Wang²,

Jiang³

et al. 2023

JIR

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“… 42 , 43 The current data on the peritoneal microbiome in CKD are from a few studies comparing the peritoneal tissue specimens obtained from non–dialysis-dependent patients with those of patients treated with PD, or the peritoneal dialysate effluent (PDE) between the peritonitis and nonperitonitis groups. 44 , 45 , 46 The peritoneal tissue of non–dialysis-dependent patients with CKD is shown to harbor a unique low-abundance microbiome dominated by Proteobacteria and Firmicutes phyla, possibly related to increased microbial translocation from the gut. 44 Other studies, using 16S rRNA gene sequences, provide the first evidence of bacterial DNA in the PDE of stable patients treated with PD without peritonitis.…”

Section: Preface To Understanding the Human Microbiome’s Role In Heal...mentioning

confidence: 99%

“… 44 Other studies, using 16S rRNA gene sequences, provide the first evidence of bacterial DNA in the PDE of stable patients treated with PD without peritonitis. 45 , 46 However, the authors caution that bacterial DNA fragments in PDE do not indicate the presence of live pathogenic bacteria. 45 …”

Section: Preface To Understanding the Human Microbiome’s Role In Heal...mentioning

confidence: 99%

“…Several other studies reported the presence of bacteria-derived DNA fragments in the PDE of patients without peritonitis. 45 , 46 In a recent comparison of host-derived and microbial-derived cell-free DNA (cfDNA) concentrations in PDE from peritonitis and nonperitonitis groups, both cfDNAs were present in the PDE of nonperitonitis groups, but the concentrations of host cfDNA were significantly lower than those in the peritonitis group. 46 Furthermore, the concentrations of microbial cfDNA did not differ between the groups at the same observation time point.…”

Section: Crosstalk Between the Gut Circulatory And Peritoneal Microbi...mentioning

confidence: 99%

“… 45 , 46 In a recent comparison of host-derived and microbial-derived cell-free DNA (cfDNA) concentrations in PDE from peritonitis and nonperitonitis groups, both cfDNAs were present in the PDE of nonperitonitis groups, but the concentrations of host cfDNA were significantly lower than those in the peritonitis group. 46 Furthermore, the concentrations of microbial cfDNA did not differ between the groups at the same observation time point. 46 Because microbial cfDNA reflects bacterial, viral, or fungal populations at the site, these results suggest that the peritoneal cavity has its own microbiome, independent of the presence of peritonitis.…”

Section: Crosstalk Between the Gut Circulatory And Peritoneal Microbi...mentioning

confidence: 99%

See 2 more Smart Citations

The Gut-Peritoneum Axis in Peritoneal Dialysis and Peritoneal Fibrosis

Stepanova¹

2023

Kidney Medicine

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Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review

Morisi,

Virzì,

Ferrarini

et al. 2024

Genes

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Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. Conclusions: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.

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Peritoneal Effluent Cell-Free DNA Sequencing in Peritoneal Dialysis Patients With and Without Peritonitis

Cited by 3 publications

References 18 publications

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps

The Gut-Peritoneum Axis in Peritoneal Dialysis and Peritoneal Fibrosis

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review

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