Preclinical assessment of adjunctive tPA and DNase for peritoneal dialysis associated peritonitis.
A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.
Translational Renal Research Group, Harry Perkins Institute of Medical Research, Perth, Australia; University of Western Australia, School of Medicine and Pharmacology, Perth, Australia.
Amanda L
AL
McGuire
Translational Renal Research Group, Harry Perkins Institute of Medical Research, Perth, Australia; University of Western Australia, School of Medicine and Pharmacology, Perth, Australia.
Sophia C
SC
Bennett
Pleural Disease Unit, Lung Institute of Western Australia, Centre for Asthma, Allergy Respiratory Research, School of Medicine and Pharmacology, Perth, Australia.
Sally M
SM
Lansley
Pleural Disease Unit, Lung Institute of Western Australia, Centre for Asthma, Allergy Respiratory Research, School of Medicine and Pharmacology, Perth, Australia.
Natalia D
ND
Popowicz
Pleural Disease Unit, Lung Institute of Western Australia, Centre for Asthma, Allergy Respiratory Research, School of Medicine and Pharmacology, Perth, Australia.
Julius F
JF
Varano della Vergiliana
Department of Anatomical Pathology, PathWest Laboratory Medicine WA, QEII Medical Centre, Perth, Australia.
Daniel
D
Wong
Pleural Disease Unit, Lung Institute of Western Australia, Centre for Asthma, Allergy Respiratory Research, School of Medicine and Pharmacology, Perth, Australia; Respiratory Department, Sir Charles Gairdner Hospital, Perth, Australia.
Y C Gary
YC
Lee
Translational Renal Research Group, Harry Perkins Institute of Medical Research, Perth, Australia; University of Western Australia, School of Medicine and Pharmacology, Perth, Australia; Renal Department, Sir Charles Gairdner Hospital, Perth, Australia.
Aron
A
Chakera
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D003851:Deoxyribonucleases / Q000008:administration & dosage*; D005260:Female; D051379:Mice; D010530:Peritoneal Dialysis; D010538:Peritonitis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D000890:Anti-Infective Agents; D003851:Deoxyribonucleases; D010959:Tissue Plasminogen Activator