BackgroundLong-term exposure to bioincompatible peritoneal dialysis (PD) solutions can cause peritoneal fibrosis (PF) and progressive loss of peritoneal membrane function. This study investigated the effects of nicotinamide N-methyltransferase (NNMT) and its metabolite 1-methylnicotinamide (MNAM) in experimental PF and examined their association with Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) expression.MethodsA rat model of PF was established using high-glucose PD fluid combined with lipopolysaccharide, and primary rat peritoneal mesothelial cells (RPMCs) were stimulated with transforming growth factor-β1 (TGF-β1). The effects of NNMT overexpression and exogenous MNAM administration were evaluated using peritoneal equilibration testing, histological analysis, quantitative real-time polymerase chain reaction, and western blot analysis.ResultsNNMT expression was decreased in TGF-β1-stimulated RPMCs and fibrotic rat peritoneal tissues. NNMT overexpression reduced fibrosis-related marker expression in RPMCs and attenuated peritoneal thickening, extracellular matrix deposition, and functional alterations in PF rats. Exogenous MNAM administration also reduced fibrotic changes and partially improved peritoneal transport parameters in PF rats. NNMT overexpression was accompanied by increased cGAS and STING expression in both models; however, pathway activity and functional involvement were not directly examined.ConclusionNNMT and MNAM exert protective effects in experimental PF. The association between NNMT overexpression and altered cGAS and STING expression requires further mechanistic investigation. The NNMT/MNAM metabolic axis may represent a potential therapeutic target for PF.
ObjectivesA successful peritoneal dialysis (PD) programme should aim to have low peritoneal dialysis-associated peritonitis (PDAP) rates. Identification of the microbial organism enables targeted antibiotic treatment and allows for a root cause analysis to be performed. Culture-negative (CN) peritonitis presents a more challenging scenario whereby empirical treatment for Gram-positive and Gram-negative organisms is commenced for 14 days, with Gram-negative cover discontinued based upon clinical response. In accordance with ISPD recommendations, we conducted a clinical quality improvement project in 2018 to decrease our culture-negative PDAP.MethodsFrom 2018 to 2021, our department had 336 cases of PDAP. The introduction of a water-lysis step and the application of 16S rRNA gene sequencing were implemented to reduce culture-negative PDAP.ResultsThere were 336 cases of PDAP between 2018 and 2021. In total, 135 cases occurred prior to the initiation of the water lysis step and 201 cases occurred after the introduction of the water lysis step and 16S rRNA sequencing. The rate of culture-negative PDAP prior to our change in PD effluent culture methodology was 33% (45/135); following changes to include a water lysis step and an increase in sample volume, the rate of culture-negative PDAP significantly fell to 20% (41/201) (p < 0.01). 16S rRNA, using Sanger sequencing of culture-negative samples, did not significantly increase pathogen detection. Five out of 6 samples remained CN in the pre-water lysis step group, and 17 out of 23 samples also remained CN in the post-water lysis group (p = 0.61).ConclusionsIntroduction of water lysis of peritoneal effluent significantly decreased culture-negative peritonitis rates, thus increasing organism identification and allowing for targeted antimicrobial therapy.
